Systematic Fe(II)-EDTA Method of Dose-Dependent Hydroxyl Radical Generation for Protein Oxidative Footprinting

Fetched: December 5th, 2023, 5:00am GMT by Jessica R Chapman

Anal Chem. 2023 Dec 4. doi: 10.1021/acs.analchem.3c02319. Online ahead of print.

ABSTRACT

Correlating the structure and dynamics of proteins with biological function is critical to understanding normal and dysfunctional cellular mechanisms. We describe a quantitative method of hydroxyl radical generation via Fe(II)-ethylenediaminetetraacetic acid (EDTA)-catalyzed Fenton chemistry that provides ready access to protein oxidative footprinting using equipment commonly found in research and process control laboratories. Robust and reproducible dose-dependent oxidation of protein samples is observed and quantitated by mass spectrometry with as fine a single residue resolution. An oxidation analysis of lysozyme provides a readily accessible benchmark for our method. The efficacy of our oxidation method is demonstrated by mapping the interface of a RAS-monobody complex, the surface of the NIST mAb, and the interface between PRC2 complex components. These studies are executed using standard laboratory tools and a few pennies of reagents; the mass spectrometry analysis can be streamlined to map the protein structure with single amino acid residue resolution.

PMID:38049117 | DOI:10.1021/acs.analchem.3c02319
Deep Learning-Enabled MS/MS Spectrum Prediction Facilitates Automated Identification Of Novel Psychoactive Substances

Fetched: December 5th, 2023, 5:00am GMT by Fei Wang

Anal Chem. 2023 Dec 4. doi: 10.1021/acs.analchem.3c02413. Online ahead of print.

ABSTRACT

The market for illicit drugs has been reshaped by the emergence of more than 1100 new psychoactive substances (NPS) over the past decade, posing a major challenge to the forensic and toxicological laboratories tasked with detecting and identifying them. Tandem mass spectrometry (MS/MS) is the primary method used to screen for NPS within seized materials or biological samples. The most contemporary workflows necessitate labor-intensive and expensive MS/MS reference standards, which may not be available for recently emerged NPS on the illicit market. Here, we present NPS-MS, a deep learning method capable of accurately predicting the MS/MS spectra of known and hypothesized NPS from their chemical structures alone. NPS-MS is trained by transfer learning from a generic MS/MS prediction model on a large data set of MS/MS spectra. We show that this approach enables a more accurate identification of NPS from experimentally acquired MS/MS spectra than any existing method. We demonstrate the application of NPS-MS to identify a novel derivative of phencyclidine (PCP) within an unknown powder seized in Denmark without the use of any reference standards. We anticipate that NPS-MS will allow forensic laboratories to identify more rapidly both known and newly emerging NPS. NPS-MS is available as a web server at [https:] which provides MS/MS spectra prediction capabilities for given NPS compounds. Additionally, it offers MS/MS spectra identification against a vast database comprising approximately 8.7 million predicted NPS compounds from DarkNPS and 24.5 million predicted ESI-QToF-MS/MS spectra for these compounds.

PMID:38048435 | DOI:10.1021/acs.analchem.3c02413
Global trends in anal cancer incidence and mortality

Fetched: December 5th, 2023, 5:00am GMT by Silvia Mignozzi

Eur J Cancer Prev. 2023 Nov 27. doi: 10.1097/CEJ.0000000000000842. Online ahead of print.

ABSTRACT

OBJECTIVE: Anal cancer is a rare disease, affecting more frequently women than men, mainly related to human papillomavirus infection (HPV). Rising incidence and mortality have been reported over the past four decades in different countries.

METHODS: To provide an up-to-date overview of recent trends in mortality from anal cancer, we analysed death certification data provided by the WHO in selected countries worldwide over the period from 1994 to 2020. We also analysed incidence derived from Cancer Incidence in Five Continents from 1990 to 2012 for all histologies as well as for anal squamous cell carcinoma (SCC).

RESULTS: The highest age-standardised mortality rates around 2020 were registered in Central and Eastern Europe, such as Slovakia (0.9/100 000 men and 0.40/100 000 women), in the UK (0.24/100 000 men and 0.35/100 000 women), and Denmark (0.33/100 000 for both sexes), while the lowest ones were in the Philippines, Mexico, and Japan, with rates below 0.10/100 000 in both sexes. Upwards trends in mortality were reported in most countries for both sexes. Similarly, incidence patterns were upward or stable in most countries considered for both sexes. In 2008-2012, Germany showed the highest incidence rates (1.65/100 000 men and 2.16/100 000 women).

CONCLUSION: Attention towards vaccination against HPV, increased awareness of risk factors, mainly related to sexual behaviours and advancements in early diagnosis and management are required to control anal cancer incidence and mortality.

PMID:38047709 | DOI:10.1097/CEJ.0000000000000842
Synthesis-based imaging-differentiation representation learning for multi-sequence 3D/4D MRI

Fetched: December 4th, 2023, 5:00am GMT by Luyi Han

Med Image Anal. 2023 Nov 29;92:103044. doi: 10.1016/j.media.2023.103044. Online ahead of print.

ABSTRACT

Multi-sequence MRIs can be necessary for reliable diagnosis in clinical practice due to the complimentary information within sequences. However, redundant information exists across sequences, which interferes with mining efficient representations by learning-based models. To handle various clinical scenarios, we propose a sequence-to-sequence generation framework (Seq2Seq) for imaging-differentiation representation learning. In this study, not only do we propose arbitrary 3D/4D sequence generation within one model to generate any specified target sequence, but also we are able to rank the importance of each sequence based on a new metric estimating the difficulty of a sequence being generated. Furthermore, we also exploit the generation inability of the model to extract regions that contain unique information for each sequence. We conduct extensive experiments using three datasets including a toy dataset of 20,000 simulated subjects, a brain MRI dataset of 1251 subjects, and a breast MRI dataset of 2101 subjects, to demonstrate that (1) top-ranking sequences can be used to replace complete sequences with non-inferior performance; (2) combining MRI with our imaging-differentiation map leads to better performance in clinical tasks such as glioblastoma MGMT promoter methylation status prediction and breast cancer pathological complete response status prediction. Our code is available at [https:]

PMID:38043455 | DOI:10.1016/j.media.2023.103044
Integrated network pharmacology and metabolomics reveal the action mechanisms of vincristine combined with celastrol against colon cancer

Fetched: December 4th, 2023, 5:00am GMT by Jin-Yu Ning

J Pharm Biomed Anal. 2023 Nov 30:115883. doi: 10.1016/j.jpba.2023.115883. Online ahead of print.

ABSTRACT

Colon cancer is associated with a high mortality rate. Vincristine (VCR) is a commonly used chemotherapeutic drug. Celastrol (CEL) is an effective component which exerts inhibitory effects on colon cancer. Combination treatment improves resistance to chemotherapeutic drugs and enhances their efficacy. Therefore, we aimed to explore the molecular mechanisms of VCR combined with CEL in colon cancer treatment. We verified the effects of VCR combined with CEL on the proliferation, cell cycle, and apoptosis of HCT-8 cells. Non-targeted metabolomic techniques were used to analyse the changes in cellular metabolites after administration. Finally, network pharmacology technology was used to screen the potential targets and pathways. VCR combined with CEL had synergistic inhibitory effects on HCT-8 colon cancer cells. Cell metabolomics identified 12 metabolites enriched in metabolic pathways, such as the phenylalanine, tyrosine and tryptophan biosynthesis pathways. Network pharmacology revealed that MAPK1, AKT1, PIK3CB, EGFR, and VEGFA were the key targets. Western blotting revealed that VCR combined with CEL activated the P53 pathway by suppressing the PI3K/AKT signalling pathway activation and Bcl-2 expression, promoting the Bax expression. Therefore, VCR combined with CEL potentially treats colon cancer by increasing the apoptosis, improving energy metabolism, and inhibiting PI3K/AKT pathway in colon cancer cells.

PMID:38044218 | DOI:10.1016/j.jpba.2023.115883
Preventive strategies for low anterior resection syndrome: a protocol for systematic review and evidence mapping

Fetched: December 2nd, 2023, 5:00am GMT by Xin-Yu Zhang

BMJ Open. 2023 Dec 1;13(12):e077279. doi: 10.1136/bmjopen-2023-077279.

ABSTRACT

INTRODUCTION: Rectal cancer is one of the top 10 cancers worldwide. Up to 80% of patients with rectal tumours have had sphincter-saving surgery, mainly due to the large expectation of anal preservation. However, patients tend to experience low anterior resection syndrome (LARS) after rectal resection, which is disordered bowel function that includes faecal incontinence, urgency, frequent defecation, constipation and evacuation difficulties. LARS, with an estimated prevalence of 41%, has been reported to substantially decrease the quality of life of patients. However, no comprehensive preventive strategies are currently available for LARS. This systematic review aims to synthesise evidence on the current LARS preventive strategies.

METHODS AND ANALYSIS: This protocol is reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) checklist. Literature in PubMed (via Medline), Embase and the Cochrane Library from inception to July 2023 will be searched to identify articles relevant to preventive effectiveness against LARS. The Cochrane Collaboration's risk of bias tool for randomised controlled trials and the Newcastle-Ottawa Scale for clinical controlled trials, cohort studies and case-control studies will be used to assess the risk of bias. We will group the included studies by the type of LARS prevention strategy and present an overview of the main findings in the form of evidence mapping. A meta-analysis is planned if there is no substantial clinical heterogeneity between the included studies. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) will be used to evaluate the quality of the evidence.

ETHICS AND DISSEMINATION: Ethical approval is not needed for systematic review of published data. The findings will be published in a peer-reviewed journal and disseminated at scientific conferences.

PROSPERO REGISTRATION NUMBER: CRD42023402886.

PMID:38040433 | PMC:PMC10693882 | DOI:10.1136/bmjopen-2023-077279
Simultaneous determination of tipiracil, trifluridine and its metabolite 5-trifluoromethyluracil in human plasma using segmented polarity LC-MS/MS: A fully validated assay with clinical application

Fetched: December 2nd, 2023, 5:00am GMT by Rong Zhang

J Pharm Biomed Anal. 2023 Nov 28;239:115885. doi: 10.1016/j.jpba.2023.115885. Online ahead of print.

ABSTRACT

Trifluridine (FTD) and tipiracil (TPI) hydrochloride tablets (TAS-102) were used for the treatment of patients with metastatic rectal cancer that was resistant to conventional chemotherapy drugs. In this study, a rapid and sensitive liquid chromatography-tandem mass spectrometry method was developed and fully validated for the simultaneous determination of TPI, FTD, and the metabolite 5-trifluoromethyluracil (FTY) of FTD in human plasma. The plasma samples were prepared by protein precipitation. The chromatography separation was performed using ACE Excel 3 AQ (100 × 2.1 mm i.d., 1.7 µm, ACE, England) column protected by a security guard cartridge (4.0 × 2.0 mm i.d., 5 µm, Phenomenex, USA) with a gradient elution of 0.05% acetic acid in water and methanol at a flow rate of 0.35 mL/min. The MS/MS analysis was performed by using multiple reaction monitoring with the segmented polarity (positive for TPI: m/z 243.1→183.0, and negative for FTD: m/z 295.1→252.0 and FTY: m/z 178.9→158.9) electrospray ionization mode. The segmented polarity mode was designed to achieve two advantages: better sensitivity and simultaneous determination of the analytes with different ion polarities. The calibration ranges were as follows: 1.00-250 ng/ for TPI, 8.00-8000 ng/mL for FTD and 5.00-1250 ng/mL for FTY. The selectivity, accuracy, precision, matrix effect, recovery, carryover, dilution integrity and stability test results meet ICH acceptance criteria. The method was evaluated using the RGB model and successfully applied to a clinical study in patients with solid tumors. For TPI, FTD and FTY, the maximum plasma concentration was 137-147 ng/mL, 6160-6240 ng/mL and 724-725 ng/mL, respectively; the plasma elimination half-life was 1.69-1.78 h, 1.70 h, and 3.09-3.14 h, respectively, after an oral administration of 60 mg TAS-102.

PMID:38039874 | DOI:10.1016/j.jpba.2023.115885
Synergistic and attenuated effects and molecular biological mechanisms of Shouhui Tongbian capsule in the treatment of slow transit constipation based on UPLC-MS/MS, network pharmacology and animal experimental validation

Fetched: December 2nd, 2023, 5:00am GMT by Na Zhang

J Pharm Biomed Anal. 2023 Nov 5;239:115846. doi: 10.1016/j.jpba.2023.115846. Online ahead of print.

ABSTRACT

BACKGROUND: Shouhui Tongbian capsule (SHTB) has been widely used for the treatment of constipation. There are few studies on SHTB at present. The current study aimed to explore the effects of multi-components compatibility of SHTB for efficacy enhancement and toxicity reduction and evaluate its molecular biological mechanisms in the treatment of slow transit constipation (STC).

METHODS: Ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to quantify 17 anthraquinone components in different compatible systems of SHTB. Network pharmacological analysis was used to probe the potential mechanisms of SHTB in treating STC. In addition, an animal experiment combined with western blot analysis was performed to further validate the predicted results.

RESULTS: After compatibility, the dissolution of 13 components with good effects in treating constipation increased, while the dissolution of 3 components with hepatotoxicity decreased. Overall, 145 common targets of 13 synergistic components and constipation were identified. A synergistic component-target-disease network showed that chrysoobtusin, obtusifolin, emodin, obtusin and 2-hydroxyl emodin-1-methyl ether were the potential key synergistic components. A protein-protein interaction network analysis identified 91 targets, and an analysis of topological characteristics was conducted to confirm the core targets. Gene Ontology function revealed that the 13 synergistic components for the treatment of STC mainly played roles via protein phosphorylation, positive regulation of phosphorylation, phosphotransferase activity, kinase activity and protein kinase activity, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that these components were enriched in pathways in cancer, MAPK signaling pathway, IL-17 signaling pathway, NF-κB signaling pathway, etc. The results of animal experimental validation showed that SHTB significantly reduced the expression levels of p-p38 and p-ERK proteins in the colon tissue of the STC rats.

CONCLUSION: This study preliminarily demonstrated that efficacy enhancement and toxicity reduction of SHTB could be achieved after compatibility, which expounded the connotation of compatibility theory of traditional Chinese medicine from the perspective of chemical composition, reflecting the rationality and scientificity of compatibility theory. Meanwhile, the study also revealed the core targets and potential molecular biological mechanisms of SHTB in the treatment of STC, which may serve as a reference for subsequent studies and clinical applications of SHTB.

PMID:38039873 | DOI:10.1016/j.jpba.2023.115846
Methylene Blue-Stained Single-Stranded DNA Aptamers as a Highly Efficient Electronic Switch for Quasi-Reagentless Exosomes Detection: An Old Dog with New Tricks

Fetched: December 2nd, 2023, 5:00am GMT by Yanhong Wang

Anal Chem. 2023 Dec 1. doi: 10.1021/acs.analchem.3c03715. Online ahead of print.

ABSTRACT

Improving the convenience, sensitivity, and cost-effectiveness of electrochemical biosensors is crucial for advancing their clinical diagnostic applications. Herein, we presented an elegant approach to construct electrochemical aptasensors for tumor-derived exosome detection by harnessing the alterable interaction between methylene blue (MB) and DNA aptamer. In detail, the anti-EpCAM aptamer, named SYL3C, was found to exhibit a strong affinity toward MB due to the specific interaction between MB and unbound guanine bases. Thereby, SYL3C could be stained with MB to arouse a strong electrochemical signal on a gold electrode (AuE). Upon binding to EpCAM-positive exosomes, SYL3C underwent a conformational transformation. The resulting conformation, or exosomes-SYL3C complex, not only reduced the accumulation of MB on SYL3C by obstructing the accessibility of guanines to MB but also impeded the transfer of electrons from the bound MB to AuE, leading to a notable decrease in the electrochemical signal. Using MB-stained SYL3C as an electronic switch, an electrochemical aptasensor was readily established for the detection of EpCAM-positive exosome detection. Without the need for signal amplification strategies, expensive auxiliary reagents, and complex operation, this unique signal transduction mechanism alone could endow the aptasensor with ultrahigh sensitivity. A limit of detection (LOD) of 234 particles mL^-1 was achieved, surpassing the performance of most reported methods. As a proof of concept, the aptasensor was applied to analyze clinical serum samples and effectively distinguish non-small-cell lung cancer (NSCLC) patients from healthy individuals. As EpCAM exhibits broad expression in exosomes derived from different tumor sources, the developed aptasensor holds promise for diagnosing other tumor types.

PMID:38037816 | DOI:10.1021/acs.analchem.3c03715
Transcriptionally activates CCL28 expression to inhibit M2 polarization of macrophages and prevent immune escape in colorectal cancer cells

Fetched: December 1st, 2023, 5:00am GMT by Shiquan Li

Transl Oncol. 2023 Nov 29;40:101842. doi: 10.1016/j.tranon.2023.101842. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to investigate the potential molecular mechanism of SPDEF in immune evasion of colorectal cancer (CRC) and examine its impact on macrophage M2 polarization using the TCGA and GEO databases.

METHODS: By combining TCGA and GEO databases, differential gene expression between CRC samples and standard tissue samples was analyzed to screen for immune-related genes (IRGs) associated with the prognosis of CRC patients. A predictive risk model was constructed based on 18 key IRGs, which were then validated using the GEO dataset. The relationship between transcription factors and IRGs was further explored to investigate their regulatory network in CRC. In vivo and in vitro experiments were carried out to validate these regulatory relationships and explore the function of SPDEF and CCL28 in CRC.

RESULTS: Twelve key IRGs associated with clinical and pathological characteristics of CRC patients were identified. Among them, CCL28 significantly impacted macrophage infiltration in CRC cells and may be a critical factor in immune evasion. In both in vitro and in vivo experiments, overexpression of SPDEF upregulated CCL28 expression, thereby suppressing M2 polarization of macrophages and inhibiting CRC cell proliferation and tumor growth. Notably, interference with CCL28 could reverse the effect of SPDEF overexpression.

CONCLUSION: SPDEF can suppress immune evasion of CRC cells by activating CCL28, which is achieved through the modulation of M2 polarization of macrophages. This provides a new research direction and potential therapeutic target for immunotherapy in CRC.

PMID:38035446 | DOI:10.1016/j.tranon.2023.101842
Potential role of a novel endoscopic retrieval bag for large colorectal resected specimen: a proof-of-concept study

Fetched: December 1st, 2023, 5:00am GMT by Yasuhiro Tani

Endosc Int Open. 2023 Aug 1;11(8):E714-E718. doi: 10.1055/a-2098-2664. eCollection 2023 Aug.

ABSTRACT

Endoscopic submucosal dissection enables en bloc resection of large superficial colorectal neoplasms. However, it is sometimes challenging to retrieve a large resected specimen via the anus without sample fragmentation. A novel "bag-type" retrieval device has been developed to accomplish complete isolation and non-destructive delivery of oversized specimens. This single-center retrospective study was performed to demonstrate the efficacy of this device for large colorectal resected specimens. Among 17 patients, we identified 18 superficial colorectal lesions for which the use of a novel retrieval device (Endo Carry Large Type) was indicated at specimen delivery at a referral cancer institute from March 2021 to July 2022. The median (interquartile range) tumor size was 62.5 (52.0-79.5) mm. Retrieval of 17 (94%) of 18 resected specimens was performed using the Endo Carry Large Type, and 16 (89%) were successfully retrieved without sample fragmentation. The median (interquartile range) retrieval time was 4 (4-8) minutes, and no apparent adverse events were observed. The novel Endo Carry Large Type device can accomplish colorectal specimen retrieval safely and quickly without specimen damage and therefore may contribute to accurate pathological diagnosis.

PMID:38033744 | PMC:PMC10683754 | DOI:10.1055/a-2098-2664
Risk of cancer in acromegaly patients: An updated meta-analysis and systematic review

Fetched: December 1st, 2023, 5:00am GMT by Zhehao Xiao

PLoS One. 2023 Nov 30;18(11):e0285335. doi: 10.1371/journal.pone.0285335. eCollection 2023.

ABSTRACT

The incidence of cancer in acromegaly patients may be higher than that in the general population, although this has not been fully elucidated yet. This study analyzed the risk of various important types of cancer in acromegaly patients. The study was registered in INPLASY (registration number: INPLASY202340037). The PubMed, Web of Science, and EMBASE databases were searched for studies based on strict inclusion and exclusion criteria, from the time of database inception up to June 30, 2022. All observational studies of acromegaly patients with cancer were included, without language restrictions. We used the Newcastle-Ottawa scale (NOS) checklist to assess the quality of evidence. A meta-analysis revealed the relationship between acromegaly and cancer using the standardized incidence rates (SIRs) and 95% confidence intervals (CIs) retrieved from the included studies. Nineteen studies were included and analyzed. The overall incidence of cancer (SIR = 1.45, 95%CI = 1.20-1.75), as well as that of thyroid (SIR = 6.96, 95%CI = 2.51-19.33), colorectal and anal (SIR = 1.95, 95%CI = 1.32-2.87), brain and central nervous system (SIR = 6.14, 95%CI = 2.73-13.84), gastric (SIR = 3.09, 95%CI = 1.47-6.50), urinary (SIR = 2.66, 95%CI = 1.88-3.76), hematological (SIR = 1.89, 95%CI = 1.17-3.06), pancreatic and small intestine (SIR = 2.59, 95%CI = 1.58-4.24), and connective tissue (SIR = 3.15, 95%CI = 1.18-8.36) cancers, was higher among patients with acromegaly than among the general population. No association between acromegaly and hepatobiliary, respiratory, reproductive, skin, breast, or prostate cancer was observed. This study demonstrated that acromegaly patients have a modestly increased chance of cancer as compared to the general population. Risk factors for cancer need to be further explored to monitor patients with acromegaly at a high risk for cancer more carefully.

PMID:38032888 | PMC:PMC10688666 | DOI:10.1371/journal.pone.0285335
Trace Sample Proteome Quantification by Data-Dependent Acquisition without Dynamic Exclusion

Fetched: December 1st, 2023, 5:00am GMT by Ci Wu

Anal Chem. 2023 Nov 30. doi: 10.1021/acs.analchem.3c03357. Online ahead of print.

ABSTRACT

Despite continuous technological improvements in sample preparation, mass-spectrometry-based proteomics for trace samples faces the challenges of sensitivity, quantification accuracy, and reproducibility. Herein, we explored the applicability of turboDDA (a method that uses data-dependent acquisition without dynamic exclusion) for quantitative proteomics of trace samples. After systematic optimization of acquisition parameters, we compared the performance of turboDDA with that of data-dependent acquisition with dynamic exclusion (DEDDA). By benchmarking the analysis of trace unlabeled human cell digests, turboDDA showed substantially better sensitivity in comparison with DEDDA, whether for unfractionated or high pH fractionated samples. Furthermore, through designing an iTRAQ-labeled three-proteome model (i.e., tryptic digest of protein lysates from yeast, human, and E. coli) to document the interference effect, we evaluated the quantification interference, accuracy, reproducibility of iTRAQ labeled trace samples, and the impact of PIF (precursor intensity fraction) cutoff for different approaches (turboDDA and DEDDA). The results showed that improved quantification accuracy and reproducibility could be achieved by turboDDA, while a more stringent PIF cutoff resulted in more accurate quantification but less peptide identification for both approaches. Finally, the turboDDA strategy was applied to the differential analysis of limited amounts of human lung cancer cell samples, showing great promise in trace proteomics sample analysis.

PMID:38032138 | DOI:10.1021/acs.analchem.3c03357
Using Functionalized Liposomes to Harvest Extracellular Vesicles of Similar Characteristics in Dermal Interstitial Fluid

Fetched: December 1st, 2023, 5:00am GMT by Tingjun Cheng

Anal Chem. 2023 Nov 30. doi: 10.1021/acs.analchem.3c04306. Online ahead of print.

ABSTRACT

Extracellular vesicles (EVs) are used by living cells for the purpose of biological information trafficking from parental-to-recipient cells and vice versa. This back-and-forth communication is enabled by two distinct kinds of biomolecules that constitute the cargo of an EV: proteins and nucleic acids. The proteomic-cum-genetic information is mediated by the physiological state of a cell (healthy or otherwise) as much as modulated by the biogenesis pathway of the EV. Therefore, in mirroring the huge diversities of human communications, the proteins and nucleic acids involved in cell communications possess seemingly near limitless diversities, and it is this characteristic that makes EVs so highly heterogeneous. Currently, there is no simple and reliable tool for the selective capture of heterogeneous EVs and the delivery of their undamaged cargo for research in extracellular protein mapping and spatial proteomics studies. Our work is a preliminary attempt to address this issue. We demonstrated our approach by using antibody functionalized liposomes to capture EVs from tumor and healthy cell-lines. To characterize their performance, we presented fluorescence and nanoparticle tracking analysis (NTA) results, TEM images, and Western blotting analysis for EV proteins. We also extracted dermal interstitial fluid (ISF) from healthy individuals and used our functionalized synthetic vesicle (FSV) method to capture EVs from their proteins. We constructed three proteomic sets [EV vs ISF, (FSV+EV) vs ISF, and (FSV+EV) vs EV] from the EV proteins and the free proteins harvested from ISF and compared their differentially expressed proteins (DEPs). The performance of our proposed method is assessed via an analysis of 1095 proteins, together with volcano plots, heatmap, GO annotation, and enriched KEGG pathways and organelle localization results of 213 DEPs.

PMID:38032052 | DOI:10.1021/acs.analchem.3c04306
Impact of screening programme to prevent anal cancer in high-risk patients with HIV

Fetched: December 1st, 2023, 5:00am GMT by Eloïse Leclerc

HIV Med. 2023 Nov 30. doi: 10.1111/hiv.13594. Online ahead of print.

ABSTRACT

INTRODUCTION: We assessed the impact of a nationwide screening programme to reduce the risk of anal cancer in a large cohort of high-risk patients with HIV.

METHODS: From a large database from one referral centre, all high-risk patients with HIV (men who have sex with men, history of anal or genital warts, or previous cervix human papillomavirus-related lesions) who were eligible to enter the French anal cancer screening programme (2011-2020) were retrospectively included. Adherence to the screening programme was defined as no interval >18 months between two visits. Standardized management included perianal visualization and standard anoscopy with biopsies of macroscopic abnormalities.

RESULTS: Overall, 700 patients with HIV were included (median follow-up 8.4 years [interquartile range 4.3-9.2] and 1491.6 patient-years), and 336 had one or more proctology visit. A total of 13 patients were diagnosed with anal squamous cell carcinomas. The risk of anal cancer was higher with anal intra-epithelial neoplasia grade 3 (AIN3; hazard ratio [HR] 44.5 [95% confidence interval {CI} 11.2-176.6], p < 0.001), AIN2 (HR 11.9 [95% CI 2.1-66.9], p = 0.005), or high-grade dysplasia (HR 23.4 [95% CI 7.9-69.1], p < 0.001) than with low-grade dysplasia or no lesion. Among the patients who were strictly adherent to the screening programme (4.6% [32/700]), we did not report any AIN or anal cancer, but we also did not observe any significant reduction in the risk of anal cancer (p = 0.51), AIN3 (p = 0.28), high-grade dysplasia (p = 0.19), or any AIN lesions (p = 0.10) compared with non-adherent patients. In contrast, screened patients were more likely to be diagnosed with anal warts (HR 3.71 [95% CI 2.14-6.42], p < 0.001).

CONCLUSION: Macroscopic high-grade dysplasia lesions are associated with a higher risk of developing anal cancer. Despite finding no cases of cancer during the screening programme, we also did not demonstrate a clear benefit from our screening programme for the prevention of anal cancer in high-risk patients with HIV.

PMID:38031816 | DOI:10.1111/hiv.13594
Smart Ratiometric SERS Nanoprobe for Real-Time Monitoring Hydrogen Peroxide in Living Cells during NADH Treatment Associated with Ferroptosis

Fetched: November 30th, 2023, 5:00am GMT by Dan Sun

Anal Chem. 2023 Nov 29. doi: 10.1021/acs.analchem.3c02912. Online ahead of print.

