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Tech Innov Patient Support Radiat Oncol. 2024 Jan 18;29:100237. doi: 10.1016/j.tipsro.2024.100237. eCollection 2024 Mar.
ABSTRACT
OBJECTIVE: To evaluate the efficacy of the balloon spacer when used to reduce the radiation dose delivered to the rectum in prostate cancer patients undergoing external beam radiotherapy.
METHOD: A single center retrospective analysis including 75 PC patients with localized T1-T3a disease who received balloon spacer followed by EBRT. Pre- and post-implantation computed tomography (CT) scans were utilized for treatment planning for standard EBRT (78-81 Gy in 1.8-2 Gy fractions). Rectal dosimetry was assessed using DVHs, and toxicities were graded with CTCAE v.4.
RESULTS: A median (IQR) prostate-rectum separation resulted in 1.6 cm (1.4-2.0) post balloon spacer implantation. Overall, 90.6 % (68/75) of patients had a clinically significant 25 % relative reduction in the rectal with a median relative reduction of 91.8 % (71.2-98.6 %) at rV70. Three (4.0 %) patients reported mild procedural adverse events, anal discomfort and dysuria. Within 90 days post-implantation, five patients (6.67 %) and 1 patient (1.33 %) reported grade 1 and grade 2 rectal toxicities (anal pain, constipation, diarrhea and hemorrhoids). Genitourinary (GU) grade 1 toxicity was reported in 37 patients (49.33 %), with only one patient (1.33 %) experiencing grade 2 GU toxicity. No grade ≥ 3 toxicity was reported.
CONCLUSION: Balloon spacer implantation effectively increased prostate-rectum separation and associated with dosimetric gains EBRT for PC stage T1-T3a. Further controlled studies are required to ascertain whether this spacer allows for radiotherapy dose escalation and minimizes gastrointestinal (GI) toxicity.
PMID:38322778 | PMC:PMC10846399 | DOI:10.1016/j.tipsro.2024.100237
Anal Sci. 2024 Feb 6. doi: 10.1007/s44211-024-00508-8. Online ahead of print.
ABSTRACT
One of the challenges in liquid biopsy for early cancer detection is ascribed to the fact that mutation DNA often represents an extremely small ratio of less than 1% compared to wild-type genes in blood. However, in conventional fragment analysis with capillary electrophoresis (CE), the detectable allele frequency could be about 5%. In this work, we developed an original reagent-based fragment analysis with single base extension (SBE) reactions for cancer-associated mutation assay using a commercially available CE device, and investigated on a possibility of improvement of limit of detection (LOD) for genetic mutation. First, after adjustment of reagent conditions for the SBE reactions, the linear relationship between gene template concentration and fluorescence intensity was obtained from 1 to 100 fmol of target genes. Next, from the results of an experiment to detect mutation EGFR L858R at abundance ratios of mutant type to wild type (100-fmol template) of 0, 1, 5, and 10%, it was shown that the target gene can be detected with LOD of 0.33%. This high sensitivity was realized in part by separating fluorescently labeled substrates into an individual tube for an each-colored SBE reaction. Moreover, mutations EGFR L858R and KRAS G12V were simultaneously detected at sensitivities equivalent to LODs of 0.57 and 0.47%, respectively. These results indicate that < 1% of mutations in multiplex gene mutations can be simultaneously detected, and that possibility suggests that the developed method can be used in clinical practice for detecting cancers.
PMID:38319561 | DOI:10.1007/s44211-024-00508-8
Abdom Radiol (NY). 2024 Feb 6. doi: 10.1007/s00261-023-04182-8. Online ahead of print.
ABSTRACT
OBJECTIVES: Pre-treatment staging of anal squamous cell carcinoma (ASCC) includes pelvic MRI and [18F]-fluorodeoxyglucose positron emission tomography with computed tomography (PET-CT). MRI criteria to define lymph node metastases (LNMs) in ASCC are currently lacking. The aim of this study was to describe the morphological characteristics of lymph nodes (LNs) on MRI in ASCC patients with PET-CT-positive LNs.
METHODS: ASCC patients treated at Skåne University Hospital between 2009 and 2017 were eligible for inclusion if at least one positive LN according to PET-CT and a pre-treatment MRI were present. All PET-CT-positive LNs and PET-CT-negative LNs were retrospectively identified on baseline MRI. Each LN was independently classified according to pre-determined morphological characteristics by two radiologists blinded to clinical patient information.
RESULTS: Sixty-seven ASCC patients were included, with a total of 181 PET-CT-positive LNs identified on baseline MRI with a median short-axis diameter of 9.0 mm (range 7.5-12 mm). MRI morphological characteristics of PET-CT-positive LNs included regular contour (87%), round shape (89%), and homogeneous signal intensity on T2-weighed images (67%). An additional 78 PET-CT-negative LNs were identified on MRI. These 78 LNs had a median size of 6.8 mm (range 5.5-8.0 mm). The majority of PET-CT-negative LNs had a regular contour, round shape, and a homogeneous signal that was congruent to the primary tumor.
CONCLUSIONS: There are MRI-specific morphological characteristics for pelvic LNs in ASCC. PET-CT-positive and negative LNs share similar morphological features apart from size, with PET-CT-positive LNs being significantly larger. Further studies are needed to determine discrimination criteria for LNM in ASCC.
PMID:38319345 | DOI:10.1007/s00261-023-04182-8
Anal Chem. 2024 Feb 5. doi: 10.1021/acs.analchem.3c05767. Online ahead of print.
ABSTRACT
To enhance our comprehension of the fundamental mechanisms driving tumor metabolism and metastasis, it is essential to dynamically monitor intratumoral lipid droplet (LD) and collagen processes in vivo. Traditional LD analysis in tumors predominantly relies on observations of in vitro cells or tissue slices, which unfortunately hinder real-time insights into the dynamic behavior of LDs during in vivo tumor progression. In this study, we developed a dual-modality imaging technique that combines coherent anti-Stokes Raman scattering (CARS) and second-harmonic generation (SHG) microscopy for in vivo monitoring of tumor LDs and collagen alterations, assisted by a murine breast cancer 4T1 cell-based dorsal skinfold window. Specifically, we accomplished real-time observations and quantitative analysis of the LD size, density, and collagen alignment within living tumors through CARS/SHG imaging. Additionally, our findings demonstrate that real-time LD monitoring provides a valuable means of assessing the efficacy of anticancer drugs in vivo. We evaluated the impact of adipose activators on lipid metabolism, oxidative stress, and tumor suppression by monitoring changes in LD size and density. Overall, this study highlights the potential of dual-modality CARS/SHG microscopy as a sensitive and flexible tool for antitumor therapeutic strategies.
PMID:38315069 | DOI:10.1021/acs.analchem.3c05767
Anal Chem. 2024 Feb 13;96(6):2550-2558. doi: 10.1021/acs.analchem.3c04991. Epub 2024 Feb 5.
ABSTRACT
Cancer-related extracellular vesicles (EVs) are considered important biomarkers for cancer diagnosis because they can convey a large amount of information about tumor cells. In order to detect cancer-related EVs efficiently, an electrochemiluminescence (ECL) sensor for the specific identification and highly sensitive detection of EVs in the plasma of cancer patients was constructed based on dual recognitions by glycosyl-imprinted polymer (GIP) and aptamer. The characteristic glycosyl Neu5Ac-α-(2,6)-Gal-β-(1-4)-GlcNAc trisaccharide on the surface of EVs was used as a template molecule and 3-aminophenylboronic acid as a functional monomer to form a glycosyl-imprinted polymer by electropolymerization. After glycosyl elution, the imprinted film specifically recognized and adsorbed the EVs in the sample, and then the CD63 aptamer-bipyridine ruthenium (Aptamer-Ru(bpy)) was added to combine with the CD63 glycoprotein on the extracellular vesicle's surface, thus providing secondary recognition of the EVs. Finally, the EVs were quantitatively detected according to the ECL signal produced by the labeled bipyridine ruthenium. When more EVs were captured by the imprinted film, more probes were obtained after incubation, and the ECL signal was stronger. Under the optimized conditions, the ECL signal showed a good linear relationship with the concentration of EVs in the range of 9.5 × 102 to 9.5 × 107 particles/mL, and the limit of detection was 641 particles/mL. The GIP sensor can discriminate between the EV contents of cancer patients and healthy controls with high accuracy. Because of its affordability, high sensitivity, and ease of use, it is anticipated to be employed for cancer early detection and diagnosis.
PMID:38314707 | DOI:10.1021/acs.analchem.3c04991
Heliyon. 2024 Jan 11;10(2):e24394. doi: 10.1016/j.heliyon.2024.e24394. eCollection 2024 Jan 30.
ABSTRACT
SIVA-1 has been shown to affect apoptotic processes in various different cell lines, and SIVA-1 significantly contributes to the decreased responsiveness of cancer cells to some chemotherapy agents. However, whether SIVA-1 has potential application in gastric cancer remains unknown. Therefore, the objective of this investigation was to clarify the distinct function of SIVA-1 in chemotherapeutic drug resistance within a living murine model with gastric malignancy, and initially elucidate the underlying mechanisms. In an established multidrug-resistant gastric cancer xenograft mouse model, lentivirus, named Lv-SIVA-1, was injected into xenograft tumors, and increased the mRNA and protein expression of endogenous SIVA-1 in tumors. Immunohistochemical assays of xenograft tumor showed that SIVA-1 was significantly upregulated, and the protein expression levels of SIVA-1 were highly increased, as detected by Western blotting. In addition, we detected the role of SIVA-1 in cell proliferation and cell apoptosis in gastric cancer cells by TUNEL and found that SIVA-1 decreased tumor cell apoptosis and promoted tumor growth in vivo. Using a TMT assay between tumor tissues of experimental and control groups, differentially expressed proteins were examined and three potential biomarkers of multidrug resistance (ARF, MDM2, and p53) were screened. We further investigated the molecular mechanism by which SIVA-1 played an efficient role against chemotherapies and found that overexpressed SIVA-1 leads to increased ARF and MDM2 expression and suppressed expression of p53 in tumor tissue. In conclusion, SIVA-1 plays a significant role in the multidrug resistance of gastric tumors. In addition, overexpressed SIVA-1 positively regulates cell proliferation, adjusts cycle progression, and reduces the response to drug treatment for gastric cancer in an ARF/MDM2/p53-dependent manner. This novel research provides a basis for chemical management of gastric cancer through regulation of SIVA-1 expression.
PMID:38312638 | PMC:PMC10834467 | DOI:10.1016/j.heliyon.2024.e24394
Radiother Oncol. 2024 Feb 8;193:110144. doi: 10.1016/j.radonc.2024.110144. Online ahead of print.
ABSTRACT
BACKGROUND: The results of the PRODIGE 42/GERICO 12 study showed that short course radiotherapy had a better tolerance profile than radiochemotherapy, with comparable oncological results. We have included Quality of Life analyses and oncogeriatric evaluations in this study.
PATIENTS AND METHODS: In all, 101 patients ≥75 years of age with resectable T3-T4 rectal adenocarcinoma less than 12 cm from the anal margin received short course radiotherapy (5X5 Gy in one week) or radiochemotherapy (50 Gy, 2 y/f and capecitabine 800 mg/m2, 5 days/week) with delayed surgery (7 weeks ± 1) in both groups. The Quality of Life analyses (EORTC QLQ C-30 et ELD14) were conducted upon inclusion, pre-operatively, at 3, 6 and 12 months post-op, together with the oncogeriatric evaluations, including an evaluation of the IADL and ADL scores, walking speed, GDS15, MMSE, MNA.
RESULTS: We did not highlight any statistical difference for the global EORTC QLQ-C30 score; several factors are statistically in favor of the short course radiotherapy group at 3 months post-op (cognitive functions, fatigue, appetite). In the case of the ELD14 score, the disease burden is perceived as more negative at 3, 6 and 12 months postop in the radiochemotherapy group. The IADL score deteriorated in 44.8 % of the radiochemotherapy group and 14.8 % of the radiotherapy group (p = 0.032); similarly, the GDS15 depression score was better preserved in the short course radiotherapy group (p = 0.05). An analysis of the other scores: ADL, walking speed, MNA, MMSE did not highlight any statistical difference.
CONCLUSION: Short course radiotherapy achieves better results in terms of Quality of Life and preservation of autonomy in patients aged ≥75 treated for locally advanced rectal cancer.
PMID:38341097 | DOI:10.1016/j.radonc.2024.110144
Med Image Anal. 2024 Feb 2;93:103100. doi: 10.1016/j.media.2024.103100. Online ahead of print.
ABSTRACT
With the massive proliferation of data-driven algorithms, such as deep learning-based approaches, the availability of high-quality data is of great interest. Volumetric data is very important in medicine, as it ranges from disease diagnoses to therapy monitoring. When the dataset is sufficient, models can be trained to help doctors with these tasks. Unfortunately, there are scenarios where large amounts of data is unavailable. For example, rare diseases and privacy issues can lead to restricted data availability. In non-medical fields, the high cost of obtaining enough high-quality data can also be a concern. A solution to these problems can be the generation of realistic synthetic data using Generative Adversarial Networks (GANs). The existence of these mechanisms is a good asset, especially in healthcare, as the data must be of good quality, realistic, and without privacy issues. Therefore, most of the publications on volumetric GANs are within the medical domain. In this review, we provide a summary of works that generate realistic volumetric synthetic data using GANs. We therefore outline GAN-based methods in these areas with common architectures, loss functions and evaluation metrics, including their advantages and disadvantages. We present a novel taxonomy, evaluations, challenges, and research opportunities to provide a holistic overview of the current state of volumetric GANs.
PMID:38340545 | DOI:10.1016/j.media.2024.103100
Diagnostics (Basel). 2024 Jan 31;14(3):315. doi: 10.3390/diagnostics14030315.
ABSTRACT
1.
BACKGROUND: Preoperative staging of rectal lesions for transanal endoscopic surgery (TES) comprises digital rectal examination, intraoperative rigid rectoscopy (IRR), endorectal ultrasound (EUS), colonoscopy and rectal magnetic resonance imaging (rMRI). The gold standard for topographic features is IRR. Are the results of the other tests sufficiently reliable to eliminate the need for IRR? rMRI is a key test in advanced rectal cancer and is not operator-dependent. Description of anatomical landmarks is variable. Can we rely on the information regarding topographic features provided by all radiologists? 2.
MATERIALS AND METHODS: This is a concordance interobservational study involving four diagnostic tests of anatomical characteristics of rectal lesions (colonoscopy, EUS, rectal MRI and IRR), performed by four expert radiologists, regarding topographic rectal features with rMRI. 3.
RESULTS: Fifty-five rectal tumors were operated on by using TES. The distance of the tumor from the anal verge, location by quadrants, size by quadrants and size of tumor were assessed (IRR as gold standard). For most of the tumors, the correlation between IRR and colonoscopy or EUS was very good (ICC > 0.75); the correlation between rMRI and IRR in respect of the size by quadrants (ICC = 0.092) and location by quadrants (ICC = 0.292) was weak. Topographic landmarks studied by the expert radiologists had an excellent correlation, except for distance from the peritoneal reflection to the anal verge (ICC = 0.606). 4.
CONCLUSIONS: Anatomical description of rectal lesions by IRR, EUS, colonoscopy and rMRI is reliable. Topographic data obtained by EUS and colonoscopy can serve as a reference to avoid IRR. Determination of these topographic data by rMRI is less reliable. As performed by the expert radiologists, the anatomical study by rMRI is accurate and reproducible.
PMID:38337831 | PMC:PMC10855339 | DOI:10.3390/diagnostics14030315
BMC Surg. 2024 Feb 9;24(1):50. doi: 10.1186/s12893-024-02335-0.
ABSTRACT
BACKGROUND: There is no criterion to guide and evaluate the anastomosis of laparoscopic low anterior resection (LAR). We developed a new technique for precise anastomosis. This study endeavored to evaluate the effectiveness and safety of this new technology.
METHODS: Patients with mid-low rectal cancer who underwent laparoscopic LAR in our department were enrolled retrospectively between January 1, 2021 and July 1, 2023. During the LAR, the distance between the sacral promontory and the rectal stump was measured and used to determine the length of the sigmoid colon, which was preserved for anastomose. The demographic characteristics and short-term outcomes were analyzed.
RESULTS: Forty-nine patients (26 men, 23 women) with low and middle rectal cancer were retrospectively enrolled in the study. The distance of the tumor from the anal verge was 6.4 ± 2.7 cm. The operative time was 193 ± 42 min. All patients underwent precise anastomosis, among which 12 patients underwent freeing of the splenic flexure of the colon. According to our criteria, there was no redundant or tense state of the colon anterior to the sacrum after the anastomosis. Only one patient had a postoperative anastomotic leak (Grade B). All 15 patients receiving neoadjuvant chemoradiotherapy underwent terminal ileostomy. No postoperative death occurred within 30 days of the surgery. The median follow-up time in our study was 12 months. One patient developed a single metastasis in the right lobe of the liver in the eighth month after surgery and underwent microwave radiofrequency ablation, which did not recur in the four months of postoperative follow-up, and the rest of the patients survived disease-free without recurrence of metastasis.
CONCLUSIONS: Precise measurement of the proximal colon of the anastomosis can ensure accurate and convenient colorectal anastomosis and this may be a technique worthy of clinical application. However, its effectiveness needs to be further verified in a multicenter clinical trial.
PMID:38336762 | PMC:PMC10858553 | DOI:10.1186/s12893-024-02335-0
Anal Chim Acta. 2024 Mar 15;1294:342292. doi: 10.1016/j.aca.2024.342292. Epub 2024 Jan 27.
ABSTRACT
BACKGROUND: Hypochlorous acid (HClO) is an important biomarker for inflammation, cardiovascular disease, and even cancer. It is of great significance to accurately monitor and quantitatively analyze the fluctuations of HClO to better understand their physiological functions. Traditional HClO detection methods such as high-performance liquid chromatography (HPLC), and mass spectrometry are preferred, but are costly and unsuitable in vivo. Near-infrared (NIR) fluorescence imaging has the advantages of high sensitivity, high temporal and spatial resolutions, minimal autofluorescence, and deep tissue penetration, which facilitates its application in biological systems. Therefore, the development of sensitivity and simple NIR fluorescence monitoring HClO methods in vivo and in vitro is essential and desirable.
RESULTS: Herein, we present a NIR probe NOF3 by integrating the rhodamine scaffold and HClO-triggered moiety for the real-time detection of HClO in vitro and in vivo. NOF3 reacts with the HClO and releases the NOF-OH fluorophore of emitted signals at 730 nm, which is in the NIR region. The designed probe detected concentrations of HClO ranging from 0 to 17 μM with a low detection limit of 0.146 μM, presenting excellent sensitivity and selectivity toward HClO over other species. NOF3 manifests significantly turn-on NIR fluorescent signals in response to HClO concentration, which makes it favorable for monitoring dynamic HClO distribution in vivo. We exemplify NOF3 for the tracking of endogenously overexpressed HClO distribution in RAW 264.7 cells, and further realize real-time in vivo bioimaging of HClO activity in inflammation mice.
SIGNIFICANCE: The facile NIR NOF3 probe was successfully applied to visualize endogenous and exogenous HClO in living cells and mice. This study provides not only an effective tool for spatial and temporal resolution HClO bioimaging in vivo but also possesses great potential for use in future research on HClO-related biology and pathology.
PMID:38336413 | DOI:10.1016/j.aca.2024.342292
Anal Chem. 2024 Feb 9. doi: 10.1021/acs.analchem.3c04801. Online ahead of print.
