32933 items (32933 unread) in 74 feeds
J Pharm Biomed Anal. 2024 Oct 9;252:116514. doi: 10.1016/j.jpba.2024.116514. Online ahead of print.
ABSTRACT
We analyzed the potential relationship between liposomes and lung cancer risk for the first time using MR analysis methods. The results showed that sterol ester, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, and triacylglycerol may affect lung cancer risk. However, molecules with different fatty acid compositions also affect lung cancer risk differently. These results may help researchers discover more mechanisms by which lipid metabolism disorders support lung cancer growth and potential targets of lipid metabolism, giving more theoretical support to lung cancer therapeutic approaches that target lipid metabolic pathways.
PMID:39405787 | DOI:10.1016/j.jpba.2024.116514
Transl Oncol. 2024 Oct 13;50:102154. doi: 10.1016/j.tranon.2024.102154. Online ahead of print.
ABSTRACT
BACKGROUND: Intravenous immune checkpoint inhibitors (ICIs) have shown efficacy in treating locally advanced rectal cancer (LARC), but concerns about systemic toxicity persist. This study developed a unique approach termed chemo-immuno-embolization with transcatheter rectal arterial intervention (CIETAI), aiming to enhance the anti-tumor response while minimizing systemic toxicity.
METHOD: This is a prospective, single-arm, phase II clinical trial conducted in Daping hospital. Patients with previously untreated stage II/III LARC underwent preoperative CIETAI combined with PD-1 inhibitor tislelizumab plus oxaliplatin, followed by standard concomitant chemoradiotherapy (capecitabine and 50.4 Gy radiation). Intravenous tislelizumab was administered for an additional two cycles.
RESULTS: Between January 2023 and December 2023, a total of 38 patients were enrolled. As the primary endpoint, 17 (44.74 %) patients achieved pathological complete response (TRG0), with a major pathologic response (MPR) rate of 65.79 %. The anal preservation rate was 84.21 % (32/38), and importantly, 15 of 21 patients with low rectal cancer achieved organ preservation with functional maintenance. Eight patients experienced grade 3-4 adverse events (AEs). All immune-related AEs were grade 1-2, with the most common being endocrine toxicity (5/6, 83.33 %). No grade 5 AEs occurred.
CONCLUSION: This study provides preliminary evidence supporting the safety and efficacy of intraarterial tislelizumab delivery in the neoadjuvant setting for LARC. These promising results encourage further exploration in larger cohorts to validate the clinical impact of this novel CIETAI strategy.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05957016.
PMID:39405605 | DOI:10.1016/j.tranon.2024.102154
Tech Innov Patient Support Radiat Oncol. 2024 Aug 21;32:100271. doi: 10.1016/j.tipsro.2024.100271. eCollection 2024 Dec.
ABSTRACT
We hypothesized that pre-consult patient education videos can improve patient understanding about their diagnosis, lead to high satisfaction and low distress. In this pilot study, we developed a patient education video curriculum for patients with newly-diagnosed anal cancer. Comprehension of key content was evaluated by comparing pre- and post-test scores. Patient satisfaction scores were collected. Patient distress scores (0-10) were collected at the beginning of their consult visit prior to seeing the physician. We found that patient education videos prior to consult improved patient understanding, resulted in high patient satisfaction, and low patient distress at the time of consult.
PMID:39403310 | PMC:PMC11472093 | DOI:10.1016/j.tipsro.2024.100271
BMC Gastroenterol. 2024 Oct 14;24(1):368. doi: 10.1186/s12876-024-03452-z.
ABSTRACT
BACKGROUND: To evaluate the effect of stoma-related factors (stoma or no stoma, stoma type, and stoma reversal time) on the occurrence of low anterior resection syndrome (LARS), a highly prevalent condition that can develop after anal sphincter-sparing surgery for rectal cancer and impair quality of life, which includes fecal incontinence, fecal urgency and frequent defecation.