ABSTRACT

Studying the oxidative stress, especially the reactive oxygen species (ROS) response of ferroptosis, is crucial for the diagnosis and treatment of cancer based on ferroptosis. However, reliable quantitative analysis of intracellular ROS in cancer treatment for drug screening is still a challenge. Herein, a superior ratiometric SERS nanoprobe was developed for in situ, real-time, and highly sensitive detection of content variation of H2O2 within living cells. The SERS nanoprobe was prepared by coassembly of the internal standard molecule p-mercaptobenzonitrile and the reporter molecule p-mercaptophenylboronic acid on the surface of gold nanoparticles, used for synergistic calibration and detection of H2O2, which enables reliable detection of the true content of intracellular H2O2 without the interference of other substances in cells. Based on the nanoprobe, we found that the level of intracellular H2O2 of cancer cells was increased after the nicotinamide adenine dinucleotide (NADH) treatment, with a dose-dependence to the concentration of NADH. High doses of NADH (above 20 mM) can induce cell death by means of ferroptosis associated with the level elevation of intracellular lipid hydroperoxides. This study highlights the potential of the SERS nanoprobe for tracking content variation of cellular H2O2 and understanding its roles in screening new anticancer drugs.

PMID:38030577 | DOI:10.1021/acs.analchem.3c02912
Temperature Effect on the Electrochemical Current Response during Scanning Electrochemical Microscopy of Living Cells

Fetched: November 30th, 2023, 5:00am GMT by Nikita Thomas

Anal Chem. 2023 Nov 29. doi: 10.1021/acs.analchem.3c03716. Online ahead of print.

ABSTRACT

Scanning electrochemical microscopy (SECM) is being used increasingly to monitor electrochemical processes at the interface of living cells and electrodes. This allows the detection and quantification of biomarkers that further the understanding of various diseases. Rapid SECM experiments are often carried out without monitoring the analyte solution temperature or are performed at room temperature. The reported research demonstrates that temperature control is crucial during SECM imaging of living cells to obtain reliable data. In this study, a SECM-integrated thermostatic ring on the sample stage enabled imaging of living biological cells in a constant height mode at various temperatures. Two-dimensional line scans were conducted while scanning single Adenocarcinoma Cervical cancer (HeLa) cells. Numerical modeling was carried out to evaluate the effect of the temperature on the electrochemical current response of living cells to compare the apparent heterogeneous rate constant (k0), representing cellular reaction kinetics. This study reveals that even slight temperature variations of approximately 2 °C affect the reaction kinetics of single living cells, altering the measured current during SECM.

PMID:38029336 | DOI:10.1021/acs.analchem.3c03716
Rectal ulcer associated with lenvatinib 15 years after definitive radiotherapy for prostate cancer: A case report

Fetched: November 30th, 2023, 5:00am GMT by Yujiro Kawata

Oncol Lett. 2023 Nov 8;27(1):6. doi: 10.3892/ol.2023.14139. eCollection 2024 Jan.

ABSTRACT

Lenvatinib is a multi-kinase inhibitor that blocks vascular endothelial growth factor, fibroblast growth factor and platelet-derived growth factor receptors. The present study describes a case of rectal ulceration triggered by lenvatinib treatment for hepatocellular carcinoma 15 years after definitive radiotherapy for prostate cancer. A 58-year-old man underwent definitive external beam radiotherapy and high-dose-rate brachytherapy for prostate cancer. A total of 15 years after radiotherapy for prostate cancer, the patient was diagnosed with hepatocellular carcinoma with multiple metastases. Treatment with 12 mg/day lenvatinib was commenced. A total of 4 months after starting lenvatinib therapy, the patient experienced persistent anal pain with a deep ulceration of the anterior wall of the lower rectum. As the pain did not improve, the patient chose to undergo a colostomy, resulting in the resolution of the anorectal pain. To the best of our knowledge, the present case report is the first to report on lenvatinib-induced rectal ulcers after radiotherapy.

PMID:38028175 | PMC:PMC10665994 | DOI:10.3892/ol.2023.14139
Histone deacetylase inhibitor pracinostat suppresses colorectal cancer by inducing CDK5-Drp1 signaling-mediated peripheral mitofission

Fetched: November 30th, 2023, 5:00am GMT by Xiao-Ling Liang

J Pharm Anal. 2023 Oct;13(10):1168-1182. doi: 10.1016/j.jpha.2023.06.005. Epub 2023 Jun 10.

ABSTRACT

Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells. Pharmacological induction of excessively asymmetric mitofission-associated cell death (MFAD) by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy. By screening a series of pan-inhibitors, we identified pracinostat, a pan-histone deacetylase (HDAC) inhibitor, as a novel MFAD inducer, that exhibited a significant anticancer effect on colorectal cancer (CRC) in vivo and in vitro. Pracinostat increased the expression of cyclin-dependent kinase 5 (CDK5) and induced its acetylation at residue lysine 33, accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynamin-related protein 1 (Drp1)-mediated mitochondrial peripheral fission. CRC cells with high level of CDK5 (CDK5-high) displayed midzone mitochondrial division that was associated with oncogenic phenotype, but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells. Mechanistically, pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor (MFF) to mitochondrial fission 1 protein (FIS1). Thus, our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells, which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.

PMID:38024857 | PMC:PMC10657975 | DOI:10.1016/j.jpha.2023.06.005
In vivo solid phase microextraction for therapeutic monitoring and pharmacometabolomic fingerprinting of lung during in vivo lung perfusion of FOLFOX

Fetched: November 30th, 2023, 5:00am GMT by Nikita Looby

J Pharm Anal. 2023 Oct;13(10):1195-1204. doi: 10.1016/j.jpha.2023.04.005. Epub 2023 Apr 12.

ABSTRACT

In vivo lung perfusion (IVLP) is a novel isolated lung technique developed to enable the local, in situ administration of high-dose chemotherapy to treat metastatic lung cancer. Combination therapy using folinic acid (FOL), 5-fluorouracil (F), and oxaliplatin (OX) (FOLFOX) is routinely employed to treat several types of solid tumours in various tissues. However, F is characterized by large interpatient variability with respect to plasma concentration, which necessitates close monitoring during treatments using of this compound. Since plasma drug concentrations often do not reflect tissue drug concentrations, it is essential to utilize sample-preparation methods specifically suited to monitoring drug levels in target organs. In this work, in vivo solid-phase microextraction (in vivo SPME) is proposed as an effective tool for quantitative therapeutic drug monitoring of FOLFOX in porcine lungs during pre-clinical IVLP and intravenous (IV) trials. The concomitant extraction of other endogenous and exogenous small molecules from the lung and their detection via liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) enabled an assessment of FOLFOX's impact on the metabolomic profile of the lung and revealed the metabolic pathways associated with the route of administration (IVLP vs. IV) and the therapy itself. This study also shows that the immediate instrumental analysis of metabolomic samples is ideal, as long-term storage at -80 °C results in changes in the metabolite content in the sample extracts.

PMID:38024854 | PMC:PMC10657970 | DOI:10.1016/j.jpha.2023.04.005
Feasibility and safety of specimen extraction via an enlarged (U-Plus) skin bridge loop ileostomy: a single-center retrospective comparative study

Fetched: November 30th, 2023, 5:00am GMT by Shang Xiang

Front Oncol. 2023 Nov 8;13:1273499. doi: 10.3389/fonc.2023.1273499. eCollection 2023.

ABSTRACT

OBJECTIVE: To investigate the feasibility and safety of specimen extraction via an enlarged (U-Plus) skin bridge loop ileostomy.

METHODS: A retrospective analysis of 95 patients with rectal cancer who underwent laparoscopic low anterior rectal resection and skin bridge loop ileostomy between August 2018 and August 2022, including 44 patients with specimen extraction via an enlarged (U-Plus) skin bridge loop ileostomy (experimental group) and 51 patients with specimen extraction via an abdominal incision (control group). Following the application of propensity score matching (PSM), 34 pairs of data were successfully matched. Subsequently, a comparative analysis was conducted on the clinical data of the two groups.

RESULTS: The experimental group exhibited significantly better outcomes than the control group in various aspects. Specifically, the experimental group had lower values for average operative time (P < 0.001), estimated blood loss (P < 0.001), median length of visible incision after surgery (P < 0.001), median VAS pain score on the first day after surgery (P = 0.015), and average postoperative hospitalization (P = 0.001). There was no statistical significance observed in the incidence of stoma-related complications in both groups (P > 0.05). Within each group, the stoma-QOL scores before stoma closure surgery were significantly higher than those at one month and two months after the surgery, with statistical significance (P < 0.05).

CONCLUSION: Specimen extraction via a U-Plus skin bridge loop ileostomy is a safe and feasible method that shortens operation time and postoperative visual incision length, decreases estimated blood loss, and reduces patient postoperative pain compared with specimen extraction via an abdominal incision.

PMID:38023201 | PMC:PMC10665085 | DOI:10.3389/fonc.2023.1273499
A multi-centric evaluation of self-learning GAN based pseudo-CT generation software for low field pelvic magnetic resonance imaging

Fetched: November 30th, 2023, 5:00am GMT by Jessica Prunaretty

Front Oncol. 2023 Nov 10;13:1245054. doi: 10.3389/fonc.2023.1245054. eCollection 2023.

ABSTRACT

PURPOSE/OBJECTIVES: An artificial intelligence-based pseudo-CT from low-field MR images is proposed and clinically evaluated to unlock the full potential of MRI-guided adaptive radiotherapy for pelvic cancer care.

MATERIALS AND METHOD: In collaboration with TheraPanacea (TheraPanacea, Paris, France) a pseudo-CT AI-model was generated using end-to-end ensembled self-supervised GANs endowed with cycle consistency using data from 350 pairs of weakly aligned data of pelvis planning CTs and TrueFisp-(0.35T)MRIs. The image accuracy of the generated pCT were evaluated using a retrospective cohort involving 20 test cases coming from eight different institutions (US: 2, EU: 5, AS: 1) and different CT vendors. Reconstruction performance was assessed using the organs at risk used for treatment. Concerning the dosimetric evaluation, twenty-nine prostate cancer patients treated on the low field MR-Linac (ViewRay) at Montpellier Cancer Institute were selected. Planning CTs were non-rigidly registered to the MRIs for each patient. Treatment plans were optimized on the planning CT with a clinical TPS fulfilling all clinical criteria and recalculated on the warped CT (wCT) and the pCT. Three different algorithms were used: AAA, AcurosXB and MonteCarlo. Dose distributions were compared using the global gamma passing rates and dose metrics.

RESULTS: The observed average scaled (between maximum and minimum HU values of the CT) difference between the pCT and the planning CT was 33.20 with significant discrepancies across organs. Femoral heads were the most reliably reconstructed (4.51 and 4.77) while anal canal and rectum were the less precise ones (63.08 and 53.13). Mean gamma passing rates for 1%1mm, 2%/2mm, and 3%/3mm tolerance criteria and 10% threshold were greater than 96%, 99% and 99%, respectively, regardless the algorithm used. Dose metrics analysis showed a good agreement between the pCT and the wCT. The mean relative difference were within 1% for the target volumes (CTV and PTV) and 2% for the OARs.

CONCLUSION: This study demonstrated the feasibility of generating clinically acceptable an artificial intelligence-based pseudo CT for low field MR in pelvis with consistent image accuracy and dosimetric results.

PMID:38023165 | PMC:PMC10667706 | DOI:10.3389/fonc.2023.1245054
Clinical application of two-port laparoscopic surgery in sigmoid colon and upper rectal cancer resection

Fetched: November 30th, 2023, 5:00am GMT by Feng Jiang

Front Oncol. 2023 Nov 6;13:1248280. doi: 10.3389/fonc.2023.1248280. eCollection 2023.

ABSTRACT

BACKGROUND: In the field of minimally invasive surgery, the two-port laparoscopic surgery is on the rise. This study investigated the safety and efficacy of two-port laparoscopic surgery (TLS) for resecting sigmoid colon and upper rectal cancers compared with conventional laparoscopic surgery (CLS).

METHODS: The clinical data of patients undergoing laparoscopic sigmoid colon cancer and upper rectal cancer resection at the Department of General Surgery of the First Affiliated Hospital of Gannan Medical College between July 2019 and January 2022 were retrospectively collected. Grouped according to different laparoscopic surgery. Based on the inclusion and exclusion criteria,A total of 81 patients were enrolled, of the 25 patients from the TLS group,and of the 56 patients from the CLS group. We mainly compared whether there were statistical differences between the two groups in terms of operative time, intraoperative bleeding, incision length, time to first ambulation, time to first flatus, time to first defecation, postoperative complication rate, and other surgical outcomes.

RESULTS: There was no statistical difference between the two groups in terms of baseline clinical characteristics (P > 0.05). In terms of the surgical outcomes, there were statistical differences in the total incision length (TLS: 6.21 ± 0.67 cm, CLS: 8.64 ± 1.08 cm, P < 0.001)), time to first ambulation (TLS: 2.0 ± 0.7 d, CLS:3.1 ± 0.9 d, P < 0.001), time to first flatus (TLS: 2.5 ± 0.8 d, CLS: 3.0 ± 0.8 d, P = 0.028), time to first defecation (TLS: 3.8 ± 1.3 d, CLS: 5.1 ± 2.1 d, P = 0.010), and time for liquid diet (TLS: 4.3 ± 1.4 d, CLS: 5.3 ± 1.9 d, P = 0.021). There was no statistical difference between the two groups in terms of the pathology (P > 0.05).

CONCLUSION: In terms of safety, TLS in sigmoid colon and upper rectal cancer resection is comparable to CLS. However, its incision is smaller and more aesthetic, and it causes lesser trauma than CLS. Additionally, it is also superior to CLS in postoperative recovery.

PMID:38023157 | PMC:PMC10658933 | DOI:10.3389/fonc.2023.1248280
Efficiency of the Robotic Platform in Improving the Rate of Sphincter Preservation in Patients With Mid and Low Rectal Cancer

Fetched: November 30th, 2023, 5:00am GMT by Thalia Petropoulou

World J Oncol. 2023 Dec;14(6):499-504. doi: 10.14740/wjon1581. Epub 2023 Oct 25.

ABSTRACT

BACKGROUND: The aim of this study was to investigate whether the robotic platform can have a positive impact on the rate of sphincter preservation in patients with rectal tumors, undergoing robotic total mesorectal excision (TME), in comparison with laparoscopic or open TME. We also analyzed and compared short-term outcomes.

METHODS: A prospectively collected robotic database was reviewed and compared with the trust and national data. Three groups were designed according to the surgical technique: open, laparoscopic and robotic. This includes all resections for mid and low rectal cancer which were performed with the robotic platform, over a period of 4 years, versus the trust data for the same period.

RESULTS: Two hundred ninety-seven patients with mid and low rectal cancers were analyzed. Demographics for the groups (gender, age, and body mass index) were similar but distance from anal verge was shorter in the robotic group (7 vs. 8.5 cm, P < 0.001). The percentage of abdominoperineal resection (APR) rate was significantly lower in the robotic group (13.5% vs. 39.6% vs. 52.4% for the open group, P < 0.001). Median length of stay, complication rate, and positive circumferential resection margin (CRM) rate for the robotic group were also statistically significantly lower than those for both laparoscopic and open groups.

CONCLUSION: Robotic surgery for mid and low rectal cancer is safe and feasible, and could help surgeons perform ultra-low anterior resections, rather than APRs and save patients' sphincters. Positive CRM is low, which could lead to improved oncological outcomes.

PMID:38022401 | PMC:PMC10681784 | DOI:10.14740/wjon1581
Radiation-Induced Peripheral Artery Disease in a 63-Year-Old Patient

Fetched: November 30th, 2023, 5:00am GMT by Claudia Aleman Oliva

Cureus. 2023 Oct 20;15(10):e47372. doi: 10.7759/cureus.47372. eCollection 2023 Oct.

ABSTRACT

Tobacco use, hypertension, diabetes, and hypercholesterolemia are known risk factors for peripheral artery disease (PAD). However, additional causes of PAD, such as radiation therapy, should be considered for the prevention and diagnosis of this disease. The patient described in this report had 36 radiation therapies directly to the pelvis and bladder area due to bladder cancer. The presence of severe PAD on this patient's right external iliac artery, the same area where he received radiation therapy, raises the question of whether radiation therapy contributed to the development of PAD. In addition, his history of anal intraepithelial neoplasia, obstructive uropathy, and chronic kidney disease further demonstrated that he possibly suffered extensive tissue damage due to radiation to the pelvis. This case report explores the current diagnosis guidelines and treatment options for patients with radiation-induced PAD. Through this case study, we aim to bring awareness to this lesser-known cause of PAD among medical providers and promote research for the prevention and treatment of this disease.

PMID:38022038 | PMC:PMC10657155 | DOI:10.7759/cureus.47372
DNA Sensor-Based Strategy to Visualize the TRPM7 mRNA-Mg2+ Signaling Pathway in Cancer Cells

Fetched: November 30th, 2023, 5:00am GMT by Shuhang Yin

Anal Chem. 2023 Nov 29. doi: 10.1021/acs.analchem.3c03323. Online ahead of print.

ABSTRACT

Technological advances and methodological innovations in cell signaling pathway analysis will facilitate progress in understanding biological processes, intervening in diseases, and screening drugs. In this work, an elaborate strategy for visualizing and monitoring the transient receptor potential melastatin 7 (TRPM7)-Mg²⁺ signaling pathway in living cells was constructed through the logical analysis of upstream mRNA and downstream molecules by two individual DNA sensors. The DNA sensors are constructed by modifying the dye-labeled DNA sequences on the surface of gold nanoparticles. By hybridizing with upstream mRNA, Cy5-modified DNA sensor 1 can detect and silence it simultaneously, outputting a red fluorescence signal. When the upstream mRNA is silenced, the concentration of downstream molecules of Mg²⁺ will be affected and down-regulated. The FAM-modified DNA sensor 2 detects this change and emits a green fluorescence as a signal. Therefore, the dynamic information on TRPM7 mRNA and the Mg²⁺-mediated signaling pathway can be successfully obtained by fluorescence imaging methods. Furthermore, the TRPM7 mRNA-Mg²⁺ signaling pathway also affects cell activity and migratory function through cell scratching and other experiments. More importantly, the proposed sensor also shows potential for screening signaling pathway inhibitors. Our work provides a simple and general strategy for the visualization of signaling pathways, which helps to understand the changes in the physiological activities of cancer cells and the causes of carcinogenesis and is crucial for cancer diagnosis and prognosis.

PMID:38019640 | DOI:10.1021/acs.analchem.3c03323
Viscoelastic-Sorting Integrated Deformability Cytometer for High-Throughput Sorting and High-Precision Mechanical Phenotyping of Tumor Cells

Fetched: November 30th, 2023, 5:00am GMT by Yao Chen

Anal Chem. 2023 Nov 29. doi: 10.1021/acs.analchem.3c03792. Online ahead of print.

ABSTRACT

The counts and phenotypes of circulating tumor cells (CTCs) in whole blood are useful for disease monitoring and prognostic assessment of cancer. However, phenotyping CTCs in the blood is difficult due to the presence of a large number of background blood cells, especially some blood cells with features similar to those of tumor cells. Herein, we presented a viscoelastic-sorting integrated deformability cytometer (VSDC) for high-throughput label-free sorting and high-precision mechanical phenotyping of tumor cells. A sorting chip for removing large background blood cells and a detection chip for detecting multiple cellular mechanical properties were integrated into our VSDC. Our VSDC has a sorting efficiency and a purity of over 95% and over 81% for tumor cells, respectively. Furthermore, multiple mechanical parameters were used to distinguish tumor cells from white blood cells using machine learning. An accuracy of over 97% for identifying tumor cells was successfully achieved with the highest identification accuracy of 99.4% for MCF-7 cells. It is envisioned that our VSDC will open up new avenues for high-throughput and label-free single-cell analysis in various biomedical applications.

PMID:38018866 | DOI:10.1021/acs.analchem.3c03792
Effects of metronidazole on colorectal cancer occurrence and colorectal cancer liver metastases by regulating Fusobacterium nucleatum in mice

Fetched: November 30th, 2023, 5:00am GMT by Maijian Wang

Immun Inflamm Dis. 2023 Nov;11(11):e1067. doi: 10.1002/iid3.1067.

ABSTRACT

OBJECTIVE: Colorectal cancer (CRC) represents a leading cause of cancer-related deaths. Metronidazole (MNZ) is exceedingly implicated in CRC. This study explored the roles of MNZ in mouse CRC occurrence and liver metastasis (CRLM).

METHODS: Male BALB/c nude mice were subjected to CRC and CRLM modeling, orally administration with MNZ (1 g/L) 1 week before modeling, and disease activity index (DAI) evaluation. Fresh stool and anal swab samples were collected on the morning of the 28th day after modeling. The relative expression of Fusobacterium nucleatum (F. nucleatum) DNA was assessed by quantitative polymerase chain reaction. After euthanasia, tumor tissues and liver tissues were separated and the tumor volume and weight change were measured. The liver tissues were stained with hematoxylin-eosin to quantitatively analyze the metastatic liver nodules. Malignant tumor biomarker Ki67 protein levels in liver tissues/DNA from stool samples were detected by immunohistochemistry/high-throughput 16S rRNA gene sequencing. Bioinformatics analysis was performed on the raw sequence data to analyze microbial community richness (Chao1 index, ACE index) and microbial community diversity (Shannon index).

RESULTS: The DAI and F. nucleatum DNA relative expression in feces and anal swabs of the CRC and CRLM groups were raised and repressed after MNZ intervention. MNZ repressed tumor occurrence and growth in mice to a certain extent, alleviated CRLM malignant degree (reduced liver metastases and Ki67-positive cell density/number), and suppressed CRC liver metastasis by regulating intestinal flora structure, which affected the intestinal characteristic flora of CRC and CRLM mice.

CONCLUSION: MNZ suppressed CRC occurrence and CRLM in mice by regulating intestinal F. nucleatum.

PMID:38018574 | PMC:PMC10683560 | DOI:10.1002/iid3.1067
Long-term overall survival in patients undergoing liver resection for metastatic anal squamous cell carcinoma

Fetched: November 30th, 2023, 5:00am GMT by Winifred M Lo

J Surg Oncol. 2023 Nov 29. doi: 10.1002/jso.27539. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: There is limited research on management of metastatic anal canal squamous cell carcinoma (SCC) to the liver. This study aimed to describe outcomes for patients undergoing liver resection of anal SCC metastases.

METHODS: A multicenter, retrospective cohort study was conducted by three tertiary-referral centers. Patients undergoing liver surgery between 2008 and 2022 were included. Cox regression analysis was performed to evaluate predictors of recurrence and survival and Kaplan-Meier analysis was performed for 1-, 3-, and 5-year survival.

RESULTS: Twenty-one patients underwent liver resection and/or ablation. None were HIV positive and 24% had known HPV infection. 20/21(95%) patients had undergone Nigro protocol for management of the primary tumor with 12/21 (57%) patients experiencing complete response. 4/21 (19%) patients had synchronous liver metastases at time of diagnosis. Median tumor size was 5.0 cm and median tumor number was one. At analysis, 52% remained alive. Median overall survival was 32.2 months. 5-year overall survival was 50%. Median recurrence-free survival was 7.7 months and 5-year recurrence-free survival was 30%. Need for salvage abdominoperineal resection was negatively associated with recurrence-free survival. The most common site of recurrence was the liver.

CONCLUSIONS: Liver resection for metastatic anal SCC can be beneficial for appropriately selected patients.

PMID:38018352 | DOI:10.1002/jso.27539
Comparison of colorimetric, fluorometric, and liquid chromatography-mass spectrometry assays for acetyl-coenzyme A

Fetched: November 29th, 2023, 5:00am GMT by Daniel S Kantner

Anal Biochem. 2023 Nov 26;685:115405. doi: 10.1016/j.ab.2023.115405. Online ahead of print.

ABSTRACT

Acetyl-Coenzyme A is a central metabolite in catabolic and anabolic pathways as well as the acyl donor for acetylation reactions. Multiple quantitative measurement techniques for acetyl-CoA have been reported, including commercially available kits. Comparisons between techniques for acetyl-CoA measurement have not been reported. This lack of comparability between assays makes context-specific assay selection and interpretation of results reporting changes in acetyl-CoA metabolism difficult. We compared commercially available colorimetric ELISA and fluorometric enzymatic-based kits to liquid chromatography-mass spectrometry-based assays using tandem mass spectrometry (LC-MS/MS) and high-resolution mass spectrometry (LC-HRMS). The colorimetric ELISA kit did not produce interpretable results even with commercially available pure standards. The fluorometric enzymatic kit produced comparable results to the LC-MS-based assays depending on matrix and extraction. LC-MS/MS and LC-HRMS assays produced well-aligned results, especially when incorporating stable isotope-labeled internal standards. In addition, we demonstrated the multiplexing capability of the LC-HRMS assay by measuring a suite of short-chain acyl-CoAs in a variety of acute myeloid leukemia cell lines and patient cells.

PMID:38016493 | DOI:10.1016/j.ab.2023.115405
Revolutionizing sphincter preservation in ultra-low rectal cancer: exploring the potential of transanal endoscopic intersphincteric resection (taE-ISR) - A propensity score-matched cohort study

Fetched: November 29th, 2023, 5:00am GMT by Ximo Xu

Int J Surg. 2023 Nov 28. doi: 10.1097/JS9.0000000000000945. Online ahead of print.

ABSTRACT

BACKGROUND: With the optimization of neoadjuvant treatment regimens, the indications for intersphincteric resection (ISR) have expanded. However, limitations such as unclear surgical field, impaired anal function, and failure of anal preservation still exist. Transanal total mesorectal excision can complement the drawbacks of ISR. Therefore, this study combined these two techniques and proposed transanal endoscopic intersphincteric resection (taE-ISR), aiming to explore the value of this novel technique in anal preservation for low rectal cancer.

MATERIAL AND METHODS: Four high-volume centers were involved. After 1:1 propensity score matching, patients with low rectal cancer underwent taE-ISR (n=90) or ISR (n=90) were included. Baseline characteristics, perioperative outcomes, pathological results, and follow-up were compared between the two groups. A nomogram model was established to assess the potential risks of anal preservation.

RESULTS: The incidence of adjacent organ injury (0.0% vs. 5.6%, P=0.059), positive distal resection margin (1.1% vs. 8.9%, P=0.034), and incomplete specimen (2.2% vs. 13.3%, P=0.012) were lower in taE-ISR group. Moreover, the anal preservation rate was significantly higher in taE-ISR group (97.8% vs. 82.2%, P=0.001). Patients in the taE-ISR group showed a better disease-free survival (P=0.044) and lower cumulative recurrence (P=0.022) compared to the ISR group. Surgery procedure, tumor distance, adjacent organ injury, and adjuvant therapy were factors influencing anal preservation in patients with ultra-low rectal cancer.

CONCLUSION: taE-ISR technique was safe, feasible, and improved surgical quality, anal preservation rate and survival outcomes in ultra-low rectal cancer patients. It held significant clinical value and showed promising application prospects for anal preservation.

PMID:38016136 | DOI:10.1097/JS9.0000000000000945
Measuring Drug Response with Single-Cell Growth Rate Quantification

Fetched: November 29th, 2023, 5:00am GMT by Fiona Xi Xu

Anal Chem. 2023 Nov 28. doi: 10.1021/acs.analchem.3c03434. Online ahead of print.

ABSTRACT

Intratumoral heterogeneity is a substantial cause of drug resistance development during chemotherapy or other drug treatments for cancer. Therefore, monitoring and measuring cell exposure and response to drugs at the single-cell level are crucial. Previous research suggested that the single-cell growth rate can be used to investigate drug-cell interactions. However, currently established methods for quantifying single-cell growth are limited to isolated or monolayer cells. Here, we introduce a technique that accurately measures both 2D and 3D cell growth rates using label-free ratiometric stimulated Raman scattering (SRS) microscopy. We use deuterated amino acids, leucine, isoleucine, and valine, as tracers and measure the C-D SRS signal from deuterium-labeled proteins and the C-H SRS signal from unlabeled proteins simultaneously to determine the cell growth rate at the single-cell level. The technique offers single-cell level drug sensitivity measurement with a shorter turnaround time (within 12 h) than most traditional assays. The submicrometer resolution of the imaging technique allows us to examine the effects of chemotherapeutic drugs, including kinase inhibitors, mitotic inhibitors, and topoisomerase II inhibitors, on both the cell growth rate and morphology. The capability of quantifying 3D cell growth rates provides insight into a deeper understanding of the cell-drug interaction in the actual tumor environment.