ABSTRACT
The combined application of nanozymes and surface-enhanced Raman scattering (SERS) provides a promising approach to obtain label-free detection. However, developing nanomaterials with both highly efficient enzyme-like activity and excellent SERS sensitivity remains a huge challenge. Herein, we proposed one-step synthesis of Mo2N nanoparticles (NPs) as a "two-in-one" substrate, which exhibits both excellent peroxidase (POD)-like activity and high SERS activity. Its mimetic POD activity can catalyze the 3,3',5,5'-tetramethylbenzidine (TMB) molecule to SERS-active oxidized TMB (ox-TMB) with high efficiency. Furthermore, combining experimental profiling with theory, the mechanism of POD-like activity and SERS enhancement of Mo2N NPs was explored in depth. Benefiting from the outstanding properties of Mo2N NPs, a versatile platform for indirect SERS detection of biomarkers was developed based on the Mo2N NPs-catalyzed product ox-TMB, which acts as the SERS signal readout. The feasibility of this platform was validated using glutathione (GSH) and target antigens alpha-fetoprotein antigen (AFP) and carcinoembryonic antigen (CEA) as representatives of small molecules with a hydroxyl radical (·OH) scavenging effect and proteins with a low Raman scattering cross-section, respectively. The limits of detection of GSH, AFP, and CEA were as low as 0.1 μmol/L, 89.1, and 74.6 pg/mL, respectively. Significantly, it also showed application in human serum samples with recoveries ranging from 96.0 to 101%. The acquired values based on this platform were compared with the standard electrochemiluminescence method, and the relative error was less than ±7.3. This work not only provides a strategy for developing highly active bifunctional nanomaterials but also manifests their widespread application for multiple biomarkers analysis.
PMID:38335969 | DOI:10.1021/acs.analchem.3c04801
Dis Colon Rectum. 2024 Feb 8. doi: 10.1097/DCR.0000000000003158. Online ahead of print.
ABSTRACT
BACKGROUND: Venous thromboembolism occurs in approximately 2% of patients undergoing abdominal and pelvic surgery for cancers of the colon, rectum, and anus, and is considered preventable. The American Society of Colon and Rectal Surgeons recommends extended prophylaxis in high-risk patients, but there is low adherence to the guidelines.
OBJECTIVE: This study aims to analyze the impact of venous thromboembolism risk-guided prophylaxis in patients undergoing elective abdominal and pelvic surgeries for colorectal and anal cancers from 2016 to 2021.
DESIGN: This was a retrospective analysis.
SETTING: The study was conducted at a multisite tertiary referral academic healthcare system.
PATIENTS: Patients who underwent elective abdominal or pelvic surgery for colon, rectal or anal cancer.
MAIN OUTCOME MEASURES: Receipt of Caprini-guided venous thromboembolism prophylaxis, 90 days postoperative rate of deep vein thrombosis, pulmonary embolism, venous thromboembolism, and bleeding events.
RESULTS: A total of 3,504 patients underwent elective operations, of which 2,224 (63%) received appropriate thromboprophylaxis in the inpatient setting. In the post-discharged cohort of 2,769 patients, only 2% received appropriate thromboprophylaxis in which no thromboembolic events were observed. In the group receiving inappropriate thromboprophylaxis, at 90 days post-discharge, the deep vein thrombosis, pulmonary embolism, and venous thromboembolism rates were 0.60%, 0.40%, and 0.88%, respectively. Postoperative bleeding was not different between the two groups.
LIMITATIONS: Limitations to our study include its retrospective nature, use of aggregated electronic medical records, and single healthcare system experience.
CONCLUSION: Most patients in our healthcare system undergoing abdominal or pelvic surgery for cancers of the colon, rectum, and anus were discharged without appropriate Caprini-guided VTE prophylaxis. Risk-guided prophylaxis was associated with decreased rates of in-hospital and discharged venous thromboembolism without an increase in bleeding complications. See Video Abstract.
PMID:38335005 | DOI:10.1097/DCR.0000000000003158
Anal Chem. 2024 Feb 9. doi: 10.1021/acs.analchem.3c04954. Online ahead of print.
ABSTRACT
Abnormal fatty acid metabolism is recognized as a key driver of tumor development and progression. Although numerous inhibitors have been developed to target this pathway, finding drugs with high specificity that do not disrupt normal cellular metabolism remains a formidable challenge. In this paper, we introduced a novel real-time NMR-based drug screening technique that operates within living cells. This technique provides a direct way to putatively identify molecular targets involved in specific metabolic processes, making it a powerful tool for cell-based drug screening. Using 2-13C acetate as a tracer, combined with 3D cell clusters and a bioreactor system, our approach enables real-time detection of inhibitors that target fatty acid metabolism within living cells. As a result, we successfully demonstrated the initial application of this method in the discovery of traditional Chinese medicines that specifically target fatty acid metabolism. Elucidating the mechanisms behind herbal medicines remains challenging due to the complex nature of their compounds and the presence of multiple targets. Remarkably, our findings demonstrate the significant inhibitory effect of P. cocos on fatty acid synthesis within cells, illustrating the potential of this approach in analyzing fatty acid metabolism events and identifying drug candidates that selectively inhibit fatty acid synthesis at the cellular level. Moreover, this systematic approach represents a valuable strategy for discovering the intricate effects of herbal medicine.
PMID:38334355 | DOI:10.1021/acs.analchem.3c04954
Anal Chem. 2024 Feb 9. doi: 10.1021/acs.analchem.3c04887. Online ahead of print.
ABSTRACT
Chemoresistance to triple-negative breast cancer (TNBC) is a critical issue in clinical practice. Lipid metabolism takes a unique role in breast cancer cells; especially, unsaturated lipids involving cell membrane fluidity and peroxidation are highly remarked. At present, for the lack of a high-resolution molecular recognition platform at the single-cell level, it is still hard to systematically study chemoresistance heterogeneity based on lipid unsaturation proportion. By designing a single-cell mass spectrometry workflow based on CyESI-MS, we profiled the unsaturated lipids of TNBC cells to evaluate lipidomic remodeling under platinum stress. Profiling revealed the heterogeneity of the polyunsaturated lipid proportion of TNBC cells under cisplatin treatment. A cluster of cells identified by polyunsaturated lipid accumulation was found to be involved in platinum sensitivity. Furthermore, we found that the chemoresistance of TNBC cells could be regulated by fatty acid supplementation, which determinates the composition of unsaturated lipids. These discoveries provide insights for monitoring and controlling cellular unsaturated lipid proportions to overcome chemoresistance in breast cancer.
PMID:38334074 | DOI:10.1021/acs.analchem.3c04887
Prev Med Rep. 2024 Feb 1;39:102636. doi: 10.1016/j.pmedr.2024.102636. eCollection 2024 Mar.
ABSTRACT
BACKGROUND: This study aimed to investigate the role of endoscopy screening in colorectal cancer (CRC).
METHODS: Up to January 2023, databases were searched for studies related to sigmoidoscopy and colonoscopy screening. The incidence of CRC, and/or CRC mortality were the main observation outcomes.
RESULTS: A total of 5 randomized controlled trials (RCTs) published from 2017 to 2022 were included. Among them, four studies used sigmoidoscopy screening and one study involved colonoscopy screening. Statistical results showed that the incidence (RR: 0.78, p < 0.001) and mortality (RR: 0.75, p < 0.001) of CRC were significantly lower in the screening group than in the control group. Further, a subgroup analysis of CRC site indicated that the incidence and mortality of CRC in the screening group were significantly lower than those in the non-screened group, regardless of distal CRC (Incidence: RR: 0.66, p < 0.001; Mortality: RR: 0.62, p < 0.001) or proximal CRC (Incidence: RR: 0.94, p = 0.038; Mortality: RR: 0.89, p = 0.038). In terms of gender, compared with the non-screening group, both males (Incidence: RR: 0.73, p < 0.001; Mortality: RR: 0.68, p < 0.001) and females (Incidence: RR: 0.85, p < 0.001; Mortality: RR: 0.85, p = 0.017), the screening group had a significant decrease in the incidence and mortality of CRC.
CONCLUSION: This meta-analysis demonstrated that sigmoidoscopy screening (including colonoscopy) could effectively reduce the incidence and mortality of CRC.
PMID:38333601 | PMC:PMC10847765 | DOI:10.1016/j.pmedr.2024.102636
J Transl Med. 2024 Feb 9;22(1):142. doi: 10.1186/s12967-024-04903-7.
ABSTRACT
BACKGROUND: Overweight is known to be an important risk factor for colorectal cancer (CRC), and the differences in intestinal flora among CRC patients with different BMI status have not been clearly defined. The purpose of this study was to elucidate the differences in the abundance, composition and biological function of intestinal flora in CRC patients with different BMI status.
METHOD: A total of 170 CRC patients were included and grouped according to the BMI data of CRC patients. BMI ≥ 24 kg/m2 was defined as overweight group, and BMI within the range of 18.5-23.9 kg/m2 was defined as normal weight group. Preoperative stool collection of patients in both groups was used for 16S rRNA sequencing. Total RNA was extracted from 17 CRC tumor tissue samples for transcriptome sequencing, and then CIBERSORT algorithm was used to convert the transcriptome data into the relative content matrix of 22 kinds of immune cells, and the correlation between different intestinal flora and immune cells and immune-related genes under different BMI states was analyzed. Finally, we identified BMI-related differential functional pathways and analyzed the correlation between these pathways and differential intestinal flora.
RESULT: There was no significant difference in α diversity and β diversity analysis between overweight group and normal weight group. Partial least square discriminant analysis (PLS-DA) could divide the flora into two different clusters according to BMI stratification. A total of 33 BMI-related differential flora were identified by linear discriminant effect size analysis (LEfSe), among which Actinomyces, Desulfovibrio and Bacteroides were significantly enriched in overweight group. ko00514: Other types of O-glycan biosynthesis are significantly enriched in overweight group. There was a significant positive correlation between Clostridium IV and Macrophages M2 and T cells regulatory (Tregs). There was a significant negative correlation with Dendritic cells activated and T cells CD4 memory activated.
CONCLUSIONS: The richness and diversity of intestinal flora of CRC patients may be related to different BMI status, and the enrichment of Actinomyces, Desulphurvibrio and Bacteroides may be related to overweight status of CRC patients. The tumor microenvironment in which BMI-related differential flora resides has different immune landscapes, suggesting that some intestinal flora may affect the biological process of CRC by regulating immune cell infiltration and immune gene expression, but further experiments are needed to confirm this.
PMID:38331839 | PMC:PMC10854193 | DOI:10.1186/s12967-024-04903-7
Anal Chim Acta. 2024 Mar 8;1293:342286. doi: 10.1016/j.aca.2024.342286. Epub 2024 Jan 23.
ABSTRACT
Dual-mode sensing has attracted more attentions which provide more accurate and reliable approach of cancer-related biomarkers. Herein, we developed a novel SERS/electrochemical dual-mode biosensor for miRNA 21 detection based on Exo III-assisted signal transformation. Firstly, the Au NPs were deposited on electrode as SERS substrate and Mn3O4/S4(DNA signal strand) was modified on Au NPs/S5 by the DNA strands S5-S4 pairing principle as hydrogen peroxide catalyst, leading to an obviously high DPV electrical signal without Raman signal. Subsequently, the presence of miRNA 21 will activate the Mn3O4/S4 to be decomposed under exonuclease III-assisted process, then the S3' chains modified with Raman molecular Cy3(Cy3-S3') is continuously connected to the Au NPs/S5 by DNA stands S5-S3' pairing principle, leading to the Raman signal response and DPV signal reduction. The biosensor shows good linear calibration curves of both SERS and electrochemical sensing modes with the detection limit of 3.98 × 10-3 nM and 6.89 × 10-5 nM, respectively. This work finds an ingenious mode for dual detection of microRNA on a same interface, which opens a new strategy for SERS and electrochemical analysis.
PMID:38331553 | DOI:10.1016/j.aca.2024.342286
Anal Chem. 2024 Feb 8. doi: 10.1021/acs.analchem.3c05891. Online ahead of print.
ABSTRACT
The shortage of specific glycan recognition reagents has proven a significant hurdle in the development of assays to detect altered glycoforms associated with cancer. Here, a carbohydrate-binding aptamer originally selected against the glycan moiety of prostate-specific antigen (PSA) is used as a lectin-mimicking reagent. As a first proof-of-principle, this aptamer has been applied to develop a sandwich-type electrochemical biosensor for the detection of the serum amyloid P (SAP) component, a glycosylated protein whose increased sialylation has been associated with pancreatic cancer. The assay combines a specific antibody for this potential tumor biomarker and the aptamer as capture and detection receptors, respectively. Two oriented antibody immobilization approaches, protein A-based and boronic ester-based attachment to self-assembled monolayers built onto gold surfaces, were comparatively evaluated, the latter being able to circumvent the unwanted interaction between the aptamer and the glycans on the electrode-attached antibody. The resulting biosensing platform allows the detection of the SAP glycoprotein at levels of nanograms per milliliter with a reproducibility value lower than 20%, both in aqueous buffer and in serum. This work represents a proof-of-concept of a promiscuous ligand of proteins with high levels of sialylated glycans typically produced by cancer cells.
PMID:38331397 | DOI:10.1021/acs.analchem.3c05891
Anal Biochem. 2024 Feb 7;688:115480. doi: 10.1016/j.ab.2024.115480. Online ahead of print.
ABSTRACT
Isothermal nucleic acid amplification methods have many advantages for use at the point of care. However, there is a lack of multiplexed isothermal amplification tests to detect multiple targets in a single reaction, which would be valuable for many diseases, such as infection with high-risk human papillomavirus (hrHPV). In this study, we developed a multiplexed loop-mediated isothermal amplification (LAMP) reaction to detect the three most common hrHPV types that cause cervical cancer (HPV16, HPV18, and HPV45) and a cellular control for sample adequacy. First, we characterized the assay limit of detection (LOD) in a real-time reaction with fluorescence readout; after 30 min of amplification the LOD was 100, 10, and 10 copies/reaction of HPV16, HPV18, and HPV45, respectively, and 0.1 ng/reaction of human genomic DNA (gDNA). Next, we implemented the assay on lateral flow strips, and the LOD was maintained for HPV16 and HPV18, but increased to 100 copies/reaction for HPV45 and to 1 ng/reaction for gDNA. Lastly, we used the LAMP test to evaluate total nucleic acid extracted from 38 clinical samples; compared to qPCR, the LAMP test had 89% sensitivity and 95% specificity. When integrated with sample preparation, this multiplexed LAMP assay could be useful for point-of-care testing.
PMID:38331373 | DOI:10.1016/j.ab.2024.115480
J Control Release. 2024 Feb 6:S0168-3659(24)00089-0. doi: 10.1016/j.jconrel.2024.02.002. Online ahead of print.
ABSTRACT
Poly(β-amino ester)s (PAEs) have emerged as a type of highly safe and efficient non-viral DNA delivery vectors. However, the influence of amphiphilicity and chain sequence on DNA transfection efficiency and safety profile remain largely unexplored. In this study, four PAEs with distinct amphiphilicity and chain sequences were synthesized. Results show that both amphiphilicity and chain sequence significantly affect the DNA binding and condensation ability of PAEs, as well as size, zeta potential and cellular uptake of PAE/DNA polyplexes. PAEs with different amphiphilicity and chain sequence exhibit cell type-dependent transfection capabilities: in human bladder transitional cell carcinoma (UM-UC-3), hydrophilic PAE (P-Philic) and amphiphilic PAE random copolymer (R-Amphilic) exhibit relatively higher gene transfection efficiency, while in human bladder epithelial immortalized cells (SV-HUC-1), hydrophobic PAE (P-Phobic), R-Amphilic, and amphiphilic PAE block copolymer (B-Amphilic) demonstrate higher transfection capability. Regardless of cell types, amphiphilic PAE block copolymer (B-Amphilic) always exhibits much lower gene transfection efficiency. In addition, in human colon cancer cells (HCT-116), P-Philic and R-Amphilic achieved superior gene transfection efficiency at high and low polymer/DNA weight ratios, respectively. Importantly, R-Amphilic can effectively deliver the gene encoding tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to human chondrosarcoma cells SW1353 to induce their apoptosis, highlighting its potential application in cancer gene therapy. This study not only establishes a new paradigm for enhancing the gene transfection efficiency of PAEs by modulating their amphiphilicity and chain sequence but also identifies R-Amphilic as a potential candidate for the effective delivery of TRAIL gene in cancer gene therapy.
PMID:38331003 | DOI:10.1016/j.jconrel.2024.02.002
World J Gastrointest Surg. 2024 Jan 27;16(1):124-133. doi: 10.4240/wjgs.v16.i1.124.
ABSTRACT
BACKGROUND: The incidence of colorectal cancer (CRC) is increasing annually. Laparoscopic radical resection of CRC is a minimally invasive procedure preferred in clinical practice.
AIM: To investigate the clinical effect of laparoscopic radical resection of CRC on the basis of propensity score matching (PSM).
METHODS: The clinical data of 100 patients who received inpatient treatment for CRC at Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City) were analyzed retrospectively. The control group included patients who underwent open surgery (n = 43), and those who underwent laparoscopic surgery formed the observation group (n = 57). The baseline information of both groups was equipoised using 1 × 1 PSM. Differences in the perioperative parameters, inflammatory response, immune function, degree of pain, and physical status between the groups were analyzed.
RESULTS: Thirty patients from both groups were successfully matched. After PSM, baseline data showed no statistically significant differences between the groups: (1) Perioperative parameters: The observation group had a longer surgery time, less intraoperative blood loss, earlier first ambulation and first anal exhaust times, and shorter gastric tube indwelling time than the control group; (2) Inflammatory response: 24 h after surgery, the levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) between groups were higher than preoperatively. IL-6, CRP, and TNF-α levels in the observation group were lower than in the control group; (3) Immune function: At 24 h after surgery, counts of CD4-positive T-lymphocytes (CD4+) and CD4+/CD8-positive T-lymphocytes (CD8+) in both groups were lower than those before surgery, whereas CD8+ was higher than that before surgery. At 24 h after surgery, both CD4+ counts and CD4+/CD8+ in the observation group were higher than those in the control group, whereas CD8+ counts were lower; (4) Degree of pain: The visual analog scale scores in the observation group were lower than those in the control group at 24 and 72 h after surgery; and (5) Physical status: One month after surgery, the Karnofsky performance score in the observation group was higher than that in the control group.
CONCLUSION: Laparoscopic radical resection of CRC has significant benefits, such as reducing postoperative pain and postoperative inflammatory response, avoiding excessive immune inhibition, and contributing to postoperative recovery.
PMID:38328309 | PMC:PMC10845282 | DOI:10.4240/wjgs.v16.i1.124
Otolaryngol Head Neck Surg. 2024 Feb 8. doi: 10.1002/ohn.664. Online ahead of print.
ABSTRACT
INTRODUCTION: Gay and bisexual males and other LGBTQ+ communities are more frequently exposed to factors associated with an increased risk of human papillomavirus (HPV) acquisition. Vaccination is critical to protect against HPV+ head and neck cancer (HNC). We characterized the association of perceived level of risk of contraction with HPV knowledge, and vaccine decision-making.
STUDY DESIGN: Cross-sectional cohort.
SETTING: LGBTQ and general survey Reddit forums (control).
METHODS: A survey was shared amongst the online forums. Descriptive statistics characterized the data. Multivariable logistic regression was used to understand factors associated with vaccination, self-perceived high risk, and knowledge of HPV + HNC.
RESULTS: Of 718 respondents, most were female (41.09%), Caucasian (59.89%), college-educated (33.01%), and insured (77.15%) with a mean age of 30.75 years. Half were vaccinated (49.16%), with most unvaccinated endorsing interest (60.58%). Few dependents were vaccinated (25.91%), with interest in vaccination among parents of unvaccinated children (38.58%). Knowledge of HIV's association with HPV (62.95%), HPV causing HNC (55.57%), and the vaccine's efficacy against HNC (55.57%) was also moderate. Identifying female (P = .042), a self-perceived high-risk (P < .001), and having vaccinated children (P < .001) increased vaccination likelihood; transgender (P = .021), or lesbian or gay sexual identity (P < .001) decreased likelihood. Personal HNC diagnosis (P < .001), self-vaccination (P < .001), having vaccinated children (P < .001), having anal sex (P = .001) or no knowledge of past HPV status (P < .001) increased likelihood of high self-perceived risk.