METHODS: Patients who underwent radical rectal cancer surgery from July 2018 to July 2022 in a tertiary hospital were included. Baseline data, tumor condition, operation condition and postoperative recovery were obtained by clinical observation. Follow-up data were collected by telephone follow-up. The chi-square and Fisher exact tests were used to analyse differences, coefficient of contingency was used to determine correlations, and independent risk factors for the occurrence of LARS (Patients with a score of 21 or more points were defined as having LARS using the LARS score) were further determined by binary logistic regression.
RESULTS: A total of 480 patients met the inclusion criteria, of which 267 used a defunctioning stoma and 213 did not use a defunctioning stoma. There was a positive correlation between defunctioning stoma (P < 0.001, P < 0.001, P < 0.05) and the occurrence of LARS at 3, 6, and 12 months postoperatively, and there was no significant correlation between the stoma type or stoma reversal time and the occurrence of LARS at 3, 6 and 12 months postoperatively (P > 0.05). In binary logistic regression analysis, high BMI (Exp(B) = 1.072, P = 0.039), tumor closer to dentate line (Exp(B) = 0.910, P = 0.016), and ultra-low anterior resection (Exp(B) = 2.264, P = 0.011) increased the possibility of LARS at 3 months postoperatively; high BMI, proximity of the tumor to the dentate line, and ultra-low anterior resection were not independent risk factors for LARS at 6 months postoperatively (P > 0.05). However, proximity of the tumor to the dentate line (Exp(B) = 0.880, P = 0.035) increased the likelihood of LARS at 12 months postoperatively, while high BMI and ultra-low anterior resection remained non-significant as independent risk factors for LARS at 12 months postoperatively (P > 0.05).
CONCLUSIONS: Defunctioning stoma was not an independent risk factor for the occurrence of LARS, whereas high BMI, tumor closer to dentate line, and ultra-low anterior resection were independent risk factors for the occurrence of LARS.
TRIAL REGISTRATION: Not applicable.
PMID:39402447 | DOI:10.1186/s12876-024-03452-z
Intern Med. 2024 Oct 11. doi: 10.2169/internalmedicine.4289-24. Online ahead of print.
ABSTRACT
Primary neuroendocrine carcinoma (NEC) of the anal canal is a rare, highly malignant tumor with a poor prognosis. Despite the standard first-line treatment with etoposide or irinotecan combined with cisplatin, effective second-line therapies are lacking. In 2019, Japan approved cancer genome profiling (CGP) tests for solid tumors to enhance genomic understanding. We present the case of a 79-year-old woman with NEC of the anal canal, treated with etoposide, carboplatin, and amrubicin. Post-standard therapy, CGP suggested pemigatinib, a tyrosine kinase inhibitor; however, the patient died before receiving it. This case highlights the potential of personalized medicine to improve outcomes in such cases.
PMID:39401914 | DOI:10.2169/internalmedicine.4289-24
AIDS Patient Care STDS. 2024 Oct 14. doi: 10.1089/apc.2024.0171. Online ahead of print.
ABSTRACT
Anal squamous cell carcinoma disproportionally affects people with HIV (PWH); however, engagement in anal cancer screening is low in many settings. This study was conducted to assess knowledge and perceptions of anal cancer screening to identify factors in the engagement and retention in prevention services among PWH. Semistructured interviews were conducted among adult PWH eligible for anal cancer screening in our Ryan White HIV/AIDS Program clinic. Descriptive statistics were tabulated; thematic analyses were performed to identify emerging motivators, facilitators, and barriers. Among 26 PWH, 9 had not been screened, 8 had undergone Papanicolaou (Pap) testing alone, and 9 had undergone anoscopy. The median age of the cohort was 55.2 years; 54% identified as men who have sex with men, and 54% identified as Black. In the unscreened cohort, participants were motivated by investing in their health and positive attitudes toward cancer prevention however were deterred by a lack of referral and low awareness about screening. Among those who had Pap testing, trust in healthcare providers and abnormal testing results were motivators to engagement, whereas lack of perceived risk of anal cancer and worry about pain of an anoscopy were prominent barriers. Among those who had anoscopy, perceived risk, positive experience with the procedure, and use of anxiolytics prior to anoscopy were motivators, whereas anxiety around a new cancer diagnosis and negative experience with anoscopy were barriers. Clinics seeking to build or strengthen their anal cancer screening programs can address the barriers described in this study to promote access to anal cancer screening among PWH.