PMID:38016067 | DOI:10.1021/acs.analchem.3c03434
Observing π-Au Interaction between Aromatic Molecules and Single Au Nanodimers with a Subnanometer Gap by SERS

Fetched: November 29th, 2023, 5:00am GMT by Guoliang Zhou

Anal Chem. 2023 Nov 28. doi: 10.1021/acs.analchem.3c03600. Online ahead of print.

ABSTRACT

Interface interaction between aromatic molecules and noble metals plays a prominent role in fundamental science and technological applications. However, probing π-metal interactions under ambient conditions remains challenging, as it requires characterization techniques to have high sensitivity and molecular specificity without any restrictions on the sample. Herein, the interactions between polycyclic aromatic hydrocarbon (PAH) molecules and Au nanodimers with a subnanometer gap are investigated by surface-enhanced Raman spectroscopy (SERS). A cleaner and stronger plasmonic field of subnanometer gap Au nanodimer structures was constructed through solvent extraction. High sensitivity and strong π-Au interaction between PAHs and Au nanodimers are observed. Additionally, the density functional theory calculation confirmed the interactions of PAHs physically absorbed on the Au surface; the binding energy and differential charge further theoretically indicated the correlation between the sensitivity and the number of PAH rings, which is consistent with SERS experimental results. This work provides a new method to understand the interactions between aromatic molecules and noble metal surfaces in an ambient environment, also paving the way for designing the interfaces in the fields of catalysis, sensors, and molecular electronics.

PMID:38016046 | DOI:10.1021/acs.analchem.3c03600
High Risk of New HPV Infection Acquisition Among Unvaccinated Young Men

Fetched: November 29th, 2023, 5:00am GMT by Anna R Giuliano

J Infect Dis. 2023 Nov 28:jiad485. doi: 10.1093/infdis/jiad485. Online ahead of print.

ABSTRACT

BACKGROUND: International data on anogenital HPV infection incidence among men are limited.

METHODS: Incidence of incident-persistent (IP) anogenital HPV infections was evaluated among 295 men who have sex with men (MSM) and 1576 heterosexual men (HM) aged 16-27 years in the placebo arm of a global, multicenter 4-valent (4v) HPV vaccine trial. We estimated IP incidence (penile/scrotal, perineal/perianal, anal) for 4vHPV and 9-valent (9v) HPV vaccine types and cumulative IP incidence over 36 months.

RESULTS: IP infection incidence per 100 person-years (95% CI) among HM for 4vHPV and 9vHPV types was 4.1 (3.5-4.9) and 6.8 (5.9-7.6) at penile/scrotal, and 1.2 (.8-1.6) and 1.9 (1.5-2.4) at perineal/perianal sites, respectively; and among MSM, IP infection incidence was 2.3 (1.3-3.8) and 3.2 (2.0-4.9) at penile/scrotal, 6.8 (4.9-9.2) and 9.0 (6.9-11.6) at perineal/perianal, and 12.0 (9.4-15.1) and 16.8 (13.7-20.2) at anal sites, respectively. Cumulative IP incidence over 36 months (excluding anal canal; any 9vHPV type) was higher among MSM versus HM (24.1% vs 18.4%).

CONCLUSIONS: A substantial proportion of unvaccinated men of catch-up vaccination age developed IP 9vHPV-related infections. Gender-neutral vaccination could decrease male HPV infection, contribute to herd protection, and reduce disease burden. Clinical Trials Registration. NCT00090285.

PMID:38012959 | DOI:10.1093/infdis/jiad485
Cytokeratin 7 Expression and Mismatch Repair Status for Survival Prediction in Patients With Low Rectal Cancer After Neoadjuvant Therapy

Fetched: November 29th, 2023, 5:00am GMT by Songli Shi

Cancer Control. 2023 Jan-Dec;30:10732748231214936. doi: 10.1177/10732748231214936.

ABSTRACT

BACKGROUND: More than half of the patients with locally advanced low rectal cancer exhibit no or minor response to nCRT. It is important to investigate the predictive and prognostic values of potential biomarkers in patients with locally advanced low rectal cancer receiving nCRT.

MATERIALS AND METHODS: This retrospective study included 162 patients with locally advanced low rectal cancer who underwent nCRT, followed by total mesorectal excision (TME) between 2016 and 2019. Cytokeratin 7 (CK7) expression and mismatch repair (MMR) status were determined by immunohistochemistry (IHC). Categorical variables were compared using the chi-square test. Overall survival (OS) and disease-free survival (DFS) curves were estimated using the Kaplan-Meier and Cox methods.

RESULTS: There were predominance significant differences in distance from anus margin (P < .0001) and circumferential extent of the tumor (P < .0001).CK7 positive expression was detected in 21 of the 162 patients (13%). The univariate and multivariate analysis revealed that patients whose tumors had CK7 positive expression had significantly shorter OS (HR = 3.878, P = .038; HR = 1.677, P = .035) and DFS (HR = 3.055, P = .027;HR = 3.569, P = .038) than those with CK7 negative expression. While patients with CK7 positive expression had a higher proportion of worse TRG compared with CK7 negative patients (P = .001). Patients with deficient mismatch repair (dMMR) just occupied a small proportion (8.6%), but there was still a close connection between the MMR status and recurrence after TME (P = .045). MMR status was an independent risk factor affecting the OS (HR = .307, P < .0001; HR = .123, P < .0001) and DFS (HR = .288, P < .0001; HR = .286, P < .0001) by univariate and multivariate analysis. But no significant difference in the proportion of TRG was observed between patients with dMMR and pMMR (P = .920).

CONCLUSIONS: The result confirms negative prognostic role of CK7-positive and dMMR statuses, which have potential predictive value for neoadjuvant chemoradiotherapy response. This provides opportunity to modify individualized treatment strategies for patients with different CK7 expression levels and dMMR statuses.

PMID:38008773 | PMC:PMC10683385 | DOI:10.1177/10732748231214936
High Throughput and Noninvasive Exosomal PD-L1 Detection for Accurate Immunotherapy Response Prediction via Tim4-Functionalized Magnetic Core-Shell Metal-Organic Frameworks

Fetched: November 28th, 2023, 5:00am GMT by Haiyan Wang

Anal Chem. 2023 Nov 27. doi: 10.1021/acs.analchem.3c04117. Online ahead of print.

ABSTRACT

Exosomal PD-L1 has been increasingly considered a noninvasive and accurate predictive marker for immunotherapy treatment response. However, the clinical monitoring of exosomal PD-L1 expression is still limited by its complex biological environment as well as the lack of a robust isolation strategy. Here, a Tim4-functionalized magnetic core-shell metal-organic framework (denoted as Fe3O4@SiO2-ILI-01@Tim4) was facilely constructed via layer-by-layer assembly. Owing to the strongly hydrophilic organic ligand of 1,3-bis(4-carboxybutyl)imidazolium bromide (ILI), magnetic Fe3O4@SiO2-ILI-01@Tim4 was endowed with the merits of low nonspecific adsorption and quick, easy, and convenient isolation of exosomes. The capture efficiency of Fe3O4@SiO2-ILI-01@Tim4 reached as high as 90.3 ± 0.5% and the recovery rate for exosomes was up to 93.0 ± 6.1%. The purity of the isolated exosomes was 7.5 times higher than that via the ultracentrifugation (UC) method. By further combination with immunofluorescence assay, high throughput and noninvasive exosomal PD-L1 detection for accurate immunotherapy response prediction was achieved. The prognosis accuracy of the developed Fe3O4@SiO2-ILI-01@Tim4-based strategy reached 85.7%, whereas the prognosis accuracy of the clinical gold standard, the PD-L1 combined positive score (CPS) test, was only 57.1%. Most interestingly, the developed method is especially suitable for those patients receiving false negative results in the CPS test. The proposed Fe3O4@SiO2-ILI-01@Tim4 is a highly efficient and robust technique showing great potential in high throughput and noninvasive exosomal PD-L1 detection for accurately predicting immunotherapy efficacy.

PMID:38011622 | DOI:10.1021/acs.analchem.3c04117
RUPE-phospho: Rapid Ultrasound-Assisted Peptide-Identification-Enhanced Phosphoproteomics Workflow for Microscale Samples

Fetched: November 28th, 2023, 5:00am GMT by Yuanxuan Huang

Anal Chem. 2023 Nov 27. doi: 10.1021/acs.analchem.3c02623. Online ahead of print.

ABSTRACT

Global phosphoproteome profiling can provide insights into cellular signaling and disease pathogenesis. To achieve comprehensive phosphoproteomic analyses with minute quantities of material, we developed a rapid and sensitive phosphoproteomics sample preparation strategy based on ultrasound. We found that ultrasonication-assisted digestion can significantly improve peptide identification by 20% due to the generation of longer peptides that can be detected by mass spectrometry. By integrating this rapid ultrasound-assisted peptide-identification-enhanced proteomic method (RUPE) with streamlined phosphopeptide enrichment steps, we established RUPE-phospho, a fast and efficient strategy to characterize protein phosphorylation in mass-limited samples. This approach dramatically reduces the sample loss and processing time: 24 samples can be processed in 3 h; 5325 phosphosites, 4549 phosphopeptides, and 1888 phosphoproteins were quantified from 5 μg of human embryonic kidney (HEK) 293T cell lysate. In addition, 9219 phosphosites were quantified from 1-2 mg of OCT-embedded mouse brain with 120 min streamlined RUPE-phospho workflow. RUPE-phospho facilitates phosphoproteome profiling for microscale samples and will provide a powerful tool for proteomics-driven precision medicine research.

PMID:38011496 | DOI:10.1021/acs.analchem.3c02623
Low Anterior Resection Syndrome in Total Mesorectal Excision: Risk Factors and Its Relationship with Quality of Life

Fetched: November 28th, 2023, 5:00am GMT by Yanfei Zhu

J Laparoendosc Adv Surg Tech A. 2023 Nov 22. doi: 10.1089/lap.2023.0414. Online ahead of print.

ABSTRACT

Background: Low anterior resection syndrome (LARS) is a bowel dysfunction following sphincter-sparing proctectomy. The occurrence of LARS may affect a patient's overall quality of life (QoL) after surgery. Current research was aimed to investigate related factors of LARS and major LARS in total mesorectal excision (TME) and its relationship with QoL. Methods: This study included patients who underwent TME at authors' institutes. LARS was evaluated with an LARS score. QoL was identified using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire, version 3.0. Appropriate statistical methods were used to ascertain risk factors for LARS and major LARS and to analyze the relationships between QoL and LARS. The primary objective was to identify related factors of LARS and major LARS. The secondary objective was to examine the relationships between QoL and LARS. Results: Multivariable analysis identified neoadjuvant chemoradiotherapy (odds ratio [OR] 4.923, 95% confidence interval [CI] 2.335-10.379, P < .001), local anal distance from the lower edge of the tumor (OR 6.199, 95% CI 2.701-14.266, P < .001), and anastomotic leakage (OR 5.624, 95% CI 1.463-21.614, P = .012) as independent predictors for development of LARS. Meanwhile, neoadjuvant chemoradiotherapy (OR 4.693, 95% CI 1.368-16.107, P = .014) and local anal distance from the lower edge of the tumor (OR 4.935, 95% CI 1.332-18.285, P = .017) were dramatically correlated with development of major LARS in a multivariable analysis. In the major LARS group, statistically significant differences (P < .05) were ascertained, include physical functioning, role functioning, emotional functioning, social functioning, and global health. In addition, pain and diarrhea were evidently higher. Conclusions: Neoadjuvant chemoradiotherapy, local anal distance from the lower edge of the tumor, and anastomotic leakage correlated strongly with development of LARS, and neoadjuvant chemoradiotherapy and local anal distance from the lower edge of the tumor correlated strongly with development of major LARS. Meanwhile, the QoL of patients with major LARS was lower than that of patients with no/minor LARS.

PMID:38010240 | DOI:10.1089/lap.2023.0414
Patient reported long-term side effects on bowel function and anal pain in anal cancer survivors - 3- and 6-year results from the Swedish national ANCA study

Fetched: November 28th, 2023, 5:00am GMT by Anna Axelsson

Colorectal Dis. 2023 Nov 27. doi: 10.1111/codi.16814. Online ahead of print.

ABSTRACT

AIM: The primary therapeutic option for anal cancer treatment is chemoradiotherapy resulting in 80% survival. The aim of this study was to assess long-term bowel function impairment and anal pain at 3 and 6 years after anal cancer diagnosis, based on a hypothesis of an increase in impairment over time. A secondary aim was to investigate if chemoradiotherapy increased the risk for bowel impairment, compared to radiotherapy alone.

METHOD: The ANal CAncer study (ANCA) consists of a national Swedish cohort of patients diagnosed with anal cancer between 2011-2013. Patients within the study were invited to respond to a study-specific questionnaire at 3- and 6-years after diagnosis. Descriptive analyses for the primary endpoint and ordinal logistic regressions for secondary endpoint were performed.

RESULTS: A total of 388 patients (84%) were included in the study. At 3 years of follow-up, 264 patients were alive. A total of 195 of these patients (74%) answered a study specific questionnaire, and at 6 years 154 patients (67%). Fifty-seven percent experienced bowel urgency at both 3 and 6 years. There was an increased risk for repeated bowel movement within 1 h (OR 2.44 [95% CI: 1.08-5.61, p = 0.03]) at 3 years in patients who had been treated by chemoradiation compared to radiotherapy alone.

CONCLUSIONS: Impairment in bowel function and anal pain after anal cancer treatment should be expected and remains after 6 years. This suggests that long-term follow-up may be necessary in some form after customary follow-up. The addition of chemotherapy increases long-term side effects of bowel function.

PMID:38010060 | DOI:10.1111/codi.16814
DNA-Encoded and Spatial Proximity Replaced Glycoprotein Analysis Reveals Glycosylation Heterogeneity of Extracellular Vesicles

Fetched: November 28th, 2023, 5:00am GMT by Ping Li

Anal Chem. 2023 Nov 27. doi: 10.1021/acs.analchem.3c01501. Online ahead of print.

ABSTRACT

Glycosylation of proteins is an essential feature of extracellular vesicles (EVs). However, while the glycosylation heterogeneity focusing on specific EV subtypes and proteins will better reveal the functions of EVs, the determination of their specific glycans remains highly challenging. Herein, we report a method of protein-specific glycan recognition using DNA-encoded affinity ligands to label proteins and glycans. Manipulating the sequences of DNA tags and employing a DNA logic gate to trigger a spatial proximity-induced DNA replacement reaction enabled the release of glycan-representative DNA strands for the quantitative detection of multiple glycoforms. After size-dependent isolation of EV subgroups and decoding of three typical glycoforms on the epithelial growth factor receptor (EGFR), we found that the different EV subgroups of the EGFR glycoprotein varied with respect to glycan types and abundance. The distinctive glycoforms of the EV subgroups could interfere with the EGFR-related EV functions. Furthermore, the sialylation of small EVs possessed the potential as a cancer biomarker. This method provides new insights into the role of protein-specific glycoforms in EV functions.

PMID:38009238 | DOI:10.1021/acs.analchem.3c01501
Mortality due to non-AIDS-defining cancers among people living with HIV in Spain over 18 years of follow-up

Fetched: November 27th, 2023, 5:00am GMT by I Suárez-García

J Cancer Res Clin Oncol. 2023 Nov 26. doi: 10.1007/s00432-023-05500-9. Online ahead of print.

ABSTRACT

PURPOSE: Our aim was to describe non-AIDS-defining cancer (NADC) mortality among people living with HIV (PLWH), to compare it with that of the general population, and to assess potential risk factors.

METHODS: We included antiretroviral-naive PLWH from the multicentre CoRIS cohort (2004-2021). We estimated mortality rates and standardised mortality ratios (SMRs). We used cause-specific Cox models to identify risk factors.

RESULTS: Among 17,978 PLWH, NADC caused 21% of all deaths observed during the follow-up. Mortality rate due to NADC was 1.58 (95%CI 1.36, 1.83) × 1000 person-years and lung and liver were the most frequent cancer-related causes of death. PLWH had 79% excess NADC mortality risk compared to the general population with the highest SMR found for Hodgkin lymphoma, anal and liver cancers. The SMRs decreased with age and were the highest in age groups under 50 years. The most important prognostic factor was low CD4 count, followed by smoking, viral hepatitis and HIV transmission through heterosexual contact or injection drug use.

CONCLUSION: Non-AIDS cancers are an important cause of death among PLWH. The excess mortality related to certain malignancies and the association with immunodeficiency, smoking, and coinfections highlights the need for early detection and treatment of cancer in this population.

PMID:38008809 | DOI:10.1007/s00432-023-05500-9
Transformer with convolution and graph-node co-embedding: An accurate and interpretable vision backbone for predicting gene expressions from local histopathological image

Fetched: November 27th, 2023, 5:00am GMT by Xiao Xiao

Med Image Anal. 2023 Nov 20;91:103040. doi: 10.1016/j.media.2023.103040. Online ahead of print.

ABSTRACT

Inferring gene expressions from histopathological images has long been a fascinating yet challenging task, primarily due to the substantial disparities between the two modality. Existing strategies using local or global features of histological images are suffering model complexity, GPU consumption, low interpretability, insufficient encoding of local features, and over-smooth prediction of gene expressions among neighboring sites. In this paper, we develop TCGN (Transformer with Convolution and Graph-Node co-embedding method) for gene expression estimation from H&E-stained pathological slide images. TCGN comprises a combination of convolutional layers, transformer encoders, and graph neural networks, and is the first to integrate these blocks in a general and interpretable computer vision backbone. Notably, TCGN uniquely operates with just a single spot image as input for histopathological image analysis, simplifying the process while maintaining interpretability. We validate TCGN on three publicly available spatial transcriptomic datasets. TCGN consistently exhibited the best performance (with median PCC 0.232). TCGN offers superior accuracy while keeping parameters to a minimum (just 86.241 million), and it consumes minimal memory, allowing it to run smoothly even on personal computers. Moreover, TCGN can be extended to handle bulk RNA-seq data while providing the interpretability. Enhancing the accuracy of omics information prediction from pathological images not only establishes a connection between genotype and phenotype, enabling the prediction of costly-to-measure biomarkers from affordable histopathological images, but also lays the groundwork for future multi-modal data modeling. Our results confirm that TCGN is a powerful tool for inferring gene expressions from histopathological images in precision health applications.

PMID:38007979 | DOI:10.1016/j.media.2023.103040
Efficiency of the Breslow estimator in semiparametric transformation models

Fetched: November 27th, 2023, 5:00am GMT by Theresa P Devasia

Lifetime Data Anal. 2023 Nov 26. doi: 10.1007/s10985-023-09611-w. Online ahead of print.

ABSTRACT

Semiparametric transformation models for failure time data consist of a parametric regression component and an unspecified cumulative baseline hazard. The nonparametric maximum likelihood estimator (NPMLE) of the cumulative baseline hazard can be summarized in terms of weights introduced into a Breslow-type estimator (Weighted Breslow). At any given time point, the weights invoke an integral over the future of the cumulative baseline hazard, which presents theoretical and computational challenges. A simpler non-MLE Breslow-type estimator (Breslow) was derived earlier from a martingale estimating equation (MEE) setting observed and expected counts of failures equal, conditional on the past history. Despite much successful theoretical and computational development, the simpler Breslow estimator continues to be commonly used as a compromise between simplicity and perceived loss of full efficiency. In this paper we derive the relative efficiency of the Breslow estimator and consider the properties of the two estimators using simulations and real data on prostate cancer survival.

PMID:38007694 | DOI:10.1007/s10985-023-09611-w
Enhancing intracellular mRNA precise imaging-guided photothermal therapy with a nucleic acid-based polydopamine nanoprobe

Fetched: November 27th, 2023, 5:00am GMT by Jiayao Xu

Anal Bioanal Chem. 2023 Nov 25. doi: 10.1007/s00216-023-05062-2. Online ahead of print.

ABSTRACT

Despite significant advancements in cancer research, real-time monitoring and effective treatment of cancer through non-invasive techniques remain a challenge. Herein, a novel polydopamine (PDA) nucleic acid nanoprobe has been developed for imaging signal amplification of intracellular mRNA and precise photothermal therapy guidance in cancer cells. The PDA nucleic acid nanoprobe (PDA@DNA) is constructed by assembling an aptamer hairpin (H1) labeled with the Cy5 fluorophore and another nucleic acid recognition hairpin (H2) onto PDA nanoparticles (PDA NPs), which have exceptionally high fluorescence quenching ability and excellent photothermal conversion properties. The nanoprobe could facilitate cellular uptake of DNA molecules and their protection from nuclease degradation. Upon recognition and binding to the intracellular mRNA target, a catalytic hairpin assembly (CHA) reaction occurs. The stem of H1 unfolds upon binding, allowing the exposed H1 to hybridize with H2, forming a flat and sturdy DNA double-stranded structure that detaches from the surface of PDA NPs. At the same time, the target mRNA is displaced and engages in a new cyclic reaction, resulting in the recovery and significant amplification of Cy5 fluorescence. Using thymidine kinase1 (TK1) mRNA as a model mRNA, this nanoprobe enables the analysis of TK1 mRNA with a detection limit of 9.34 pM, which is at least two orders of magnitude lower than that of a non-amplifying imaging nucleic acid probe. Moreover, with its outstanding performance for in vitro detection, this nanoprobe excels in precisely imaging tumor cells. Through live-cell TK1 mRNA imaging, it can accurately distinguish between tumor cells and normal cells. Furthermore, when exposed to 808-nm laser irradiation, the nanoprobe fully harnesses exceptional photothermal conversion properties of PDA NPs. This results in a localized temperature increase within tumor cells, which ultimately triggers apoptosis in these tumor cells. The integration of PDA@DNA presents innovative prospects for tumor diagnosis and image-guided tumor therapy, offering the potential for high-precision diagnosis and treatment of tumors.

PMID:38006441 | DOI:10.1007/s00216-023-05062-2
High Prevalence of Anal Sexually Transmitted Infections among Men Who Have Sex with Men and Transgender Women Attending a Clinic for Prevention of Anal Cancer in Salvador, Brazil

Fetched: November 26th, 2023, 5:00am GMT by Ivana Luz

Pathogens. 2023 Oct 30;12(11):1297. doi: 10.3390/pathogens12111297.

ABSTRACT

Men who have sex with men (MSM) and transgender women (TGW) are highly vulnerable to anal sexually transmitted infections (STIs). Objectives-to evaluate the prevalence of anal STIs among MSM and TGW attending a referral clinic for anal cancer prevention. Methods-MSM and TGW attending a medical visit for high-resolution anoscopy in Salvador, Brazil, from February 2021 to June 2022 were screened for HPV, gonorrhea, and chlamydial infection by PCR of anal swab and by serum VDRL titration for syphilis screening. They also responded to a questionnaire on sociodemographic characteristics and sexual behavior. Results-we evaluated 141 participants: 117 (82.9%) MSM, 9 (6.4%) bisexual men (BSM), and 15 (10.6%) TGW. Most (111/141, 78.7%) were older than 30 years, 89 (63.1%) had over 12 years of education, and 124 (87.9%) had a family income of up to five minimum wages. At least one STI was detected in 112 (79.4%) of the participants (86.7% among TGW). HIV infection was detected in 102 (72.3%) participants; HIV frequency was higher in BSM (7/9, 88.9%) and in MSM (89/116, 76.1%) than in TGW (5/15, 33.3%). A lower income (p = 0.004) was predictive of anal STIs, while syphilis was significantly more frequent among participants with HIV (29.1% vs. 5,3%, for HIV positive and negative, respectively, p = 0.002). Presenting at least one active STI was also associated with having had group sex in the last year (p = 0.03) and with use of sexualized drugs (p = 0.02). Conclusions-MSM and TGW present a high vulnerability to anal STIs. Number of sexual partners, use of sexualized drugs, and lower income are predictive of a higher risk of acquiring an STI in such populations.

PMID:38003762 | PMC:PMC10675476 | DOI:10.3390/pathogens12111297
Methylation-Powered Assembly of a Single Quantum Dot-Based FRET Nanosensor for Antibody-Free and Enzyme-Free Monitoring of Locus-Specific N6-Methyladenosine in Clinical Tissues

Fetched: November 26th, 2023, 5:00am GMT by Jinping Hu

Anal Chem. 2023 Nov 24. doi: 10.1021/acs.analchem.3c04571. Online ahead of print.

ABSTRACT

N⁶-Methyladenosine (m⁶A) is the most pervasive and evolutionarily conserved epitranscriptomic modification in long noncoding RNA (lncRNA), and its dysregulation may induce aberrant transcription and translation programs. Herein, we demonstrate the methylation-powered assembly of a single quantum dot (QD)-based fluorescence resonance energy transfer (FRET) nanosensor for antibody- and enzyme-free monitoring of locus-specific m⁶A in clinical tissues. The m⁶A-sensitive DNAzyme VMC10 is employed to identify a specific m⁶A site in lncRNA, and it catalyzes the hydrolytic cleavage of unmethylated lncRNA. The cleaved lncRNA fails to trigger the subsequent catalytic hairpin assembly (CHA) reaction due to the energy barrier. In contrast, when m⁶A-lncRNA is present, the methyl group in m⁶A protects lncRNA from VMC10-mediated cleavage. With the aid of an assistant probe, the retained intact m⁶A-lncRNA is released from the VMC10/lncRNA complex and subsequently triggers the CHA reaction, generating abundant AF647/biotin dual-labeled duplexes. The assembly of AF647/biotin dual-labeled duplexes onto 605QD results in efficient FRET between 605QD and AF647. The FRET signal can be simply quantified by single-molecule detection. Notably, this assay can be implemented in an antibody-free and enzyme-free manner. This nanosensor can sensitively quantify target m⁶A with a detection limit of 0.47 fM, and it can discriminate as low as a 0.001% m⁶A level from excess coexisting counterparts. Importantly, this nanosensor can monitor the cellular m⁶A level with single-cell sensitivity and profile target m⁶A expression in breast cancer and healthy para-cancerous tissues, providing a powerful tool for studying the physiological and pathological functions of m⁶A.

PMID:38000786 | DOI:10.1021/acs.analchem.3c04571
Comparison of Ethos template-based planning and AI-based dose prediction: General performance, patient optimality, and limitations

Fetched: November 26th, 2023, 5:00am GMT by Benjamin Roberfroid

Phys Med. 2023 Nov 23;116:103178. doi: 10.1016/j.ejmp.2023.103178. Online ahead of print.

ABSTRACT

PURPOSE: Ethos proposes a template-based automatic dose planning (Etb) for online adaptive radiotherapy. This study evaluates the general performance of Etb for prostate cancer, as well as the ability to generate patient-optimal plans, by comparing it with another state-of-the-art automatic planning method, i.e., deep learning dose prediction followed by dose mimicking (DP + DM).

MATERIALS: General performances and capability to produce patient-optimal plan were investigated through two studies: Study-S1 generated plans for 45 patients using our initial Ethos clinical goals template (EG_init), and compared them to manually generated plans (MG). For study-S2, 10 patients which showed poor performances at study-S1 were selected. S2 compared the quality of plans generated with four different methods: 1) Ethos initial template (EG_init_selected), 2) Ethos updated template-based on S1 results (EG_upd_selected), 3) DP + DM, and 4) MG plans.

RESULTS: EG_init plans showed satisfactory performance for dose level above 50 Gy: reported mean metrics differences (EG_init minus MG) never exceeded 0.6 %. However, lower dose levels showed loosely optimized metrics, mean differences for V30Gy to rectum and V20Gy to anal canal were of 6.6 % and 13.0 %. EG_init_selected showed amplified differences in V30Gy to rectum and V20Gy to anal canal: 8.5 % and 16.9 %, respectively. These dropped to 5.7 % and 11.5 % for EG_upd_selected plans but strongly increased V60Gy to rectum for 2 patients. DP + DM plans achieved differences of 3.4 % and 4.6 % without compromising any V60Gy.