CONCLUSION: Efforts to improve public education regarding the association between HPV and HNC and vaccination efficacy are required to better inform vaccine decision-making among individuals at risk for HPV infection.
PMID:38327242 | DOI:10.1002/ohn.664
Med Image Anal. 2024 Feb 1;93:103097. doi: 10.1016/j.media.2024.103097. Online ahead of print.
ABSTRACT
Determining early-stage prognostic markers and stratifying patients for effective treatment are two key challenges for improving outcomes for melanoma patients. Previous studies have used tumour transcriptome data to stratify patients into immune subgroups, which were associated with differential melanoma specific survival and potential predictive biomarkers. However, acquiring transcriptome data is a time-consuming and costly process. Moreover, it is not routinely used in the current clinical workflow. Here, we attempt to overcome this by developing deep learning models to classify gigapixel haematoxylin and eosin (H&E) stained pathology slides, which are well established in clinical workflows, into these immune subgroups. We systematically assess six different multiple instance learning (MIL) frameworks, using five different image resolutions and three different feature extraction methods. We show that pathology-specific self-supervised models using 10x resolution patches generate superior representations for the classification of immune subtypes. In addition, in a primary melanoma dataset, we achieve a mean area under the receiver operating characteristic curve (AUC) of 0.80 for classifying histopathology images into 'high' or 'low immune' subgroups and a mean AUC of 0.82 in an independent TCGA melanoma dataset. Furthermore, we show that these models are able to stratify patients into 'high' and 'low immune' subgroups with significantly different melanoma specific survival outcomes (log rank test, P< 0.005). We anticipate that MIL methods will allow us to find new biomarkers of high importance, act as a tool for clinicians to infer the immune landscape of tumours and stratify patients, without needing to carry out additional expensive genetic tests.
PMID:38325154 | DOI:10.1016/j.media.2024.103097
Anal Bioanal Chem. 2024 Feb 7. doi: 10.1007/s00216-024-05178-z. Online ahead of print.
ABSTRACT
Mass spectrometry (MS) and MS imaging (MSI) are used extensively for both the spatial and bulk characterization of samples in lipidomics and proteomics workflows. These datasets are typically generated independently due to different requirements for sample preparation. However, modern omics technologies now provide higher sample throughput and deeper molecular coverage, which, in combination with more sophisticated bioinformatic and statistical pipelines, make generating multiomics data from a single sample a reality. In this workflow, we use spatial lipidomics data generated by matrix-assisted laser desorption/ionization MSI (MALDI-MSI) on prostate cancer (PCa) radical prostatectomy cores to guide the definition of tumor and benign tissue regions for laser capture microdissection (LCM) and bottom-up proteomics all on the same sample and using the same mass spectrometer. Accurate region of interest (ROI) mapping was facilitated by the SCiLS region mapper software and dissected regions were analyzed using a dia-PASEF workflow. A total of 5525 unique protein groups were identified from all dissected regions. Lysophosphatidylcholine acyltransferase 1 (LPCAT1), a lipid remodelling enzyme, was significantly enriched in the dissected regions of cancerous epithelium (CE) compared to benign epithelium (BE). The increased abundance of this protein was reflected in the lipidomics data with an increased ion intensity ratio for pairs of phosphatidylcholines (PC) and lysophosphatidylcholines (LPC) in CE compared to BE.
PMID:38324070 | DOI:10.1007/s00216-024-05178-z
DEN Open. 2024 Feb 9;4(1):e340. doi: 10.1002/deo2.340. eCollection 2024 Apr.
ABSTRACT
A 57-year-old woman with no significant medical history was referred after a colonoscopy for abdominal distension, which revealed a tumor in the lower rectum. Pre-operative colonoscopy showed the tumor was 12 mm in size, located from the anorectal junction to beyond the dentate line, and was diagnosed as high-grade intramucosal neoplasia or shallow submucosal invasive cancer. Endoscopic submucosal dissection was performed, and the lesion was resected en bloc. Pathological examination revealed moderately differentiated tubular adenocarcinoma with tubulovillous adenoma. The stratified squamous epithelium adjacent to the anal side of the lesion showed pagetoid spread of atypical cells with positive horizontal margins. We referred her to a surgeon for radical treatment. The mucosa surrounding the endoscopic submucosal dissection scar was normal on narrow-band imaging magnification. We marked its oral side endoscopically as the resected boundary. Transanal local excision was performed. The horizontal margins were positive because atypical cells had spread into the stratified squamous epithelium of the anorectal side of the lesion. The patient was followed on an outpatient basis. Sixty days postoperatively, residual tumor growth was observed. The second local resection was performed after mapping biopsy. All resection margins were negative, there was no lymphovascular invasion. One year after surgery, no recurrence was observed. Regarding endoscopic findings, there are no reports of endoscopic findings of the rectal mucosa, or the squamous epithelium of the anus of pagetoid spread. Here, we report a review of perianal Paget's Disease that resulted in difficulties in borderline diagnosis of pagetoid spread, resulting in multiple therapeutic interventions.
PMID:38343421 | PMC:PMC10858325 | DOI:10.1002/deo2.340
Anal Bioanal Chem. 2024 Feb 12. doi: 10.1007/s00216-024-05180-5. Online ahead of print.
ABSTRACT
Hydrogen sulfide (H2S) plays a significant role in the onset and progression of cancer. It has led to increased interest in its potential as a diagnostic tool owing to its overexpression in cancer. However, research into the anti-cancer activity of H2S, particularly its ability to promote apoptosis, is hindered by the lack of effective detection tools. To gain a comprehensive understanding of the targeted efficacy of H2S in promoting cancer cell apoptosis, we designed and synthesized a self-immolative near-infrared fluorescent diagnostic probe, named YH-NO2. The activation of this self-immolative reaction is dependent on the presence of nitroreductase (NTR) overexpressed in tumor cells. The design of YH-NO2 involves releasing fluorophores through the activated self-immolative reaction for detection, while simultaneously releasing H2S-loaded self-immolative spacers to promote cancer cell apoptosis. Consequently, YH-NO2 achieves a seamless integration of recognizing and promoting cancer cell apoptosis through its self-immolative structure. This dual function allows YH-NO2 to recognize NTR activity in cells under varying hypoxia levels and differentiate between normal cells and cancer cells using imaging technology. Notably, YH-NO2 exhibits remarkable stability in cellular environments, providing controlled and selective H2S release, thereby targeting the elimination of cancer cells through the promotion of apoptosis. Furthermore, in vivo experiments have demonstrated that YH-NO2 can accurately identify tumor tissue and effectively reduce its size by utilizing its apoptosis-promoting properties. These findings not only provide further evidence for the anti-cancer activity of H2S but also offer valuable tools for understanding the complex relationship between H2S and cancer.
PMID:38342788 | DOI:10.1007/s00216-024-05180-5
Clin Oncol (R Coll Radiol). 2024 Jan 29:S0936-6555(24)00044-X. doi: 10.1016/j.clon.2024.01.015. Online ahead of print.
ABSTRACT
AIMS: The PCAR study aimed to assess the efficacy and safety of preoperative transcatheter rectal arterial chemoembolisation (TRACE) in patients with locally advanced rectal cancer (LARC).
MATERIALS AND METHODS: This was a single-centre, prospective, phase II trial conducted in China. Eligible patients were adults aged 18 years and older with histologically confirmed stage II or III rectal carcinoma and an Eastern Cooperative Oncology Group performance status of 0-1. Patients received TRACE with oxaliplatin, followed by radiotherapy with a cumulative dose of 45 Gy (1.8 Gy/time/day, five times a week for 5 weeks) and received oral S1 capsules twice daily (7 days a week for 4 weeks). Patients underwent total mesorectal excision 4-8 weeks after the completion of chemoradiotherapy, followed by mFOLFOX6 or CAPOX regimens for 4-6 months. The hypothesis of this study was that adding TRACE to preoperative neoadjuvant chemoradiotherapy would improve tumour regression and prognosis. The primary end point was the pathological complete response rate; secondary end points included the major pathological response rate, anal preservation rate, 5-year disease-free survival (DFS), 5-year overall survival and treatment-related adverse events.
RESULTS: In total, 111 LARC patients received TRACE and subsequent scheduled treatment plans. The pathological complete response and major pathological response rates were 20.72% and 48.65%, respectively. The 5-year DFS and 5-year overall survival were 61.89% (95% confidence interval 51.45-74.45) and 74.80% (95% confidence interval 65.05-86.01), respectively. Grade 3-4 toxicities were reported in 29 patients (26.13%). The postoperative complication rate was 21.62%, without serious surgical complications. Multivariate Cox regression analysis showed that ypN stage (hazard ratio = 4.242, 95% confidence interval 2.101-8.564, P = 0.00017) and perineural invasion (hazard ratio = 2.319, 95% confidence interval 1.058-5.084, P = 0.0487) were independent risk factors associated with DFS, whereas ypN stage (hazard ratio = 3.164, 95% confidence interval 1.347-7.432, P = 0.0101), perineural invasion (hazard ratio = 4.118, 95% confidence interval 1.664-10.188, P = 0.0134) and serum carbohydrate antigen 199 (CA199; hazard ratio = 4.142, 95% confidence interval 1.290-13.306, P = 0.0344) were independent predictors for overall survival.
CONCLUSION: The current study provides evidence that adding TRACE to neoadjuvant chemoradiotherapy can improve the pathological remission rate in LARC patients with acceptable toxicity. Given its promising effectiveness and safe profile, incorporating TRACE into the standard treatment strategy for patients with LARC should be considered.
PMID:38342657 | DOI:10.1016/j.clon.2024.01.015
Anal Chem. 2024 Feb 27;96(8):3454-3461. doi: 10.1021/acs.analchem.3c04809. Epub 2024 Feb 15.
ABSTRACT
Estrogen receptor α (ERα) is an important biomarker in breast cancer diagnosis and treatment. Sensitive and accurate detection of ERα protein expression is crucial in guiding selection of an appropriate therapeutic strategy to improve the effectiveness and prognosis of breast cancer treatment. Herein, we report a liquid-gated graphene field-effect transistor (FET) biosensor that enables rapid, sensitive, and label-free detection of the ERα protein by employing a novel drug molecule as a capture probe. The drug molecule was synthesized and subsequently immobilized onto the sensing surface of the fabricated graphene FET, which was able to distinguish the ERα-positive from the ERα-negative protein. The developed sensor not only demonstrated a low detection limit (LOD: 2.62 fM) but also achieved a fast response to ERα protein samples within 30 min. Moreover, depending on the relationship between the change of dirac point and the ERα protein concentrations, the dissociation constant (Kd) was estimated to be 7.35 ± 0.06 pM, indicating that the drug probe-modified graphene FET had a good affinity with ERα protein. The nanosensor was able to analyze ERα proteins from 36 cell samples lysates. These results show that the graphene FET sensor was able to differentiate between ERα-positive and ERα-negative cells, indicating a promising biosensor for the ultrasensitive and rapid detection of ERα protein without antibody labeling.
PMID:38359782 | DOI:10.1021/acs.analchem.3c04809
J Pharm Biomed Anal. 2024 Feb 7;242:116011. doi: 10.1016/j.jpba.2024.116011. Online ahead of print.
ABSTRACT
Liver cancer and gastric cancer have extremely high morbidity and mortality rates worldwide. It is well known that an increase or decrease in trace metals may be associated with the formation and development of a variety of diseases, including cancer. Therefore, this study aimed to evaluate the contents of aluminium (Al), arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), selenium (Se), and zinc (Zn) in cancerous liver and gastric tissues, compared to adjacent healthy tissues, and to investigate the relationship between trace metals and cancer progression. During surgery, multiple samples were taken from the cancerous and adjacent healthy tissues of patients with liver and gastric cancer, and trace metal levels within these samples were analysed using inductively coupled plasma mass spectrometry (ICP-MS). We found that concentrations of As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Se, and Zn in tissues from patients with liver cancer were significantly lower than those in healthy controls (P < 0.05). Similarly, patients with gastric cancer also showed lower levels of Cd, Co, Cr, Mn, Ni, and Zn-but higher levels of Cu and Se-compared to the controls (P < 0.05). In addition, patients with liver and gastric cancers who had poorly differentiated tumours and positive lymph node metastases showed lower levels of trace metals (P < 0.05), although no significant changes in their concentrations were observed to correlate with sex, age, or body mass index (BMI). Logistic regression, principal component analysis (PCA), Bayesian kernel regression (BKMR), weighted quantile sum (WQS) regression, and quantile-based g computing (qgcomp) models were used to analyse the relationships between trace metal concentrations in liver and gastric cancer tissues and the progression of these cancers. We found that single or mixed trace metal levels were negatively associated with poor differentiation and lymph node metastasis in both liver and gastric cancer, and the posterior inclusion probability (PIP) of each metal showed that Cd contributed the most to poor differentiation and lymph node metastasis in both liver and gastric cancer (all PIP = 1.000). These data help to clarify the relationship between changes in trace metal levels in cancerous liver and gastric tissues and the progression of these cancers. Further research is warranted, however, to fully elucidate the mechanisms and causations underlying these findings.
PMID:38359492 | DOI:10.1016/j.jpba.2024.116011
Anal Chem. 2024 Feb 15. doi: 10.1021/acs.analchem.3c05233. Online ahead of print.
ABSTRACT
We present an integrated, open-source device for parahydrogen-based hyperpolarization processes in the microtesla field regime with a cost of components of less than $7000. The device is designed to produce a batch of 13C and 15N hyperpolarized (HP) compounds via hydrogenative or non-hydrogenative parahydrogen-induced polarization methods that employ microtesla magnetic fields for efficient polarization transfer of parahydrogen-derived spin order to X-nuclei (e.g., 13C and 15N). The apparatus employs a layered structure (reminiscent of a Russian doll "Matryoshka") that includes a nonmagnetic variable-temperature sample chamber, a microtesla magnetic field coil (operating in the range of 0.02-75 microtesla), a three-layered mu-metal shield (to attenuate the ambient magnetic field), and a magnetic shield degaussing coil placed in the overall device enclosure. The gas-handling manifold allows for parahydrogen-gas flow and pressure control (up to 9.2 bar of total parahydrogen pressure). The sample temperature can be varied either using a water bath or a PID-controlled heat exchanger in the range from -12 to 80 °C. This benchtop device measures 62 cm (length) × 47 cm (width) × 47 cm (height), weighs 30 kg, and requires only connections to a high-pressure parahydrogen gas supply and a single 110/220 VAC power source. The utility of the device has been demonstrated using an example of parahydrogen pairwise addition to form HP ethyl [1-13C]acetate (P13C = 7%, [c] = 1 M). Moreover, the Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) technique was employed to demonstrate efficient hyperpolarization of 13C and 15N spins in a wide range of biologically relevant molecules, including [1-13C]pyruvate (P13C = 14%, [c] = 27 mM), [1-13C]-α-ketoglutarate (P13C = 17%), [1-13C]ketoisocaproate (P13C = 18%), [15N3]metronidazole (P15N = 13%, [c] = 20 mM), and others. While the vast majority of the utility studies have been performed in standard 5 mm NMR tubes, the sample chamber of the device can accommodate a wide range of sample container sizes and geometries of up to 1 L sample volume. The device establishes an integrated, simple, inexpensive, and versatile equipment gateway needed to facilitate parahydrogen-based hyperpolarization experiments ranging from basic science to preclinical applications; indeed, detailed technical drawings and a bill of materials are provided to support the ready translation of this design to other laboratories.
PMID:38358916 | DOI:10.1021/acs.analchem.3c05233
Anal Chem. 2024 Feb 27;96(8):3462-3469. doi: 10.1021/acs.analchem.3c05064. Epub 2024 Feb 15.
ABSTRACT
It remains a challenge to use a single probe to simultaneously detect extracellular pH fluctuations and specifically recognize cancer cells for precise drug delivery. Here, we engineered a tetrahedral framework nucleic acid-based logic nanoprobe (isgc8-tFNA) on live cell membranes for simultaneously monitoring extracellular pH and targeted drug delivery. Isgc8-tFNA was anchored stably on the cell surface through three cholesterol molecules inserting into the bilayer of the cell membrane. Once responding to the acidic tumor microenvironment, isgc8-tFNA formed an i-motif structure, leading to turn-on FRET signals for monitoring changes of extracellular pH. The nanoprobe exhibited a narrow pH-response window and excellent reversibility. Moreover, the nanoprobe could execute logic identification on the cell surface for precise drug delivery. Only if both in the acidic microenvironment and aptamer-targeting marker are present on the cell surface, the sgc8-ASO-chimera strand, carrying an antisense oligonucleotide drug, was released from the nanoprobe and entered into targeted cancer cells for gene silence. Additionally, the in situ drug release facilitated the uptake of drugs mediated by the interaction between sgc8 aptamer and membrane proteins, resulting in enhanced inhibition of cancer cell migration and proliferation. This logic nanoprobe will provide inspiration for designing smart devices for diagnosis of pH-related diseases and targeted drug delivery.
PMID:38358853 | DOI:10.1021/acs.analchem.3c05064
Anal Chem. 2024 Feb 27;96(8):3517-3524. doi: 10.1021/acs.analchem.3c05336. Epub 2024 Feb 15.
ABSTRACT
The digital immunoassay is a highly sensitive detection technique based on single-molecule counting and is widely used in the ultrasensitive detection of biomarkers. Herein, we developed a fluorescent microsphere-based digital immunoassay (FMDIA) by employing fluorescent microspheres as both the carriers for immunoreaction and fluorescent reports for imaging. In this approach, the target protein in the sample was captured by fluorescent microspheres to form a biotin-labeled sandwich immunocomplex, and then, the fluorescent microspheres containing the target protein molecules were captured by adding streptavidin-coated magnetic beads (SA-MBs). By counting the proportion of fluorescence-positive magnetic beads, the concentration of the target protein can be precisely quantified. As a proof of concept, α fetoprotein (AFP) and human interleukin-6 (IL-6) were used to assess the analytical performance of the proposed FMDIA, and limit of detection (LOD) values of 21 pg/mL (0.30 pM) and 0.19 pg/mL (7.3 fM) were achieved, respectively. The results of AFP detection in serum samples of patients and healthy people were consistent with the reference values given by the hospital. Furthermore, by adding fluorescent microspheres of various colors for encoding, the proposed FMDIA can easily realize the simultaneous detection of multiple proteins without the need to introduce multiple modified magnetic beads. This multiplex protein detection strategy, in which the reactions are first carried out on the fluorescent microspheres and then magnetic beads are used to capture the fluorescent reporters containing the target molecules, provides a new idea for digital assays.
PMID:38358834 | DOI:10.1021/acs.analchem.3c05336
Funct Integr Genomics. 2024 Feb 15;24(1):30. doi: 10.1007/s10142-024-01311-4.
ABSTRACT
LTBP1 is closely related to TGF-β1 function as an essential component, which was unclear in gastric cancer (GC). Harbin Medical University (HMU)-GC cohort and The Cancer Genome Atlas (TCGA) dataset were combined to form a training cohort to calculate the connection between LTBP1 mRNA expression, prognosis and clinicopathological features. The training cohort was also used to verify the biological function of LTBP1 and its relationship with immune microenvironment and chemosensitivity. In the tissue microarrays (TMAs), immunohistochemical (IHC) staining was performed to observe LTBP1 protein expression. The correlation between LTBP1 protein expression level and prognosis was also analyzed, and a nomogram model was constructed. Western blotting (WB) was used in cell lines to assess LTBP1 expression. Transwell assays and CCK-8 were employed to assess LTBP1's biological roles. In compared to normal gastric tissues, LTBP1 expression was upregulated in GC tissues, and high expression was linked to a bad prognosis for GC patients. Based on a gene enrichment analysis, LTBP1 was primarily enriched in the TGF-β and EMT signaling pathways. Furthermore, high expression of LTBP1 in the tumor microenvironment was positively correlated with an immunosuppressive response. We also found that LTBP1 expression (p = 0.006) and metastatic lymph node ratio (p = 0.044) were independent prognostic risk factors for GC patients. The prognostic model combining LTBP1 expression and lymph node metastasis ratio reliably predicted the prognosis of GC patients. In vitro proliferation and invasion of MKN-45 GC cells were inhibited and their viability was decreased by LTBP1 knockout. LTBP1 plays an essential role in the development and progression of GC, and is a potential prognostic biomarker and therapeutic target for GC.