PMID:39401138 | DOI:10.1089/apc.2024.0171
J Med Virol. 2024 Oct;96(10):e70002. doi: 10.1002/jmv.70002.
ABSTRACT
High-risk human papillomavirus (HPV) infections are responsible for cervical cancer. However, little is known about the differences between HPV types and risk categories regarding their genetic diversity and particularly APOBEC3-induced mutations - which contribute to the innate immune response to HPV. Using a capture-based next-generation sequencing, 156 HPV whole genome sequences covering 43 HPV types were generated from paired cervical and anal swabs of 30 Togolese female sex workers (FSWs) sampled in 2017. Genetic diversity and APOBEC3-induced mutations were assessed at the viral whole genome and gene levels. Thirty-four pairwise sequence comparisons covering 24 HPV types in cervical and anal swabs revealed identical infections in the two anatomical sites. Differences in genetic diversity among HPV types was observed between patients. The E6 gene was significantly less conserved in low-risk HPVs (lrHPVs) compared to high-risk HPVs (hrHPVs) (p = 0.009). APOBEC3-induced mutations were found to be more common in lrHPVs than in hrHPVs (p = 0.005), supported by our data and by using large HPV sequence collections from the GenBank database. Focusing on the most common lrHPVs 6 and 11 and hrHPVs 16 and 18, APOBEC3-induced mutations were predominantly found in the E4 and E6 genes in lrHPVs, but were almost absent in these genes in hrHPVs. The variable APOBEC3 mutational signatures could contribute to the different oncogenic potentials between HPVs. Further studies are needed to conclusively determine whether APOBEC3 editing levels are associated to the carcinogenic potential of HPVs at the type and sublineage scales.
PMID:39400339 | DOI:10.1002/jmv.70002
Anal Chem. 2024 Oct 14. doi: 10.1021/acs.analchem.4c03142. Online ahead of print.
ABSTRACT
A key challenge for achieving high-efficient DNA strand displacement reaction (SDR) with existing technologies is the inferior kinetic performance due to the alternately cumbersome conjunction and dissociation of dsDNA. In this work, a novel multidriven SDR collaborated by toehold initiator, strand towing, and click chemistry is engineered. The invasion strand (O) endows the hybridization with a basal strand (M) in dsDNA for releasing a displacement strand (P), which can be significantly boosted by the towing of a helper strand and impetus from the click reaction. Accordingly, the hybridization rate and dissociation extent of P can be largely improved and showed a desiring displacement rate close to 6-fold compared with the traditional method, providing a newly high-efficient SDR strategy for potential application in biosensing, clinical diagnostics, and DNA nanotechnology. In view of this, a practical biosensing platform by combining the multidriven SDR (MSDR) with waste-free DNA multi-cycle amplification is constructed for the rapid and ultrasensitive electrochemical detection of cancer-related miRNA-21. The substantial output DNA as an invasion strand (O) from target-triggered waste-free DNA multicycle can high-efficiently release a signal probe (Fc)-labeled displacement strand (P) on an electrode by using the proposed MSDR, obtaining a low detection limit below 106.8 aM.
PMID:39400171 | DOI:10.1021/acs.analchem.4c03142
Anal Chem. 2024 Oct 14. doi: 10.1021/acs.analchem.4c05111. Online ahead of print.