CONCLUSION: General performances of Etb were satisfactory. However, optimizing with template of goals might be limiting for some complex cases. Over our test patients, DP + DM outperformed the Etb approach.

PMID:38000099 | DOI:10.1016/j.ejmp.2023.103178
Exploring capabilities of elemental mass spectrometry for determination of metal and biomolecules in extracellular vesicles

Fetched: November 25th, 2023, 5:00am GMT by Jaime Martínez-García

Anal Bioanal Chem. 2023 Nov 24. doi: 10.1007/s00216-023-05056-0. Online ahead of print.

ABSTRACT

Extracellular vesicles (EVs) are increasingly recognized as crucial components influencing various pathophysiological processes, such as cellular homeostasis, cancer progression, and neurological disease. However, the lack of standardized methods for EV isolation and classification, coupled with ambiguity in biochemical markers associated with EV subtypes, remains a major challenge. This Trends article highlights the most common approaches for EV isolation and characterization, along with recent applications of elemental mass spectrometry (MS) to analyse metals and biomolecules in EVs obtained from biofluids or in vitro cellular models. Considering the promising capabilities of elemental MS, the article also looks ahead to the potential analysis of EVs at the single-vesicle and single-cell levels using ICP-MS. These approaches may offer valuable insights into individual characteristics of EVs and their functions, contributing to a deeper understanding of their role in various biological processes.

PMID:37999724 | DOI:10.1007/s00216-023-05056-0
A novel cuproptosis-related prognostic gene signature in adrenocortical carcinoma

Fetched: November 25th, 2023, 5:00am GMT by Wenjun Gao

J Clin Lab Anal. 2023 Nov 23:e24981. doi: 10.1002/jcla.24981. Online ahead of print.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive and rare malignant tumor associated with poor outcomes. Cuproptosis, a new pattern of cell death, relies on mitochondrial respiration and is associated with protein lipoylation. Increasing evidence has demonstrated the potential roles of cuproptosis in several tumor entities. However, the relationship between cuproptosis and ACC remains unclear.

METHODS: In total, 10 cuproptosis-related genes (CRGs) of patients with ACC were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and differential expression analysis of CRGs was analyzed. Functional enrichment of the CRGs was performed and protein-protein interaction analysis was utilized to explore the association between the CRGs. Cuproptosis-related risk score (CRRS) was constructed by Lasso Cox regression and validated.

RESULTS: In the current study, the alteration and expression patterns of 10 CRGs in TCGA-ACC datasets were analyzed. We identified different expression patterns of CRGs in ACCs, discovered strong associations between CRGs and ACCs, and found that the CRGs were associated with immune infiltration in ACCs. A CRRS was created thereafter to predict overall survival (OS). CRRS = (0.083103718) *FDX1 + (-0.278423862) *LIAS+(0.090985682) *DLAT+(-0.018784047) *PDHA1 + (0.297218951) *MTF1 + (0.310197964) *CDKN2A. Patients were divided into high- and low-risk groups based on their CRRS, and independent prognostic factors were investigated. Finally, CDKN2A and FDX1 were found to be independent prognostic predictors of patients with ACC.

CONCLUSIONS: CDKN2A and FDX1 are independent prognostic predictors of patients with ACC. Cuproptosis may play a role in the development of ACC, providing a new perspective on therapeutic strategies related to CRGs for cancer prevention and treatment.

PMID:37997497 | DOI:10.1002/jcla.24981
Integrated FET sensing microsystem for specific detection of pancreatic cancer exosomal miRNA10b

Fetched: November 24th, 2023, 5:00am GMT by Yi Yu

Anal Chim Acta. 2023 Dec 15;1284:341995. doi: 10.1016/j.aca.2023.341995. Epub 2023 Nov 2.

ABSTRACT

Tumor-derived exosome (TD-Ex) serves as a crucial early diagnostic biomarker of pancreatic cancer (PC). However, accurate identification of TD-Ex from PC is still a challenging work. In this paper, a detection microsystem that integrates magnetic separation and FET biosensor is developed, which is capable of selectively separating TD-Ex of PC from the plasma and detecting exosomal miRNA10b in a sensitive and specific manner. The magnetic beads were functionalized with dual antibody (GPC-1 antibody and EpCAM antibody), enabling selective recognition and capture of PC-derived exosomes. On the other hand, a peptide nucleic acid (PNA)- functionalized reduced graphene oxide field-effect transistor (RGO FET) biosensor was subsequently utilized to detect the exosomal miRNA10b, which is highly expressed in PC- derived exosomes. This system could achieve a low detection limit down to 78 fM, and selectively identify miRNA10b from single-base mismatched miRNA. In addition, 40 clinical plasma samples were tested with this microsystem, and the results indicate that it could effectively distinguish PC patients from healthy individuals. The assay combines specific capture and enrichment of PC-derived exosomes with sensitive and selective detection of exosomal miRNA, showing its potential to be used as an effective scheme for PC early diagnosis.

PMID:37996166 | DOI:10.1016/j.aca.2023.341995
(Eu-MOF)-derived Smart luminescent sensing for Ultrasensitive on-site detection of MiR-892b

Fetched: November 24th, 2023, 5:00am GMT by Yuchi Zhang

Anal Chim Acta. 2023 Dec 15;1284:341990. doi: 10.1016/j.aca.2023.341990. Epub 2023 Nov 1.

ABSTRACT

MicroRNAs (miRNAs) are important biomacromolecules used as biomarkers for the diagnosis of several diseases. However, current detection strategies are limited by expensive equipment and complicated procedures. Here, we develop a portable, sensitive, and stable (Eu-MOF)-based sensing platform to detect miRNA via smartphone. The Eu-MOF absorbs the carboxyfluorescein (FAM)-tagged probe DNA (pDNA) to generate hybrid pDNA@Eu-MOF, which can efficiently quench the fluorescence of FAM through a photoinduced electron transfer (PET) process. When integrated with a smartphone, the nonemissive pDNA@ Eu-MOF hybrid could be utilized as a portable and sensitive platform to sense miRNA (miR-892b) with a detection limit of 0.32 pM, which could be even distinguished by the naked eye. Moreover, this system demonstrates high selectivity for identifying miRNA family members with single-base mismatches. Furthermore, the expression levels of miRNA in cancer cell samples could be analyzed accurately. Therefore, the proposed method offers a promising guideline for the design of MOF-based sensing strategies and expands their potential applications for diagnostic purposes.

PMID:37996164 | DOI:10.1016/j.aca.2023.341990
Edge-generated N-doped carbon-supported dual-metal active sites for enhancing electrochemical immunoassay

Fetched: November 24th, 2023, 5:00am GMT by Yunsen Wang

Anal Chim Acta. 2023 Dec 15;1284:342006. doi: 10.1016/j.aca.2023.342006. Epub 2023 Nov 8.

ABSTRACT

Development of high-precision human epidermal growth factor receptor 2 (HER2) assay is essential for the early diagnostic and prevention of breast cancer. In this work, an innovative Fe/Mn bimetallic nanozyme at the edge of N-doped carbon defects (FeMn-NCedge) with abundant active sites was prepared through the hydrothermal synthetic method. FeMn-NCedge nanozyme displayed excellent peroxidase-like activity relative to the H2O2-catalyzed 3,3',5,5'-tetramethylbenzidine (TMB) system for generation of the oxidized TMB (oxTMB). As a proof-of-concept application, we constructed an electrochemical immunoassay for the detection of HER2 based on the unique merits of FeMn-NCedge. Initially, a sandwiched immunoreaction was carried out in the microtiter plate coated with monoclonal anti-HER2 capture antibodies using glucose oxidase (GOx)-labeled anti-HER2 as detection antibody. The carried GOx could catalyze glucose to produce H2O2, thus resulting in the formation of oxTMB with the assistance of TMB and FeMn-NCedge nanozyme. The produced oxTMB could be determined on the electrode by the chronoamperometry at an applied potential of +10 mV. Experimental results revealed that the steady-state current increased with the increasing HER2 concentration in the sample, and gave a good linear relationship within the dynamic range of 0.01-10 ng/mL at a limit of detection of 5.4 pg/mL HER2. In addition, good reproducibility, high specificity and acceptable accuracy were acquired for the measurement of human serum samples. Importantly, this method can be extended for quantitative monitoring other disease-related proteins by changing the corresponding antibodies.

PMID:37996161 | DOI:10.1016/j.aca.2023.342006
Combiner and HyperCombiner networks: Rules to combine multimodality MR images for prostate cancer localisation

Fetched: November 24th, 2023, 5:00am GMT by Wen Yan

Med Image Anal. 2023 Nov 21;91:103030. doi: 10.1016/j.media.2023.103030. Online ahead of print.

ABSTRACT

One of the distinct characteristics of radiologists reading multiparametric prostate MR scans, using reporting systems like PI-RADS v2.1, is to score individual types of MR modalities, including T2-weighted, diffusion-weighted, and dynamic contrast-enhanced, and then combine these image-modality-specific scores using standardised decision rules to predict the likelihood of clinically significant cancer. This work aims to demonstrate that it is feasible for low-dimensional parametric models to model such decision rules in the proposed Combiner networks, without compromising the accuracy of predicting radiologic labels. First, we demonstrate that either a linear mixture model or a nonlinear stacking model is sufficient to model PI-RADS decision rules for localising prostate cancer. Second, parameters of these combining models are proposed as hyperparameters, weighing independent representations of individual image modalities in the Combiner network training, as opposed to end-to-end modality ensemble. A HyperCombiner network is developed to train a single image segmentation network that can be conditioned on these hyperparameters during inference for much-improved efficiency. Experimental results based on 751 cases from 651 patients compare the proposed rule-modelling approaches with other commonly-adopted end-to-end networks, in this downstream application of automating radiologist labelling on multiparametric MR. By acquiring and interpreting the modality combining rules, specifically the linear-weights or odds ratios associated with individual image modalities, three clinical applications are quantitatively presented and contextualised in the prostate cancer segmentation application, including modality availability assessment, importance quantification and rule discovery.

PMID:37995627 | DOI:10.1016/j.media.2023.103030
Quantitative Recoveries of Exosomes and Monoclonal Antibodies from Chinese Hamster Ovary Cell Cultures by Use of a Single, Integrated Two-Dimensional Liquid Chromatography Method

Fetched: November 24th, 2023, 5:00am GMT by Sarah K Wysor

Anal Chem. 2023 Nov 23. doi: 10.1021/acs.analchem.3c04044. Online ahead of print.

ABSTRACT

Cultured cell lines are very commonly used for the mass production of therapeutic proteins, such as monoclonal antibodies (mAbs). In particular, Chinese hamster ovary (CHO) cell lines are widely employed due to their high tolerance to variations in experimental conditions and their ability to grow in suspension or serum free media. CHO cell lines are known for their ability to produce high titers of biotherapeutic products such as immunoglobulin G (IgG). An emergent alternative means of treating diseases, such as cancer, is the use of gene therapies, wherein genetic cargo is "packaged" in nanosized vesicular structures, referred to as "vectors". One particularly attractive vector option is extracellular vesicles (EVs), of which exosomes are of greatest interest. While exosomes can be harvested from virtually any human body fluid, bovine milk, or even plants, their production in cell cultures is an attractive commercial approach. In fact, the same CHO cell types employed for mAb production also produce exosomes as a natural byproduct. Here, we describe a single integrated 2D liquid chromatography (2DLC) method for the quantitative recovery of both exosomes and antibodies from a singular sample aliquot. At the heart of the method is the use of polyester capillary-channeled polymer (C-CP) fibers as the first dimension column, wherein exosomes/EVs are captured from the supernatant sample and subsequently determined by multiangle light scattering (MALS), while the mAbs are captured, eluted, and quantified using a protein A-modified C-CP fiber column in the second dimension, all in a 10 min workflow. These efforts demonstrate the versatility of the C-CP fiber phases with the capacity to harvest both forms of therapeutics from a single bioreactor, suggesting an appreciable potential impact in the field of biotherapeutics production.

PMID:37995145 | DOI:10.1021/acs.analchem.3c04044
The role of radiotherapy in the management of squamous cell cancer of the penis

Fetched: November 24th, 2023, 5:00am GMT by Juanita Crook

World J Urol. 2023 Dec;41(12):3913-3920. doi: 10.1007/s00345-023-04683-7. Epub 2023 Nov 23.

ABSTRACT

PURPOSE: To review the evidence for radiotherapy in the management of primary penile cancer, either as brachytherapy or external beam radiation, and the role of external beam radiotherapy in node positive penile cancer.

METHODS: English language literature was reviewed for the past 3 decades. As penile cancer is uncommon in developed nations, high quality evidence to guide management is limited. Single institution reports often span decades during which time staging systems and treatments have evolved, reducing their relevance to current practice. Successful clinical trials require collaboration not only among disciplines but also among multiple institutions and nations.

RESULTS: Radiotherapy is a definitive organ-preserving option for T1-T2 penile cancers. Interstitial brachytherapy is associated with penile preservation in 85% of men at 5 years, maintained in 70% by 10 years. Results of external radiotherapy are not quite as promising but nonetheless 60% of men will have an intact penis at 5 years. Inguino-pelvic external radiotherapy has been reported to increase overall survival when delivered as adjuvant treatment for men with pN3 groin but pN0 pelvic nodes, and improve disease specific survival for those with involved pelvic nodes. InPACT (ECOG-ACRIN_8134) is investigating the role of inguino-pelvic chemo-radiotherapy for men with pN3 inguinal nodes but imaging negative pelvic nodes.

CONCLUSIONS: Radiotherapy has a well-defined role to play in treatment of squamous cell cancers of other sites, such as vulva, anal canal, uterine cervix and head and neck malignancies. Emerging data support the incorporation of radiotherapy into treatment paradigms for penile cancer.

PMID:37994970 | DOI:10.1007/s00345-023-04683-7
Correction to: PET/MRI in colorectal and anal cancers: an update

Fetched: November 24th, 2023, 5:00am GMT by Vetri Sudar Jayaprakasam

Abdom Radiol (NY). 2023 Dec;48(12):3584. doi: 10.1007/s00261-023-04120-8.

NO ABSTRACT

PMID:37994921 | DOI:10.1007/s00261-023-04120-8
Long-Term Imaging of Cys in Cells and Tumor Mice by a Solid-State Fluorescence Probe

Fetched: November 24th, 2023, 5:00am GMT by Gui-Qin Fu

Anal Chem. 2023 Nov 23. doi: 10.1021/acs.analchem.3c02872. Online ahead of print.

ABSTRACT

Cysteine is an important biological thiol and is closely related to cancer. It remains a challenge to develop a probe that can provide long-term fluorescence detection and imaging of Cys in cells as well as in living organisms. Here, a solid-state fluorophore HTPQ is combined with an acrylate group to construct a solid-state fluorescent probe HTPQC for Cys recognition. The fluorescence of the probe is quenched when the photoinduced electron transfer (PET) process is turned on and the excited-state intramolecular proton transfer (ESIPT) process is turned off. In the presence of Cys, an obvious solid-state fluorescence signal can be observed. The double quenching mechanism makes the probe HTPQC have the advantages of high sensitivity, good selectivity, and high contrast of biological imaging. Due to low cytotoxicity, the probe HTPQC can be used to detect exogenous and endogenous Cys in living cells and is capable of imaging over long periods of time. By making full use of long wavelengths, the probe can be applied for the detection of Cys levels in tumor mice and equipped with the ability to conduct long-term imaging in vivo.

PMID:37994418 | DOI:10.1021/acs.analchem.3c02872
CRISPR/Cas9: a powerful tool in colorectal cancer research

Fetched: November 24th, 2023, 5:00am GMT by Yang Hu

J Exp Clin Cancer Res. 2023 Nov 22;42(1):308. doi: 10.1186/s13046-023-02901-z.

ABSTRACT

Colorectal cancer (CRC) is one of the most common malignant cancers worldwide and seriously threatens human health. The clustered regulatory interspaced short palindromic repeat/CRISPR-associate nuclease 9 (CRISPR/Cas9) system is an adaptive immune system of bacteria or archaea. Since its introduction, research into various aspects of treatment approaches for CRC has been accelerated, including investigation of the oncogenes, tumor suppressor genes (TSGs), drug resistance genes, target genes, mouse model construction, and especially in genome-wide library screening. Furthermore, the CRISPR/Cas9 system can be utilized for gene therapy for CRC, specifically involving in the molecular targeted drug delivery or targeted knockout in vivo. In this review, we elucidate the mechanism of the CRISPR/Cas9 system and its comprehensive applications in CRC. Additionally, we discussed the issue of off-target effects associated with CRISPR/Cas9, which serves to restrict its practical application. Future research on CRC should in-depth and systematically utilize the CRISPR/Cas9 system thereby achieving clinical practice.

PMID:37993945 | PMC:PMC10664500 | DOI:10.1186/s13046-023-02901-z
Clickable Photoreactive ATP-Affinity Probe for Global Profiling of ATP-Binding Proteins

Fetched: November 23rd, 2023, 5:00am GMT by Zhiming Wang

Anal Chem. 2023 Nov 22. doi: 10.1021/acs.analchem.3c02694. Online ahead of print.

ABSTRACT

Adenosine triphosphate (ATP) is the major energy carrier in organisms, and there are many cellular proteins that can bind to ATP. Among these proteins, kinases are key regulators in several cell signaling processes, and aberrant kinase signaling contributes to the development of many human diseases, including cancer. Hence, small-molecule kinase inhibitors have been successfully used for the treatment of various diseases. Since the ATP-binding pockets are similar for many kinases, it is very important to evaluate the selectivity of different kinase inhibitors. We report here a clickable ATP photoaffinity probe for the global profiling of ATP-binding proteins. After incubating the protein lysate with the ATP probe followed by ultraviolet (UV) irradiation, ATP-binding proteins were labeled with an alkyne handle for subsequent biotin conjugation through click chemistry. Labeled proteins were enriched with streptavidin beads, digested with trypsin, and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). More than 400 ATP-binding proteins, including approximately 200 kinases, could be identified in a single LC-MS/MS run in the data-dependent acquisition mode. We then applied this method to the analysis of targets of three selected ATP-competitive kinase inhibitors. We were able to successfully identify some of their reported target proteins from label-free quantification results and validated the results using Western blot analyses. Together, we developed a clickable ATP photoaffinity probe for proteome-wide profiling of ATP-binding proteins and demonstrated that this chemoproteomic method is amenable to high-throughput target identification of kinase inhibitors.

PMID:37993803 | DOI:10.1021/acs.analchem.3c02694
Uterine transposition versus uterine ventrofixation before radiotherapy as a fertility sparing option in young women with pelvic malignancies: Systematic review of the literature and dose simulation

Fetched: November 23rd, 2023, 5:00am GMT by Matteo Pavone

Eur J Surg Oncol. 2023 Nov 15;50(1):107270. doi: 10.1016/j.ejso.2023.107270. Online ahead of print.

ABSTRACT

BACKGROUND: (Chemo)radiation may be a required treatment in young women with pelvic malignancies. Irradiation may result in ovarian and uterine failure, compromising the fertility of those patients. While ovarian transposition is an established method to move the ovaries away from the irradiation field, similar surgical procedures regarding the uterus remain investigational. The aim of this study was to carry out a systematic review of the literature on uterine displacement techniques (ventrofixation/transposition) and to simulate the radiation dose received by the uterus in different heights place after the procedures.

METHODS: The systematic review was performed according PRISMA guidelines. PubMed, Scopus, Web of Science and EMBASE were queried to identify included study until March 2023. Retrospectively, a dosimetric study was also performed and Volumetric Modulated Arc Therapy (VMAT) radiotherapy treatment plans were calculated, to assess the dose received by the uterus according to hypothetical different displacement positions taking the case of irradiation for rectal or anal cancer as model.

RESULTS: A total of 187 studies were included, after the screening 9 studies were selected for synthesis. Data from the dose simulation revealed that the transposition approach was the most protective with a maximum dose of about 3 and 8 Gy for anal and rectal cancer respectively. None of the simulated ventrofixation positions received a Dmean surpassing 14 Gy.

CONCLUSION: According to the literature review and the simulation results of the present study we may conclude are feasible and safe as fertility sparing approach in young rectal/anal cancer patients.

PMID:37992415 | DOI:10.1016/j.ejso.2023.107270
Dual-Signal Mode Ratiometric Photoelectrochemical Sensor Based on G-Quadruplex Hole Transport for Rapid and Sensitive Detection of miRNA-210

Fetched: November 23rd, 2023, 5:00am GMT by Jing Li

Anal Chem. 2023 Nov 22. doi: 10.1021/acs.analchem.3c03447. Online ahead of print.

ABSTRACT

For rapid and sensitive detection of miRNA-210, which is important for improving the reliability of clinical diagnosis of breast cancer, a dual-signal mode ratiometric photoelectrochemical (PEC) sensor based on a Au/GaN photoanode is proposed. First, a DNA probe was designed that could complement the target miRNA-210. Then, another G-rich DNA sequence was designed to mismatch the probe and form a double-stranded DNA (dsDNA). Upon addition of the target, the dsDNA unwinds from its binding site and releases G-rich single-stranded DNA. In the presence of Mg²⁺ and K⁺, this single-stranded DNA molecule spontaneously forms a G-quadruplex structure, facilitating the rapid transport of photogenerated holes, thereby increasing the photocurrent response of Au/GaN and enabling sensitive label-free detection of miRNA-210. By control of different pH values, a response signal was generated at pH 8, while a reference signal was produced at pH 5. The designed PEC system shows a high potential for the development of miRNA-210 detection. Ultimately, the response signal-to-reference signal ratio was used as the variable, and a broad linear span ranging from 10 fM to 1 nM (R² = 0.993) has been exhibited, with a detection threshold of 3 fM (S/N = 3). The designed PEC platform shows potential for the development of other disease markers.

PMID:37992131 | DOI:10.1021/acs.analchem.3c03447
Proximity-Enhanced Electrochemiluminescence Sensing Platform for Effective Capturing of Exosomes and Probing Internal MicroRNAs Involved in Cancer Cell Apoptosis

Fetched: November 23rd, 2023, 5:00am GMT by Lin Shi

Anal Chem. 2023 Nov 22. doi: 10.1021/acs.analchem.3c03412. Online ahead of print.

ABSTRACT

Exosomal microRNAs (miRNAs) play critical regulatory roles in many cellular processes, and so how to probe them has attracted increasing interest. Here we propose an aptamer-functionalized dimeric framework nucleic acid (FNA) nanoplatform for effective capture of exosomes and directly probing internal miRNAs with electrochemiluminescence (ECL) detection, not requiring RNA extraction in conventional counterparts. A CD63 protein-binding aptamer is tethered to one of the FNA structures, allowing exosomes to be immobilized there and release internal miRNAs after lysis. The target miRNA induces the formation of a Y-shaped junction on another FNA structure in a close proximity state, which benefits the loading of covalently hemin-modified spherical nucleic acid enzymes for enhanced ECL readout in the luminol-H2O2 system. In this facile way, the ultrasensitive detection of exosomal miR-21 from cancer cells is accomplished and then used for cell apoptosis analysis, indicating that the oncogene miR-21 negatively participates in the regulation of the apoptotic process; namely, downregulating the miR-21 level is unbeneficial for cancer cell growth.

PMID:37991490 | DOI:10.1021/acs.analchem.3c03412
Cell-free DNA extraction from urine of lung cancer patients and healthy individuals: Evaluation of a simple method using sample volume up-scaling

Fetched: November 23rd, 2023, 5:00am GMT by Tilman Ruppert

J Clin Lab Anal. 2023 Nov 22:e24984. doi: 10.1002/jcla.24984. Online ahead of print.

ABSTRACT

BACKGROUND: Urine holds promise as a source for cell-free DNA (cfDNA) analysis of cancer genetics due to its nature as a self-collectable biospecimen available in large quantities. However, pre-analytical variables such as preservation of cfDNA or efficiency of up-scaling specimen volume need to be better explored to increase analysis sensitivity.

PATIENTS AND METHODS: Initially effects of pH levels on cfDNA stability of urine preserved with EDTA were investigated in three healthy probands. Furthermore, the efficiency of urine volume up-scaling was examined using a simple DNA extraction method and cfDNA in urine of 32 individuals. Quantification was performed by PCR detection of three relevant targets used for EGFR and KRAS gene mutational analysis.

RESULTS: Only samples preserved with EDTA at alkaline pH levels showed cfDNA stability of up to 10 days at room temperature. Moreover, it was found that increasing the volume up to 100 mL was highly efficient. A similar amount of copies was detected in three different gene sites in all specimens indicating both a good availability and a non-random distribution pattern across genes. Since the median cfDNA copy number was 1642 copies/mL, abundance of cfDNA in this type of liquid biopsy is low.

CONCLUSION: Predictable sensitivities with different urine volumes on the ground of detectable cfDNA in our study population revealed that up-scaling (>5 mL) is mandatory if the mutation allele frequency is less than 1%.

PMID:37991151 | DOI:10.1002/jcla.24984
Bioproperties, Nanostructured System and Analytical and Bioanalytical Methods for Determination of Rapamycin: A Review

Fetched: November 23rd, 2023, 5:00am GMT by Karen Cristina Dos Santos

Crit Rev Anal Chem. 2023 Nov 22:1-9. doi: 10.1080/10408347.2020.1839737-test. Online ahead of print.

ABSTRACT

The drug rapamycin is a potent inhibitor of the mTOR complex, acting directly in the signaling cascade of this protein complex; interrupting cell proliferation, in addition to being an extremely efficient immunosuppressant. Currently this drug is being used in several types of cancer. Rapamycin has been a target of great interest within nanomedicine involving nanostructured systems for drug delivery aiming to increase the bioactivity and bioavailability of this drug. In addition, there is a constant search for analytical methods to identify and quantify this drug. Numerous high-performance liquid chromatography analytical techniques, mass spectrometry and immunoassay techniques have been employed efficiently in an attempt to develop increasingly sensitive analytical methods. Thus, this review sought to bring together current and relevant scientific works involving rapamycin and; besides analytical methods more used for quantification of this molecule.

PMID:37990513 | DOI:10.1080/10408347.2020.1839737-test
Survey of rectal cancer MRI technique and reporting tumour descriptors in the UK: a multi-centre British Society of Gastrointestinal and Abdominal Radiology (BSGAR) audit

Fetched: November 22nd, 2023, 5:00am GMT by E Robinson

Clin Radiol. 2023 Nov 20:S0009-9260(23)00509-3. doi: 10.1016/j.crad.2023.10.025. Online ahead of print.

ABSTRACT

AIM: To evaluate variation in magnetic resonance imaging (MRI) technique and reporting of rectal cancer staging examinations across the UK.

MATERIALS AND METHODS: A retrospective, multi-centre audit was undertaken of imaging protocols and information documented within consecutive MRI rectal cancer reports between March 2020 and August 2021, which were compared against American and European guidelines. Inclusion criteria included histologically proven rectal adenocarcinoma and baseline staging MRI rectum only.

RESULTS: Fully anonymised data from 924 MRI reports by 78 radiologists at 24 centres were evaluated. Thirty-two per cent of radiologists used template reporting, but these reports offered superior documentation of 13 out of 18 key tumour features compared to free-text reports including T-stage, relation to peritoneal reflection and mesorectal fascia (MRF), nodal status, and presence of extramural venous invasion (EMVI; p<0.027 in each). There was no significant differences in the remaining five features. Across all tumour locations, the tumour relationship to the MRF, the presence of EMVI, and the presence of tumour deposits were reported in 79.5%, 85.6%, and 44% of cases, respectively, and tumour, nodal, and distant metastatic stage documented in 94.4%, 97.7%, and 78.3%. In low rectal tumours, the relationship to the anal sphincter complex was reported in only 54.6%.

CONCLUSION: Considerable variation exists in rectal cancer MRI acquisition and reporting in this sample of UK centres. Inclusion of key radiological features in reports must be improved for risk stratification and treatment decisions. Template reporting is superior to free-text reporting. Routine adoption of standardised radiology practices should now be considered to improve standards to facilitate personalised precision treatment for patients to improve outcomes.