PMID:38358412 | DOI:10.1007/s10142-024-01311-4
Ann Afr Med. 2023 Oct-Dec;22(4):497-500. doi: 10.4103/aam.aam_177_22.
ABSTRACT
BACKGROUND AND OBJECTIVE: Restorative proctocolectomy with ileal pouch-anal anastomosis (RPC-IPAA) is usually preferred surgical treatment for ulcerative colitis (UC). Although treated primarily medically, some refractory and complicated cases of UC may require surgical intervention. It eliminates chronic UC and the risk of colonic cancer. This research aims to study the risk factors associated with the development of postoperative complications.
METHODOLOGY: For this cohort study, we included all the patients who underwent RPC-IPAA in the Department of Gastroenterology, Sheth Vadilal Sarabhai General Hospital, Ahmedabad, over 6 years. Data of the patients were obtained retrospectively from the medical records. We collected the data and analyzed using appropriate statistical tests to look for preoperative patient variables associated with late complications. Late complications were defined as those developed after 1 month.
RESULTS: Out of 32 patients, 19 were male and 13 were female, with an average age of 32.3 years at the time of operation. Thirteen patients developed complications such as pouchitis (n = 6), incisional hernia (n = 3), bowel obstruction (n = 2), pouch leakage (n = 1), and erectile dysfunction (n = 1). We found serum albumin <3 mg/dl and pancolitis associated with more postoperative late complications with P = 0.007 and 0.04, respectively, which is statistically significant.
CONCLUSION: This study demonstrates that low preoperative albumin level and pancolitis are risk factors for late complications of IPAA. Preoperative nutritional support, especially albumin, could reduce late complications.
PMID:38358151 | PMC:PMC10775946 | DOI:10.4103/aam.aam_177_22
Anal Chem. 2024 Feb 15. doi: 10.1021/acs.analchem.3c05766. Online ahead of print.
ABSTRACT
Breast cancer remains the most frequently diagnosed cancer globally, and the metastasis of this malignancy is the primary cause of mortality in breast cancer patients. Hence, prompt diagnosis and timely detection of metastatic breast cancer are critical for effective therapeutic intervention. Both progression and metastasis of this malignancy are closely associated with aberrant expression of specific microRNAs (miRNAs) and enzymes. To facilitate breast cancer diagnosis and concomitant identification of metastatic breast cancer, we have engineered an innovative electrochemiluminescence (ECL)-based sensing platform integrated with enzyme-free DNA amplification circuits for dual functionality. Specifically, microRNA-21 (miR-21) is employed as a biomarker for breast cancer, and miR-21 induces the quenching of the ECL signal from luminophores via a strategically designed catalytic three-hairpin assembly (CTHA) circuit. Subsequently, miR-105 levels are measured via toehold-mediated strand displacement reactions (TSDR). Here, miR-105 restores the initially quenched ECL signal, enabling the assessment of the metastatic propensity. Our experimental data demonstrate that the devised ECL biosensor offers broad linear detection ranges and low detection limits for both miR-21 and miR-105. Importantly, our novel platform was also successfully validated by using cellular and serum samples. This biosensor not only discriminates breast cancer cell lines MCF-7 and MDA-MB-231 from nonbreast cancer cells like HepG2, TPC-1, and HeLa, but it also distinguishes between malignant MCF-7 and metastatic MDA-MB-231 cells. Consequently, our novel approach holds significant promise for clinical applications and precise cancer screening.
PMID:38357821 | DOI:10.1021/acs.analchem.3c05766
Anal Chem. 2024 Feb 14. doi: 10.1021/acs.analchem.3c05782. Online ahead of print.
ABSTRACT
Accurate measurement of cancer markers in urine is a convenient method for tumor monitoring. However, the concentration of cancer markers in urine is so low that it is difficult to achieve their measurement. Photoelectrochemical (PEC) sensors are a promising technology to realize the detection of trace cancer markers due to their high sensitivity. Currently, the interference of nonspecific biomolecules in urine is the main reason affecting the high sensitivity and selectivity of PEC sensors in detecting cancer markers. In this work, a strategy of oxygen vacancy (OV) modulation is proposed to construct a fouling-resistant PEC aptamer sensing platform for the detection of α-fetoprotein (AFP), a liver cancer marker. The introduction of OVs induces the formation of intermediate localized states in the photoelectric material, which not only facilitates the separation of photogenerated carriers but also leads to the redshift of the light absorption edge. More importantly, OVs with positive electrical properties can be employed to modify the antifouling layer (C-PEG) with negatively charged groups through an electrostatic interaction. The synergistic effect of OVs, antifouling layer, and aptamer resulted in a TiO2/OVs/C-PEG-based PEC sensor achieves a wide linear range from 1 pg/mL to 100 ng/mL and a low detection limit of 0.3 pg/mL for AFP. In addition, the sensor successfully realized the determination of AFP in urine samples and accurately differentiated between normal people and liver cancer patients in the early and advanced stages. This project is of great significance in advancing the application of photoelectrochemical bioanalytical technology to achieve the detection of cancer markers in urine by investigating the construction of an OVs-regulated fouling-resistant sensing interface.
PMID:38356334 | DOI:10.1021/acs.analchem.3c05782
Anal Chim Acta. 2024 Mar 22;1295:342273. doi: 10.1016/j.aca.2024.342273. Epub 2024 Jan 27.
ABSTRACT
Several microRNAs (miRNAs) are expressed at lower levels in specific tumors, e.g., miR-let-7a in non-small cell lung cancer (NSCLC). This makes it challenging to analyze their lower abundance versus specifically elevated miRNAs. Here, we describe a novel fluorescent biosensor for the highly selective and sensitive detection of miR-let-7a constructed by combining miRNA screening assisted by a duplex-specific nuclease (DSN) with CRISPR-Cas12a system signal amplification. We meticulously designed a mismatch in the first three to four bases at the 5'-end of the capture DNA to improve the signal-to-noise ratio of the CRISPR-Cas12a system. Within this "DSN-mismatched CRISPR" fluorescence strategy, miR-let-7a was accurately screened by DSN-assisted cleavage, and the mismatched capture DNA unbound to target miRNA could trigger the CRISPR-Cas12a system to produce a mass of trans-cleave fluorescence signals. This "turn-off" approach was suitable for detecting decreased levels of miRNAs. This approach can not only discriminate the single-base mismatched let-7 family but also reach a limit of detection at 64.17 fM as well as be quantified from 100 fM to 500 pM. The miR-let-7a levels were then measured in clinical serum samples from healthy volunteers and patients with NSCLC. This study holds promise for the development of a universal under-expressed miRNA assay for early diagnosis and treatment of cancers.
PMID:38355234 | DOI:10.1016/j.aca.2024.342273
J Pharm Biomed Anal. 2024 Feb 2;242:116001. doi: 10.1016/j.jpba.2024.116001. Online ahead of print.
ABSTRACT
Saikosaponin D (SsD), a natural triterpenoid saponin compound, exhibits notable potential in suppressing tumor growth and inhibiting metastasis, particularly in breast cancer. However, its underlying mechanism of action for SsD remains unclear. In this study, a combination strategy to reveal the metabolism modulation of SsD on breast cancer was performed by integration of histopathological assessments and untargeted metabolomics analysis. Pathological evaluation of the efficacy of SsD from a visual and intuitive perspective. Accordingly, a non-targeted metabolomics study was used to investigate the pharmacological efficacy using a set of serum samples from mice before and after (0-30 days) modulated with SsD based on ultra-high performance liquid chromatography tandem orbitrap mass spectrometry to discover metabolite biomarkers for finding the key metabolic mechanism in a molecular perspective. As a result, 20 metabolites were selected as potential biomarkers for SsD efficacy evaluation with high sensitivity and specificity. These metabolites changes were involved in sphingolipid metabolism, glycerophospholipid metabolism, phenylalanine and tryptophan metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis pathways, suggesting that SsD exerted anti-breast cancer effects through the regulation of the underlying metabolism. In conclusion, we developed a new analysis strategy that effectively discovers tumor-progressing related metabolite biomarkers in serum for pharmacological efficacy evaluation.
PMID:38354536 | DOI:10.1016/j.jpba.2024.116001
Colorectal Dis. 2024 Feb 14. doi: 10.1111/codi.16878. Online ahead of print.
NO ABSTRACT
PMID:38353474 | DOI:10.1111/codi.16878
J Gastrointest Surg. 2024 Jan;28(1):57-63. doi: 10.1016/j.gassur.2023.11.006.
ABSTRACT
BACKGROUND: High-risk patients undergoing abdominoperineal resection and pelvic exenteration may benefit from immediate flap reconstruction. However, there is currently no consensus on the ideal flap choice or patient for whom this is necessary. This study aimed to evaluate the long-term outcomes of using pedicled gracilis flaps for pelvic reconstruction and to analyze predictors of postoperative complications.
METHODS: This was a retrospective review of a single reconstructive surgeon's cases between January 2012 and June 2021 identifying patients who underwent perineal reconstruction secondary to oncologic resection. Preoperative and outcome variables were collected and analyzed to determine the risk of developing minor and major wound complications.
RESULTS: A total of 101 patients were included in the study with most patients (n = 88) undergoing unilateral gracilis flap reconstruction after oncologic resection. The mean follow-up period was 75 months. Of 101 patients, 8 (7.9%) developed early major complications, and an additional 13 (12.9%) developed late major complications. Minor complications developed in 33 patients (32.7%) with most cases being minor wound breakdown requiring local wound care. Most patients (n = 92, 91.1%) did not develop donor site complications. Anal cancer was significantly associated with early major complications, whereas younger age and elevated body mass index were significant predictors of developing minor wound complications.
CONCLUSIONS: This study builds on our previous work that demonstrated the long-term success rate of gracilis flap reconstruction after large pelvic oncologic resections. A few patients developed donor site complications, and perineal complications were usually easily managed with local wound care, thus making the gracilis flap an attractive alternative to abdominal-based flaps.
PMID:38353075 | DOI:10.1016/j.gassur.2023.11.006
J Pharm Anal. 2024 Jan;14(1):1-15. doi: 10.1016/j.jpha.2023.08.019. Epub 2023 Sep 1.
ABSTRACT
Esophageal cancer is an upper gastrointestinal malignancy with a bleak prognosis. It is still being explored in depth due to its complex molecular mechanisms of occurrence and development. Lipids play a crucial role in cells by participating in energy supply, biofilm formation, and signal transduction processes, and lipid metabolic reprogramming also constitutes a significant characteristic of malignant tumors. More and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning, progress, and treatment resistance. The inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid metabolism. Therefore, we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer, and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer, as well as its significance in exploring potential therapeutic targets and biomarkers.
PMID:38352954 | PMC:PMC10859535 | DOI:10.1016/j.jpha.2023.08.019
J Pharm Anal. 2024 Jan;14(1):128-139. doi: 10.1016/j.jpha.2023.08.021. Epub 2023 Aug 31.
ABSTRACT
Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.
PMID:38352953 | PMC:PMC10859532 | DOI:10.1016/j.jpha.2023.08.021
Anal Chem. 2024 Feb 14. doi: 10.1021/acs.analchem.3c04717. Online ahead of print.
ABSTRACT
The subtypes of hematological malignancies (HM) with minimal molecular profile differences display an extremely heterogeneous clinical course and a discrepant response to certain treatment regimens. Profiling the surface protein markers offers a potent solution for precision diagnosis of HM by differentiating among the subtypes of cancer cells. Herein, we report the use of Cell-SELEX technology to generate a panel of high-affinity aptamer probes that are able to discriminate subtle differences among surface protein profiles between different HM cells. Experimental results show that these aptamers with apparent dissociation constants (Kd) below 10 nM display a unique recognition pattern on different HM subtypes. By combining a machine learning model on the basis of partial least-squares discriminant analysis, 100% accuracy was achieved for the classification of different HM cells. Furthermore, we preliminarily validated the effectiveness of the aptamer-based multiparameter analysis strategy from a clinical perspective by accurately classifying complex clinical samples, thus providing a promising molecular tool for precise HM phenotyping.
PMID:38351845 | DOI:10.1021/acs.analchem.3c04717
J Pharm Biomed Anal. 2024 Jan 15;242:115976. doi: 10.1016/j.jpba.2024.115976. Online ahead of print.
ABSTRACT
Lung cancer is the most common malignancy worldwide. Early diagnosis helps to reduce mortality and improve survival. Aptamers are widely used in cancer screening because of their high specificity, good stability and low cost. In this study, using the specific aptamer of lung cancer serum, the sandwich method colloidal gold test strip was prepared by isothermal amplification technique and the principle of nucleic acid hybridisation for the early diagnosis of lung cancer. The results showed that the test strip was positive in 8 patients with lung cancer, which was consistent with the actual cases. The test strip can accurately identify lung cancer patients. The concentration range of nucleic acid detection is 1 × 10-4 - 7 × 10-4 mol/L, and the detection limit is 0.67 mM. The test strip detection method has low cost and simple operation, and provides a reference for the development of home portable tumor early detection.
PMID:38350371 | DOI:10.1016/j.jpba.2024.115976
Anal Chem. 2024 Feb 13. doi: 10.1021/acs.analchem.3c05474. Online ahead of print.
ABSTRACT
This work reports the first electrochemical bioplatforms developed for the determination of the total contents of either target miRNA or methylated target miRNA. The bioplatforms are based on the hybridization of the target miRNA with a synthetic biotinylated DNA probe, the capture of the formed DNA/miRNA heterohybrids on the surface of magnetic microcarriers, and their recognition with an antibody selective to these heterohybrids or to the N6-methyladenosine (m6A) epimark. The determination of the total or methylated target miRNA was accomplished by labeling such secondary antibodies with the horseradish peroxidase (HRP) enzyme. In both cases, amperometric transduction was performed on the surface of disposable electrodes after capturing the resulting HRP-tagged magnetic bioconjugates. Because of their increasing relevance in colorectal cancer (CRC) diagnosis and prognosis, miRNA let-7a and m6A methylation were selected. The proposed electrochemical bioplatforms showed attractive analytical and operational characteristics for the determination of the total and m6A-methylated target miRNA in less than 75 min. These bioplatforms, innovative in design and application, were applied to the analysis of total RNA samples extracted from cultured cancer cells with different metastatic profiles and from paired healthy and tumor tissues of patients diagnosed with CRC at different stages. The obtained results demonstrated, for the first time using electrochemical platforms, the potential of interrogating the target miRNA methylation level to discriminate the metastatic capacities of cancer cells and to identify tumor tissues and, in a pioneering way, the potential of the m6A methylation in miRNA let-7a to serve as a prognostic biomarker for CRC.
PMID:38348822 | DOI:10.1021/acs.analchem.3c05474
Front Oncol. 2024 Jan 29;13:1252253. doi: 10.3389/fonc.2023.1252253. eCollection 2023.
ABSTRACT
BACKGROUND: Natural orifice specimen extraction surgery (NOSES) has been widely applied to the treatment of colorectal cancer. This study aim to investigate the short-term and survival outcomes of transrectal specimen extraction after laparoscopic right hemicolectomy.
METHODS: From January 2016 to December 2021, a total of 166 consecutive patients with right colon cancer who underwent laparoscopic right hemicolectomy in Cancer Hospital of Chinese Academy of Medical Sciences and Beijing Hospital were identified. Baseline data, perioperative parameters, anal function, inflammatory indicators and survival outcomes were collected and compared.
RESULTS: Totally, 24 patients who underwent transrectal NOSE were matched with 24 patients who received conventional laparoscopic surgery (LAP). Patients in NOSES group had a significantly lower incidence of incision infection (0 vs 20.8%, P=0.048), faster recovery of gastrointestinal function (2.1 vs 3,1 days, P=0.032) compared with those in LAP group. In addition, patients in the NOSE group experienced significantly less postoperative pain on POD1 (2.3 vs 4.4, P<0.001), POD3 (2.1 vs 3.9, P<0.001), and POD5 (1.7 vs 2.8, P=0.011). Regarding to anal function 6 months after surgery, no significant difference was observed in Wexner incontinence scale (9.8 vs 9.5, P=0.559) between the two groups. In terms of indicators of the inflammatory response, there were no significant differences in body temperature, neutrophils, and PCT levels between the two groups. However, CRP levels in the NOSES group on POD 3 (6.9 vs 5.1 mg/L, P=0.016) and POD 5 (3.8 vs 2.6 mg/L, P=0.027) were significantly higher than in the LAP group. With regarded to survival outcomes, patients in the NOSES group were similar to those in the LAP group for 3-year OS (100% vs 91.2%, P=0.949), 3-year DFS (86.2% vs 84.8%, P=0.949), and 3-year LRFS (94.2% vs 88.7%, P=0.549).
CONCLUSION: For total laparoscopic right hemicolectomy, transrectal NOSE is effective and safe, and associated with lower incidence of wound infection, less pain, faster recovery, and similar survival outcomes compared to conventional laparoscopic surgery.
PMID:38348119 | PMC:PMC10860336 | DOI:10.3389/fonc.2023.1252253
Anal Chem. 2024 Feb 12. doi: 10.1021/acs.analchem.3c05337. Online ahead of print.
ABSTRACT
Anaplastic lymphoma kinase (ALK) rearrangements have been identified as key oncogenic drivers of a subset of nonsmall cell lung cancer (NSCLC). The final chimeric protein of the fusion gene can be constitutively activated, which accounts for the growth and proliferation of ALK-rearranged tumors and thus strongly associates with cancer invasion and metastasis. Diagnostic tools enabling the visualization of ALK activity in a structure-function-based approach are highly desirable to determine ALK status and guide ALK tyrosine kinase inhibitor (ALK-TKI) treatment making. Here, we describe the design, synthesis, and application of a new environment-sensitive fluorescent probe HX16 by introducing an environment-sensitive fluorophore 4-sulfonamidebenzoxadiazole to visualize ALK activity in living cancer cells and tumor tissue slices (mouse model and human biopsy sample). HX16 is a multifunctional chemical tool based on the pharmacophore of ALK-TKI (ceritinib) and can specifically target the kinase domain of ALK with a high sensitivity. Using flow cytometry and confocal microscopy, HX16 enables visualization of ALK activity in various cancer cells with distinct ALK fusion genes, as well as xenograft mouse models. Importantly, HX16 was also applied to visualize ALK activity in a tumor biopsy from a NSCLC patient with ALK-echinoderm microtubule-associated protein-like-4 fusion gene for prediction of ALK-TKI sensitivity. These results demonstrate that strategically designed ALK-TKI-based probe allows the assessment of ALK activity in tumor tissues and hold promise as a useful diagnostic tool in predicting ALK-TKI therapy response.
PMID:38345335 | DOI:10.1021/acs.analchem.3c05337
Anal Methods. 2024 Feb 12. doi: 10.1039/d3ay02268d. Online ahead of print.