ABSTRACT
Genetically sequencing patient-derived organoids (PDOs) at the single-cell level has emerged as a promising method to infer cell-level heterogeneity of original organs and improve cancer precision medicine. Unfortunately, because of the limited starting quantity and uncontrolled establishing process of PDOs, the existing single-cell sequencing technologies, either manual-operation-based or microfluid-based, are inefficient in processing PDOs originating from clinical tissue samples. To address such issues, this study presents a microfluidic chip-based automatic system for sequencing organoids at the single-cell level, named as MASSO. By performing all required procedures, including PDO establishment/culturing/digesting and single-cell isolation/lysis/whole-genome amplification, in a single microfluidic chip, the possible loss of precious PDO is avoided, and the high quality of on-chip whole-genome amplification of a single PDO cell is ensured. By automating the entire operation process, possible human error is eliminated, and the data repeatability is improved, therefore bridging the technical gap between laboratorial proof-of-concept studies and clinical practices. After characterizing the organoid single-cell whole-genome amplification chip (named as OSA-Chip) and the MASSO, the first successful attempt, to the best of our knowledge, on whole-genome sequencing lung cancer PDO at the single-cell level was performed by MASSO. The results reveal that the MASSO is capable of not only identifying common cancer-related mutations but also discovering specific mutations that affect drug responses, therefore laying the technical foundation for efficiently understanding the cell-level heterogeneities of PDOs and corresponding original organs.
PMID:39399894 | DOI:10.1021/acs.analchem.4c05111
Lifetime Data Anal. 2024 Oct 13. doi: 10.1007/s10985-024-09638-7. Online ahead of print.
ABSTRACT
Putative surrogate endpoints must undergo a rigorous statistical evaluation before they can be used in clinical trials. Numerous frameworks have been introduced for this purpose. In this study, we extend the scope of the information-theoretic causal-inference approach to encompass scenarios where both outcomes are time-to-event endpoints, using the flexibility provided by D-vine copulas. We evaluate the quality of the putative surrogate using the individual causal association (ICA)-a measure based on the mutual information between the individual causal treatment effects. However, in spite of its appealing mathematical properties, the ICA may be ill defined for composite endpoints. Therefore, we also propose an alternative rank-based metric for assessing the ICA. Due to the fundamental problem of causal inference, the joint distribution of all potential outcomes is only partially identifiable and, consequently, the ICA cannot be estimated without strong unverifiable assumptions. This is addressed by a formal sensitivity analysis that is summarized by the so-called intervals of ignorance and uncertainty. The frequentist properties of these intervals are discussed in detail. Finally, the proposed methods are illustrated with an analysis of pooled data from two advanced colorectal cancer trials. The newly developed techniques have been implemented in the R package Surrogate.
PMID:39397147 | DOI:10.1007/s10985-024-09638-7
Anal Chim Acta. 2024 Nov 15;1329:343263. doi: 10.1016/j.aca.2024.343263. Epub 2024 Sep 19.
ABSTRACT
N-acetylneuraminic acid (NANA) can be used as a biomarker for many types of cancers. Currently, there are various methods for detecting NANA but showing some shortcomings that limit the real-time diagnosis of cancer. In contrast, fluorescence analysis has obvious advantages such as low cost, fast response time, and easy operation, and it also enables visual detection for real-time cancer monitoring. Therefore, the establishment of an efficient and rapid detection method is essential for the early prevention and treatment of the disease. Based on the properties of layered rare-earth hydroxide (LRH), we synthesized a dual-emission fluorescent material (NDC/SDS-LEuH), and further fabricated a fluorescent nanoprobe (ANP) for the detection of NANA. The probe has the advantages of high sensitivity (LOD = 32.9 μM) and high selectivity with fast response. During the sensing process, the dual emission of the probe shows opposite changes due to the photoinduced electron transfer (PET) effect and the interaction between NANA and the probe. The color changes of the system can be observed under UV irradiation. Therefore, a visual platform was developed to detect NANA with a LOD of 0.09 mM. In addition, a probe hydrogel was prepared, which can be applied in the anti-counterfeiting to improve the difficulty of counterfeiting and the security of anti-counterfeiting. The probe achieves ratiometric fluorescence detection of NANA, which reduces background interference and improves the accuracy of detection. A visual detection platform was fabricated to realize the real-time detection. In addition, the prepared probe hydrogel showed the potential applications in anti-counterfeiting, which provided new ideas for the design and application of anti-counterfeiting materials.
PMID:39396320 | DOI:10.1016/j.aca.2024.343263
Anal Chim Acta. 2024 Nov 15;1329:343255. doi: 10.1016/j.aca.2024.343255. Epub 2024 Sep 19.