PMID:37989667 | DOI:10.1016/j.crad.2023.10.025
Where is VALDO? VAscular Lesions Detection and segmentatiOn challenge at MICCAI 2021

Fetched: November 22nd, 2023, 5:00am GMT by Carole H Sudre

Med Image Anal. 2023 Nov 19;91:103029. doi: 10.1016/j.media.2023.103029. Online ahead of print.

ABSTRACT

Imaging markers of cerebral small vessel disease provide valuable information on brain health, but their manual assessment is time-consuming and hampered by substantial intra- and interrater variability. Automated rating may benefit biomedical research, as well as clinical assessment, but diagnostic reliability of existing algorithms is unknown. Here, we present the results of the VAscular Lesions DetectiOn and Segmentation (Where is VALDO?) challenge that was run as a satellite event at the international conference on Medical Image Computing and Computer Aided Intervention (MICCAI) 2021. This challenge aimed to promote the development of methods for automated detection and segmentation of small and sparse imaging markers of cerebral small vessel disease, namely enlarged perivascular spaces (EPVS) (Task 1), cerebral microbleeds (Task 2) and lacunes of presumed vascular origin (Task 3) while leveraging weak and noisy labels. Overall, 12 teams participated in the challenge proposing solutions for one or more tasks (4 for Task 1-EPVS, 9 for Task 2-Microbleeds and 6 for Task 3-Lacunes). Multi-cohort data was used in both training and evaluation. Results showed a large variability in performance both across teams and across tasks, with promising results notably for Task 1-EPVS and Task 2-Microbleeds and not practically useful results yet for Task 3-Lacunes. It also highlighted the performance inconsistency across cases that may deter use at an individual level, while still proving useful at a population level.

PMID:37988921 | DOI:10.1016/j.media.2023.103029
Integrating Reliable Pt-S Bond-Mediated 3D DNA Nanomachine with Magnetic Separation in a Homogeneous Electrochemical Strategy for Exosomal MicroRNA Detection with Low Background and High Sensitivity

Fetched: November 22nd, 2023, 5:00am GMT by Limin Yang

Anal Chem. 2023 Nov 21. doi: 10.1021/acs.analchem.3c03914. Online ahead of print.

ABSTRACT

Precise and sensitive analysis of exosomal microRNA (miRNA) is of great importance for noninvasive early disease diagnosis, but it remains a great challenge to detect exosomal miRNA in human blood samples because of their small size, high sequence homology, and low abundance. Herein, we integrated reliable Pt-S bond-mediated three-dimensional (3D) DNA nanomachine and magnetic separation in a homogeneous electrochemical strategy for the detection of exosomal miRNA with low background and high sensitivity. The 3D DNA nanomachine was easily prepared via a facile and rapid freezing method, and it was capable of resisting the influence of biothiols, thus endowing it with high stability. Notably, the as-developed magnetic 3D DNA nanomachine not only enabled the detection system to have a low background but also coupled with liposome nanocarriers to synergistically amplify the current signal. Consequently, by ingeniously combining the low background and multiple signal-amplification strategies in homogeneous electrochemical biosensing, highly sensitive detection of exosomal miRNA was successfully achieved. More significantly, with good anti-interference ability, the as-proposed method could effectively discriminate plasma samples from cancer patients and healthy subjects, thus showing a high potential for application in the nondestructive early clinical diagnosis of disease.

PMID:37988125 | DOI:10.1021/acs.analchem.3c03914
Prediction of the invasion depth of superficial non-ampullary duodenal adenocarcinoma

Fetched: November 22nd, 2023, 5:00am GMT by Yuki Morita

Dig Endosc. 2023 Nov 20. doi: 10.1111/den.14729. Online ahead of print.

ABSTRACT

OBJECTIVES: Distinguishing between intramucosal cancer and submucosal invasive cancer is vital for optimal treatment selection for patients with superficial non-ampullary duodenal adenocarcinoma; however, standard diagnostic systems for diagnosing invasion depth are as yet undetermined.

METHODS: Of 205 patients with superficial non-ampullary duodenal adenocarcinoma who underwent treatment at our institution between 2006 and 2022, 188 had intramucosal cancer and 17 had submucosal invasive cancer. The clinical, endoscopic, and pathological features used in preoperative diagnosis of invasion depth and the diagnostic performance of endoscopic ultrasonography were retrospectively analyzed in 85 patients.

RESULTS: Oral side of the papilla tumor location, protruded or mixed macroscopic type, and moderately-to-poorly differentiated adenocarcinoma based on biopsy specimens were significantly more frequent in submucosal invasive cancer than in intramucosal cancer (88% vs. 48%; 94% vs. 42%; 47% vs. 0%, respectively). From the relationship between the endoscopic features and the submucosal invasive cancer incidence, submucosal invasion risk was stratified as 1) Low-risk (risk, 2 %): all lesions located on the anal side of the papilla and superficial macroscopic type on the oral side of the papilla, and 2) High-risk (risk, 23 %): protruded or mixed macroscopic type on the oral side of the papilla. Based on biopsy specimens, all eight patients with moderately-to-poorly differentiated adenocarcinoma had submucosal invasive cancer. Furthermore, endoscopic ultrasonography was not associated with invasion depth's diagnostic accuracy improvements.

CONCLUSION: Optimal treatment indications for superficial non-ampullary duodenal adenocarcinoma can be selected based on the risk factors of submucosal invasion by tumor location, macroscopic type, and biopsy diagnosis.

PMID:37986266 | DOI:10.1111/den.14729
Successful management of malignant colovesical fistula using covered colonic self-expanding metallic stent: a case report

Fetched: November 22nd, 2023, 5:00am GMT by Goro Takahashi

Surg Case Rep. 2023 Nov 21;9(1):201. doi: 10.1186/s40792-023-01784-8.

ABSTRACT

BACKGROUND: A colovesical fistula (CVF) is commonly treated by resection of the intestine containing the fistula or creation of a defunctioning stoma. We herein report a case of successful fistula closure and avoidance of colostomy after placement of a covered colonic self-expanding metallic stent (SEMS) as a palliative treatment for a malignant CVF.

CASE PRESENTATION: A 75-year-old man undergoing infusional 5-fluorouracil and irinotecan chemotherapy plus bevacizumab for recurrent peritoneal dissemination of rectal cancer was admitted to our hospital because of fecaluria with a high-grade fever. Blood tests showed a moderate inflammatory reaction (white blood cell count, 9200/mm³; C-reactive protein, 11.03 mg/dL; procalcitonin, 1.33 ng/mL). Urinary sediment examination showed severe bacteriuria. Abdominal contrast-enhanced computed tomography showed intravesical gas, thickening of the posterior wall of the bladder, and irregular thickening of the sigmoid colon wall contiguous with the posterior bladder wall. Magnetic resonance imaging (MRI) clearly showed a fistula between the bladder and sigmoid colon. Colonoscopy revealed a circumferential malignant stricture 15 cm from the anal verge, and a fistula to the bladder was identified by water-soluble contrast medium. We diagnosed a complicated urinary tract infection (UTI) associated with a CVF due to peritoneal dissemination and started empirical treatment with sulbactam/ampicillin. Given the absence of active inflammatory findings around the fistula on MRI and the patient's physical frailty, we decided to place a covered SEMS to close the fistula. Under fluoroscopic and endoscopic guidance, a covered colonic SEMS of 80-mm length and 20-mm diameter was successfully deployed, and the fistula was sealed immediately after placement. Urine culture on day 3 after stenting was negative for bacteria, and a contrast study on day 5 showed no fistula. The patient was discharged home on day 6 with no complications. The UTI did not recur for 4 months after discharge.

CONCLUSIONS: A covered colonic SEMS was useful for sealing a malignant CVF in a patient unfit for surgery, and MRI was valuable to determine the status of the fistula. A covered colonic SEMS could be an alternative to surgical treatment for CVFs in patients who require palliative care.

PMID:37985577 | PMC:PMC10661602 | DOI:10.1186/s40792-023-01784-8
Novel stent-assisted ileal bypass is applied to avoid protective stoma and prevent anastomotic leakage for rectal cancer

Fetched: November 22nd, 2023, 5:00am GMT by Ze-Lin Wen

ANZ J Surg. 2023 Nov 20. doi: 10.1111/ans.18781. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to investigate the safety and feasibility of a novel stent-assisted ileal bypass for rectal cancer patients who received sphincter-preserving surgery.

METHODS: Patients who were diagnosed with rectal cancer and received sphincter-preserving surgery plus a novel stent-assisted ileal bypass were respectively included from January 2022 to January 2023. Biofragmentable ileal stent with diaphragm sheet in the cavity was placed in the terminal ileum using absorbable sutures after anastomosis. At the proximal end of the stent, an intestinal diversion tube was placed in the prefabricated purse-string, through which faeces were drained. The stent completely disintegrated in the body after 3-4 weeks, which protected the anastomosis after surgery and avoided protective stoma. Clinical characteristics and surgical outcomes were collected.

RESULTS: Eleven patients who successfully received surgery were included. There were seven (63.6%) males and four (36.4%) females. The tumour size was 3.2 ± 1.7 cm and the lower verge of tumour to anal verge was 6.8 ± 1.3 cm. As for surgical outcomes, operation time was 216.4 ± 54.1 min, blood loss was 43.6 ± 64.6 mL, time to first flatus via intestinal diversion tube was 3.2 ± 1.1 days, time to discharge stent was 22.8 ± 3.0 days, and postoperative hospital stay was 21.0 ± 5.4 days. Two patients suffered from postoperative complications including pneumonia and incision infection.

CONCLUSION: This novel stent-assisted ileal bypass is safe and feasible, it provides a new choice for rectal cancer patients to avoid protective stoma and secondary surgery.

PMID:37984380 | DOI:10.1111/ans.18781
Drug repurposing of rimantadine for treatment of cancer

Fetched: November 22nd, 2023, 5:00am GMT by Nemesio Villa-Ruano

Pharm Pat Anal. 2023 Nov 20. doi: 10.4155/ppa-2023-0019. Online ahead of print.

ABSTRACT

Repurposing of approved drugs allows strong savings in time and investment. Rimantadine is an FDA-approved drug for prevention and treatment of influenza A infection. Patent US2021330605 describes the use of rimantadine, an adamantane derivative, for the treatment of melanoma, breast cancer and head and neck squamous cell carcinoma. Rimantadine inhibited proliferation of cell lines of melanoma, breast cancer, and head and neck squamous cell carcinoma, increased the survival of mice injected with cancer cell lines and restores the expression of MHC class I. Rimantadine has the potential to be used successfully in the treatment of head and neck squamous cell carcinoma.

PMID:37982658 | DOI:10.4155/ppa-2023-0019
Prominence of bioresponsive DNA nanococoons in tackling post-surgery cancer recurrence

Fetched: November 22nd, 2023, 5:00am GMT by Sravani Yerram

Pharm Pat Anal. 2023 Nov 20. doi: 10.4155/ppa-2023-0013. Online ahead of print.

ABSTRACT

Post-surgery cancer recurrence is one of the reasons for increased cancer cases. The effective usage of the enhanced permeability and retention effect of a nanocarrier infused with the bioresponsive release mechanism of checkpoint inhibitors (aPD1 and aCTLA4) can become a boon to mankind. DNA nanococoons (DNCs) comprising Cytosine-phosphorothioate-Guanine oligodeoxynucleotides (CpG-ODNs) with potent immunostimulatory effects can significantly enhance anti-cancer activity. Triglycerylmonostearate (TGMS) with enzymatic cleavage potential at the wound sites of tumor resection, upon caging with restriction enzyme (HhaI) followed by attaching to DNCs, makes the immunotherapy bioresponsive. Hhal-TGMS-DNCs-aPD1 triggered by the inflammation at the wound site undergoes enzymatic cleavage, releases the restriction enzyme, converts DNCs to CpG ODNs sequentially and with sustained aPD1 release exerts an appreciable anti-cancer effect.

PMID:37982642 | DOI:10.4155/ppa-2023-0013
6-Plex mdSUGAR Isobaric-Labeling Guide Fingerprint Embedding for Glycomics Analysis

Fetched: November 22nd, 2023, 5:00am GMT by Min Ma

Anal Chem. 2023 Nov 20. doi: 10.1021/acs.analchem.3c03342. Online ahead of print.

ABSTRACT

Glycans are vital biomolecules with diverse functions in biological processes. Mass spectrometry (MS) has become the most widely employed technology for glycomics studies. However, in the traditional data-dependent acquisition mode, only a subset of the abundant ions during MS1 scans are isolated and fragmented in subsequent MS2 events, which reduces reproducibility and prevents the measurement of low-abundance glycan species. Here, we reported a new method termed 6-plex mdSUGAR isobaric-labeling guide fingerprint embedding (MAGNI), to achieve multiplexed, quantitative, and targeted glycan analysis. The glycan peak signature was embedded by a triplicate-labeling strategy with a 6-plex mdSUGAR tag, and using ultrahigh-resolution mass spectrometers, the low-abundance glycans that carry the mass fingerprints can be recognized on the MS1 spectra through an in-house developed software tool, MAGNIFinder. These embedded unique fingerprints can guide the selection and fragmentation of targeted precursor ions and further provide rich information on glycan structures. Quantitative analysis of two standard glycoproteins demonstrated the accuracy and precision of MAGNI. Using this approach, we identified 304 N-glycans in two ovarian cancer cell lines. Among them, 65 unique N-glycans were found differentially expressed, which indicates a distinct glycosylation pattern for each cell line. Remarkably, 31 N-glycans can be quantified in only 1 × 10³ cells, demonstrating the high sensitivity of our method. Taken together, our MAGNI method offers a useful tool for low-abundance N-glycan characterization and is capable of determining small quantitative differences in N-glycan profiling. Therefore, it will be beneficial to the field of glycobiology and will expand our understanding of glycosylation.

PMID:37982459 | DOI:10.1021/acs.analchem.3c03342
Moutan cortex exerts blood-activating and anti-inflammatory effects by regulating coagulation-inflammation cascades pathway in cells, rats and zebrafish

Fetched: November 20th, 2023, 5:00am GMT by Yuting Huang

J Ethnopharmacol. 2023 Nov 18;320:117398. doi: 10.1016/j.jep.2023.117398. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, raw Moutan Cortex (RMC) has been used in clinical practice for thousands of years. However, its blood-cooling and blood-activating medicinal effects as well as the underlying mechanisms have not been preliminarily verified until recent years.

AIM OF THE STUDY: Our group's previous network pharmacological studies suggested that RMC might exert its blood-activating and anti-inflammatory effects by modulating the coagulation-inflammation cascade pathway. Therefore, the present study aimed to further investigate the mechanisms relevant to the blood-activating and anti-inflammatory effects of RMC so as to provide more robust data supporting its clinical application.

MATERIALS AND METHODS: The inflammation and coagulation models of human umbilical vein endothelial cells (HUVECs) were induced by TNF-α; The rat models with blood-heat and blood-stasis syndrome (BHS) were constructed by ice-water bath with a combined use of epinephrine hydrochloride and dried yeast; The thrombus models of zebrafish were induced by arachidonic acid, and the inflammation models were established using LPS and CuSO4. The regulatory effects of RMC on the key targets in the pathway of the coagulation-inflammation cascade were investigated by combining ELISA, RT-PCR, and western blot techniques in an attempt to provide multiple validations concerning RMC's pharmacological efficacy and mechanism associated with cooling blood and activating blood circulation.

RESULT: The findings from the pharmacodynamic research demonstrated that RMC could inhibit the coagulation and inflammation process of HUVECs. Besides, it lowered the anal temperature and whole blood viscosity in BHS rats in addition to a prolongation of their prothrombin time (PT), thrombin time (TT), and activated partial thromboplastin time (APTT). Successfully constrained thrombotic area and reduced inflammatory cell counts were also observed in zebrafish models. Meanwhile, ELISA, RT-PCR and WB showed that RMC were capable of inhibiting the factors related to coagulation-MARK inflammation pathway-FⅡ, TF, FⅦ, FⅧ, FⅩ, and PAI, as well as down-regulating the expression of IL-6, COX-2, iNOS, TNF-α, ERK, JNK and p38.

CONCLUSION: RMC exerts blood-activating and anti-inflammatory effects through regulating the target genes of the coagulation-MARK inflammation cascade pathway.

PMID:37981122 | DOI:10.1016/j.jep.2023.117398
A near-infrared fluorescent probe with viscosity sensitivity in lysosome for cancer visualization

Fetched: November 20th, 2023, 5:00am GMT by Yong Wang

Anal Bioanal Chem. 2023 Nov 20. doi: 10.1007/s00216-023-05050-6. Online ahead of print.

ABSTRACT

A viscosity-sensitive, lysosome-targeted near-infrared fluorescent probe (PYATT) was reported in this paper. The fluorescent spectra of PYATT are strongly dependent on viscosity, resulting in a Stokes shift of about 190 nm. Given its photostability, low cytotoxicity, and high fluorescence quantum yield, PYATT is expected to be used in cell imaging. Due to the higher viscosity of tumor cells than normal cells, the fluorescence intensity of PYATT in tumor cells is higher than normal cells, which can realize the visualization of tumors. The near-infrared probe (PYATT) is viscosity-dependent in lysosomes, which is valuable in early diagnosis and treatment of tumor.

PMID:37981588 | DOI:10.1007/s00216-023-05050-6
HPV-related lesions after hysterectomy for high-grade cervical intraepithelial neoplasia and early-stage cervical cancer: A focus on the potential role of vaccination

Fetched: November 19th, 2023, 5:00am GMT by Giorgio Bogani

Tumori. 2023 Nov 17:3008916231208344. doi: 10.1177/03008916231208344. Online ahead of print.

ABSTRACT

OBJECTIVE: To date, no data supports the execution of vaccination after hysterectomy for high-grade cervical intraepithelial neoplasia (CIN2+) and early-stage cervical cancer. We aim to evaluate the potential effect of vaccination after hysterectomy for high-grade cervical intraepithelial neoplasia and early-stage cervical cancer.

METHODS: This is a multi-center retrospective study evaluating data of women who develop lower genital tract dysplasia (including anal, vulvar and vaginal intra-epithelial neoplasia) after having hysterectomy for CIN2+ and FIGO stage IA1- IB1 cervical cancer.

RESULTS: Overall, charts for 77 patients who developed lower genital tract dysplasia were collected. The study population included 62 (80.5%) and 15 (19.5%) patients with CIN2+ and early-stage cervical cancer, respectively. The median (range) time between hysterectomy and diagnosis of develop lower genital tract dysplasia was 38 (range, 14-62) months. HPV types covered by the nonavalent HPV vaccination would potentially cover 94.8% of the development of lower genital tract dysplasia. Restricting the analysis to the 18 patients with available HPV data at the time of hysterectomy, the beneficial effect of nonvalent vaccination was 89%. However, considering that patients with persistent HPV types (with the same HPV types at the time of hysterectomy and who developed lower genital tract dysplasia) would not benefit from vaccination, we estimated the potential protective effect of vaccination to be 67% (12 out of 18 patients; four patients had a persistent infection for the same HPV type(s)).

CONCLUSIONS: Our retrospective analysis supported the adoption of HPV vaccination in patients having treatment for HPV-related disease. Even in the absence of the uterine cervix, HPV vaccination would protect against develop lower genital tract dysplasia. Further prospective studies have to confirm our preliminary research.

PMID:37978580 | DOI:10.1177/03008916231208344
A micro-nano interface integrated SERS-based microfluidic sensor for miRNA detection using DNAzyme walker amplification

Fetched: November 19th, 2023, 5:00am GMT by Yang Lu

Anal Chim Acta. 2023 Dec 1;1283:341957. doi: 10.1016/j.aca.2023.341957. Epub 2023 Oct 24.

ABSTRACT

BACKGROUND: Precise and specific miRNA detection plays a vital role in exploring development mechanisms of cancer disease, thereby it can significantly improve relevant prevention and treatment strategies.

RESULTS: In this work, a surface-enhanced Raman spectroscopy (SERS)-based microfluidic chip has been devised with a microcone array SERS substrate (MCASS) for the miR-141 detection. This substrate excels in unique SERS activity and large surface area for DNA oligonucleotide modification. As the presence of miR-141, the DNAzyme walker induced cleavage reaction took place on the finely designed and prepared dual DNA conjugated SERS nanoprobes. The SERS nanoprobes can anchor on MCASS by the DNA hybridization that achieved an impressive detection limit in the femtomolar level.

SIGNIFICANCE: With this integrated SERS-based microfluidic chip, we provided a miRNA detection strategy using DNAzyme walker amplification technology. It is believed that this strategy could be a powerful tool for miRNA detection and related cancer screening test.

PMID:37977782 | DOI:10.1016/j.aca.2023.341957
Integrative analysis of transcriptome and metabolome provide new insights into mechanisms of Capilliposide A against cisplatin-induced nephrotoxicity

Fetched: November 19th, 2023, 5:00am GMT by Jiaxi Fang

J Pharm Biomed Anal. 2023 Oct 27;238:115814. doi: 10.1016/j.jpba.2023.115814. Online ahead of print.

ABSTRACT

OBJECTIVE: Cisplatin (CDDP) has been widely used for chemotherapy against tumours. However，the nephrotoxicity has limited its clinical use. Here, we reported a novel compound, Capilliposide A (CPS-A), to exhibit therapeutic effects on CDDP-induced acute kidney injury (AKI) and explored its potential mechanisms via transcriptome and metabolome.

MATERIALS AND METHODS: HK-2 cells were treated with CPS-A, after which cell viability, apoptosis and inflammation were investigated. A mouse model of AKI was constructed by single injection of CDDP in vivo. The renal function and morphology and mitochondrial function were assessed by pathological section and transmission electron microscope (TEM). Transcriptomics and metabolomics are used to explore possible mechanisms which was later verified in vitro.

RESULTS: CPS-A administration improved the survival rates of HK-2 cells with a significant decrease in the expression of KIM-1, NGAL, IL-6, IL-8 and IL-1β. In vivo results also suggested that CPS-A attenuates CDDP-induced kidney injury by reducing serum creatinine (Cr) and blood urea nitrogen (BUN) levels. Furthermore, TEM also showed the improvement of mitochondrial ultrastructure both in vivo and vitro. Transcriptomics analysis of the mice's renal cortex indicated the expression of ATF4 and CHOP were upregulated, which was further validated by qPCR and Western blotting in vitro. Integrative analysis of transcriptome and metabolome indicated that L-Leucine enriched in Valine, leucine and isoleucine degradation might be potential targets.

CONCLUSIONS: CPS-A can effectively regulate endogenous metabolites associated with amino acid metabolism and ameliorate apoptosis and oxidative stress in CDDP-induced AKI by reducing endoplasmic reticulum stress.

PMID:37976990 | DOI:10.1016/j.jpba.2023.115814
Evaluation of the effect of CYP2D6*3, *4,*10, and *17 polymorphisms on the pharmacokinetic of tamoxifen and its metabolites in patients with hormone-positive breast cancer

Fetched: November 19th, 2023, 5:00am GMT by Fatemeh Saghafi

J Pharm Biomed Anal. 2023 Nov 2;238:115839. doi: 10.1016/j.jpba.2023.115839. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: A high rate of interindividual variability in response to tamoxifen (TAM) in breast cancer patients with CYP2D6 polymorphism has been reported, which affects the patient's therapeutic outcome. The objective of this study was to investigate the pharmacogenomics of CYP2D6 genotyping in Iranian patients with breast cancer treated with adjuvant TAM.

METHODS: A peripheral blood sample was obtained to determine the steady-state plasma concentrations of TAM and its metabolites (Endoxifen (EN) and 4-Hydroxytamoxifen (4-OHT)) using high-performance liquid chromatography with fluorescence detection (HPLC-FLU) assay. We detected CYP2D6 * 3, * 4, * 10, and * 17 single nucleotide polymorphisms via polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method.

RESULTS: A total of 84 Iranian estrogen receptor‑positive breast cancer patients receiving the daily dose of 20 mg tamoxifen were recruited. Although a consequent decrease in the median EN and 4-OHT concentrations was observed by comparing poor or intermediate metabolizer patients with an extensive metabolizer population, this difference did not reach a significant level. The mean plasma EN concentrations in poor and intermediate metabolizers were 46.1% (95% CI, 7.4-27.8%) and 59.4% (95% CI, 11.9-37.3%) of extensive metabolizer subjects, respectively. Poor and intermediate metabolizers had the mean plasma 4-OHT concentrations that were 46.6% (95% CI, 0.9-61.7%) and 73.2% (95% CI, 2.7-93.1%) of those of subjects who were extensive metabolizer, respectively.

CONCLUSIONS: The possible role of genotyping in Iranian patients' response to treatment may explain inter-individual differences in the plasma concentrations of active metabolites of TAM.

PMID:37976989 | DOI:10.1016/j.jpba.2023.115839
Application of SNAP-tag-EGFR cell membrane chromatography model in screening antitumor active components of Silybum marianum (L.) Gaertn

Fetched: November 19th, 2023, 5:00am GMT by Xin Zhang

J Pharm Biomed Anal. 2023 Oct 26;238:115816. doi: 10.1016/j.jpba.2023.115816. Online ahead of print.

ABSTRACT

The SNAP-tag-epidermal growth factor receptor (SNAP-tag-EGFR) cell membrane chromatography (CMC) model is a powerful tool for investigating ligand-receptor interactions and screening active ingredients in traditional Chinese medicine. Most tyrosine kinase inhibitors (TKIs) target epidermal growth factor receptors. However, TKIs associated with significant side effects and drug resistance must be addressed immediately. Therefore, there is an urgent need to develop new TKIs with high efficiency and low toxicity. Because of its low toxicity and side effects, traditional Chinese medicine has been widely employed to treat various diseases, including cancer. Hence, this study aimed to use the SNAP-tag-EGFR/CMC-high-performance liquid chromatography-mass spectrometry (HPLC-MS) two-dimensional system model as the research tool to screen and identify potential EGFR antagonists from the Chinese medicine Silybum marianum (L.) Gaertn. The applicability of the system was verified using the positive control drug osimertinib. Four potential EGFR antagonists were screened from the Chinese medicine Silybum marianum (L.) Gaertn.. They were identified as silydianin, silychristin, silybin, and isosilybin. Additionally, their pharmacological activity was preliminarily verified using a CCK-8 assay. The kinetic parameters of the four active ingredients interacting with EGFR and their binding modes with EGFR were analyzed using nonlinear chromatography (NLC) and molecular docking. This study identified silydianin, silychristin, silybin, and isosilybin from Silybum marianum (L.) Gaertn. and verified their potential antitumor effects on EGFR.

PMID:37976988 | DOI:10.1016/j.jpba.2023.115816
Selective and reliable fluorometric quantitation of anti-cancer drug in real plasma samples using nitrogen-doped carbon dots after MMIPs solid phase microextraction: Monitoring methotrexate plasma level

Fetched: November 19th, 2023, 5:00am GMT by Ahmed Z Alanazi

J Pharm Biomed Anal. 2023 Nov 10;238:115862. doi: 10.1016/j.jpba.2023.115862. Online ahead of print.

ABSTRACT

A novel selective and reliable ratiometric fluorescence probe has been successfully synthesized for precise, sensitive, and simple quantitation of methotrexate (MTX). Hydrothermal method was employed to fabricate nitrogen-doped carbon dots using Annona squamosa seeds (AS-CDs) as a starting material, and their characteristics were confirmed using transmission electron microscopy (TEM), UV-Vis spectroscopy, fluorescence spectroscopy, X-ray diffractometry (XRD), and Fourier Transform Infrared Spectroscopy (FTIR). The ratiometric fluorometric assay, which is based on measuring the ratio of emissions (F355/F430), has a wide detection range of 5-2000 ng /mL and a limit of detection (LOD, S/N = 3) of 1.5 ng /mL. The developed sensing method was successfully applied to the quantification of MTX in rabbit plasma samples and parenteral formulations, achieving satisfactory recoveries %. Magnetic molecularly imprinted solid-phase microextraction was used for selective extraction of MTX from plasma samples. The pharmacokinetic parameters were successfully determined in real rabbit plasma samples after intravenous administration of MTX. The as-designed probe does not only improve the sensitivity, but also enhances the precision and accuracy of the proposed method. Overall, this study presents a promising approach for the detection of MTX in genuine samples with acceptable degree of selectivity and sensitivity.