ABSTRACT
Exosomal microRNA (miRNA) is a potential biomarker for cancer diagnosis, metastasis, and treatment. In situ detection of exosomal miRNA is an attractive option due to its simplicity and high accuracy. However, in situ exosomal miRNA detection has encountered challenges because of the low target abundance of targets and limited probe permeability. Herein, a label-free and activatable biosensor was developed for in situ exosomal miRNA assays by utilizing hairpin-shaped nucleic acid probes and DNA-hosted silver nanoclusters (DNA-AgNCs). The probe is directly internalized into the exosomes, and then hybridized with the target miRNA-21. Subsequently, the DNA-AgNCs are pulled closer to the G-rich sequence, ultimately leading to in situ red fluorescence activation. The biosensor not only can detect exosomal miRNA-21 but also distinguish cancer cells from normal cells. Under optimal reaction conditions, the detection limit (LOD) of exosomal miRNA-21 is 1.53 × 107 particles per mL. Furthermore, DNA-AgNCs are used as label-free signal elements for in situ detection of exosomal miRNAs for the first time, expanding the application of nanomaterials in this field. This strategy does not require tedious RNA extraction steps and expensive instruments, and may develop into a non-invasive diagnostic tool for ovarian cancer.
PMID:38344752 | DOI:10.1039/d3ay02268d
Case Rep Oncol. 2024 Feb 9;17(1):225-231. doi: 10.1159/000535956. eCollection 2024 Jan-Dec.
ABSTRACT
INTRODUCTION: Anal canal melanoma is a rare form of both anal cancer and skin melanoma, representing 1% of all anal cancers. Diagnosis is often made at an advanced disease stage. Because of late diagnosis and aggressive clinical course, anal canal melanoma has a very poor prognosis.
CASE PRESENTATION: We present the case of a 61-year-old female with anal canal melanoma and lung, liver, pelvic and central nervous system (CNS) metastasis, BRAF V600E mutated. Combined BRAF/MEK inhibition and CNS radiation therapy were able to achieve excellent local and distant disease control.
CONCLUSION: Anal canal melanoma is a rare and aggressive form of melanoma. Multidisciplinary management in experienced centers is mandatory for good clinical outcomes.
PMID:38344421 | PMC:PMC10857807 | DOI:10.1159/000535956
Med Image Anal. 2023 Dec 17;93:103063. doi: 10.1016/j.media.2023.103063. Online ahead of print.
ABSTRACT
The frequency of basal cell carcinoma (BCC) cases is putting an increasing strain on dermatopathologists. BCC is the most common type of skin cancer, and its incidence is increasing rapidly worldwide. AI can play a significant role in reducing the time and effort required for BCC diagnostics and thus improve the overall efficiency of the process. To train such an AI system in a fully-supervised fashion however, would require a large amount of pixel-level annotation by already strained dermatopathologists. Therefore, in this study, our primary objective was to develop a weakly-supervised for the identification of basal cell carcinoma (BCC) and the stratification of BCC into low-risk and high-risk categories within histopathology whole-slide images (WSI). We compared Clustering-constrained Attention Multiple instance learning (CLAM) with StreamingCLAM and hypothesized that the latter would be the superior approach. A total of 5147 images were used to train and validate the models, which were subsequently tested on an internal set of 949 images and an external set of 183 images. The labels for training were automatically extracted from free-text pathology reports using a rule-based approach. All data has been made available through the COBRA dataset. The results showed that both the CLAM and StreamingCLAM models achieved high performance for the detection of BCC, with an area under the ROC curve (AUC) of 0.994 and 0.997, respectively, on the internal test set and 0.983 and 0.993 on the external dataset. Furthermore, the models performed well on risk stratification, with AUC values of 0.912 and 0.931, respectively, on the internal set, and 0.851 and 0.883 on the external set. In every single metric the StreamingCLAM model outperformed the CLAM model or is on par. The performance of both models was comparable to that of two pathologists who scored 240 BCC positive slides. Additionally, in the public test set, StreamingCLAM demonstrated a comparable AUC of 0.958, markedly superior to CLAM's 0.803. This difference was statistically significant and emphasized the strength and better adaptability of the StreamingCLAM approach.
PMID:38194735 | DOI:10.1016/j.media.2023.103063
Anal Chem. 2024 Jan 9. doi: 10.1021/acs.analchem.3c03740. Online ahead of print.
ABSTRACT
Dielectrophoresis (DEP) utilizes a spatially varying nonuniform electrical field to induce forces on suspended polarizable soft matter including particles and cells. Such nonuniformities are conventionally created using 2D or 3D micrometer-scale electrode arrays. Alternatively, insulator-based dielectrophoresis (iDEP) uses small micrometer-scale insulating structures to spatially distort and generate regions of localized field gradients to selectively trap, isolate, and concentrate bioparticles, including bacteria, viruses, red blood cells, and cancer cells from a suspending electrolyte solution. Despite significant advances in the microfabrication technology, the commercial adoption of DEP devices for soft matter manipulation remains elusive. One reason for low market penetration is a lack of low-cost and scalable fabrication methods to quickly microfabricate field-deforming structures to generate localized DEP-inducing electric field gradients. We propose here that paper-based devices can offer a low-cost and easy-to-use alternative to traditional iDEP devices. In this article, we demonstrate for the first time the ability to perform iDEP-style particle trapping using the naturally occurring micrometer-scale insulating porous structures of paper. In particular, we use polymeric laminated nonwoven fiberglass paper channels as a source of insulating structures for iDEP. We apply a flow of polarizable microparticles directly within the nonwoven channel and simultaneously drop an electric field perpendicular to the flow direction to induce DEP. We show the ability to readily trap and concentrate particles in paper by DEP with an applied voltage as low as 2 V using two different flow mechanisms: a constant fluid flow rate using an external pump and passive fluid flow by capillary wicking. Using a combination of micro computed tomography and finite element analysis, we then present a computational model to probe the microscale DEP force formation dynamics within the paper structure. This new paper-based iDEP platform enables the development of robust, low-cost, and portable next-generation iDEP systems for a wide variety of sample purification and liquid handling applications.
PMID:38194698 | DOI:10.1021/acs.analchem.3c03740
JAMA Netw Open. 2024 Jan 2;7(1):e2350903. doi: 10.1001/jamanetworkopen.2023.50903.
ABSTRACT
IMPORTANCE: Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients for watch-and-wait treatment.
OBJECTIVE: To assess organ preservation (OP) and oncologic outcomes according to clinical tumor response grade.
DESIGN, SETTING, AND PARTICIPANTS: This was secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial, a phase 2, nonblinded, multicenter, randomized clinical trial. Randomization occurred between April 2014 and March 2020. Eligible participants included patients with stage II or III rectal adenocarcinoma. Data analysis occurred from March 2022 to July 2023.
INTERVENTION: Patients were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Tumor response was assessed 8 (±4) weeks after TNT by digital rectal examination and endoscopy and categorized by clinical tumor response grade. A 3-tier grading schema that stratifies clinical tumor response into clinical complete response (CCR), near complete response (NCR), and incomplete clinical response (ICR) was devised to maximize patient eligibility for OP.
MAIN OUTCOMES AND MEASURES: OP and survival rates by clinical tumor response grade were analyzed using the Kaplan-Meier method and log-rank test.
RESULTS: There were 304 eligible patients, including 125 patients with a CCR (median [IQR] age, 60.6 [50.4-68.0] years; 76 male [60.8%]), 114 with an NCR (median [IQR] age, 57.6 [49.1-67.9] years; 80 male [70.2%]), and 65 with an ICR (median [IQR] age, 55.5 [47.7-64.2] years; 41 male [63.1%]) based on endoscopic imaging. Age, sex, tumor distance from the anal verge, pathological tumor classification, and clinical nodal classification were similar among the clinical tumor response grades. Median (IQR) follow-up for patients with OP was 4.09 (2.99-4.93) years. The 3-year probability of OP was 77% (95% CI, 70%-85%) for patients with a CCR and 40% (95% CI, 32%-51%) for patients with an NCR (P < .001). Clinical tumor response grade was associated with disease-free survival, local recurrence-free survival, distant metastasis-free survival, and overall survival.
CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial, most patients with a CCR after TNT achieved OP, with few developing tumor regrowth. Although the probability of tumor regrowth was higher for patients with an NCR compared with patients with a CCR, a significant proportion of patients achieved OP. These findings suggest the 3-tier grading schema can be used to estimate recurrence and survival outcomes in patients with locally advanced rectal cancer who receive TNT.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02008656.
PMID:38194231 | DOI:10.1001/jamanetworkopen.2023.50903
Anal Chem. 2024 Jan 8. doi: 10.1021/acs.analchem.3c03156. Online ahead of print.
ABSTRACT
Picosecond infrared laser mass spectrometry (PIRL-MS) is shown, through a retrospective patient tissue study, to differentiate medulloblastoma cancers from pilocytic astrocytoma and two molecular subtypes of ependymoma (PF-EPN-A, ST-EPN-RELA) using laser-extracted lipids profiled with PIRL-MS in 10 s of sampling and analysis time. The average sensitivity and specificity values for this classification, taking genomic profiling data as standard, were 96.41 and 99.54%, and this classification used many molecular features resolvable in 10 s PIRL-MS spectra. Data analysis and liquid chromatography coupled with tandem high-resolution mass spectrometry (LC-MS/MS) further allowed us to reduce the molecular feature list to only 18 metabolic lipid markers most strongly involved in this classification. The identified 'metabolite array' was comprised of a variety of phosphatidic and fatty acids, ceramides, and phosphatidylcholine/ethanolamine and could mediate the above-mentioned classification with average sensitivity and specificity values of 94.39 and 98.78%, respectively, at a 95% confidence in prediction probability threshold. Therefore, a rapid and accurate pathology classification of select pediatric brain cancer types from 10 s PIRL-MS analysis using known metabolic biomarkers can now be available to the neurosurgeon. Based on retrospective mining of 'survival' versus 'extent-of-resection' data, we further identified pediatric cancer types that may benefit from actionable 10 s PIRL-MS pathology feedback. In such cases, aggressiveness of the surgical resection can be optimized in a manner that is expected to benefit the patient's overall or progression-free survival. PIRL-MS is a promising tool to drive such personalized decision-making in the operating theater.
PMID:38190738 | DOI:10.1021/acs.analchem.3c03156
Anal Chem. 2024 Jan 8. doi: 10.1021/acs.analchem.3c04873. Online ahead of print.
ABSTRACT
Tumor-derived small extracellular vesicles (tEVs) as potential biomarkers possess abundant surface proteins closely related to parent cells, which are crucial for noninvasive cancer diagnosis. However, tEVs exhibit phenotype heterogeneity and low abundance, posing a significant challenge for multiplex detection with a high sensitivity. Herein, we developed a DNA gate-based exponential amplification CRISPR-Cas (DGEAC) system for accurate and ultrasensitive detection of tEVs, which can greatly improve the accuracy of breast cancer (BC) diagnosis. Based on the coexpression of CD63 and vascular endothelial growth factor (VEGF) on BC-derived tEVs, we developed a dual-aptamer-based AND gate fluorescent probe by proximity hybridization. By integrating the target recognition and trans-cleavage activity of Cas12a, an autocatalysis-driven exponential amplification circuit was developed for ultrasensitive detection of CD63 and VEGF proteins on tEVs, which could avoid false negative signals from single protein or other interfering proteins. We achieved highly sensitive detection of tEVs over a linear range from 1.75 × 103 to 3.5 × 108 particles/mL with a detection limit as low as 1.02 × 103 particles/mL. Furthermore, the DGEAC system can distinguish tEVs from tEVs derived from different BC cell lines, including MDA-MB-231, MCF-7, SKBR3, and MCF-10A. Compared to linear amplification (AUC 90.0%), the DGEAC system effectively differentiates BC in different stages (AUC 98.3%).
PMID:38190500 | DOI:10.1021/acs.analchem.3c04873
Anal Chem. 2024 Jan 8. doi: 10.1021/acs.analchem.3c03659. Online ahead of print.
ABSTRACT
In this work, an integrated strategy with excellent accuracy and high throughput is proposed for the precise indication of single nucleotide polymorphism (SNP) in nonsmall cell lung cancer diseases. Two types of point mutations (L858R and T790M) and the corresponding wild types could be identified together in a single high-performance liquid chromatographic run. Signal amplification was achieved through a series of enzyme ligation, primer extension, and enzyme cleavage strategies, and a large number of DNA probes with different fluorescence signals were finally generated. The factors affecting the spatiotemporal separation efficiency of four DNA probes were systematically investigated. The limits of detection of wild types (WTs) or mutant types (MTs) abbreviated as L858R-MT, L858R-WT, T790M-MT, and T790M-WT were 26, 24, 19, and 22 aM, respectively. In addition, the levels of mutant types and wild types in the serum of 40 nonsmall cell lung cancer patients at different stages were detected using the method, and the correlation between the mutation ratios and cancer stages was preliminarily verified. The proposed highly selective and sensitive method may serve as an alternative approach for early diagnosis and staging of nonsmall cell lung cancer.
PMID:38190445 | DOI:10.1021/acs.analchem.3c03659
Anal Chem. 2024 Jan 8. doi: 10.1021/acs.analchem.3c04666. Online ahead of print.
ABSTRACT
Due to the substantial heterogeneity among extracellular vesicle (EV) subpopulations, single-EV analysis has the potential to elucidate the mechanisms behind EV biogenesis and shed light on the myriad functions, leading to the development of novel diagnostics and therapeutics. While many studies have been devoted to reveal between-EV variations in surface proteins and RNAs, DNA cargos (EV-DNA) have received little attention. Here, we report a hydrogel-based droplet digital multiple displacement amplification approach for the comprehensive analysis of EV-DNA at the single-EV level. Single EVs are dispersed in thousands of hydrogel droplets and lysed for DNA amplification and identification. The droplet microfluidics strategy empowers the assay with single-molecule sensitivity and capability for absolute quantification of DNA-containing EVs. In particular, our findings indicate that 5-40% EVs are associated with DNA, depending on the cell of origin. Large EVs exhibit a higher proportion of DNA-containing EVs and a more substantial presence of intraluminal DNA, compared to small EVs. These DNA-containing EVs carry multiple DNA fragments on average. Furthermore, both double-stranded DNA and single-stranded DNA were able to be detected at the single-EV level. Utilizing this method, the abundance, distribution, and biophysical properties of EV-DNA in various EV populations are evaluated. The DNA level within EVs provides insight into the status of the originating cells and offers valuable information on the outcomes of anticancer treatments. The utilization of single-EV analysis for EV-DNA holds significant promise for early cancer detection and treatment response monitoring.
PMID:38189229 | DOI:10.1021/acs.analchem.3c04666
Clin Colon Rectal Surg. 2023 Mar 29;37(1):41-45. doi: 10.1055/s-0043-1762928. eCollection 2024 Jan.
ABSTRACT
Fistula-associated anal cancer in Crohn's disease (CD) can be challenging to diagnose and treat. Patients with longstanding fistulas in the setting of CD who present with a sudden change in their symptoms should undergo biopsy under anesthesia with extensive sampling, followed by staging imaging. Pelvic magnetic resonance imaging (MRI) can be helpful in identifying the extent of the disease locally. Patients often present in the later stages due to the challenges associated with diagnosing these patients. Two subtypes of this disease include squamous cell carcinoma and adenocarcinoma, and treatment depends on diagnosis. Small sample size and lack of uniform data on treatments make it difficult to say which treatment modalities are optimal, but aggressive combined therapy is likely the best approach for survival. This will include chemotherapy and radiation and often radical resection as well. Despite this, survival is poor, although more recent data suggest that outcomes are improving.
PMID:38188072 | PMC:PMC10769575 | DOI:10.1055/s-0043-1762928
Clin Colon Rectal Surg. 2023 Mar 15;37(1):22-29. doi: 10.1055/s-0043-1762560. eCollection 2024 Jan.
ABSTRACT
Colorectal cancer (CRC) is a known complication of inflammatory bowel disease (IBD). Widely accepted guidelines recommend that patients with ulcerative colitis diagnosed with CRC undergo total proctocolectomy with or without ileal pouch-anal anastomosis, and that patients with Crohn's disease and CRC undergo either total colectomy or proctocolectomy. These approaches are ideal for preventing synchronous and metachronous cancer, minimizing risk of refractory colitis requiring reoperation, and is the appropriate treatment for the vast majority of patients with IBD who are diagnosed with CRC and require surgical intervention. Segmental colectomy, however, may be considered in select patients with IBD and CRC, specifically in elderly patients with short disease duration, in patients with mild colitis identified preoperatively, in patients with high operative risk and prohibitive comorbidities, and in patients whose CRC appears to be sporadic as opposed to colitis-associated. Patients undergoing segmental resection must be closely surveilled postoperatively for dysplasia, recurrent cancer, and refractory colitis.
PMID:38188068 | PMC:PMC10769584 | DOI:10.1055/s-0043-1762560
Clin Colon Rectal Surg. 2023 Feb 22;37(1):30-36. doi: 10.1055/s-0043-1762561. eCollection 2024 Jan.
ABSTRACT
Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer. When IBD patients develop a rectal cancer, this should be treated with the same oncological principles and guidelines as the general population. Rectal cancer treatment includes surgery, chemotherapy, and radiation therapy (RT). Many IBD patients will require a total proctocolectomy with an ileal-pouch anal anastomosis (IPAA) and others, restoration of intestinal continuity may not be feasible or advisable. The literature is scarce regarding outcomes of IPAA after RT. In the present review, we will summarize the evidence regarding RT toxicity in IBD patients and review surgical strategies and outcomes of IPAA after RT.
PMID:38188064 | PMC:PMC10769583 | DOI:10.1055/s-0043-1762561
Clin Colon Rectal Surg. 2023 Mar 24;37(1):37-40. doi: 10.1055/s-0043-1762562. eCollection 2024 Jan.
ABSTRACT
Restorative proctocolectomy with ileal pouch-anal anastomosis remains the gold standard treatment for patients with ulcerative colitis who desire restoration of intestinal continuity. Despite a significant cancer risk reduction after surgical removal of the colon and rectum, dysplasia and cancers of the ileal pouch or anal transition zone still occur and are a risk even if an anal canal mucosectomy is performed. Surgical care and maintenance after ileoanal anastomosis must include consideration of malignant potential along with other commonly monitored variables such as bowel function and quality of life. Cancers and dysplasia of the ileal pouch are rare but sometimes difficult-to-manage sequelae of pouch surgery.
PMID:38188063 | PMC:PMC10769578 | DOI:10.1055/s-0043-1762562
Am J Transl Res. 2023 Dec 15;15(12):6740-6750. eCollection 2023.
ABSTRACT
OBJECTIVE: To assess the impact of a precision-based tertiary care protocol, including participatory dietary care, on the nutritional status, immune function, and quality of life in gastric cancer patients after radical gastrectomy.
METHODS: The clinical and laboratory data of 124 patients diagnosed with gastric cancer at the Second People's Hospital of Lanzhou City from June 2020 to May 2022 were collected and retrospectively analyzed. The patients were grouped into a control group of 54 patients who received standard care and a study group of 70 patients who additionally received detailed tertiary care and bundled nutritional interventions. The clinical data (age, gender, surgical method, clinical staging, chemotherapy regimen, histories of diabetes, hypertension, smoking, alcohol consumption, time to first flatus and bowel movement, time to first liquid intake, length of hospital stay, complications at discharge, PG-SGA score, and QLQ-C30 score) and lab indices (serum albumin (ALB), prealbumin (PA), transferrin (TRF), hemoglobin (Hb), immunoglobulin A (IgA), M (IgM), and G (IgG)) were compared between the two groups.
RESULTS: Study group had significantly higher levels of ALB, PA, TRF, Hb, IgA, IgM, and IgG compared to the control group after intervention (all P<0.001). QLQ-C30 score was higher while PG-SGA score was lower in the study group (both P<0.01). Postoperative digestive system recovery was faster in the study group, as evidenced by a shorter time to first anal defecation, bowel movement, liquid food intake, and hospital stay (P<0.001). Complication rate was significantly lower in the study group (P<0.05). Cox regression analysis showed age (P=0.021) and clinical stage (P=0.039) as independent prognostic factors, while treatment regimen was not (P>0.05).