ABSTRACT
Abnormal alkaline phosphatase (ALP) levels have been linked to breast cancer, prostate cancer, bone damage, gingivitis and abnormal liver function. Monitoring ALP levels is important for better diagnosis and treatment of these diseases. Detection of ALP by colorimetric methods is very portable in terms of signal reading, but still suffers from low sensitivity. SERS can achieve high sensitivity detection, but cannot be separated from large precision instruments. Therefore, researchers have worked to optimize various aspects of the sensor, such as sensitivity, detection time, and operating procedures, to enable portable and rapid ALP detection. Isothermal amplification using simple system components meets the current demand for rapid, portable assays. We have developed a novel one-pot high-efficiency ALP assay strategy called IHP-GT. IHP-GT performs a one-step cascade amplification using only one probe (IGHP) as a template. The phosphorylated primer P binds to IGHP, forming a P/IGHP structure. At this point, the G-quadruplex closes and no signal is generated. In the presence of ALP, primer P is dephosphorylated to remove the restriction and then amplified in a cascade using IGHP as a template to release the full G-quadruplex structure. The single-stranded G-quadruplex will bend to form a secondary structure, facilitating secondary amplification starting with primer AT to produce PrG and P'. The PrG structure will trigger triple amplification, enabling cascade amplification. The G-quadruplex structure produced by cascade amplification has the dual role of promoting amplification of primer AT and binding to ThT to produce a fluorescent signal. The IHP-GT method provides a highly sensitive detection of ALP in less than 90 min and has been successfully used to analyze ALP in human serum samples. In addition, IHP-GT can be used to screen for ALP inhibitors. Importantly, we lyophilized the IHP-GT reaction components into powder form for user-friendly poc testing.
PMID:39396314 | DOI:10.1016/j.aca.2024.343255
Anal Chim Acta. 2024 Nov 15;1329:343245. doi: 10.1016/j.aca.2024.343245. Epub 2024 Sep 14.
ABSTRACT
BACKGROUND: Autophagy, as an essential physiological process in eukaryotes, has been revealed to be closely related to aging and many major diseases. Real-time in situ imaging of autophagy processes in living cells is necessary for timely detection of autophagy defects and the development of treatment methods. Currently, many studies are dedicated to the design of autophagy probes, and various types of fluorescent probes for autophagy detection have been reported. However, most of them are single fluorescence signal outputs, which may lead to non-specific signals. Nowadays a reliable and sensitive autophagy monitoring probe is still essential.
RESULTS: A supramolecular fluorescent probe was prepared via the controllable self-assembly of a thiacyanine dye named PTC for tracking autophagy in living cells. PTC was very sensitive to viscosity, and its aggregates were completely converted into monomers as viscosity increased. This process led to a significant increase of over 2000 times in the fluorescence intensity ratio between monomers and aggregates. PTC also exhibited selective affinity for G-quadruplex (G4) structure, which decomposed PTC aggregates into monomers, resulting in a fluorescence ratio increase of up to tens of folds. In living cells, PTC existed as aggregates in lysosomes, maintaining sensitivity to viscosity and G4s. In confocal imaging experiments, PTC sensitively responded to the induction and inhibition of cellular autophagy, displaying opposite changes in the monomer and aggregate fluorescent channels.
SIGNIFICANCE: This work provides a reliable fluorescent probe for autophagy detection in live cells, which has the advantages of high sensitivity, low cost, and ease of use, making it have the potential for widespread application. This study also offers a new strategy for designing autophagy probes with both high sensitivity and high specificity.
PMID:39396306 | DOI:10.1016/j.aca.2024.343245
Anal Chim Acta. 2024 Nov 15;1329:343240. doi: 10.1016/j.aca.2024.343240. Epub 2024 Sep 11.
ABSTRACT
BACKGROUND: The detection of tyrosine kinase inhibitors (TKIs) in biological fluids is essential due to their critical role in cancer therapy and the variability in individual drug metabolism, which necessitates precise dosing. Traditional methods for analyzing TKIs in biological fluids, such as blood plasma, typically involve complex sample preparation techniques that can be resource-intensive, environmentally burdensome, and not sufficiently sensitive for low-concentration analytes. There is a pressing need for more efficient, economical, and environmentally friendly methods that can enhance sensitivity and throughput without compromising accuracy.