PMID:37976985 | DOI:10.1016/j.jpba.2023.115862
Enhancing Single-Cell Western Blotting Sensitivity Using Diffusive Analyte Blotting and Antibody Conjugate Amplification

Fetched: November 18th, 2023, 5:00am GMT by Mariia Alibekova Long

Anal Chem. 2023 Nov 16. doi: 10.1021/acs.analchem.3c04130. Online ahead of print.

ABSTRACT

While there are many techniques to achieve highly sensitive, multiplex detection of RNA and DNA from single cells, detecting protein content often suffers from low limits of detection and throughput. Miniaturized, high-sensitivity Western blots on single cells (scWesterns) are attractive because they do not require advanced instrumentation. By physically separating analytes, scWesterns also uniquely mitigate limitations to target protein multiplexing posed by the affinity reagent performance. However, a fundamental limitation of scWesterns is their limited sensitivity for detecting low-abundance proteins, which arises from transport barriers posed by the separation gel against detection species. Here we address the sensitivity by decoupling the electrophoretic separation medium from the detection medium. We transfer scWestern separations to a nitrocellulose blotting medium with distinct mass transfer advantages over traditional in-gel probing, yielding a 5.9-fold improvement in the limit of detection. We next amplify probing of blotted proteins with enzyme-antibody conjugates, which are incompatible with traditional in-gel probing to achieve further improvement in the limit of detection to 1000 molecules, a 120-fold improvement. This enables us to detect 100% of cells in an EGFP-expressing population using fluorescently tagged and enzyme-conjugated antibodies compared to 84.5% of cells using in-gel detection. These results suggest the compatibility of nitrocellulose-immobilized scWesterns with a variety of affinity reagents─not previously accessible for in-gel use─for further signal amplification and detection of low-abundance targets.

PMID:37974303 | DOI:10.1021/acs.analchem.3c04130
Spindle Monitor: A Tool for Real-Time Assessment and Concurrent Treatment of Postoperative Tumor Prognosis

Fetched: November 18th, 2023, 5:00am GMT by Jukun Yang

Anal Chem. 2023 Nov 16. doi: 10.1021/acs.analchem.3c03403. Online ahead of print.

ABSTRACT

Cancer surgery remains a mainstay in clinical treatment. However, the efficacy of subsequent therapies largely depends on the precise evaluation of postoperative prognoses, underscoring the critical need for a comprehensive and accurate assessment of surgical outcomes. Nanoprobes targeting tumors offer a promising solution for visual prognostic assessment. In this study, we developed a "Spindle Monitor" system, designated as APPADs (Au NBPs@PDA-pep-AS1411-Dox), composed of core-shell nanoparticles. The core was made up of gold nanobipyramids (Au NBPs), coated with polydopamine (PDA), and subsequently loaded with peptide chains, AS1411, and doxorubicin (Dox). Upon deployment in the acidic tumor microenvironment (TME), APPADs released substantial amounts of Dox, initiating the apoptotic process. This triggered the activity of caspase-3, which is a crucial executor in the apoptotic pathway. Consequently, DEVD, a specific recognition site for caspase-3, was cleaved, enabling the disconnection of FITC-conjugated peptide chains and the recovery of fluorescence. Through assessing this fluorescence imaging effect, local laser irradiation could be precisely guided to the postoperative site, facilitating a synergistic combination of photothermal therapy and chemotherapy. Specifically, our "Spindle Monitor" APPADs had been validated to achieve accurate fluorescence imaging in vitro and in vivo, which demonstrated its potential value as a versatile tool for evaluating postoperative prognosis in surgical treatments, such as thyroid cancer, and assessing chemotherapy efficacy in difficult cases, like late-stage osteosarcoma. This promising tool lays a good foundation for development in visual prognosis evaluation after tumor surgery.

PMID:37972234 | DOI:10.1021/acs.analchem.3c03403
Radiomics; Contemporary Applications in the Management of Anal Cancer; A Systematic Review

Fetched: November 18th, 2023, 5:00am GMT by Hugo C Temperley

Am Surg. 2023 Nov 16:31348231216494. doi: 10.1177/00031348231216494. Online ahead of print.

ABSTRACT

INTRODUCTION: The management of anal cancer relies on clinical and histopathological features for treatment decisions. In recent years, the field of radiomics, which involves the extraction and analysis of quantitative imaging features, has shown promise in improving management of pelvic cancers. The aim of this study was to evaluate the current application of radiomics in the management of anal cancer.

METHODS: A systematic search was conducted in Medline, EMBASE, and Web of Science databases. Inclusion criteria encompassed randomized and non-randomized trials investigating the use of radiomics to predict post-operative recurrence in anal cancer. Study quality was assessed using the QUADAS-2 and Radiomics Quality Score tools.

RESULTS: The systematic review identified a total of nine studies, with 589 patients examined. There were three main outcomes assessed in included studies: recurrence (6 studies), progression-free survival (2 studies), and prediction of human papillomavirus (HPV) status (1 study). Radiomics-based risk stratification models were found to provide valuable insights into treatment response and patient outcomes, with all developed signatures demonstrating at least modest accuracy (range: .68-1.0) in predicting their primary outcome.

CONCLUSION: Radiomics has emerged as a promising tool in the management of anal cancer. It offers the potential for improved risk stratification, treatment planning, and response assessment, thereby guiding personalized therapeutic approaches.

PMID:37972216 | DOI:10.1177/00031348231216494
Tweezer PCR: A Highly Specific Method for Accurate Identification of Low-Abundance Mutations

Fetched: November 18th, 2023, 5:00am GMT by Shanglin Li

Anal Chem. 2023 Nov 16. doi: 10.1021/acs.analchem.3c03467. Online ahead of print.

ABSTRACT

Somatic mutation is a valuable biomarker for tracking tumor progression and migration due to its distinctive feature in various tumors and its wide distribution throughout body fluids. However, accurately detecting somatic mutations from the abundant DNA of noncancerous origins remains a practical challenge in the clinic. Herein, we developed an ultraspecific method, called tweezer PCR, for detecting low-abundance mutations inspired by the design of DNA origami. The high specificity of tweezer PCR relies on a tweezer-shaped primer containing six basic functional units: a primer, a hairpin, a linker, a blocker, a spacer, and a toehold. After optimizing the structure of the tweezer-shaped primer and enhancing its specificity by adding additional Mg²⁺ and Na⁺, tweezer PCR distinguished as low as 20 copies of mutations from 2 million copies of wild-type templates per test. By testing synthesized plasmids and plasma samples gathered from nonsmall-cell lung cancer patients, tweezer PCR showed higher specificity and robustness for detecting low-copy-number mutations in contrast with digital droplet PCR. Additionally, the need for conventional instruments makes tweezer PCR a practically accessible method for testing low-abundance mutations. Because of its numerous advantages, we believe that tweezer PCR offers a precise, robust, and pragmatic tool for cancer screening, prognosis, and genotyping in the clinic.

PMID:37971891 | DOI:10.1021/acs.analchem.3c03467
Cumulative detection of anal high-grade squamous intraepithelial lesions over two-year follow-up in men who have sex with men living with HIV in France

Fetched: November 18th, 2023, 5:00am GMT by Jean-Damien Combes

J Infect Dis. 2023 Nov 16:jiad506. doi: 10.1093/infdis/jiad506. Online ahead of print.

ABSTRACT

We assessed cumulative detection and determinants of anal high-grade squamous intraepithelial lesions (HSIL) in men who have sex with men living with HIV who underwent three visits over two years, with cytology and high-resolution anoscopy (HRA), within the ANRS-EP57-APACHES study. Cumulative HSIL detection was 33% (134/410), of which 48% were detected at baseline. HSIL detection varied considerably by center (13-51%). Strongest HSIL determinants were baseline HPV16 (adjusted odds ratio [aOR] 8.2; 95% confidence interval [95%CI] 3.6-18.9), and p16/Ki67 (aOR 4.6; 95%CI 2.3-9.1). Repeat annual cytology and HRA improved HSIL detection but did not fully compensate between-center heterogeneity.

PMID:37970975 | DOI:10.1093/infdis/jiad506
Robotic natural orifice specimen extraction surgery I-type F method vs conventional robotic resection for lower rectal cancer

Fetched: November 17th, 2023, 5:01am GMT by Fang Tao

World J Gastrointest Surg. 2023 Oct 27;15(10):2142-2153. doi: 10.4240/wjgs.v15.i10.2142.

ABSTRACT

BACKGROUND: Robotic resection using the natural orifice specimen extraction surgery I-type F method (R-NOSES I-F) is a novel minimally invasive surgical strategy for the treatment of lower rectal cancer. However, the current literature on this method is limited to case reports, and further investigation into its safety and feasibility is warranted.

AIM: To evaluate the safety and feasibility of R-NOSES I-F for the treatment of low rectal cancer.

METHODS: From September 2018 to February 2022, 206 patients diagnosed with low rectal cancer at First Affiliated Hospital of Nanchang University were included in this retrospective analysis. Of these patients, 22 underwent R-NOSES I-F surgery (R-NOSES I-F group) and 76 underwent conventional robotic-assisted low rectal cancer resection (RLRC group). Clinicopathological data of all patients were collected and analyzed. Postoperative outcomes and prognoses were compared between the two groups. Statistical analysis was performed using SPSS software.

RESULTS: Patients in the R-NOSES I-F group had a significantly lower visual analog score for pain on postoperative day 1 (1.7 ± 0.7 vs 2.2 ± 0.6, P = 0.003) and shorter postoperative anal venting time (2.7 ± 0.6 vs 3.5 ± 0.7, P < 0.001) than those in the RLRC group. There were no significant differences between the two groups in terms of sex, age, body mass index, tumor size, TNM stage, operative time, intraoperative bleeding, postoperative complications, or inflammatory response (P > 0.05). Postoperative anal and urinary functions, as assessed by Wexner, low anterior resection syndrome, and International Prostate Symptom Scale scores, were similar in both groups (P > 0.05). Long-term follow-up revealed no significant differences in the rates of local recurrence and distant metastasis between the two groups (P > 0.05).

CONCLUSION: R-NOSES I-F is a safe and effective minimally invasive procedure for the treatment of lower rectal cancer. It improves pain relief, promotes gastrointestinal function recovery, and helps avoid incision-related complications.

PMID:37969697 | PMC:PMC10642453 | DOI:10.4240/wjgs.v15.i10.2142
Modular Pelvic Exenteration for Advanced Rectal Cancer in Frozen Pelvis

Fetched: November 17th, 2023, 5:01am GMT by Rui Wang

Am J Case Rep. 2023 Nov 16;24:e941684. doi: 10.12659/AJCR.941684.

ABSTRACT

BACKGROUND Surgery for locally advanced rectal cancer with frozen pelvis is challenging. Therefore, we designed the "modular pelvic exenteration" surgical strategy to achieve better radical resection. CASE REPORT A 51-year-old man with rectal cancer refused surgery and received chemotherapy and radiotherapy. He was intolerant to chemotherapy and did not respond well to radiotherapy. With cancer progression, he presented at our hospital with emaciation, fatigue, dysuria, bloody urine, bloody stool, and anal pain. Computed tomography and magnetic resonance imaging revealed the rectal tumor involved multiple adjacent organs and caused rectovesical fistula, bilateral hydronephrosis, hydroureterosis, and local pelvic infection. The rectal tumor was fixed in the pelvic cavity, presenting a frozen pelvis pattern. There was no distant metastasis. As the patient could not tolerate chemotherapy, was unsuitable for immune-check point inhibitor because the tumor had microsatellite stability, and did not respond well to radiotherapy, surgical resection seemed the most suitable treatment option. After the patient's anemia and malnutrition improved, our designed modular pelvic exenteration surgery was performed. In this strategy, we divided pelvic organs and tissues into 4 independent modules. After combining the modules planned to be resected, we delineated the pre-resection margin. By this strategy, the tumor was removed en bloc, with a clear resection margin. The patient was discharged 13 days after the operation, without complications. Follow-up for 24 months revealed no signs of tumor recurrence. CONCLUSIONS For locally advanced rectal cancer with frozen pelvis, the modular pelvic exenteration strategy may help to achieve satisfactory surgical effects in selected patients.

PMID:37968899 | PMC:PMC10660309 | DOI:10.12659/AJCR.941684
The Role of Ileostomy in the Prevention and Treatment of Anastomotic Leakage after Elective Rectal Cancer Surgery - A Retrospective Analysis of Specific Risk Factors, Outcomes, and Complications

Fetched: November 16th, 2023, 5:00am GMT by Elena Luminiţa Albulescu

Chirurgia (Bucur). 2023 Oct;118(5):502-512. doi: 10.21614/chirurgia.2023.v.118.i.5.p.502.

ABSTRACT

Background: The objective of this paper is to highlight the role and place of ileostomy from the perspective of the risk of anastomotic leakage (AL). Materials and method: This was a retrospective study of 74 (46.54%) low and ultra-low anterior resections from 159 cases of rectal cancer operated on in a seven-year interval (2015 - 2021). The cases were divided into two groups: Group A with protective ileostomy (47 cases = 63.51%) and Group B without protective ileostomy (27 cases = 35.49%). Results: The type of anastomosis was low colorectal for 15 cases and ileorectal for two cases, both in Group A, with either mechanical or manual sutures. Continuous loop ileostomy was the only fecal diversion procedure used for protection. The ileostomy-specific complications recorded in Group A were peristomal skin lesions (8 cases), early peristomal hernia (2 cases), and severe dehydration with acute renal-insufficency (7 cases). The closure of the ileostomy was performed in 42 cases (89.36%), with the time between the primary operation and the closure being 4.28 months on average, with limits between 12 days and 10 months. AL treatment was conservative in 13 (76.47%) cases and surgical in four cases, with the types of operations performed at reintervention being take-down of the anastomosis + left terminal colostomy + ileostomy closure in three cases (2 in Group A and 1 in Group B) and terminal ileostomy in one case in Group A. Conclusions: To reduce its specific complications, ileostomy should be performed in well-selected patients. Those with risk factors for leakage include males, the elderly, and those having important comorbidities, neoadjuvant chemoradiotherapy, low tumors below 5 cm from the anal verge, or complete circumferential stenosis and peritumoral inflammatory infiltrate.

PMID:37965834 | DOI:10.21614/chirurgia.2023.v.118.i.5.p.502
The emerging role of m6A modification of non-coding RNA in gastrointestinal cancers: a comprehensive review

Fetched: November 16th, 2023, 5:00am GMT by Meiqi Wang

Front Cell Dev Biol. 2023 Oct 30;11:1264552. doi: 10.3389/fcell.2023.1264552. eCollection 2023.

ABSTRACT

Gastrointestinal (GI) cancer is a series of malignant tumors with a high incidence globally. Although approaches for tumor diagnosis and therapy have advanced substantially, the mechanisms underlying the occurrence and progression of GI cancer are still unclear. Increasing evidence supports an important role for N⁶-methyladenosine (m⁶A) modification in many biological processes, including cancer-related processes via splicing, export, degradation, and translation of mRNAs. Under distinct cancer contexts, m⁶A regulators have different expression patterns and can regulate or be regulated by mRNAs and non-coding RNAs, especially long non-coding RNAs. The roles of m⁶A in cancer development have attracted increasing attention in epigenetics research. In this review, we synthesize progress in our understanding of m⁶A and its roles in GI cancer, especially esophageal, gastric, and colorectal cancers. Furthermore, we clarify the mechanism by which m⁶A contributes to GI cancer, providing a basis for the development of diagnostic, prognostic, and therapeutic targets.

PMID:37965577 | PMC:PMC10642577 | DOI:10.3389/fcell.2023.1264552
Combinational antibody detection approach increases the clinical validity of colorectal cancer screening

Fetched: November 16th, 2023, 5:00am GMT by Sohei Kobayashi

J Clin Lab Anal. 2023 Nov 14:e24978. doi: 10.1002/jcla.24978. Online ahead of print.

ABSTRACT

BACKGROUND: At different stages of the disease, biomarkers can help to determine disease progression and recurrence and provide a personalized indicator of therapeutic effectiveness. The serological identification of antigens by recombinant cDNA expression cloning (SEREX) has identified five SEREX antigens.

RESULTS: Compared with healthy donors, anti-FIRΔexon2 and anti-SOHLH antibodies (Abs) in the sera of patients with colorectal cancer (CRC) were markedly higher. Furthermore, no correlation was noted between five SEREX antigens and the three tumor markers (CEA, CA19-9, and anti-p53 Abs), indicating that anti-FIRΔexon2 Abs are an independent candidate marker for patients with CRC. Generally, the levels of anti-FIRΔexon2 Abs combined with clinically available tumor markers were determined to be significantly higher compared with CEA, CA19-9. Moreover, in early-stage CRC, the levels of anti-FIRΔexon2 Abs combined with existing tumor markers were higher than those of CEA, CA19-9.

CONCLUSION: Due to the highly heterogeneous nature of CRC, a single tumor marker is unlikely to become a standalone diagnostic test due to its commonly insufficient sensitivity and/or specificity. Using a combination antibody detection approach of tumor markers for CRC diagnosis has the potential to be an effective approach. Therefore, the use of serum protein biomarker candidates holds promise for the development of inexpensive, noninvasive, and inexpensive tests for the detection of CRC.

PMID:37964630 | DOI:10.1002/jcla.24978
IAP inhibitor plus chemoradiotherapy for the treatment of bulky anal canal carcinoma

Fetched: November 16th, 2023, 5:00am GMT by Francesca De Felice

Med Oncol. 2023 Nov 14;40(12):356. doi: 10.1007/s12032-023-02224-1.

ABSTRACT

The aim of this editorial is to focus on the urgent need to improve clinical outcomes in patients with bulky primary anal canal carcinoma.

PMID:37962690 | PMC:PMC10645633 | DOI:10.1007/s12032-023-02224-1
Global Urinary Volatolomics with (GC×)GC-TOF-MS

Fetched: November 16th, 2023, 5:00am GMT by Antonis Myridakis

Anal Chem. 2023 Nov 15. doi: 10.1021/acs.analchem.3c02523. Online ahead of print.

ABSTRACT

Urinary volatolomics offers a noninvasive approach for disease detection and monitoring. Herein we present an improved methodology for global volatolomic profiling. Wide coverage was achieved by utilizing a multiphase sorbent for volatile organic compound (VOC) extraction. A single, midpolar column gas chromatography (GC) assay yielded substantially higher numbers of monitored VOCs compared to our previously reported single-sorbent method. Multidimensional GC (GC×GC) enhanced further biomarker discovery while data analysis was simplified by using a tile-based approach. At the same time, the required urine volume was reduced 5-fold from 2 to 0.4 mL. The applicability of the methodology was demonstrated in a pancreatic ductal adenocarcinoma cohort where previous findings were confirmed while a series of additional VOCs with diagnostic potential were discovered.

PMID:37967208 | DOI:10.1021/acs.analchem.3c02523
Identification of Emerging Novel Psychoactive Substances by Retrospective Analysis of Population-Scale Mass Spectrometry Data Sets

Fetched: November 16th, 2023, 5:00am GMT by Michael A Skinnider

Anal Chem. 2023 Nov 15. doi: 10.1021/acs.analchem.3c03451. Online ahead of print.

ABSTRACT

Over the last two decades, hundreds of new psychoactive substances (NPSs), also known as "designer drugs", have emerged on the illicit drug market. The toxic and potentially fatal effects of these compounds oblige laboratories around the world to screen for NPS in seized materials and biological samples, commonly using high-resolution mass spectrometry. However, unambiguous identification of a NPS by mass spectrometry requires comparison to data from analytical reference materials, acquired on the same instrument. The sheer number of NPSs that are available on the illicit market, and the pace at which new compounds are introduced, means that forensic laboratories must make difficult decisions about which reference materials to acquire. Here, we asked whether retrospective suspect screening of population-scale mass spectrometry data could provide a data-driven platform to prioritize emerging NPSs for assay development. We curated a suspect database of precursor and diagnostic fragment ion masses for 83 emerging NPSs and used this database to retrospectively screen mass spectrometry data from 12,727 urine drug screens from one Canadian province. We developed integrative computational strategies to prioritize the most reliable identifications and tracked the frequency of these identifications over a 3 year study period between August 2019 and August 2022. The resulting data were used to guide the acquisition of new reference materials, which were in turn used to validate a subset of the retrospective identifications. Last, we took advantage of matching clinical reports for all 12,727 samples to systematically benchmark the accuracy of our retrospective data analysis approach. Our work opens up new avenues to enable the rapid detection of emerging illicit drugs through large-scale reanalysis of mass spectrometry data.

PMID:37966487 | DOI:10.1021/acs.analchem.3c03451
Incidental Dysplasia During Total Proctocolectomy With Ileoanal Pouch: Is It Associated With Worse Outcomes?

Fetched: November 15th, 2023, 5:01am GMT by Marianna Maspero

Inflamm Bowel Dis. 2023 Nov 14:izad263. doi: 10.1093/ibd/izad263. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal cancer. In cases of invisible or nonendoscopically resectable dysplasia found at colonoscopy, total proctocolectomy with ileal pouch anal anastomosis can be offered with good long-term outcomes; however, little is known regarding cancer-related outcomes when dysplasia is found incidentally after surgery on final pathology.

METHODS: Using our prospectively collected pouch registry, we identified patients who had preoperative colonic dysplasia or dysplasia found only after colectomy. Patients with cancer preoperatively or after colectomy were excluded. Included patients were divided into 3 groups: PRE (+preoperative biopsy, negative final pathology), BOTH (+preoperative biopsy and final pathology), and POST (negative preoperative biopsy, +final pathology). Long-term outcomes in the 3 groups were assessed.

RESULTS: In total, 517 patients were included: PRE = 125, BOTH = 254, POST = 137. After a median follow-up of 12 years (IQR 3-21), there were no differences in overall, disease-free, or pouch survival between groups. Cancer/dysplasia developed in 11 patients: 3 (2%) in the PRE, 5 (2%) in the BOTH, and 3 (2%) in the POST group. Only 1 cancer-related death occurred in the entire cohort (PRE group). Disease-free survival at 10 years was 98% for all groups (P = .97). Pouch survival at 10 years was 96% for PRE, 99% for BOTH, and 97% for POST (P = .24).

CONCLUSIONS: The incidental finding of dysplasia on final pathology after proctocolectomy was not associated with worsened outcomes compared with preoperatively diagnosed dysplasia.

PMID:37963567 | DOI:10.1093/ibd/izad263
Tumor Microenvironment-Responsive One-for-All Molecular-Engineered Nanoplatform Enables NIR-II Fluorescence Imaging-Guided Combinational Cancer Therapy

Fetched: November 15th, 2023, 5:01am GMT by Gui-Long Wu

Anal Chem. 2023 Nov 14. doi: 10.1021/acs.analchem.3c03827. Online ahead of print.

ABSTRACT

The activable NIR-based phototheranostic nanoplatform (NP) is considered an efficient and reliable tumor treatment due to its strong targeting ability, flexible controllability, minimal side effects, and ideal therapeutic effect. This work describes the rational design of a second near-infrared (NIR-II) fluorescence imaging-guided organic phototheranostic NP (FTEP-TBFc NP). The molecular-engineered phototheranostic NP has a sensitive response to glutathione (GSH), generating hydrogen sulfide (H2S) gas, and delivering ferrocene molecules in the tumor microenvironment (TME). Under 808 nm irradiation, FTEP-TBFc could not only simultaneously generate fluorescence, heat, and singlet oxygen but also greatly enhance the generation of reactive oxygen species to improve chemodynamic therapy (CDT) and photodynamic therapy (PDT) at a biosafe laser power of 0.33 W/cm². H2S inhibits the activity of catalase and cytochrome c oxidase (COX IV) to cause the enhancement of CDT and hypothermal photothermal therapy (HPTT). Moreover, the decreased intracellular GSH concentration further increases CDT's efficacy and downregulates glutathione peroxidase 4 (GPX4) for the accumulation of lipid hydroperoxides, thus causing the ferroptosis process. Collectively, FTEP-TBFc NPs show great potential as a versatile and efficient NP for specific tumor imaging-guided multimodal cancer therapy. This unique strategy provides new perspectives and methods for designing and applying activable biomedical phototheranostics.

PMID:37963241 | DOI:10.1021/acs.analchem.3c03827
Resection of anorectal fistula cancer associated with Crohn's disease after preoperative chemoradiotherapy: a case report

Fetched: November 15th, 2023, 5:01am GMT by Takuya Inoue

Surg Case Rep. 2023 Nov 14;9(1):197. doi: 10.1186/s40792-023-01778-6.

ABSTRACT

BACKGROUND: Anorectal fistula cancer is often diagnosed in an advanced state, and radical resection is difficult when invasion of the pelvic wall is observed. In addition, there is currently no clear evidence for perioperative treatment of locally advanced cases. We report a case of anorectal fistula cancer with widespread infiltration diagnosed during the course of Crohn's disease, which was curatively resected after preoperative chemoradiotherapy.

CASE PRESENTATION: A 49-year-old man who had been diagnosed with Crohn's disease (ileocolonic type) at the age of 25 and was found to have an anorectal fistula and perianal abscess at the age of 44 was referred to our department with complaints of abdominal pain and diarrhea. Computed tomography (CT) showed anal stenosis due to a pelvic mass. Pathological analysis of a biopsy taken under general anesthesia indicated mucinous carcinoma. Magnetic resonance imaging (MRI) revealed infiltration into the prostate, seminal vesicles, levator ani muscle, and left internal obturator muscle, and the patient was diagnosed with cT4N0M0 cStage IIIB anorectal fistula cancer (UICC TNM classification 8th edition). After performing a laparoscopic sigmoid colostomy, chemoradiation therapy (capecitabine + oxaliplatin, 50.4 Gy/28fr) was initiated. The patient then underwent laparoscopic total pelvic exenteration, colonic conduit diversion, extensive perineal resection, and reconstruction using bilateral gluteus maximus flaps and a right rectus abdominis musculocutaneous flap. The pathological diagnosis was mucinous adenocarcinoma, pT4, and all margins were negative. No recurrence was evident 6 months after the operation without adjuvant chemotherapy.

CONCLUSION: We described a case of curative resection after preoperative chemoradiotherapy for anorectal fistula cancer with extensive invasion that was diagnosed during the course of Crohn's disease.An accumulation of cases is needed to determine the usefulness of preoperative chemoradiation therapy for local control of anorectal fistula cancer associated with Crohn's disease.

PMID:37962718 | PMC:PMC10645675 | DOI:10.1186/s40792-023-01778-6
Cell-Derived N/P/S-Codoped Fluorescent Carbon Nanodots with Intrinsic Targeting Ability for Tumor-Specific Phototheranostics

Fetched: November 15th, 2023, 5:01am GMT by Kai Jiang

Anal Chem. 2023 Nov 14. doi: 10.1021/acs.analchem.3c03926. Online ahead of print.

ABSTRACT

Combining targeting ability, imaging function, and photothermal/photodynamic therapy into a single agent is highly desired for cancer theranostics. Herein, we developed a one-for-all nanoplatform with N/P/S-codoped fluorescent carbon nanodots (CNDs) for tumor-specific phototheranostics. The CNDs were prepared via a one-pot hydrothermal process using cancer cells as sources of carbon, nitrogen, phosphorus, and sulfur. The obtained N/P/S-codoped CNDs exhibit wide light absorption in the range of 200-900 nm and excitation-dependent emission with high photostability. Importantly, the cancer cell-derived N/P/S-codoped CNDs have outstanding biocompatibility and naturally intrinsic targeted ability for cancer cells as well as dual photothermal/photodynamic effects under 795 nm laser irradiation. Moreover, the photothermal conversion efficiency and singlet oxygen (¹O2) generation efficiency were calculated to be 52 and 34%, respectively. These exceptional properties enable CNDs to act as fine theranostic agents for targeted imaging and photothermal-photodynamic synergistic therapy within the NIR therapeutic window. The CNDs prepared in this work are promising for construction as a universal tumor phototheranostic platform.