CONCLUSION: Precision-based tertiary care protocol can improve nutritional status, enhance immune function, and facilitate faster postoperative recovery for gastric cancer patients following gastrectomy, thus greatly improving the quality of life of the patient. However, age and clinical staging, rather than the care protocol, are independent prognostic factors for patients' 1-year survival.
PMID:38186971 | PMC:PMC10767524
Prev Med Rep. 2023 Dec 12;37:102546. doi: 10.1016/j.pmedr.2023.102546. eCollection 2024 Jan.
ABSTRACT
BACKGROUND: Limited research exists regarding the association between smoking and anal warts. In this study, we evaluated this association among a clinic-based Hispanic population in Puerto Rico.
METHODS: Cross-sectional study among eligible patients seen at the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center (2016-2023) (n = 920). Sociodemographic and clinical variables were collected from medical records. Patients underwent a high-resolution anoscopy (HRA) during the clinical visit; physicians assessed anal condylomas on HRA. Poisson regression models with robust standard errors were used to evaluate the association between smoking and anal warts. Demographic and clinical factors were also assessed.
RESULTS: The mean age of participants was 45.8 ± 13.1 years, 66.4 % were men, and 21.6 % were current smokers. While 10.8 % self-reported a history of anogenital condylomas, 18.9 % had anal condylomas on clinical evaluation. A higher prevalence of anal condylomas was observed among current smokers (PR = 1.28, 95 % CI: 0.94-1.75) in comparison to non-smokers in adjusted analysis, but this was not statistically significant. However, a higher prevalence of anal condylomas was observed among younger individuals (PR = 0.96, 95 % CI: 0.96-0.98) and individuals with anal high-grade squamous intraepithelial lesions (HSIL) as compared to those with benign histology (PR = 1.74. 95 % CI: 1.09-2.77).
CONCLUSIONS: Although current smoking seemed to be positively associated with anal condylomas in this high-risk Hispanic population, this finding was not statistically significant as the power to detect an association was limited. However, younger age and HSIL diagnosis were associated with a higher prevalence of anal condylomas.
PMID:38186663 | PMC:PMC10767185 | DOI:10.1016/j.pmedr.2023.102546
Int J Radiat Oncol Biol Phys. 2024 Jan 5:S0360-3016(23)08261-5. doi: 10.1016/j.ijrobp.2023.12.027. Online ahead of print.
ABSTRACT
PURPOSE: To determine whether LARC with negative mesorectal fascia (MRF) predicted by magnetic resonance imaging (MRI) can be excluded from preoperative radiotherapy treatment.
METHOD: This multicenter, open-label, non-inferiority, randomized clinical trial enrolled patients with LARC within 6-12 cm from the anal verge and with negative MRI-predicted MRF. Participants were randomized to the intervention group (primary surgery, in which the patients with positive pathological circumferential margins (CRM) were subjected to CRT while negative CRM undergone adjuvant chemotherapy according to pathologic staging) or the control group (preoperative CRT, in which all patients were followed by surgery and adjuvant chemotherapy). The primary endpoint was 3-year disease-free survival (DFS).
RESULTS: A total of 275 patients were randomly assigned to intervention (n=140) and control group (n=135), in which 33.57% and 28.15% patients were at clinical T4 stage, 85.92% and 80.45 % patients were at 'bad or ugly' risk in the intervention and control group, respectively. There were two (1.52%) and one (0.77%) patient with positive circumferential margins in the intervention and control groups, respectively (P >0.05). The non-adherence rate for intervention and control group was 3.6% and 23.7%. After a median follow-up of 34.6 (IQR: 18.2-45.7) months, 43 patients had positive events (28 patients and 15 patients in the intervention and control groups, respectively). There were six (4.4%) patients with local recurrence in the intervention group and none in the control group, which led to the stopping of the trial. The 3-year DFS rate was 81.82% (95%CI: 78.18%-85.46%) in the intervention group and 85.37% (95%CI: 81.75%-88.99%) in the control group, with a difference of -3.55% (95%CI: -3.71%- -3.39%) (HR=1.76, 95%CI: 0.94-3.30). In the per protocol dataset, the difference between 3-year DFS rate was -5.44% (95%CI: -5.63%- -5.25%) (HR=2.02, 95%CI: 1.01-4.06).
CONCLUSION: Based on the outcomes of this trial, in patients with LARC and MRI-negative MRF, primary surgery could negatively influence their DFS rates. Therefore, primary surgery was an inferior strategy, compared to preoperative CRT followed by surgery, and cannot be recommended for LARC patients in the clinical practice.
PMID:38185388 | DOI:10.1016/j.ijrobp.2023.12.027
Br J Cancer. 2024 Jan 6. doi: 10.1038/s41416-023-02564-9. Online ahead of print.
ABSTRACT
BACKGROUND: Standard care for non-metastatic squamous cell carcinoma of the anus (SCCA) is chemoradiotherapy, data about elderly patients are scarce.
METHODS: All consecutive patients treated for non-metastatic SCCA from the French multicenter FFCD-ANABASE cohort were included. Two groups were defined according to age: elderly (≥75 years) and non-elderly (<75).
RESULTS: Of 1015 patients, 202 (19.9%) were included in the elderly group; median follow-up was 35.5 months. Among the elderly, there were more women (p = 0.015); frailer patients (p < 0.001), fewer smokers (p < 0.001) and fewer HIV-infected (p < 0.001) than in the non-elderly group. Concomitant chemotherapy and inguinal irradiation were less frequent (p < 0.001 and p = 0.04). In the elderly group; 3-year overall survival (OS), recurrence-free survival (RFS) and colostomy-free survival (CFS) were 82.9%, 72.4% and 78.0%, respectively; complete response rate at 4-6 months was 70.3%. There were no differences between groups for all outcomes and toxicity. In multivariate analyses for the elderly, PS ≥ 2 and locally-advanced tumors were significantly associated with poor OS (HR = 3.4 and HR = 2.80), RFS (HR = 2.4 and HR = 3.1) and CFS (HR = 3.8 and HR = 3.0); and treatment interruption with poor RFS (HR = 1.9).
CONCLUSION: In the FFCD-ANABASE cohort, age did not influence tumor and tolerance outcomes of non-metastatic SCCA. Optimal curative treatment should be offered to elderly patients.
PMID:38184691 | DOI:10.1038/s41416-023-02564-9
J Transl Med. 2024 Jan 6;22(1):30. doi: 10.1186/s12967-023-04809-w.
ABSTRACT
BACKGROUND: Colorectal cancer (CRC) has been the third most prevalent cancer worldwide. Liver metastasis is the critical factor for the poor prognosis of CRC. Here, we investigated the expression and role of PLOD3 in CRC.
METHODS: Different liver metastasis models were established by injecting PLOD3 stable knockdown or overexpression CT26 or MC38 mouse CRC cells into the spleen of mice to verify the tumorigenicity and metastasis ability in vivo.
RESULTS: We identified PLOD3 is significantly overexpressed in liver metastasis samples of CRC. High expression of PLOD3 was significantly associated with poor survival of CRC patients. The knockdown of PLOD3 exhibited remarkable inhibition of proliferation, migration, and invasion in CRC cells, while the opposite results could be found in different PLOD3-overexpressed CRC cells. Stable knockdown of PLOD3 also significantly inhibited liver metastasis of CRC cells in different xenografts models, while stable overexpression of PLOD3 promotes liver metastasis and tumor progression. Further studies showed that PLOD3 facilitated the T cell activation in the tumor microenvironment and affected the TNF-α/ NF-κB pathway.
CONCLUSIONS: This study revealed the essential biological functions of PLOD3 in colon cancer progression and metastasis, suggesting that PLOD3 is a promising translational medicine target and bioengineering targeting PLOD3 overcomes CRC liver metastasis.
PMID:38184566 | PMC:PMC10771005 | DOI:10.1186/s12967-023-04809-w
Anal Biochem. 2024 Jan 4:115457. doi: 10.1016/j.ab.2024.115457. Online ahead of print.
ABSTRACT
Circulating tumor DNA (ctDNA) is a crucial cancer biomarker for early or noninvasive monitoring, which is essential for developing ultrasensitive and selective assays in cancer diagnosis and treatment. Herein, a cascade signal amplification of duplex-functional split-DNAzyme and dendritic probes was proposed for ultrasensitive and specific detection of nasopharyngeal carcinoma-associated Epstein-Barr virus (EBV) DNA on microfluidic microbead array chips. With the assistance of Pb2+, the duplex-functional split-DNAzyme recognizes EBV DNA and then rapidly cleaves the substrate strand. Subsequently, the released target could be recycled, and its exposed capture probe, triggered the dendritic enzyme-free signal amplification. As the enhanced mass transfer capability, target recycling, and dendritic DNA structure signal amplification inherent to microfluidic bead arrays were integrated, it achieved an excellent detection limit of 0.36 fM and a wide linear range of 1 fM∼103 fM. Further, it was applied to content detect simulated samples of EBV DNA, recovery ranged from 97.2 % to 108.1 %, and relative standard deviation (RSD) from 3.3 % to 5.9 %, exhibiting satisfactory recovery results. The developed microfluidic biosensor was a high-sensitivity and anti-interference system for ctDNA analysis, with minimal reagent volumes (microlitres) required. Thus, it is a promising platform for ctDNA at the lowest level at their earliest incidence.
PMID:38184137 | DOI:10.1016/j.ab.2024.115457
Anal Chim Acta. 2024 Jan 25;1287:342117. doi: 10.1016/j.aca.2023.342117. Epub 2023 Dec 9.
ABSTRACT
BACKGROUND: Carbonyl-containing metabolites are a class of key intermediate in metabolism, which has potentials to be biomarkers. Since their poor ionization, derivatization reagents, such as dansylhydrazine, are usually used to improve the sensitivity and/or to facilitate quantification. However, most current carbonyl derivatization reagents only have two channels, one is isotopically labeled and the other one is non-labeled. To quantify more samples in a run and using data-independent acquisition (DIA) mode to get comprehensive and unbiased mass fragmentation, we proposed a fragment-controlled isotopic tag, called DiMe-FP-NHNH2 (FP) which has five channels: Δ0, Δ3, Δ6, Δ9, and Δ12, thus up to 5 samples can be analyzed in a run.
RESULTS: The most important improvement is that the FP tag can produce multiple characteristic signals in tandem mass, diagnostic ions and neutral losses, which helps to selectively detect aldehydes/ketones for targeted and untargeted analysis. To exhibit all capabilities of the FP tag, we mimicked an untargeted metabolomics experiment, which comprises two steps. First, discovery step, using Data-Independent Analysis (SWATH-MS) and the labeling of two channels (Δ0 and Δ3), we picked out aldehyde/ketone from the pooled urine samples based on three characteristic signals, including isotope patterns, diagnostic ions, and neutral losses. Second, five-plex quantification, relative and absolute quantification were achieved in a single LC-MS analysis. Notably, because of different nominal masses, the FP tag can be used on any low or high resolution mass spectrometers.
SIGNIFICANCE: The benefits and performance of the FP tag are demonstrated by the analysis of urine samples collected from patients from a prostate cancer study, in which more than a thousand features were found based on MS1 fingerprint, but only around 120 aldehyde/ketone candidates were confirmed with characteristic signals and nine of which were quantified showing significant differences from healthy and reference urine samples.
PMID:38182390 | DOI:10.1016/j.aca.2023.342117
Anal Chim Acta. 2024 Jan 25;1287:342085. doi: 10.1016/j.aca.2023.342085. Epub 2023 Nov 29.
ABSTRACT
BACKGROUND: Human telomerase is a ribonucleoprotein complex that includes proteins and human telomerase RNA (hTR). Emerging evidence suggested that the expression level of hTR was high related with the development of tumor, so it is important to accurately detect the content of hTR. Optical control of DNAzyme activity shows a promising strategy for precise biosensing, biomedical imaging and modulation of biological processes. Although DNAzyme-based sensors can be controlled spatiotemporally by light, its application in the detection of hTR in living cells is still rare. Therefore, designing DNAzyme activity spatiotemporal controllable sensors for hTR detection is highly needed.
RESULTS: We developed a UV light-activated DNAzyme-based nanoprobe for spatially accurate imaging of intracellular hTR. The proposed nanoprobe was named MDPH, which composed of an 8-17 DNAzyme (D) inactivated by a protector strand (P), a substrate strand (H), and MnO2 nanosheets. The MnO2 nanosheets can enhance the cellular uptake of DNA strands, so that MDPH probe can enter cells autonomously through endocytosis. Under the high concentration of GSH in cancer cells, MnO2 nanosheets can self-generate cofactors to maintain the catalytic activity of DNAzyme. When exposing UV light and in presence of target hTR, DNAzyme could cleave substrate H, resulting in the recovery of fluorescence of the system. The cells imaging results show that MDPH probe could be spatiotemporally controlled to image endogenous hTR in cancer cells.
SIGNIFICANCE: With this design, telomerase RNA-specific fluorescent imaging was achieved by MDPH probe in both cancer and normal cells. Our probe made a promising new platform for spatiotemporal controllable intracellular hTR monitoring. This current method can be applied to monitor a variety of other biomarkers in living cells and perform medical diagnosis, so it may has broad applications in the field of medicine.
PMID:38182380 | DOI:10.1016/j.aca.2023.342085
Anal Chim Acta. 2024 Jan 25;1287:342084. doi: 10.1016/j.aca.2023.342084. Epub 2023 Nov 29.
ABSTRACT
BACKGROUND: Human 8-oxoG DNA glycosylase 1 (hOGG1) is one of the important members of DNA glycosylase for Base excision repair (BER), the abnormal activity of which can lead to the failure of BER and the appearance of various diseases, such as breast cancer, bladder cancer, Parkinson's disease and lung cancer. Therefore, it is important to detect the activity of hOGG1. However, traditional detection methods suffer from time consuming, complicated operation, high false positive results and low sensitivity. Thus, it remains a challenge to develop simple and sensitive hOGG1 analysis strategies to facilitate early diagnosis and treatment of the relative disease.
RESULTS: A target-induced rolling circle amplification (TIRCA) strategy for label-free fluorescence detection of hOGG1 activity was proposed with high sensitivity and specificity. The TIRCA strategy was constructed by a hairpin probe (HP) containing 8-oxoG site and a primer probe (PP). In the presence of hOGG1, the HP transformed into dumbbell DNA probe (DDP) after the 8-oxoG site of which was removed. Then the DDP formed closed circular dumbbell probe (CCDP) by ligase. CCDP could be used as amplification template of RCA to trigger RCA. The RCA products containing repeated G4 sequences could combine with ThT to produce enhanced fluorescence, achieving label-free fluorescence sensing of hOGG1. Given the high amplification efficiency of RCA and the high fluorescence quantum yield of the G4/ThT, the proposed TIRCA achieved highly sensitive measurement of hOGG1 activity with a detection limit of 0.00143 U/mL. The TIRCA strategy also exhibited excellent specificity for hOGG1 analysis over other interference enzymes.
SIGNIFICANCE: This novel TIRCA strategy demonstrates high sensitivity and high specificity for the detection of hOGG1, which has also been successfully used for the screening of inhibitors and the analysis of hOGG1 in real samples. We believe that this TIRCA strategy provides new insight into the use of the isothermal nucleic acid amplification as a useful tool for hOGG1 detection and will play an important role in disease early diagnosis and treatment.
PMID:38182379 | DOI:10.1016/j.aca.2023.342084
Anal Chim Acta. 2024 Jan 25;1287:342055. doi: 10.1016/j.aca.2023.342055. Epub 2023 Nov 27.
ABSTRACT
It is of great interest and necessity to develop a nonenzymatic, simple but highly sensitive biosensor for early diagnosis of oral cancer. Present here is an electrochemical DNA biosensor which integrates a target-triggered, entropy-driven, nonenzymatic and isothermal amplification strategy with gold nanoparticles/zeolitic imidazolate frameworks-8 (AuNPs@ZIF-8) nanocomposites for ultra-sensitive detection of oral cancer-related biomarker (ORAOV 1) in saliva. It is worth noting that the nuclease is not involved in the whole reaction process, which is simple and flexible in design only using a series of linear single-stranded DNA, avoiding undesired secondary structure interference. Meanwhile, due to the synergistic effect of AuNPs and ZIF-8, AuNPs@ZIF-8 nanocomposites display high stability, excellent electrical conductivity and exceptional electrocatalytic activity, further enhancing the electrochemical signal and avoiding labeling electrochemical signal probes. Experimental results demonstrate that this electrochemical DNA biosensor has a wide linear range (1 fM ∼1 nM), a low limit of detection (163 aM), excellent specificity, superior reproducibility and stability to ORAOV 1. More importantly, the actual application of the newly developed electrochemical biosensor is exemplified in human saliva with satisfactory recoveries. Therefore, the newly developed electrochemical biosensor has a broad application prospect in the nondestructive and early screening of oral cancer.
PMID:38182366 | DOI:10.1016/j.aca.2023.342055
Anal Chim Acta. 2024 Jan 25;1287:342058. doi: 10.1016/j.aca.2023.342058. Epub 2023 Nov 23.
ABSTRACT
N-glycopeptide is considered as one of significant biomarkers which provide guidance for the diagnosis and drug design of diseases. However, the direct analysis of N-glycopeptides is nearly impracticable mainly owing to their extremely low abundance and grave signal suppression from other interfering substances in the bio-samples. In this research, a multiply-mesoporous hydrophilic TiO2 nanohybrid (mM-TiO2@Cys) was synthesized by immobilizing Cys on a TiO2 substrate with hierarchical mesopores to achieve the highly-performed enrichment of N-glycopeptides. With the advantages of superior hydrophilicity and multiply-mesoporous structure, the obtained material exhibited an excellent selectivity (IgG digests and BSA digests at the molar ratio of 1/500), a high sensitivity (1 fmol μL-1 for IgG digests) and a good size-exclusion ability (IgG digests, IgG and BSA at the molar ratio of 1/500/500) in the enrichment of N-glycopeptides from IgG digests. As a result, 281 N-glycopeptides corresponded with 109 glycoproteins were identified from 2 μL serum digests of the patients with nasopharyngeal carcinoma, and 181 N-glycopeptides corresponded with 78 glycoproteins were identified from 2 μL serum digests of the healthy volunteers, revealing the potential application value of mM-TiO2@Cys in glycoproteomics.
PMID:38182336 | DOI:10.1016/j.aca.2023.342058
Anal Chim Acta. 2024 Jan 25;1287:342109. doi: 10.1016/j.aca.2023.342109. Epub 2023 Dec 6.
ABSTRACT
BACKGROUND: Tumor-derived exosomes (TEXs) play an important role in the development process of cancer, which can transport a large number of carcinogenic molecules to normal cells, and subsequently promote tumor metastasis. However, TEXs that were utilized in most of previous researches were obtained from the cell medium of tumor cell lines, which cannot reflect the physiological state of primary cells in vivo. Isolation of native TEXs from human plasma with intact function is contributed to exploring the interaction between TEXs and recipient cells for understanding their true biological functions.
RESULTS: We developed a strategy that involves both capture and release processes to obtain native TEXs from plasma of cancer patients. An MoS2-based immunomagnetic probe (Fe3O4@MoS2-Au-Aptamer, named as FMAA) with the advantages of high surface area, magnetic response and abundant affinity sites was designed and synthesized to capture TEXs through recognizing high-expression tumor-associated antigens of EpCAM. With the assistance of complementary sequences of EpCAM, TEXs were released with non-destruction and no residual labels. According to NTA analysis, 107-108 TEXs were recovered from per mL plasma of breast cancer patients. The interaction between native TEXs and normal epithelial cells confirms TEXs could induce significant activation of autophagy of recipient cells with co-culture for 12 h. Proteomics analysis demonstrated a total of 637 proteins inside epithelial cells had dynamic expression with the stimulation of TEXs and 5 proteins in the pathway of autophagy had elevated expression level.