RESULTS: This study explores the use of melt-blown polypropylene nonwoven (MBPP), commonly found in face masks, as a novel sorbent for pipette-tip micro-solid phase extraction (PT-μSPE). MBPP demonstrated excellent hydrophobicity and significant mesoporous adsorption capacity. An extraction device was fashioned by inserting a segment of MBPP (15 mg) into a 200 μL disposable plastic pipette tip, which was then attached to a 2.5 mL disposable plastic syringe. The MBPP's fabric form removes the need for a frit, allowing the extraction process to be completed in just 3 min through simple plunger manipulation. The method achieved extraction recoveries ranging from 60.5 % to nearly 100 %. Subsequent method validation using liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed satisfactory linearity (coefficient of determination R2 > 0.993), accuracy (relative recoveries: 86.3%-114.8 %), and precision (relative standard deviation: 3.4%-11.3 %), with detection limits between 0.022 and 0.135 ng mL-1.
SIGNIFICANCE: The introduction of MBPP for PT-μSPE represents a significant advancement in the bioanalytical detection of TKIs, offering a highly efficient, cost-effective, and environmentally sustainable method. It compares favorably with existing techniques, offering advantages in terms of cost, environmental impact, and ease of use. This approach has the potential to be widely adopted for routine monitoring of TKIs in clinical settings.
PMID:39396303 | DOI:10.1016/j.aca.2024.343240
Anal Chim Acta. 2024 Nov 15;1329:343238. doi: 10.1016/j.aca.2024.343238. Epub 2024 Sep 11.
ABSTRACT
The apurinic/apyrimidinic (AP) site is an important intermediate in the DNA base excision repair (BER) pathway, having the potential of being a biomarker for DNA damage. AP sites could lead to the stalling of polymerases, the misincorporation of bases and DNA strand breaks, which might affect physiological function of cells. However, the abundance of AP sites in genomic DNA is very low (less than 2 AP sites/106 nts), which requires a sensitive and accurate method to meet its detection requirements. Here, we described an ultrasensitive quantification method based on a hydrazine-s-triazine reagent (i-Pr2N) labeling for AP sites combining with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The limit of detection reached an ultralow level (40 amol), realizing the most sensitive MS-based quantification for the AP site. To guarantee the accuracy of the quantitative results, the labeling reaction was carried out directly on DNA strands instead of labeling after DNA enzymatic digestion to reduce artifacts that might be produced during the enzymatic process of DNA strands. And selective detection was realized by MS to avoid introducing the false-positive signals from other aldehyde species, which could also react with i-Pr2N. Genomic DNA samples from different mammalian cell lines were successfully analyzed using this method. There were 0.4-0.8 AP sites per 106 nucleotides, and the values would increase 16.1 and 2.75 times when cells were treated with genotoxic substances methyl methanesulfonate and 5-fluorouracil, respectively. This method has good potential in the analysis of a small number of cell samples and clinical samples, is expected to be useful for evaluating the damage level of DNA bases, the genotoxicity of compounds and the drug resistance of cancer cells, and provides a new tool for cell function research and clinical precise treatment.
PMID:39396301 | DOI:10.1016/j.aca.2024.343238
Anal Chim Acta. 2024 Nov 15;1329:343235. doi: 10.1016/j.aca.2024.343235. Epub 2024 Sep 14.
NO ABSTRACT
PMID:39396298 | DOI:10.1016/j.aca.2024.343235
Anal Chim Acta. 2024 Nov 15;1329:343234. doi: 10.1016/j.aca.2024.343234. Epub 2024 Sep 12.