PMID:37961783 | DOI:10.1021/acs.analchem.3c03926
Unveiling the Association between HPV and Pan-Cancers: A Bidirectional Two-Sample Mendelian Randomization Study

Fetched: November 15th, 2023, 5:01am GMT by Jianxuan Sun

Cancers (Basel). 2023 Oct 26;15(21):5147. doi: 10.3390/cancers15215147.

ABSTRACT

INTRODUCTION: More and more studies have focused on the associations between human papillomavirus (HPV) infection and pan-cancers. However, current evidence is largely based on retrospective studies, which are susceptible to confounding factors and do not enable the establishment of causal relationships.

METHODS: A bidirectional two-sample Mendelian randomization (MR) design was employed to thoroughly evaluate the causal relationships between HPV and 12 site-specific cancers except cervical cancer. Single nucleoside polymers (SNPs) with strong evidence from genome-wide association studies (GWAS) were selected from HPV exposure datasets and used as instrumental variables (IVs) in this study. For the MR analysis results, MR-Egger's intercept P test, MR-PRESSO global test, Cochran's Q test and a leave-one-out test were applied for sensitivity analysis. Using HPVTIMER, we also performed immune infiltration analyses in head and neck squamous cell carcinoma (HNSCC), oropharyngeal squamous cell carcinoma (OPSCC) and vulval squamous cell carcinoma (VSCC) to evaluate the tumor-immune microenvironment.

RESULTS: Based on the evidence of MR analysis, our study conclusively identified HPV16 as a risk factor implicated in the development of bladder cancer, colorectal cancer, and breast cancer, while HPV18 was identified as a risk factor for prostate cancer, ovarian cancer, lung cancer and breast cancer. The MR results also showed that HPV16 may be a protective factor for prostate cancer, anal cancer, lung cancer and oropharyngeal cancer, while HPV18 may be a protective factor for vaginal cancer.

CONCLUSION: An HPV infection may modulate the immune microenvironment and therefore has a potential inhibitory effect on the development of certain cancers. These conclusions provided new insights into the potential mechanisms of carcinogenesis and needed further research for validation.

PMID:37958321 | PMC:PMC10650873 | DOI:10.3390/cancers15215147
Endoscopic management of anastomotic leakage after colorectal cancer surgery in a Moroccan center: A case series and literature review

Fetched: November 14th, 2023, 5:00am GMT by Benayad Aourarh

SAGE Open Med Case Rep. 2023 Nov 9;11:2050313X231205716. doi: 10.1177/2050313X231205716. eCollection 2023.

ABSTRACT

Endoscopic management has become an alternate treatment to a revision surgery for colorectal fistulas. Eight patients who were treated by endoscopy for postoperative anastomotic leakage to colorectal cancer were included. A univariate analysis was carried out to determine the predictive factors of success. All our patients were treated using metallic clips. The primary efficiency of this technique was 50%. In a univariate analysis, the size of the fistula and its distance from the anal margin had an influence on the efficiency of the endoscopic treatment, which was not the case for either the surgical technique or the use of neoadjuvant radiotherapy. This endoscopic treatment is effective and represents a more secure alternative than revision surgery. In our study, the use of metallic clips showed a 50% success rate, going up to 100% for the group of patients with a fistula ostium of a size ⩽1 cm, proving the necessity of using this technique.

PMID:37954544 | PMC:PMC10637152 | DOI:10.1177/2050313X231205716

Trial - Anal Cancers

Effect of Intraperitoneal Ropivacaine on Visceral Pain After Laparoscopic Gastrectomy

Posted: November 24th, 2023, 3:00am GMT

Conditions: Laparoscopic Gastrectomy; Ropivacaine
Interventions: Drug: 0.5% Ropivacaine; Drug: Saline
Sponsors: SanQing Jin
Not yet recruiting
A Real-World Study to Learn More About the Order of Different Treatments and Their Effects in People With Metastatic Colorectal Cancer Receiving Their Third and Fourth Line of Treatment

Posted: November 17th, 2023, 3:00am GMT

Conditions: Metastatic Colorectal Cancer
Interventions: Drug: Regorafenib (Stivarga, BAY73-4506)
Sponsors: Bayer
Not yet recruiting
Electroacupuncture (EA) Promotes Gastrointestinal Functional Recovery After Radical Colorectal Cancer Surgery

Posted: November 13th, 2023, 3:00am GMT

Conditions: Colorectal Cancer; Gastrointestinal Dysfunction
Interventions: Device: Electroacupuncture group; Other: Sham EA group
Sponsors: Shanghai Yueyang Integrated Medicine Hospital; ShuGuang Hospital; Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Baoshan hospital of Integrated Traditional Chinese and Western Medicine
Not yet recruiting
Global Burden Estimation of Human Papillomavirus (GLOBE-HPV)

Posted: November 13th, 2023, 3:00am GMT

Conditions: HPV Infection
Interventions: Other: Urine Sample Collection; Other: Self-collected Vaginal Swab; Other: Blood Samples
Sponsors: International Vaccine Institute; London School of Hygiene and Tropical Medicine; Karolinska Institutet; Centers for Disease Control and Prevention
Not yet recruiting
The Impact of Preoperative Bowel Exercise on Postoperative Bowel Functions in Gynecologic Malignancies

Posted: November 2nd, 2023, 2:00am GMT

Conditions: Paralytic Ileus; Nausea; Defecation Disorder
Interventions: Procedure: Abdominal Exercise (digital rectal stimulation, abdominal massage)
Sponsors: Tepecik Training and Research Hospital
Completed
RATME vs LATME in Middle and Low Rectal Cancer

Posted: October 27th, 2023, 2:00am GMT

Conditions: Total Mesorectal Excision; Rectal Neoplasms; Robotic Surgical Procedures; Laparoscopy
Interventions: Procedure: Robotic-assisted total mesorectal excision; Procedure: laparoscopic-assisted total mesorectal excision
Sponsors: The First Hospital of Jilin University; Jilin Provincial Tumor Hospital; Daping Hospital and the Research Institute of Surgery of the Third Military Medical University; The Second Affiliated Hospital of Dalian Medical University; The Second Affiliated Hospital of Harbin Medical University
Not yet recruiting
Total Neoadjuvant Treatment for pMMR Locally Advanced Low Rectal Cancer: Anti-PD-1 Antibody With FOLFOXIRI and Preoperative Radiation Therapy

Posted: October 25th, 2023, 2:00am GMT

Conditions: Colorectal Cancer
Interventions: Drug: Serplulimab + FOLFOXIRI; Radiation: Radiation therapy
Sponsors: Sun Yat-sen University
Not yet recruiting
Study of Patients With Thrombotic Microangiopathy Associated With Mitomycin C, Treated or Not With Eculizumab

Posted: October 24th, 2023, 2:00am GMT

Conditions: Thrombotic Microangiopathies
Sponsors: University Hospital, Strasbourg, France
Recruiting
Reconstruction of the Pelvic Floor and Perineal Wound After Rectal ELAPE

Posted: October 4th, 2023, 2:00am GMT

Conditions: Rectum Cancer
Interventions: Procedure: Plastic surgery of the pelvic floor and perineal wound with counter-displaced skin-subcutaneous fascial flaps after extralevatory abdominal-perineal extirpation of the rectum; Procedure: Plastic surgery of the pelvic floor and perineal wound with local tissues; Procedure: Plastic surgery of the pelvic floor and perineal wound with mesh endoprosthesis
Sponsors: Kuban State Medical University; State Budget Public Health Institution Scientific Research Institute - Ochapovsky Regional Clinical Hospital; City Clinical Oncology Hospital No 1
Not yet recruiting
Pre-Rehabilitation for Female Patients Undergoing Pelvic Radiotherapy

Posted: September 28th, 2023, 2:00am GMT

Conditions: Dyspareunia; Pelvic Pain; Sexual Dysfunction; Radiation Toxicity
Interventions: Behavioral: Pelvic health therapy; Device: Dilator feasability
Sponsors: Indiana University
Not yet recruiting
Neoadjuvant Chemoradiotherapy Combined With PD-1 Inhibitor and Thymalfasin for pMMR/MSS Locally Advanced Mid-low Rectal Cancer

Posted: September 27th, 2023, 2:00am GMT

Conditions: Locally Advanced Rectal Cancer
Interventions: Drug: capecitabine; Drug: tislelizumab; Drug: thymalfasin; Radiation: long-term radiotherapy
Sponsors: Beijing Friendship Hospital; Peking Union Medical College Hospital
Not yet recruiting
Evaluation of Intra- and Peri-operative Complications and Disease-free Survival in Rectal Cancer Patients Undergoing Oncological Resective Surgery and Concomitant Bariatric Surgery

Posted: September 27th, 2023, 2:00am GMT

Conditions: Morbid Obesity; Rectal Cancer; Surgical Outcomes
Interventions: Procedure: BIB positioning
Sponsors: Federico II University
Recruiting
Phase II Study of Pacritinib in Kaposi Sarcoma Herpesvirus (KSHV)-Associated Multicentric Castleman Disease and KSHV-Associated Inflammatory Cytokine Syndrome (KICS)

Posted: September 25th, 2023, 2:00am GMT

Conditions: KSHV Inflammatory Cytokine Syndrome (KICS); Kaposi Sarcoma Herpesvirus -Associated Multicentric Castleman Disease
Interventions: Drug: Pacritinib
Sponsors: National Cancer Institute (NCI)
Not yet recruiting
MR-Adaptive Radiation Therapy for Anal Cancer With EScalated-Treatment in a Risk-Optimized Approach

Posted: September 22nd, 2023, 2:00pm GMT

Conditions: Anal Squamous Cell Carcinoma
Interventions: Radiation: Radiotherapy - Low risk group; Radiation: Radiotherapy - Standard risk group; Radiation: Radiotherapy - Intermediate risk group; Radiation: Radiotherapy - High risk group
Sponsors: University Health Network, Toronto
Recruiting
Preoperative FOLFOXIRI Chemotherapy Combined With Lateral Lymph Node Dissection in Rectal Cancer

Posted: September 21st, 2023, 2:00am GMT

Conditions: Lymph Node Metastasis; Cancer of Rectum and Anus; Oxaliplatin; Intestinal Neoplasms; Gastrointestinal Neoplasms; Rectal Diseases; Rectal Neoplasms
Interventions: Drug: Experimental: FOLFOXIRI and Lateral lymph node dissection; Drug: Preoperative long-term concurrent chemoradiotherapy and Lateral lymph node dissection
Sponsors: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Enrolling by invitation
Salvage Chemotherapy Versus Total Mesorectal Resection for Local Resection Rectal Cancer Patients

Posted: September 21st, 2023, 2:00am GMT

Conditions: Chemotherapy Effect; Rectal Cancer
Interventions: Procedure: Radical total mesorectal excision; Other: Salavge Adjuvant Chemoradiotherapy
Sponsors: Sun Yat-sen University
Recruiting
A Study to Evaluate the Efficacy, Safety, and Immunogenicity of SCT1000 in Healthy Women Aged 18-45 Years

Posted: September 18th, 2023, 2:00am GMT

Conditions: HPV InfectioN; HPV-Related Carcinoma
Interventions: Biological: Recombinant 14-Valent Human Papillomavirus Vaccine（Insect Cell）; Biological: placebo
Sponsors: Sinocelltech Ltd.; Guangxi Center for Disease Control and Prevention; Henan Center for Disease Control and Prevention; Sichuan Center for Disease Control and Prevention; Shanxi Center for Disease Control and Prevention; Yunnan Center for Disease Control and Prevention
Active, not recruiting
Utilization of Transanal Endoscopy in the Treatment of Anastomotic Stenosis

Posted: September 14th, 2023, 2:00am GMT

Conditions: Anastomotic Stenosis
Interventions: Procedure: Transanal and transabdominal combined endoscopic resection of rectal stenosis and anal reconstruction
Sponsors: Sun Yat-sen University
Recruiting
Treatment of Low Locally Advanced Rectal Cancer With Radiotherapy Removal TNT Plus Neoadjuvant Therapy

Posted: September 13th, 2023, 2:00pm GMT

Conditions: Rectal Cancer
Interventions: Drug: CapeOX + cetuximab; Drug: CapeOX + bevacizumab; Radiation: radiotherapy
Sponsors: Tang-Du Hospital
Not yet recruiting
Applications of Fluorescence Imaging Guided Lymph Node Dissection and Fluorescence Angiography of Inferior Mesenteric Artery Assisted Left Colic Artery Preservation

Posted: September 13th, 2023, 2:00am GMT

Conditions: Fluorescence; Indocyanine Green; Rectal Cancer Surgery
Interventions: Device: Fluorescence laparoscopic system
Sponsors: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Recruiting
An Observational Study to Learn More About the Long-Term Responses to Treatment With Regorafenib in Patients With Metastatic Colorectal Cancer in the United States

Posted: September 8th, 2023, 2:00am GMT

Conditions: Metastatic Colorectal Cancer
Interventions: Drug: Regorafenib (Stivarga, BAY73-4506)
Sponsors: Bayer
Completed
Clostridioides Difficile Infection: Analyzing CLInic Evolution and Bacterial Clearance

Posted: September 8th, 2023, 2:00am GMT

Conditions: Clostridium Difficile Infections
Sponsors: Fondation Hôpital Saint-Joseph
Recruiting
Conservative Treatment or Resuturing Among Women With Perineal Wound Dehiscence After Vaginal Labour

Posted: September 7th, 2023, 2:00am GMT

Conditions: Dehiscence Wound; Secondary Perineal Tear; Episiotomy; Dehiscence
Interventions: Other: Clinical examination and pictures; Other: Questionnaire
Sponsors: Herlev Hospital
Recruiting
Neoadjuvant Chemoradiotherapy Combined With PD-1 Inhibitor and Thymalfasin for Locally Advanced Mid-low Rectal Cancer

Posted: September 6th, 2023, 2:00am GMT

Conditions: Colorectal Neoplasms
Interventions: Drug: Thymalfasin
Sponsors: Beijing Friendship Hospital
Not yet recruiting
Efficacy of Ultrasound-assisted Caudal Epidural Pulsed Radiofrequency for Anal Pain in Cancer Patients,

Posted: August 24th, 2023, 2:00pm GMT

Condition: Perineal Pain
Intervention: Procedure: US assisted caudal epidural pulsed radiofrequency
Sponsor: Assiut University
Not yet recruiting
Pudendal Nerve Block With Bupivacaine Alone and Bupivacaine With Methylene Blue for Postoperative Analgesia

Posted: August 14th, 2023, 2:00am GMT

Conditions: Hemorrhoids; Anal Fissure and Fistula; Perianal Abscess; Perianal Fistula; Pilonidal Sinus; Perianal Skin Tags
Interventions: Other: Ultrasound guided Pudendal nerve block
Sponsors: Nepal Mediciti Hospital
Recruiting
Combination of AK104 and Neoadjuvant Chemoradiotherapy in pMMR/MSS Locally Advanced Rectal Cancer

Posted: August 8th, 2023, 2:00am GMT

Conditions: Locally Advanced Rectal Cancer
Interventions: Drug: AK104; Drug: Capecitabine; Radiation: Neoadjuvant Radiotherapy
Sponsors: Sun Yat-sen University; Akeso; Haplox Biotechnology Co., Ltd.
Recruiting
A Basket Study of Customized Autologous TCR-T Cell Therapies in Patients With Locally Advanced (Unresectable) or Metastatic Solid Tumors

Posted: August 3rd, 2023, 2:00am GMT

Conditions: Head and Neck Cancer; Cervical Cancer; Non-small Cell Carcinoma; Melanoma; Ovarian Cancer; Anogenital Cancers; HPV - Anogenital Human Papilloma Virus Infection; HPV-Related Cervical Carcinoma; HPV-Related Carcinoma; HPV-Related Squamous Cell Carcinoma; HPV-Related Malignancy; HPV-Related Adenocarcinoma; HPV Positive Oropharyngeal Squamous Cell Carcinoma; HPV-Related Adenosquamous Carcinoma; HPV-Associated Vaginal Adenocarcinoma; HPV-Related Endocervical Adenocarcinoma; HPV-Related Anal Squamous Cell Carcinoma; HPV-Related Verrucous Carcinoma; HPV-Related Penile Squamous Cell Carcinoma; HPV-Related Vulvar Squamous Cell Carcinoma; HPV Positive Rectal Squamous Cell Carcinoma
Interventions: Biological: TSC-204-A0201; Biological: TSC-204-C0702; Biological: TSC-200-A0201; Biological: TSC-204-A0201 + TSC-204-C0702; Biological: TSC-204-A0201 + TSC-200-A0201; Biological: TSC-204-C0702 + TSC-200-A0201; Biological: TSC-204-A0201 + TSC-203-A0201; Biological: TSC-204-C0702 + TSC-203-A0201; Biological: TSC-200-A0201 + TSC-203-A0201
Sponsors: TScan Therapeutics, Inc.
Recruiting
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer, Cancer CARE Beyond Walls

Posted: August 1st, 2023, 2:00pm GMT

Conditions: Advanced Malignant Solid Neoplasm; Anal Carcinoma; Biliary Tract Carcinoma; Bladder Carcinoma; Breast Carcinoma; Carcinoid Tumor; Cervical Carcinoma; Colorectal Carcinoma; Gastric Carcinoma; Glioblastoma; Head and Neck Carcinoma; HER2-Positive Breast Carcinoma; Lung Carcinoma; Lung Small Cell Carcinoma; Malignant Germ Cell Tumor; Neuroendocrine Carcinoma; Ovarian Carcinoma; Pancreatic Carcinoma; Prostate Small Cell Neuroendocrine Carcinoma; Prostate Carcinoma
Interventions: Procedure: Clinical Encounter; Other: Home Health Encounter; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Sponsors: Mayo Clinic
Recruiting
Study to Assess the Safety and Efficacy of Subcutaneously Injected Risankizumab in Adult Participants With Genital or Scalp Psoriasis

Posted: August 1st, 2023, 2:00am GMT

Conditions: Genital Psoriasis; Scalp Psoriasis
Interventions: Drug: Risankizumab; Drug: Placebo for Risankizumab
Sponsors: AbbVie
Recruiting
Radical vs Local Excision for Rectal Cancer With Clinically Complete Remission

Posted: July 28th, 2023, 2:00pm GMT

Condition: Rectal Cancer
Intervention: Procedure: Surgery
Sponsor: National Taiwan University Hospital
Recruiting
A Chatbot Intervention for Reducing HPV Vaccine Hesitancy

Posted: July 25th, 2023, 2:00pm GMT

Conditions: Cervical Cancer; Anal Cancer; Penile Cancer
Interventions: Behavioral: Personalized Chatbot Intervention; Behavioral: Non-Personalized Chatbot Intervention; Behavioral: No Chatbot Control
Sponsor: University of Maryland, College Park
Recruiting
HRYZ-T101 Injection for HPV18 Positive Solid Tumor

Posted: July 19th, 2023, 2:00pm GMT

Conditions: Cervical Cancer; Head and Neck Squamous Cell Carcinoma; Carcinoma of Vagina; Carcinoma of Penis; Anal Cancer; Carcinoma of Vulva
Interventions: Biological: HRYZ-T101 Injection; Drug: Fludarabine + Cyclophosphamide
Sponsor: SYZ Cell Therapy Co..
Not yet recruiting
Comparison of Postoperative Anal Function Between Parks and Bacon Techniques in Low Rectal Cancer

Posted: July 13th, 2023, 2:00pm GMT

Conditions: Rectal Neoplasms; Low Anterior Resection Syndrome; Anastomotic Leak; Quality of Life
Interventions: Procedure: Parks technique; Procedure: Bacon technique
Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
Not yet recruiting
Phase 1/2 Study to Evaluate TROP2 ADC LCB84 Single Agent and in Combination With an Anti-PD-1 Ab in Advanced Solid Tumors

Posted: July 12th, 2023, 2:00pm GMT

Conditions: Advanced Solid Tumors
Interventions: Drug: LCB84; Drug: Anti-PD-1 monoclonal antibody
Sponsors: LegoChem Biosciences, Inc; AntibodyChem Biosciences, Inc.
Recruiting
A Study Regarding Tissue Response During and After Treatment for Anal Cancer

Posted: July 11th, 2023, 2:00pm GMT

Conditions: Anal Cancer
Interventions: Other: Biopsies
Sponsors: Sahlgrenska University Hospital, Sweden; Göteborg University
Not yet recruiting
A Multicenter Single-arm P2 to Evaluate Safety and Efficacy of the Total Neoadjuvant Therapy for cT2 Rectal Cancer

Posted: July 11th, 2023, 2:00pm GMT

Condition: Rectal Cancer
Interventions: Radiation: Radiation; Drug: Chemotherapy; Procedure: Surgery
Sponsor: Osaka University
Recruiting
Transanal Irrigation - Best Treatment Possibility for Low Anterior Resection Syndrome? Multicenter, Randomized Clinical Trial

Posted: June 27th, 2023, 2:00pm GMT

Conditions: Low Anterior Resection Syndrome
Interventions: Procedure: Transanal irrigation; Combination Product: Best supportive care
Sponsors: National Cancer Institute, Lithuania
Recruiting
REDEL Trial: Reduced Elective Nodal Dose for Anal Cancer Toxicity Mitigation

Posted: June 14th, 2023, 2:00pm GMT

Condition: Anal Cancer
Interventions: Radiation: Radiation (reduced elective nodal dose (30.6 Gy); Drug: Capecitabine; Drug: Mitomycin c
Sponsor: University of Cincinnati
Recruiting
A Study to Assess Change in Disease Activity and Adverse Events of Oral Upadacitinib in Adult and Adolescent Participants With Moderate to Severe Hidradenitis Suppurativa Who Have Failed Anti-TNF Therapy

Posted: June 5th, 2023, 2:00am GMT

Conditions: Hidradenitis Suppurativa
Interventions: Drug: Upadacitinib; Drug: Placebo
Sponsors: AbbVie
Recruiting
Indocyanine Green-guided Lymphadenectomy in Laparoscopic Total Mesorectal Excision for Low Rectal Cancer After Neoadjuvant Chemoradiotherapy

Posted: May 24th, 2023, 2:00pm GMT

Conditions: Rectal Cancer; Lymph Node Cancer Metastatic
Intervention: Procedure: ICG-guided lymphadenectomy
Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Recruiting
COrSIcA: Disease Measurement

Posted: May 15th, 2023, 2:00pm GMT

Conditions: Anal Intraepithelial Neoplasia; Anal High-grade Squamous Intraepithelial Lesion; Anal HSIL
Intervention: Diagnostic Test: Physical examination
Sponsors: David Finch; Lancashire Teaching Hospitals NHS Foundation Trust
Not yet recruiting
Safety, PK and Efficacy of AI-061 in Advanced Solid Tumors

Posted: May 15th, 2023, 2:00pm GMT

Conditions: Melanoma; Non Small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; High Grade Serous Adenocarcinoma of Ovary; Primary Peritoneal Carcinoma; Fallopian Tube Cancer; Endometrial Cancer; Cervical Cancer; Renal Cell Carcinoma; Bladder Cancer; Esophageal Cancer; Gastric Cancer; Gastroesophageal-junction Cancer; Colorectal Cancer; Anal Cancer; Hepatocellular Carcinoma; Bile Duct Cancer
Interventions: Drug: AI-061
Sponsors: OncoC4, Inc.; OncoC4 AU Pty Ltd; Avance Clinical
Recruiting
Total Neoadjuvant Therapy Combined With Tislelizumab for Local Advanced of Middle and Low Rectal Cancer

Posted: May 5th, 2023, 2:00pm GMT

Condition: Locally Advanced Rectal Cancer
Interventions: Combination Product: Long-course chemoradiation, with Tislelizumab (PD-1 inhibitor); Combination Product: Long-course chemoradiation, without Tislelizumab (PD-1 inhibitor)
Sponsor: Beijing Friendship Hospital
Recruiting
An Observational Study Called STAR-T to Learn More About the Sequential Treatment With Regorafenib and TAS-102 in Adults With Metastatic Colorectal Cancer Under Real World Conditions

Posted: May 3rd, 2023, 2:00am GMT

Conditions: Metastatic Colorectal Cancer (mCRC)
Interventions: Drug: Regorafenib (BAY73-4506, Stivarga®); Drug: TAS-102 (trifluridine and tipiracil, Lonsurf®); Drug: Bevacizumab
Sponsors: Bayer
Active, not recruiting
Adaptive Radiation in Anal Cancer

Posted: May 1st, 2023, 2:00pm GMT

Condition: Anal Squamous Cell Carcinoma
Interventions: Radiation: Artificial Intelligence Guided Daily Radiotherapy Treatment Planning and Delivery; Drug: Mitomycin-C; Drug: 5-Fluorouracil; Drug: Capecitabine
Sponsors: Columbia University; Varian Medical Systems
Recruiting
Anal Cancer Risk In Women

Posted: April 28th, 2023, 2:00pm GMT

Conditions: Anal Cancer; Human Papilloma Virus; Anal Intraepithelial Neoplasia; Genital Neoplasm; Genital Cancer
Intervention: Other: Dual Pathology
Sponsor: Imperial College London
Recruiting
Anal Intraepithelial Neoplasia and Anal Squamous Cell Carcinoma

Posted: April 28th, 2023, 2:00pm GMT

Conditions: Anal Cancer; Anal Squamous Intraepithelial Neoplasia
Intervention:
Sponsor: Imperial College London
Recruiting
Effects of Different Radiation Dosimetry for Anorectal Function of Patients With Pelvic Cancer

Posted: April 27th, 2023, 2:00pm GMT

Condition: Anorectal Cancer
Intervention: Radiation: IMRT
Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
Not yet recruiting
Safety and Effectiveness Evaluations of the COLO-BT as an Treatment to the Proctectomy.