SIGNIFICANCE: This work not only obtains native TEXs from human plasma with non-destruction and no residual labels, but also explores the interaction between TEXs and recipient cells for understanding their true biological functions, which will accelerate the application of TEXs in the field of biomarkers and therapeutic drugs.
PMID:38182386 | DOI:10.1016/j.aca.2023.342109
J Cancer Surviv. 2024 Jan 6. doi: 10.1007/s11764-023-01527-6. Online ahead of print.
ABSTRACT
PURPOSE: We explored survivors' experiences of chronic bowel symptoms following pelvic radiotherapy, strategies employed in living with these symptoms, effects on daily activities, and roles at home and in the workplace.
METHODS: Semi-structured interviews were conducted with 28 individuals (10 gynaecological, 14 prostate, four anal/rectal cancer survivors) who had completed pelvic radiotherapy at least six months prior to data collection and who had experience of bowel symptoms during this post-treatment period. Reflexive thematic analysis was undertaken.
RESULTS: We propose four themes describing a process leading from experience of symptoms to withdrawal from activities and roles. These are (1) losing control (the experience of unintended anal leakage or discharge); (2) experiencing embarrassment and fear (the experience of embarrassment or fear of embarrassment as a result of discharge becoming public); (3) managing and reacting (acting to reduce the likelihood of discharge or to prevent this becoming public); and (4) restriction and withdrawal (avoiding specific activities or situations so as to reduce or remove the risk of embarrassment). Returning to the workplace presented additional challenges across these themes.
CONCLUSIONS: Impacts of chronic bowel symptoms can be severe. Survivors employ a variety of methods and strategies in living with their symptoms. Some of these support continued role fulfilment but some constitute a withdrawal from pre-treatment roles. Current healthcare provision and statutory protections fail to fully meet needs following pelvic radiotherapy.
IMPLICATIONS FOR CANCER SURVIVORS: There is a need to develop and implement evidence-based services and supported self-management programmes for survivors experiencing chronic bowel problems post-radiotherapy.
PMID:38182936 | DOI:10.1007/s11764-023-01527-6
Anal Chim Acta. 2024 Jan 25;1287:342126. doi: 10.1016/j.aca.2023.342126. Epub 2023 Dec 11.
ABSTRACT
BACKGROUND: The detection of cancer gene mutations in biofluids plays a pivotal role in revolutionizing disease diagnosis. The presence of a large background of wild-type sequences poses a challenge to liquid biopsy of tumor mutation genes. Suppressing the detection of wild-type sequences can reduce their interference, however, due to the minimal difference between mutant and wild-type sequences (such as single nucleotide variants differing by only one nucleotide), how to suppress the detection of wild-type sequences to the greatest extent without compromising the sensitivity of mutant sequence detection remains to be explored.
SIGNIFICANCE: The RLP system addresses the incompatibility between RPA and RT-PCR reactions through a physical separation strategy. Besides, due to the remarkable flexibility of locked nucleic acid probes, the RLP system emerges as a potent tool for detecting mutations across diverse genes. It excels in sensitivity and speed, tolerates plasma matrix, and is cost-effective. This bodes well for advancing the field of precision medicine.
RESULTS: The recombinase-assisted locked nucleic acid (LNA) probe-mediated dual amplification biosensing platform (namely RLP), which combines recombinase polymerase amplification (RPA) and LNA clamp PCR method in one tube, enabling highly sensitive and selective detection of EGFR T790M mutation under the help of well-designed LNA probes. This technique can quantify DNA targets with a limit of detection (LoD) at the single copy level and identify point mutation with mutant allelic fractions as low as 0.007 % in 45 min. Moreover, RLP has the potential for the direct detection of plasma samples without the need for nucleic acid extraction and the cost of a single test is less than 1USD. Furthermore, the RLP system is a cascading dual amplification reaction conducted in a single tube, which eliminates the risk of cross-contamination associated with opening multiple tubes and ensures the reliability of the results.
PMID:38182396 | DOI:10.1016/j.aca.2023.342126
Anal Chim Acta. 2024 Jan 25;1287:342125. doi: 10.1016/j.aca.2023.342125. Epub 2023 Dec 12.
ABSTRACT
BACKGROUND: MicroRNA-21 has been determined to be the only microRNA overexpressed in 11 types of solid tumors, making it an excellent candidate as a biomarker for disease diagnosis and therapy. Photoelectrochemical (PEC) biosensors have been widely used for quantification of microRNA-21. However, most PEC biosensing processes still suffer from some problems, such as the difficulty of avoiding the influence of interferents in complex matrices and the false-positive signals. There is a pressing need for establishing a sensitive and stable PEC method to detect microRNA-21.
RESULTS: Herein, a nicking endonuclease-mediated rolling circle amplification (RCA)-assisted CRISPR/Cas12a PEC biosensor was fabricated for ultrasensitive detection of microRNA-21. The p-p type heterojunction PbS QDs/Co3O4 polyhedra were prepared as the quencher, thus the initial PEC signal attained the "off" state. Furthermore, the target was specifically identified and amplified by the RCA process. Then, its product single-stranded DNA S1 activated the cis- and trans-cleavage abilities of CRISPR/Cas12a, leading to almost all of the PbS QDs/Co3O4 polyhedra to leave the electrode surface, the p-n semiconductor quenching effect to be disrupted, and the signal achieving the "super-on" state. This pattern of PEC signal changed from "off" to "on" eliminated the interference of false-positive signals. The proposed PEC biosensor presented a satisfactory linear relationship ranging from 1 fM to 10 nM with a detection limit of 0.76 fM (3 Sb/N).
SIGNIFICANCE AND NOVELTY: With innovatively synthesized PbS QDs/Co3O4 polyhedra as the effective quencher for PEC signal, the CRISPR/Cas12a dual-cleavage PEC biosensor possessed excellent selectivity, stability and repeatability. Furthermore, the detection of various miRNAs can be realized by changing the relevant base sequences in the constructed PEC biosensor. It also provides a powerful strategy for early clinical diagnosis and biomedical research.
PMID:38182395 | DOI:10.1016/j.aca.2023.342125
Cell Rep. 2024 Jan 4;43(1):113640. doi: 10.1016/j.celrep.2023.113640. Online ahead of print.
ABSTRACT
Adhesion G-protein-coupled receptors (aGPCRs) form a large family of cell surface molecules with versatile tasks in organ development. Many aGPCRs still await their functional and pharmacological deorphanization. Here, we characterized the orphan aGPCR CG11318/mayo of Drosophila melanogaster and found it expressed in specific regions of the gastrointestinal canal and anal plates, epithelial specializations that control ion homeostasis. Genetic removal of mayo results in tachycardia, which is caused by hyperkalemia of the larval hemolymph. The hyperkalemic effect can be mimicked by a raise in ambient potassium concentration, while normal potassium levels in mayoKO mutants can be restored by pharmacological inhibition of potassium channels. Intriguingly, hyperkalemia and tachycardia are caused non-cell autonomously through mayo-dependent control of enterocyte proliferation in the larval midgut, which is the primary function of this aGPCR. These findings characterize the ancestral aGPCR Mayo as a homeostatic regulator of gut development.
PMID:38180839 | DOI:10.1016/j.celrep.2023.113640
Anal Chem. 2024 Jan 5. doi: 10.1021/acs.analchem.3c03255. Online ahead of print.
ABSTRACT
Metaproteomics offers a direct avenue to identify microbial proteins in microbiota, enabling the compositional and functional characterization of microbiota. Due to the complexity and heterogeneity of microbial communities, in-depth and accurate metaproteomics faces tremendous limitations. One challenge in metaproteomics is the construction of a suitable protein sequence database to interpret the highly complex metaproteomic data, especially in the absence of metagenomic sequencing data. Herein, we present a high-abundance protein-guided hybrid spectral library strategy for in-depth data independent acquisition (DIA) metaproteomic analysis (HAPs-hyblibDIA). A dedicated high-abundance protein database of gut microbial species is constructed and used to mine the taxonomic information on microbiota samples. Then, a sample-specific protein sequence database is built based on the taxonomic information using Uniprot protein sequence for subsequent analysis of the DIA data using hybrid spectral library-based DIA analysis. We evaluated the accuracy and sensitivity of the method using synthetic microbial community samples and human gut microbiome samples. It was demonstrated that the strategy can successfully identify taxonomic compositions of microbiota samples and that the peptides identified by HAPs-hyblibDIA overlapped greatly with the peptides identified using a metagenomic sequencing-derived database. At the peptide and species level, our results can serve as a complement to the results obtained using a metagenomic sequencing-derived database. Furthermore, we validated the applicability of the HAPs-hyblibDIA strategy in a cohort of human gut microbiota samples of colorectal cancer patients and controls, highlighting its usability in biomedical research.
PMID:38180447 | DOI:10.1021/acs.analchem.3c03255
Front Oncol. 2023 Dec 21;13:1212475. doi: 10.3389/fonc.2023.1212475. eCollection 2023.
ABSTRACT
Small round cell undifferentiated sarcoma is a rare and highly invasive group of malignant bone and soft tissue tumors, often associated with a high misdiagnosis rate. The patient in this case was a 34-year-old male who presented with a two-month history of abdominal pain that worsened over the past two weeks. Elevated levels of tumor markers CA19-9 and CA72-4 were observed. Imaging revealed a substantial, well-vascularized mass in the lower left abdomen, located in the posterior abdominal cavity, invading the descending colon and the root of the small mesentery, and infiltrating the serous layer. The lesion was extensively resected without any postoperative complications. Microscopic examination indicated a combination of mucinous adenocarcinoma (approximately 30%) and small round cell undifferentiated sarcoma (approximately 70%). The patient was followed up for six months, and one month after surgery, a recurrence of the tumor was observed in the left paracolonic sulcus area, with metastases to the abdominal wall, peritoneum, and medial iliac muscles. Chemotherapy and targeted therapy were administered, and the patient currently survives with the presence of tumors. Small round cell undifferentiated sarcoma is an uncommon and highly invasive tumor, and clinical surgeons need to raise their awareness and realize to the maximum extent possible that this disease can be described through a multi-modal combination of immunohistochemistry and genetic test to improve diagnostic accuracy and reduce missed diagnoses. Further research in the field of biology is necessary to explore targeted drugs specifically suitable for this disease.
PMID:38179167 | PMC:PMC10764574 | DOI:10.3389/fonc.2023.1212475
J Med Virol. 2024 Jan;96(1):e29360. doi: 10.1002/jmv.29360.
ABSTRACT
Human papillomavirus (HPV) infection can lead to HPV-related cancer in men, including the anus, penile, and oropharyngeal cancers and precancerous lesions. This study retrospectively investigated HPV prevalence and genotype distribution in Liaocheng men between 2016 and 2022. The total HPV positive rate was 64.87% (2388/3681, 95% confidence interval [CI]: 63.32%-66.40%), where high risk (HR)-HPV and low risk (LR)-HPV accounted for 42.49% (1564/3681, 95% CI: 40.90%-44.09%) and 69.71% (2566/3681, 95% CI: 68.20%-71.17%), respectively. The mixed HPV infection rate of two and more genotypes was 35.72%. The infection rate of HR-HPV increased with the number of positive cases annually from 2016 (16.91%) to 2022 (46.59%). The most common HR-HPV genotypes were HPV16 (11.60%), HPV52 (6.95%), and HPV59 (6.28%), whereas the least common HR-HPV was HPV26. The most common LR-HPV genotypes were HPV6 (56.99%), HPV11 (23.79%), and HPV43 (6.37%). The 9 v HPV vaccine preventable for LR-HPV and HR-HPV accounted for 80.78% and 30.40%, respectively, in this study. Most HPV-positive patients aged 1-86 were in the 30-39 age group. This study confirmed that HPV prevalence in Liaocheng men was common and diverse. HPV16, HPV52, and HPV59 are widely distributed in Liaocheng men, and the male HR-HPV infection rate remained high in this region. Regarding public health and cancer prevention, it is recommended and effective to include the HPV vaccination in the national vaccination program for men.
PMID:38178597 | DOI:10.1002/jmv.29360
J Med Virol. 2024 Jan;96(1):e29363. doi: 10.1002/jmv.29363.
ABSTRACT
Oncovirus infections account for an estimated 12%-20% of human cancers worldwide. High-risk human papillomavirus (HPV) infection is the etiological agent of some malignancies such as cervical, oropharyngeal, anal, penile, vaginal, and vulvar cancers. However, HPV infection is not the only cause of these cancers or may not be sufficient to initiate cancer development. Actually, certain other risk factors including additional oncoviruses coinfections have been reported to increase the risk of patients exposed to HPV for developing different HPV-related cancers. In the current review, we summarize recent findings about coinfections with different oncoviruses in HPV+ patients from both clinical and mechanistic studies. We believe such efforts may lead to an interesting direction for improving our understanding and developing new treatments for virus-induced cancers.
PMID:38178584 | DOI:10.1002/jmv.29363
Med Image Anal. 2023 Dec 28;93:103070. doi: 10.1016/j.media.2023.103070. Online ahead of print.
ABSTRACT
We propose DiRL, a Diversity-inducing Representation Learning technique for histopathology imaging. Self-supervised learning (SSL) techniques, such as contrastive and non-contrastive approaches, have been shown to learn rich and effective representations of digitized tissue samples with limited pathologist supervision. Our analysis of vanilla SSL-pretrained models' attention distribution reveals an insightful observation: sparsity in attention, i.e, models tends to localize most of their attention to some prominent patterns in the image. Although attention sparsity can be beneficial in natural images due to these prominent patterns being the object of interest itself, this can be sub-optimal in digital pathology; this is because, unlike natural images, digital pathology scans are not object-centric, but rather a complex phenotype of various spatially intermixed biological components. Inadequate diversification of attention in these complex images could result in crucial information loss. To address this, we leverage cell segmentation to densely extract multiple histopathology-specific representations, and then propose a prior-guided dense pretext task, designed to match the multiple corresponding representations between the views. Through this, the model learns to attend to various components more closely and evenly, thus inducing adequate diversification in attention for capturing context-rich representations. Through quantitative and qualitative analysis on multiple tasks across cancer types, we demonstrate the efficacy of our method and observe that the attention is more globally distributed.
PMID:38176354 | DOI:10.1016/j.media.2023.103070
Acad Radiol. 2024 Jan 3:S1076-6332(23)00695-5. doi: 10.1016/j.acra.2023.12.020. Online ahead of print.
ABSTRACT
RATIONALE AND OBJECTIVES: The use of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) in assessing inflammatory diseases has shown significant promise. Uptake patterns in perianal fistulas, which may be an incidental finding on PET/CT, have not been purposefully studied. Our aim was to compare FDG uptake of perianal fistulas to that of the liver and anal canal in patients who underwent PET/CT for hematologic/oncologic diagnosis or staging.
MATERIALS AND METHODS: We retrospectively identified patients who underwent FDG-PET/CT imaging between January 2011 and May 2023, where the report described a perianal fistula or abscess. PET/CTs of patients included in the study were retrospectively analyzed to record the maximum standardized uptake value (SUVmax) of the fistula, abscess, anal canal, rectum, and liver. Fistula-to-liver and Fistula-to-anus SUVmax ratios were calculated. We statistically compared FDG activity among the fistula, liver, and anal canal. We also assessed FDG activity in patients with vs. without anorectal cancer, as well as across different St. James fistula grades.
RESULTS: The study included 24 patients with identifiable fistulas. Fistula SUVmax (mean=10.8 ± 5.28) was significantly higher than both the liver (mean=3.09 ± 0.584, p < 0.0001) and the anal canal (mean=5.98 ± 2.63, p = 0.0005). Abscess fistula SUVmax was 15.8 ± 4.91. St. James grade 1 fistulas had significantly lower SUVmax compared to grades 2 and 4 (p = 0.0224 and p = 0.0295, respectively). No significant differences existed in SUVmax ratios between anorectal and non-anorectal cancer groups.
CONCLUSION: Perianal fistulas have increased FDG avidity with fistula SUVmax values that are significantly higher than the anal canal.
PMID:38177032 | DOI:10.1016/j.acra.2023.12.020
Anal Chem. 2024 Jan 4. doi: 10.1021/acs.analchem.3c03441. Online ahead of print.
ABSTRACT
Lead is a widespread environmental hazard that can adversely affect multiple biological functions. Blood cells are the initial targets that face lead exposure. However, a systematic assessment of lead dynamics in blood cells at single-cell resolution is still absent. Herein, C57BL/6 mice were fed with lead-contaminated food. Peripheral blood was harvested at different days. Extracted red blood cells and leukocytes were stained with 19 metal-conjugated antibodies and analyzed by mass cytometry. We quantified the time-lapse lead levels in 12 major blood cell subpopulations and established the distribution of lead heterogeneity. Our results show that the lead levels in all major blood cell subtypes follow lognormal distributions but with distinctively individual skewness. The lognormal distribution suggests a multiplicative accumulation of lead with stochastic turnover of cells, which allows us to estimate the lead lifespan of different blood cell populations by calculating the distribution skewness. These findings suggest that lead accumulation by single blood cells follows a stochastic multiplicative process.
PMID:38176010 | DOI:10.1021/acs.analchem.3c03441
Anal Chem. 2024 Jan 4. doi: 10.1021/acs.analchem.3c03704. Online ahead of print.
ABSTRACT
Accurate point-of-care (POC) analysis of cancer markers is the essence in the comprehensive early screening and treatment of cancer. Dual-mode synchronous detection is one of the effective approaches to reduce the probability of false negatives or false positives. As a result, this can greatly improve the accuracy of diagnosis. In this work, a surface-enhanced Raman scattering (SERS)-temperature dual-mode T-type lateral flow strip was fabricated to direct and simultaneous POC detection of total and free prostate-specific antigens (t-PSA and f-PSA) in blood. With the advantage of high stability of T-type lateral flow strip and simultaneous acquirement of assay results for t-PSA and f:t PSA ratio, the proposed method has high accuracy in the diagnosis of prostate cancer, especially in the diagnostic gray zone between 4.0 and 10.0 ng/mL. The SERS-temperature dual-signal has a good linear correlation with either f-PSA or t-PSA. To evaluate the clinical diagnostic performance of the proposed method, spiked human serum samples and the whole blood sample were analyzed. The assay results showed good recovery, and compared with traditional electrochemiluminescence immunoassay (ECLIA) method (t-PSA: 43.151; f/t ratio: 0.08), the results obtained by the proposed method were similar (t-PSA: 40.15 (SERS), 36.21 (temperature); f/t ratio: 0.08 (SERS), 0.08 (temperature), but the detection time (15 min) and cost ($0.05) had been greatly reduced. Therefore, the proposed SERS-temperature synchronous dual-mode T-type lateral flow strip has a strong application potential in the field of accurate large-scale diagnostics of prostate cancer on-site by simultaneous POC detection of t-PSA and f-PSA in blood.
PMID:38176009 | DOI:10.1021/acs.analchem.3c03704
J Am Anim Hosp Assoc. 2024 Jan 1;60(1):20-24. doi: 10.5326/JAAHA-MS-7379.
ABSTRACT
In this case report, we describe the presentation, diagnosis, and outcome of septic peritonitis secondary to neoplasia in patients lacking evidence of gastrointestinal content leakage, liver abscessation, or other treatment-associated risk factors. Two dogs presented with a diagnosis of neoplasia and nonspecific clinical signs such as lethargy, hyporexia, vomiting, and discomfort that was localized to the abdomen. The diagnoses at presentation consisted of a perianal tumor consistent with apocrine gland anal sac adenocarcinoma and systemic mastocytosis. Neither of the dogs was considered systemically immunocompromised or had received recent cytotoxic chemotherapy treatment or surgical procedures. A common finding on blood work in the two dogs was the presence of band neutrophils. The diagnosis of septic peritonitis via fluid analysis and cytology was delayed in both cases. No treatment for the supposed underlying cause of septic peritonitis was pursued and euthanasia was pursued in both cases owing to poor prognosis. On necropsy, one dog was suspected to have developed septic peritonitis because of an abscessed lymph node, and in the other case, no definitive source was identified. Septic peritonitis can arise secondary to neoplasia that is not primarily involving the liver or gastrointestinal tract in canine patients that lack treatment-associated risk factors.
PMID:38175981 | DOI:10.5326/JAAHA-MS-7379
Cureus. 2023 Dec 4;15(12):e49898. doi: 10.7759/cureus.49898. eCollection 2023 Dec.
ABSTRACT
5-fluorouracil (5-FU) is a well-known chemotherapeutic agent used for the treatment of colon cancer and other solid malignancies. Dihydropyrimidine dehydrogenase (DPD) is an enzyme that catalyzes 5-FU, and if a patient is deficient, such as through a gene mutation, they can be predisposed to severe toxicity. Although 5-FU-induced neurotoxicity is extremely rare, it can be fatal. We report a case of 5-FU neurotoxicity in a 56-year-old male patient with keratinizing squamous cell carcinoma of the anal canal on concurrent chemoradiation therapy consisting of 5-FU, mitomycin, and radiotherapy. Encephalopathy, dysarthria, and ataxia were noted on day three of treatment. MRI of the brain showed a pattern of global anoxic brain injury. DPD testing was negative for polymorphism, and the patient's symptoms improved after treatment with uridine triacetate, the treatment for 5-FU toxicity.
PMID:38174188 | PMC:PMC10762876 | DOI:10.7759/cureus.49898
J Pharm Anal. 2023 Nov;13(11):1353-1364. doi: 10.1016/j.jpha.2023.06.009. Epub 2023 Jun 26.
ABSTRACT
Amino-containing compounds, including amino acids, aliphatic amines, aromatic amines, small peptides and catecholamines, are involved in various biological processes and play vital roles in multiple metabolic pathways. Previous studies indicated that some amino-containing metabolites are significant diagnostic and prognostic biomarkers of gastric cancer. However, the discovery of precise biomarkers for the preoperative diagnosis of gastric cancer is still in an urgent need. Herein, we established a polarity-regulated derivatization method coupled with liquid chromatography-mass spectrometry (LC-MS) for amino-containing metabolites profiling in the serum samples of patients with gastric cancer and healthy controls, based on our newly designed and synthesized derivatization reagent (S)-3-(1-(diisopropoxyphosphoryl) pyrrolidine-2-carboxamido)-N-hydroxysuccinimidyl ester (3-DP-NHS). Enhanced separation efficiency and detection sensitivity for amino-containing metabolites were achieved after derivatization. This method exhibited good linearity, recovery, intra- and inter-day precision and accuracy. Only 5 μL serum is needed for untargeted analysis, enabling 202 amino-containing metabolites to be detected. Statistical analysis revealed altered amino acid metabolisms in patients with gastric cancer. Furthermore, ultra high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS) analysis quantification revealed increased serum levels of tryptamine and decreased concentrations of arginine and tryptophan in patients with gastric cancer. Receiver operating characteristic (ROC) curves indicated that an increased tryptamine/tryptophan ratio could serve as a potential biomarker for gastric cancer diagnosis. This study demostrated the possibility of using serum amino acid biomarkers for gastric cancer diagnosis, providing new avenues for the treatment of gastric cancer.
PMID:38174119 | PMC:PMC10759254 | DOI:10.1016/j.jpha.2023.06.009
J Pharm Anal. 2023 Nov;13(11):1235-1251. doi: 10.1016/j.jpha.2023.07.008. Epub 2023 Jul 17.
ABSTRACT
Colorectal cancer (CRC) is among the leading causes of cancer mortality. The lifetime risk of developing CRC is about 5% in adult males and females. CRC is usually diagnosed at an advanced stage, and at this point therapy has a limited impact on cure rates and long-term survival. Novel and/or improved CRC therapeutic options are needed. The involvement of microRNAs (miRNAs) in cancer development has been reported, and their regulation in many oncogenic pathways suggests their potent tumor suppressor action. Although miRNAs provide a promising therapeutic approach for cancer, challenges such as biodegradation, specificity, stability and toxicity, impede their progression into clinical trials. Nanotechnology strategies offer diverse advantages for the use of miRNAs for CRC-targeted delivery and therapy. The merits of using nanocarriers for targeted delivery of miRNA-formulations are presented herein to highlight the role they can play in miRNA-based CRC therapy by targeting different stages of the disease.
PMID:38174117 | PMC:PMC10759263 | DOI:10.1016/j.jpha.2023.07.008
J Pharm Anal. 2023 Nov;13(11):1296-1308. doi: 10.1016/j.jpha.2023.06.004. Epub 2023 Jun 7.
ABSTRACT
Ginsenoside Rg5 is a rare ginsenoside showing promising tumor-suppressive effects. This study aimed to explore its radio-sensitizing effects and the underlying mechanisms. Human lung adenocarcinoma cell lines A549 and Calu-3 were used for in vitro and in vivo analysis. Bioinformatic molecular docking prediction and following validation by surface plasmon resonance (SPR) technology, cellular thermal shift assay (CETSA), and isothermal titration calorimetry (ITC) were conducted to explore the binding between ginsenoside Rg5 and 90 kD heat shock protein alpha (HSP90α). The effects of ginsenoside Rg5 on HSP90-cell division cycle 37 (CDC37) interaction, the client protein stability, and the downstream regulations were further explored. Results showed that ginsenoside Rg5 could induce cell-cycle arrest at the G1 phase and enhance irradiation-induced cell apoptosis. It could bind to HSP90α with a high affinity, but the affinity was drastically decreased by HSP90α Y61A mutation. Co-immunoprecipitation (Co-IP) and ITC assays confirmed that ginsenoside Rg5 disrupts the HSP90-CDC37 interaction in a dose-dependent manner. It reduced irradiation-induced upregulation of the HSP90-CDC37 client proteins, including SRC, CDK4, RAF1, and ULK1 in A549 cell-derived xenograft (CDX) tumors. Ginsenoside Rg5 or MRT67307 (an IKKε/TBK1 inhibitor) pretreatment suppressed irradiation-induced elevation of the LC3-II/β ratio and restored irradiation-induced downregulation of p62 expression. In A549 CDX tumors, ginsenoside Rg5 treatment suppressed LC3 expression and enhanced irradiation-induced DNA damage. In conclusion, ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma. It interacts with HSP90α and reduces the binding between HSP90 and CDC37, thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.
PMID:38174116 | PMC:PMC10759260 | DOI:10.1016/j.jpha.2023.06.004
J Pharm Anal. 2023 Nov;13(11):1365-1373. doi: 10.1016/j.jpha.2023.08.016. Epub 2023 Sep 22.
ABSTRACT
In this work, a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry (LC-MS) method was developed for metabolite profiling of the glutathione anabolic pathway (GAP) in cancer tissues and cells. The pyrylium salt of 6,7-dimethoxy-3-methyl isochromenylium tetrafluoroborate (DMMIC) was used to label the amino group of metabolites, and a reductant of dithiothreitol (DTT) was employed to stabilize the thiol group. By combining DMMIC derivatization with LC-MS, it was feasible to quantify the 13 main metabolites on the GAP in complex biological samples, which had good linearity (R2 = 0.9981-0.9999), precision (interday precision of 1.6%-19.0% and intraday precision of 1.4%-19.8%) and accuracy (83.4%-115.7%). Moreover, the recovery assessments in tissues (82.5%-107.3%) and in cells (98.1%-118.9%) with GSH-13C2, 15N, and Cys-15N demonstrated the reliability of the method in detecting tissues and cells. Following a methodological evaluation, the method was applied successfully to investigate difference in the GAP between the carcinoma and para-carcinoma tissues of esophageal squamous cell carcinoma (ESCC) and the effect of p-hydroxycinnamaldehyde (CMSP) on the GAP in KYSE-150 esophageal cancer cells. The results demonstrate that the developed method provides a promising new tool to elucidate the roles of GAP in physiological and pathological processes, which can contribute to research on drugs and diseases.
PMID:38174115 | PMC:PMC10759256 | DOI:10.1016/j.jpha.2023.08.016
Front Oncol. 2023 Dec 18;13:1278137. doi: 10.3389/fonc.2023.1278137. eCollection 2023.
ABSTRACT
PURPOSE: The purpose of this study is to determine what variables contribute to the early death of elderly colorectal cancer patients (ECRC) and to generate predictive nomograms for this population.
METHODS: This retrospective cohort analysis included elderly individuals (≥75 years old) diagnosed with colorectal cancer (CRC) from 2010-2015 in the Surveillance, Epidemiology, and End Result databases (SEER) databases. The external validation was conducted using a sample of the Chinese population obtained from the China-Japan Union Hospital of Jilin University. Logistic regression analyses were used to ascertain variables associated with early death and to develop nomograms. The nomograms were internally and externally validated with the help of the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA).
RESULTS: The SEER cohort consisted of 28,111 individuals, while the Chinese cohort contained 315 cases. Logistic regression analyses shown that race, marital status, tumor size, Grade, T stage, N stage, M stage, brain metastasis, liver metastasis, bone metastasis, surgery, chemotherapy, and radiotherapy were independent prognostic factors for all-cause and cancer-specific early death in ECRC patients; The variable of sex was only related to an increased risk of all-cause early death, whereas the factor of insurance status was solely associated with an increased risk of cancer-specific early death. Subsequently, two nomograms were devised to estimate the likelihood of all-cause and cancer-specific early death among individuals with ECRC. The nomograms exhibited robust predictive accuracy for predicting early death of ECRC patients, as evidenced by both internal and external validation.
CONCLUSION: We developed two easy-to-use nomograms to predicting the likelihood of early death in ECRC patients, which would contribute significantly to the improvement of clinical decision-making and the formulation of personalized treatment approaches for this particular population.
PMID:38173840 | PMC:PMC10764026 | DOI:10.3389/fonc.2023.1278137
Anal Chem. 2024 Jan 3. doi: 10.1021/acs.analchem.3c03408. Online ahead of print.
ABSTRACT
We report a dual-signal chemical exchange saturation transfer (Dusi-CEST) strategy for drug delivery and detection in living cells. The two signals can be detected by operators in complex environments. This strategy is demonstrated on a cucurbit[6]uril (CB[6]) nanoparticle probe, as an example. The CB[6] probe is equipped with two kinds of hydrophobic cavities: one is found inside CB[6] itself, whereas the other exists inside the nanoparticle. When the probe is dispersed in aqueous solution as part of a hyperpolarized 129Xe NMR experiment, two signals appear at two different chemical shifts (100 and 200 ppm). These two resonances correspond to the NMR signals of 129Xe in the two different cavities. Upon loading with hydrophobic drugs, such as paclitaxel, for intracellular drug delivery, the two resonances undergo significant changes upon drug loading and cargo release, giving rise to a metric enabling the assessment of drug delivery success. The simultaneous change of Dusi-CEST likes a mobile phone that can receive both LTE and Wi-Fi signals, which can help reduce the occurrence of false positives and false negatives in complex biological environments and help improve the accuracy and sensitivity of single-shot detection.
PMID:38173081 | DOI:10.1021/acs.analchem.3c03408
Anal Chem. 2024 Jan 3. doi: 10.1021/acs.analchem.3c03517. Online ahead of print.
ABSTRACT
Identification of the phosphatidylserine (PS) discrepancies occurring on the cellular membrane during apoptotic processes is of the utmost importance. However, monitoring the quantity of PS molecules in real-time at a single-cell level currently remains a challenging task. Here, we demonstrate this objective by leveraging the specific binding and reversible interaction exhibited by the zinc(II) dipyridinamine complex (ZnDPA) with PS. Lipoic acid-functionalized ZnDPA (LP-ZnDPA) was subsequently immobilized onto the surface of an atomic force microscopy cantilever to form a force probe, ALP-ZnDPA, enabling a PS-specific dynamic imaging and detection mode. By utilizing this technique, we can not only create a heat map of the expression level of PS with submicron resolution but also quantify the number of molecules present on a single cell's surface with a detection limit of 1.86 × 104 molecules. The feasibility of the proposed method is demonstrated through the analysis of PS expression levels in different cancer cell lines and at various stages of paclitaxel-induced apoptosis. This study represents the first application of a force probe to quantify PS molecules on the surface of individual cells, providing insight into dynamic changes in PS content during apoptosis at the molecular level and introducing a novel dimension to current detection methodologies.
PMID:38173079 | DOI:10.1021/acs.analchem.3c03517
Anal Chem. 2024 Jan 3. doi: 10.1021/acs.analchem.3c05041. Online ahead of print.
ABSTRACT
A high-sensitivity, low-cost, self-powered biomass electrochemical biosensor based on the "evaporating potential" theory is developed for protein detection. The feasibility of experimental evaluation methods was verified with a probe protein of bovine serum albumin. The sensor was then used to detect lung cancer marker CYFRA21-1, and the potential of our sensor for clinical diagnosis was demonstrated by serum analysis. This work innovatively exploits the osmotic power generation capability of natural wood to construct a promising electrochemical biosensor that was driven by kinetics during testing. The detection methods used for this sensor, chronoamperometry and AC impedance, showed potential for quantitative analysis and specific detection, respectively. Furthermore, the sensor could facilitate new insights into the development of high-sensitivity, low-cost, and easy-to-use electrochemical biosensors.
PMID:38171538 | DOI:10.1021/acs.analchem.3c05041
Anal Chem. 2024 Jan 3. doi: 10.1021/acs.analchem.3c05013. Online ahead of print.
ABSTRACT
Early tumor diagnosis is crucial to successful treatment. Earlier studies have shown that microRNA is a biomarker for early tumor diagnosis. The development of highly sensitive miRNA detection methods, especially in living cells, plays an indispensable role for early diagnosis and treatment of tumor. Although the catalytic hairpin assembly (CHA)-based miRNA analysis strategy is commonly used for disease diagnosis, further application of CHA is hindered due to its low amplification efficiency and low tumor recognition contrast. To address these limitations, we propose a dual-signal amplification strategy based on CHA and APE1-assisted amplification, enabling highly sensitive and high-contrast miRNA imaging. The miR-221 was selected as a target model. This dual-signal amplification strategy has exhibited high amplification efficiency, which could analyze miRNA as low as 21 fM. This strategy also exhibited high specificity, which could distinguish target miRNA and nontarget with single-base differences. Moreover, this method showed significant potential for practical application, as it could successfully distinguish the expression difference of miR-221 in the plasma samples of normal people and patients. Most importantly, the expression level of the APE1 enzyme in tumor cells is higher than that in normal cells, allowing this strategy to sensitively and specifically image miRNA within tumor cells. This proposed method has also been successfully used to indicate fluctuations of intracellular miRNA and to distinguish miRNA expression between normal cells and cancer cells with high contrast. We anticipate that this method will provide fresh insights and can be a powerful tool for tumor diagnosis and treatment based on miRNA analysis.
PMID:38171356 | DOI:10.1021/acs.analchem.3c05013
Anal Chem. 2024 Jan 3. doi: 10.1021/acs.analchem.3c05263. Online ahead of print.
ABSTRACT
Prokaryotic Argonautes (pAgos) have been recently used in many nucleic acid biosensing applications but have rarely been used for regulating the isothermal amplification system. Herein, we reported Thermus thermophilus Argonaute (TtAgo)-mediated background-suppressed exponential isothermal amplification (EXPAR) as the first example to explore the binding activity of pAgos toward regulation of the amplification template. It was demonstrated that thermophilic pAgos efficiently eliminated nonspecific hybridization between templates by their binding affinity with the template, resulting in greatly enhancing the specificity of EXPAR. TtAgo-mediated, background-suppressed EXPAR was employed to detect miRNA with a detection limit of 10-15 M, which was 1000 times and 100 times more sensitive than that of traditional RT-PCR and EXPAR, respectively. This method further showed good performance in discriminating cancer patients from healthy individuals, indicating its potential for practical clinical applications.
PMID:38170960 | DOI:10.1021/acs.analchem.3c05263
Anal Chem. 2024 Jan 3. doi: 10.1021/acs.analchem.3c03952. Online ahead of print.
ABSTRACT
In situ monitoring of the actions of correlated enzymes in living cells is crucial for expanding our understanding of disease progression and evaluating drug efficacy. However, due to the diverse functions of different enzymes, currently available methods for comprehensive analysis of these events are limited. Here, we present an in situ track-generated DNA walker for AND-gate logic imaging of telomerase (TE) and flap endonuclease 1 (FEN1) activities in live cells. TE is in charge of generating the tracks for the walking strands by extending the TE primer on a gold nanoparticle, while FEN1 is responsible for recognizing the overlapping structure formed by the walking strands and the tracks and then cleaving the fluorescent reporter to produce signals. By utilizing the DNA walker, we successfully determined the expression levels and activities of TE and FEN1 in various cancer cell lines, offering promising prospects for screening inhibitors and investigating the biomolecular mechanisms of diseases.
PMID:38170958 | DOI:10.1021/acs.analchem.3c03952
Anal Chem. 2024 Jan 3. doi: 10.1021/acs.analchem.3c04124. Online ahead of print.
ABSTRACT
In the clinic, small-molecule metabolites (SMMs) in blood are highly convincing indicators for disease diagnosis, such as cancer. However, challenges still exist for detection of SMMs due to their low concentration and complicated components in blood. In this work, we report the design of a novel "selenium signature" nanoprobe (Se nanoprobe) for efficient identification of multiple aldehyde metabolites in blood. This Se nanoprobe consists of magnetic nanoparticles that can enrich aldehyde metabolites from a complex environment, functionalized with photosensitive "selenium signature" hydrazide molecules that can react with aldehyde metabolites. Upon irradiation with UV, the aldehyde derivatives can be released from the Se nanoprobe and further sprayed by mass spectrometry through ambient ionization (AIMS). By quantifying the selenium isotope distribution (MS/MS) from the derivatization product, accurate detection of several aldehyde metabolites, including valeraldehyde (Val), heptaldehyde (Hep), 2-furaldehyde (2-Fur), 10-undecenal aldehyde (10-Und), and benzaldehyde (Ben), is realized. This strategy reveals a new solution for quick and accurate cancer diagnosis in the clinic.
PMID:38170819 | DOI:10.1021/acs.analchem.3c04124
Anal Methods. 2024 Jan 3. doi: 10.1039/d3ay01827j. Online ahead of print.
ABSTRACT
The studies of drug-induced apoptosis play a vital role in the identification of potential drugs that could treat diseases such as cancer. Alterations in the native morphology of cancer cells following treatment with anticancer drugs serve as one of the indicators that reveal drug efficacy. Various techniques such as optical microscopy, electron microscopy (EM), and atomic force microscopy (AFM) have been used to map the three dimensional (3D) morphological changes in cells induced with drugs. However, caution should be exercised when interpreting morphological data from techniques that might alter the native morphology of cells, caused by phototoxicity, electron beam invasiveness, intrusive sample preparation, and cell membrane deformation. Herein, we have used scanning ion conductance microscopy (SICM) to study the 3D morphology and roughness of A549 adenocarcinoma cells under physiological conditions before and after cisplatin induced apoptosis, where we observed an increase in height, overall shrinkage of the cells, and irregular features form on the cell membrane. Tracking the morphology of the same single A549 cells exposed to cisplatin unveiled heterogeneity in response to the drug, formation of membrane blebs, and an increase in membrane roughness. We have also demonstrated the use of SICM for studying the effect of cisplatin on the dynamic changes in the volume of A549 cells over days. SICM is demonstrated as a technique for studying the effect of drug induced apoptosis in the same cells over time, and for multiple different single cells.
PMID:38167666 | DOI:10.1039/d3ay01827j