Posted: April 24th, 2023, 2:00am GMT

Conditions: Colorectal Surgery; Colorectal Cancer; Rectal/Anal
Interventions: Device: COLO BT™; Other: Stoma Creation
Sponsors: JSR Medical Co., Ltd.
Recruiting
Implementation of Anal Cancer Screening and Treatment in Nigeria

Posted: April 18th, 2023, 2:00pm GMT

Condition: Education, Medical
Intervention: Behavioral: Enhanced Training on screening and treatment of HSIL (e-STH)
Sponsors: University of Maryland, Baltimore; National Cancer Institute (NCI)
Recruiting
HRYZ-T101 TCR-T Cell for HPV-18 Positive Advanced Solid Tumor

Posted: March 28th, 2023, 2:00pm GMT

Conditions: Cervical Cancer; Head and Neck Squamous Cell Carcinoma; Oropharyngeal Cancer; Vagina Tumor; Carcinoma of Penis; Anal Carcinoma; Carcinoma of Vulva
Interventions: Drug: Fludarabine + Cyclophosphamide; Biological: HRYZ-T101 TCR-T Cell
Sponsors: HRYZ Biotech Co.
Recruiting
Natural Orifice Specimen Extraction Surgery for Colorectal Cancer

Posted: February 23rd, 2023, 3:00pm GMT

Condition: Colorectal Cancer
Intervention: Procedure: Natural Orifice Specimen Extraction
Sponsor: Chang Gung Memorial Hospital
Not yet recruiting
Defining the Natural History of Squamous Cell Carcinoma in Fanconi Anemia

Posted: January 18th, 2023, 3:00am GMT

Conditions: Fanconi Anemia; Inherited Bone Marrow Failure Syndrome
Sponsors: National Cancer Institute (NCI)
Recruiting
E7 TCR-T Cell Immunotherapy for Human Papillomavirus (HPV) Associated Cancers

Posted: January 17th, 2023, 3:00pm GMT

Conditions: Cervical Cancer; Throat Cancer; Oropharynx Cancer; Anal Cancer; Vulva Cancer; Vaginal Cancer; Penile Cancer; Metastatic Cancer; HPV-Related Malignancy; HPV-Related Carcinoma; HPV-Related Cervical Carcinoma; HPV-Related Squamous Cell Carcinoma; HPV-Related Adenocarcinoma; HPV Positive Oropharyngeal Squamous Cell Carcinoma; HPV-Associated Vaginal Adenocarcinoma; HPV-Related Adenosquamous Carcinoma; HPV-Related Endocervical Adenocarcinoma; HPV-Related Anal Squamous Cell Carcinoma; HPV-Related Penile Squamous Cell Carcinoma; HPV-Related Vulvar Squamous Cell Carcinoma; HPV Positive Rectal Squamous Cell Carcinoma
Interventions: Biological: E7 TCR-T cells
Sponsors: Christian Hinrichs
Recruiting
Paula Method of Exercises in Patients With LARS Syndrome:Randomized Controlled Trial

Posted: January 12th, 2023, 3:00am GMT

Conditions: Low Anterior Resection Syndrome
Interventions: Other: Paula Method of muscle exercises
Sponsors: Hadassah Medical Organization
Recruiting
The Application Value of da Vinci Linear Cutting Stapler SureForm in Robotic Anus Preserving Surgery for Rectal Cancer

Posted: December 28th, 2022, 3:00pm GMT

Conditions: Rectal Cancer; Robotic; Anastomotic Leak; Laparoscopic
Interventions: Device: Surform
Sponsors: Nanchang University
Recruiting
Collecting Blood and Tissue Sample Donations for Research for HIV/AIDS-Related Cancers

Posted: December 23rd, 2022, 3:00pm GMT

Conditions: Anal Carcinoma; Hematopoietic and Lymphoid Cell Neoplasm; HIV Infection; Kaposi Sarcoma; Lymphoma; Malignant Solid Neoplasm; Multicentric Castleman Disease; Plasmablastic Lymphoma; Recurrent Kaposi Sarcoma; Recurrent Lymphoma; Recurrent Plasmablastic Lymphoma; Transplant-Related Kaposi Sarcoma
Interventions: Procedure: Biospecimen Collection
Sponsors: AIDS Malignancy Consortium; National Cancer Institute (NCI)
Recruiting
Impact of Dietary Fiber Supplementation on Colonic Mucosal Microbiome

Posted: December 9th, 2022, 3:00pm GMT

Conditions: Benign Colorectal Neoplasm; Non-Neoplastic Anal Disorder
Interventions: Dietary Supplement: Dietary Fiber; Procedure: Proctoscopy or anoscopy with Biopsy; Other: Questionnaire Administration
Sponsor: OHSU Knight Cancer Institute
Recruiting
Anastomotic Leakage After Colon Cancer Surgery

Posted: December 8th, 2022, 3:00am GMT

Conditions: Adult Patients; Intestinal Continuity (Anastomosis); Colon Cancer
Interventions: Procedure: Any kind of colectomy
Sponsors: Hospital San Carlos, Madrid; Spanish Association of Surgeons (AEC); Hospital Universitario La Fe; Complejo Hospitalario Universitario de Vigo
Enrolling by invitation
E7 T-cell Receptor (TCR) -T Cell Induction Therapy for Locoregionally Advanced HPV-associated Cancers

Posted: December 7th, 2022, 3:00am GMT

Conditions: HPV-Associated Cervical Carcinoma; HPV-Related Carcinoma; HPV-Related Malignancy; HPV Positive Oropharyngeal Squamous Cell Carcinoma; HPV-Related Adenocarcinoma; HPV-Related Adenosquamous Carcinoma; HPV-Related Squamous Cell Carcinoma; HPV-Related Anal Squamous Cell Carcinoma; HPV-Related Penile Squamous Cell Carcinoma; HPV-Related Vulvar Squamous Cell Carcinoma; HPV-Related Endocervical Adenocarcinoma; Cervical Cancer; Oropharynx Cancer; Anal Cancer; Vulvar Cancer; Penile Cancer; Vaginal Cancer
Interventions: Drug: Conditioning, E7 TCR-T cells, and aldesleukin
Sponsors: Christian Hinrichs; National Cancer Institute (NCI)
Not yet recruiting
Human Papillomavirus in Young People Epidemiological Research 4

Posted: October 20th, 2022, 2:00pm GMT

Conditions: Human Papillomavirus Infection; HPV; HPV Infection; Anal Cancer; Cancer; Men; HPV 16 Infection
Intervention:
Sponsors: Monash University; The Alfred; University of Melbourne
Recruiting
Human Papillomavirus in Young People Epidemiological Research 3

Posted: October 20th, 2022, 2:00pm GMT

Conditions: Human Papillomavirus Infection; HPV; HPV Infection; Anal Cancer; Cancer; Men; HPV 16 Infection
Intervention:
Sponsors: Monash University; The Alfred; University of Melbourne
Recruiting
Optimizing Screening for Cervical Cancer Among Women Living With HIV in the Dominican Republic

Posted: September 27th, 2022, 2:00pm GMT

Conditions: Malignant Female Reproductive System Neoplasm
Interventions: Procedure: Biospecimen Collection; Other: Interview
Sponsors: Fred Hutchinson Cancer Center; National Cancer Institute (NCI); US-Latin American-Caribbean HIV/HPV-Cancer Prevention Clinical Trials Network (ULACNet); Instituto Dermatológico Dominicano y Cirugía de Piel (IDCP)
Recruiting
Anal HSIL Screening Algorithm

Posted: September 8th, 2022, 2:00am GMT

Conditions: Anal High-grade Squamous Intraepithelial Lesion
Interventions: Procedure: OPTIMIZATION PHASE
Sponsors: Institute of HIV Research and Innovation Foundation, Thailand; National Institutes of Health (NIH); amfAR, The Foundation for AIDS Research
Recruiting
Use of a Screening Tool to Describe HIV-Related Cancer Burden and Patient Characteristics in the AMC

Posted: August 22nd, 2022, 2:00pm GMT

Conditions: HIV-Associated Malignant Neoplasm; HIV Infections; Cancer; AIDS Related Lymphoma; AIDS-related Kaposi Sarcoma; AIDS-Related Malignancy; Anal Cancer; HPV-Related Malignancy
Interventions: Other: Non-Interventional; Other: Non-Interventional Follow-up
Sponsors: AIDS Malignancy Consortium; National Cancer Institute (NCI)
Recruiting
CRP-guided Transanal Drainage Removal After Rectal Surgery

Posted: August 16th, 2022, 2:00am GMT

Conditions: Rectal Cancer; Anastomotic Leak
Interventions: Device: removal of transanal drainage tube
Sponsors: Qilu Hospital of Shandong University
Recruiting
Timing of Transcutaneous Acupoint Electrical Stimulation on Postoperative Recovery in Geriatric Patients With Gastrointestinal Tumor

Posted: August 1st, 2022, 2:00am GMT

Conditions: Postoperative Cognitive Dysfunction
Interventions: Other: Transcutaneous acupoint electrical stimulation
Sponsors: Subei People's Hospital of Jiangsu Province
Not yet recruiting
Mass Response of Tumor Cells as a Biomarker for Rapid Therapy Guidance (TraveraRTGx)

Posted: July 18th, 2022, 2:00pm GMT

Conditions: Pleural Effusion, Malignant; Ascites, Malignant; Carcinoma; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Carcinoma, Renal; Carcinoma, Small Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Neuroendocrine; Carcinoma, Thymic; Carcinoma, Pancreatic; Carcinoma Breast; Carcinoma, Ovarian; Carcinoma Bladder; Carcinoma of Unknown Primary; Carcinoma of the Head and Neck; Carcinoma of the Oropharynx; Carcinoma of the Larynx; Carcinoma of the Bladder; Carcinoma of Esophagus; Carcinoma of the Nasopharynx; Carcinoma of the Penis; Carcinoma of the Cervix; Carcinoma of the Anus; Carcinoma of the Vulva; Carcinoma of the Appendix; Carcinoma of the Oral Cavity; Cholangiocarcinoma; Melanoma; Mesothelioma; Pancreatic Cancer
Intervention:
Sponsors: Travera Inc; xCures
Recruiting
Re-optimization Based Online Adaptive Radiotherapy of Anal Cancer

Posted: June 30th, 2022, 2:00pm GMT

Conditions: Anal Cancer; Anal Carcinoma; Anal Squamous Cell Carcinoma
Interventions: Radiation: online adaptive radiotherapy
Sponsors: Herlev Hospital
Recruiting
The Argentina Brief Colonoscopy Difficulty Score (ABCD)

Posted: June 21st, 2022, 2:00am GMT

Conditions: Colorectal Cancer; Diagnoses Disease; Polyp of Colon; Adenoma Colon
Interventions: Diagnostic Test: Diagnostic high-definition white-light (HDWL) colonoscopy
Sponsors: Institute of Gastroenterology and Advance Endoscopy; Austral University, Argentina; Hospital Nacional Profesor Alejandro Posadas
Completed
Study of SQZ-eAPC-HPV in Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors

Posted: May 3rd, 2022, 2:00pm GMT

Conditions: Adult Solid Tumor
Interventions: Biological: SQZ-eAPC-HPV; Biological: Pembrolizumab
Sponsors: SQZ Biotechnologies
Active, not recruiting
Chemotherapy Combined With High-dose Radiotherapy for Low Rectal Cancer Using MR Guided Linear Accelerator

Posted: April 21st, 2022, 2:00am GMT

Conditions: Rectal Cancer
Interventions: Radiation: Magnetic resonance guided radiotherapy; Drug: Chemotherapy
Sponsors: Sun Yat-sen University
Enrolling by invitation
Lopinavir/Ritonavir in PLWH With High-Grade AIN

Posted: April 19th, 2022, 2:00pm GMT

Conditions: High-Grade Anal Intraepithelial Neoplasia
Interventions: Drug: Lopinavir / Ritonavir
Sponsors: University of Wisconsin, Madison; Wisconsin Partnership Program
Recruiting
A Study to Assess the Reduction of Human Papillomavirus (HPV) Viral Infectivity and Transmission in HPV-Positive Women After Vaccination With 9vHPV (RIFT-HPV)

Posted: April 19th, 2022, 2:00pm GMT

Conditions: Cervical Intraepithelial Neoplasia Grade I/ II/ III (CIN I/II/III); Human Papillomavirus (HPV) Infections; High-risk HPV; HPV-16/ 18
Intervention: Biological: Nonavalent HPV vaccine (9vHPV/Gardasil-9™).
Sponsors: Miquel Angel Pavon Ribas; Hospital del Mar; Catalan Institute of Health
Recruiting
Prospective Evaluation of Pencil Beam Scanning Proton Therapy for Previously Irradiated Tumors

Posted: April 6th, 2022, 2:00am GMT

Conditions: CNS Cancer; Head and Neck Cancer; GI Cancer; Gynecologic Cancer; Prostate Cancer; Thoracic Cancer; Breast Cancer
Interventions: Radiation: Pencil Beam Scanning Proton Therapy
Sponsors: The New York Proton Center
Recruiting
An Integrated Optimization of Surgery and Radiotherapy Techniques to Improve Cosmetic Outcome and Quality of Life in Breast Conserving Therapy for Breast Cancer Patients (STARLINGS Study)

Posted: March 2nd, 2022, 3:00am GMT

Conditions: Breast Fibrosis; Breast Cancer; Breast Cancer Female; Breast Neoplasms; Breast Carcinoma in Situ; Breast Carcinoma
Interventions: Other: no intervention
Sponsors: Erasmus Medical Center; Stichting BeterKeten, the Netherlands; Albert Schweitzer hospital, Dordrecht, the Netherlands; Franciscus Gasthuis and Vlietland Hospital, Rotterdam and Schiedam, the Netherlands; Maasstad hospital, Rotterdam, the Netherlands
Enrolling by invitation
HPV Vaccine Effectiveness Study in Rwandan Women Living With HIV

Posted: February 21st, 2022, 3:00am GMT

Conditions: Cervical Cancer; Human Papilloma Virus; Human Immunodeficiency Virus; HPV-Related Carcinoma
Interventions: Procedure: Blood collection; Procedure: Oral, cervicovaginal and anal specimen collection; Procedure: Anoscopy & Biopsy of Acetowhite Lesions; Procedure: Colposcopy & Biopsy of Acetowhite Lesions; Procedure: Ablative Treatment; Procedure: LEEP (Loop Electrosurgical Excision Procedure)
Sponsors: Montefiore Medical Center; National Cancer Institute (NCI); Rwanda Military Hospital; University of Rwanda
Recruiting
Effects of Modified Precision Functional Sphincter-Preserving Surgery (PPS) on Ultralow Rectal Cancer

Posted: February 18th, 2022, 3:00pm GMT

Conditions: Rectum Cancer; Stoma Colostomy; Faecal Incontinence; Leakage, Anastomotic
Intervention:
Sponsor: Shanghai 10th People's Hospital
Recruiting
Myriad™ Augmented Soft Tissue Reconstruction Registry

Posted: February 17th, 2022, 3:00am GMT

Conditions: Abdominal Wound Dehiscence; Necrotizing Soft Tissue Infection; Lower Extremity Wound; Pilonidal Sinus; Anal Fistula; Hidradenitis Suppurativa; Pressure Injury
Interventions: Device: Myriad Matrix™ and Myriad Morcells™
Sponsors: Aroa Biosurgery Limited
Recruiting
Single-Dose HPV Vaccination for the Prevention of Cervical Cancer in Young Adult Women in Costa Rica, The PRISMA ESCUDDO Trial

Posted: February 14th, 2022, 3:00am GMT

Conditions: Cervical Carcinoma; Human Papillomavirus Infection
Interventions: Biological: Diphtheria Toxoid/Tetanus Toxoid/Acellular Pertussis Vaccine Adsorbed; Other: Questionnaire Administration; Biological: Recombinant Human Papillomavirus Bivalent Vaccine; Biological: Recombinant Human Papillomavirus Nonavalent Vaccine
Sponsors: National Cancer Institute (NCI)
Active, not recruiting
Screening Women With Prior HPV for Anal Neoplasia

Posted: February 1st, 2022, 3:00pm GMT

Conditions: HPV-related Lower Genital Tract Neoplasias; HPV-related Anal Neoplasias; Early Stage Lower Genital Tract Cancers
Interventions: Diagnostic Test: Diagnostic tests for anal cancer screening
Sponsors: Icahn School of Medicine at Mount Sinai; M.D. Anderson Cancer Center; Medical University of South Carolina
Recruiting
4-Point Therapy Response Score With PET/CT for Anal Squamous Cell Cancer

Posted: November 22nd, 2021, 3:00pm GMT

Conditions: Anal Squamous Cell Carcinoma; Stage 0 Anal Cancer AJCC v8; Stage I Anal Cancer AJCC v8; Stage II Anal Cancer AJCC v8; Stage IIA Anal Cancer AJCC v8; Stage IIB Anal Cancer AJCC v8; Stage III Anal Cancer AJCC v8; Stage IIIA Anal Cancer AJCC v8; Stage IIIB Anal Cancer AJCC v8; Stage IIIC Anal Cancer AJCC v8
Interventions: Procedure: Computed Tomography; Other: Electronic Health Record Review; Procedure: Follow-Up; Procedure: Positron Emission Tomography
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Active, not recruiting
Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery

Posted: November 8th, 2021, 3:00am GMT

Conditions: Anal Melanoma; Bladder Melanoma; Cervical Melanoma; Esophageal Melanoma; Gallbladder Melanoma; Mucosal Melanoma; Mucosal Melanoma of the Head and Neck; Mucosal Melanoma of the Urinary System; Oral Cavity Mucosal Melanoma; Penile Mucosal Melanoma; Rectal Melanoma; Recurrent Mucosal Melanoma; Sinonasal Mucosal Melanoma; Stage II Vulvar Cancer AJCC v8; Stage III Vulvar Cancer AJCC v8; Stage IV Vulvar Cancer AJCC v8; Urethral Melanoma; Vaginal Melanoma; Vulvar Melanoma
Interventions: Drug: Cabozantinib S-malate; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Drug: Placebo Administration; Procedure: Positron Emission Tomography
Sponsors: National Cancer Institute (NCI)
Suspended
Screening Algorithms for Cervical and Anal High-Grade Squamous Intraepithelial Lesions in People With HIV in Mexico and Puerto Rico

Posted: October 12th, 2021, 2:00pm GMT

Conditions: AIDS-Related Anal Carcinoma; AIDS-Related Cervical Carcinoma; High Grade Anal Intraepithelial Neoplasia; High Grade Cervical Intraepithelial Neoplasia; HIV Infection
Interventions: Procedure: Biopsy; Procedure: Biospecimen Collection - Anal; Procedure: Biospecimen Collection - Cervical; Procedure: Colposcopy; Procedure: High Resolution Anoscopy; Procedure: Imaging Technique
Sponsors: University of California, San Francisco; National Cancer Institute (NCI); US-Latin American-Caribbean HIV/HPV-Cancer Prevention Clinical Trials Network (ULACNet)
Recruiting
Inguinal Node Sparing Radiotherapy For Patients With Early Stage Anal Cancer

Posted: September 10th, 2021, 2:00pm GMT

Condition: Anal Canal Cancer
Intervention: Radiation: chemo-radiation treatment
Sponsor: AHS Cancer Control Alberta
Recruiting
Natural History, Epidemiology and Pathogenesis of Severe HPV-Related Diseases (Neptune)

Posted: August 30th, 2021, 2:00am GMT

Conditions: Human Papillomavirus
Sponsors: National Institute of Allergy and Infectious Diseases (NIAID)
Recruiting
$Permalink for 'A Prospective Pilot Study to Assess the Efficacy of BOTOX-A in Patients With Low Anterior Resection Syndrome (LARS>20) and Refractory Medical Treatment After Rectal Resection'$
A Prospective Pilot Study to Assess the Efficacy of BOTOX-A in Patients With Low Anterior Resection Syndrome (LARS>20) and Refractory Medical Treatment After Rectal Resection

Posted: August 5th, 2021, 2:00am GMT

Conditions: Low Anterior Resection Syndrome (LARS>20); Refractory Medical Treatment After Rectal Resection
Interventions: Drug: BOTOX-A
Sponsors: University Hospital, Bordeaux
Terminated
Defining the Clinical Potential of Mass Response as a Biomarker for Patient Tumor Sensitivity to Drugs

Posted: August 2nd, 2021, 2:00pm GMT

Conditions: Stage III Breast Cancer; Stage IV Breast Cancer; Stage III Lung Cancer; Stage IV Lung Cancer; AML; Multiple Myeloma in Relapse; Carcinoma; Carcinoma, Pancreatic; Carcinoma of Lung; Carcinoma, Non-Small-Cell Lung; Carcinoma Breast; Carcinoma Prostate; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Carcinoma, Neuroendocrine; Carcinoma, Small Cell Lung; Carcinoma, Ovarian; Carcinoma Bladder; Carcinoma of Esophagus; Carcinoma Cervix; Carcinoma, Thymic; Carcinoma, Ductal; Carcinoma of the Head and Neck; Carcinoma of the Lip; Carcinoma of the Oral Cavity; Carcinoma of Unknown Primary; Carcinoma of the Skin; Carcinoma of the Anus; Carcinoma of the Larynx; Carcinoma of the Penis; Carcinoma of the Oropharynx; Carcinoma of the Appendix; Carcinoma of the Paranasal Sinus; Carcinoma of the Vulva; Malignant Pleural Effusion; Malignant Ascites; Mesothelioma; Cholangiocarcinoma
Intervention:
Sponsor: Travera Inc
Not yet recruiting
HPV Vaccination in HIV Infected and HIV Uninfected Adolescents in Eswatini

Posted: July 29th, 2021, 2:00am GMT

Conditions: HPV Infection; Hiv; HPV Vaccine
Interventions: Biological: Gardasil ® 9
Sponsors: Columbia University
Active, not recruiting
Therapy Adapted for High Risk and Low Risk HIV-Associated Anal Cancer

Posted: June 18th, 2021, 2:00pm GMT

Conditions: AIDS-Related Anal Carcinoma; Anal Basaloid Squamous Cell Carcinoma; Anal Canal Cloacogenic Carcinoma; Anal Margin Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; HIV Infection; Rectal Squamous Cell Carcinoma; Stage I Anal Cancer AJCC v8; Stage II Anal Cancer AJCC v8; Stage II Rectal Cancer AJCC v8; Stage III Anal Cancer AJCC v8; Stage III Rectal Cancer AJCC v8
Interventions: Drug: Capecitabine; Drug: Fluorouracil; Radiation: Intensity-Modulated Radiation Therapy; Drug: Mitomycin; Biological: Nivolumab
Sponsors: National Cancer Institute (NCI)
Recruiting
Virtual Reality for GI Cancer Pain to Improve Patient Reported Outcomes

Posted: June 1st, 2021, 2:00pm GMT

Conditions: Cancer Pain; Visceral Pain; Gastrointestinal Neoplasms; Cancer of Gastrointestinal Tract; Small Intestine Cancer; Pancreas Cancer; Liver Cancer; Colon Cancer; Biliary Tract Cancer; Stomach Cancer; Rectum Cancer; Peritoneal Cancer; Gastrointestinal Cancer Metastatic; Gastrointestinal Cancers - Anus; Gastrointestinal Cancers - Stomach; Gastrointestinal Cancers - Colorectal; Gastrointestinal Cancers - Small Intestine; Small Intestine Cancer Stage III; Small Intestine Cancer Stage IV; Small Intestine Cancer, Recurrent; Pancreas Cancer, Stage III; Pancreas Cancer, Stage IV; Pancreas Cancer, Metastatic; Pancreas Cancer, Recurrent; Liver Cancer Stage IIIa; Liver Cancer Stage IIIb; Liver Cancer Stage IIIc; Liver Cancer Stage IV; Colon Cancer Stage III; Colon Cancer Stage IV; Stomach Cancer Stage III; Stomach Cancer Stage IV; Stomach Cancer Recurrent; Rectum Cancer, Recurrent; Gastrointestinal Cancers - Liver; Anal Cancer; Anal Cancer Stage III; Anal Cancer Stage IV; Anal Cancer Recurrent; Anal Cancer Metastatic; Anal Cancer, Stage IIIA; Anal Cancer, Stage IIIB; Appendix Cancer; Ampullary Cancer; Bile Duct Cancer; Bile Duct Cancer Stage III; Bile Duct Cancer Stage IV; Bile Duct Cancer Stage IVA; Bile Duct Cancer Stage IVB; Bile Duct Cancer Recurrent; Carcinoid Tumor; Carcinoid Tumor of Pancreas; Carcinoid Tumor of Large Intestine; Carcinoid Tumor of GI System; Carcinoid Tumor of Colon; Carcinoid Tumor of Liver; Carcinoid Tumor of Cecum; Carcinoid Tumor of Ileum; Carcinoid Tumor of Rectum; Carcinoid Tumor of the Small Bowel; Carcinoid Tumor of the Stomach; Large Intestine Cancer; Esophagus Cancer; Esophagus Cancer, Stage III; Esophagus Cancer, Stage IV; Esophagus Cancer, Recurrent; Gallbladder Cancer; Gallbladder Cancer Stage III; Gallbladder Cancer Stage IV; Gastric (Stomach) Cancer; Neuroendocrine Tumor; Peritoneum Cancer; Rectal Cancer; Esophagus Cancer, Stage I; Esophagus Cancer, Stage II; Gallbladder Cancer Stage I; Gallbladder Cancer Stage II; Bile Duct Cancer Stage I; Bile Duct Cancer Stage II
Intervention: Device: PICO G2 4k
Sponsors: Cedars-Sinai Medical Center; National Cancer Institute (NCI)
Recruiting
Total Neoadjuvant Treatment Plus PD-1 in Mid-Low Locally Advanced Rectal Cancer

Posted: May 28th, 2021, 2:00am GMT

Conditions: Tislelizumab; Locally Advanced Rectal Cancer; Total Neoadjuvant Treatment; PD-1
Interventions: Drug: Sintilimab
Sponsors: The First Hospital of Jilin University
Active, not recruiting
Pomalidomide and Nivolumab in People With Virus-Associated Malignancies With or Without HIV

Posted: May 26th, 2021, 2:00pm GMT

Conditions: Viral Associated Malignancies; Kaposi Sarcoma; EBV/KSHV-associated Lymphomas
Interventions: Drug: Pomalidomide; Drug: Nivolumab
Sponsors: National Cancer Institute (NCI)
Recruiting
Combination of Spartalizumab, mDCF and Radiotherapy in Patients With Metastatic Squamous Cell Anal Carcinoma

Posted: May 20th, 2021, 2:00pm GMT

Conditions: Squamous Cell Anal Carcinoma; Metastatic Squamous Cell Carcinoma
Intervention: Biological: Sample collection
Sponsors: Centre Hospitalier Universitaire de Besancon; National Cancer Institute, France; Novartis
Recruiting
Study of SQZ-AAC-HPV in Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors

Posted: May 19th, 2021, 2:00pm GMT

Conditions: Adult Solid Tumor
Interventions: Biological: SQZ-AAC-HPV; Drug: Ipilimumab; Drug: Nivolumab
Sponsors: SQZ Biotechnologies
Active, not recruiting
Detecting HPV DNA in Anal and Cervical Cancers

Posted: April 23rd, 2021, 2:00pm GMT

Conditions: Cervical Cancer; Anal Cancer; HPV-Related Anal Squamous Cell Carcinoma; HPV-Related Cervical Carcinoma; HPV-Related Carcinoma; Uterine Cervical Cancer
Interventions: Radiation: Radiation Treatment With or Without Chemotherapy; Other: Blood Sample Collection; Diagnostic Test: HPV Genotyping (HPV DNA Test); Diagnostic Test: Testing Archival Tumor Tissue; Other: Physical Exam; Diagnostic Test: Positron Emission Tomography Scan (PET Scan)/ Computed Tomography Scan (CT Scan)
Sponsor: University of Chicago
Recruiting
Efficacy of Tislelizumab and Spartalizumab Across Multiple Cancer-types in Patients With PD1-high mRNA Expressing Tumors

Posted: March 17th, 2021, 2:00pm GMT

Conditions: MSI-H Colorectal Cancer; Melanoma; Anal Carcinoma; Mesothelioma; Triple Negative Breast Cancer; Lung Adenocarcinoma; Cholangiocarcinoma; Cervical Carcinoma; Kidney Clear Cell Carcinoma; Stomach Adenocarcinoma; Esophageal Adenocarcinoma; Uterine Adenocarcinoma; Head and Neck Squamous Cell Carcinoma; Sarcoma; Lung Squamous Cell Carcinoma; Urothelial Carcinoma; Thyroid Carcinoma; Hepatocellular Carcinoma; Uveal Melanoma; HER2-positive Breast Cancer; Pancreatic Adenocarcinoma; Squamous Esophageal Carcinoma; Epithelial Ovarian Cancer; Uterine Carcinosarcoma; Small Cell Lung Cancer; Hormone Receptor Positive / HER2-negative Breast Cancer; Lung Adenocarcinoma EGFR-mutated/ ALK Traslocation; Colorectal Adenocarcinoma; Prostate Adenocarcinoma; Carcinoma of Unknown Primary; Other Histology
Interventions: Drug: Spartalizumab; Drug: Tislelizumab
Sponsors: SOLTI Breast Cancer Research Group; Novartis
Recruiting
Comparison of Functional Outcomes Between Transanal and Laparoscopic vs Open Ileal Pouch-Anal Anastomosis

Posted: January 25th, 2021, 3:00am GMT

Conditions: Ulcerative Colitis; Inflammatory Bowel Diseases; Ileal Pouch
Interventions: Procedure: ta-IPAA; Procedure: tabd-IPAA
Sponsors: Mount Sinai Hospital, Canada; Cedars-Sinai Medical Center; St Mary's Hospital, London; Universitaire Ziekenhuizen KU Leuven
Recruiting
Anti-PD-1 and mDCF Followed by Chemoradiotherapy in Patients With Stage III Squamous Cell Anal Carcinoma.

Posted: January 22nd, 2021, 3:00pm GMT

Condition: Squamous Cell Carcinoma of the Anus Stage III
Interventions: Biological: Blood sample collection; Procedure: Biopsy
Sponsors: Centre Hospitalier Universitaire de Besancon; Boehringer Ingelheim
Recruiting

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