ABSTRACT
Exosomes are extracellular vesicles of 30-200 nm in diameter that inherit molecular markers from their parent cells, including proteins, lipids, nucleic acids, and glycoconjugates. The detection and protein profiling of exosome could provide noninvasive access to disease diagnosis and treatment. In recent years, it has been found that Zr-MOFs can capture exosomes by forming Zr-O-P bonds through the phospholipid bilayer of exosomes. In addition, gold nanoparticles with optical response are used for colorimetric biological analysis, such as proteins, peptides, DNA. In this work, we proposed an aptasensor for exosome capture and sensitive colorimetric detection. The Zr-MOF (PCN-224) is innovatively used to capture exosome by Zr-O-P bond, and sodium tripolyphosphate (STPP) is used to block the non-specific adsorption of DNA aptamers on the surface of PCN-224 by site occupying effect. The aptamer binds to exosome immunity, and the remaining aptamer binds to Au NPs, resulting in an increase in steric hindrance and electrostatic repulsion, which makes the dispersion of Au NPs better and avoids the aggregation of Au NPs induced by dopamine (DA). The ratio of absorbance A650/A520 represents the aggregate degree of Au NPs, which correlates with the concentration of exosomes, and achieves sensitive colorimetric detection of exosomes with a linear range of 1.0 × 105-1.0 × 107 particles/mL. Further studies reveal that our work has excellent selectivity and anti-interference, breast cancer patients and healthy individuals can be distinguished by analyzing the differences in the expression of CD63 protein on exosome. The proposed biosensor integrates the capture and detection of exosomes, the multiple colors of Au NPs changed significantly from red to gray, which was conducive to the naked-eye identification of exosome detection.
PMID:39396297 | DOI:10.1016/j.aca.2024.343234
Anal Chim Acta. 2024 Nov 15;1329:343227. doi: 10.1016/j.aca.2024.343227. Epub 2024 Sep 10.
ABSTRACT
BACKGROUND: Cysteine (Cys) is the major intracellular thiol and plays a key role in human pathology. Furthermore, endogenous sulfur dioxide (SO2) is produced in mammals. Abnormal levels of SO2 are commonly associated with a variety of respiratory, cardiovascular, and neurological diseases. Therefore, given their important role in life activities, it is significant to construct a fluorescent probe that can detection between Cys and SO2.
RESULTS: We have designed and synthesized a two-site fluorescent probe CUM with coumarin derivative and benzaldehyde molecules, which can detect and differentiate between Cys and SO2 through dual excitation wavelengths. Its carbon-carbon double bond reacts with Cys and undergoes a nucleophilic reaction, emitting green fluorescence at 520 nm, while SO32- reacts with benzaldehyde molecules in the probe CUM and undergoes a blue fluorescence at 460 nm. SO32- reacts with the benzaldehyde molecule of probe CUM and fluoresces blue at 460 nm. Thus, the probe CUM with two reaction sites can distinguish between Cys and SO2 and shows good selectivity and fast reaction speed. In addition, we successfully utilized probe CUM to image Cys and SO2 in human breast cancer cells (MDA-MB-231).
SIGNIFICANCE: This work provides an effective method for the molecular design of coumarin-based fluorescent probes. Probe CUM as a promising and reliable tool for the meticulous discrimination and quantification of Cys and SO2 in diverse biological matrices, thereby opening up new avenues for various biological systems.
PMID:39396292 | DOI:10.1016/j.aca.2024.343227
Anal Chim Acta. 2024 Nov 15;1329:343222. doi: 10.1016/j.aca.2024.343222. Epub 2024 Sep 7.
ABSTRACT
BACKGROUND: Photodynamic therapy (PDT) is emerging as a promising cancer treatment. The PDT efficacy is primarily attributed to the generation of singlet oxygen (1O2), stemming from the integrated effects of the photosensitizer, oxygen, and light. The singlet oxygen quantum yield (ΦΔ) serves as a bridge that links these parameters to the overall efficacy of PDT. The near-infrared luminescence of 1O2 provides a direct way for determining ΦΔ, but suffers from a poor signal-to-noise ratio. While the chemical trap probe method is detection-friendly, but it has a strict requirement for the excitation wavelength. Therefore, the existing methods for ΦΔ measurement are insufficient.
RESULTS: In this work, we developed an approach to determine ΦΔ of a broader range of photosensitizers using only the commonly used solvent dimethyl sulfoxide (DMSO), which can be oxidized by 1O2 to dimethyl sulfone. This method establishes the relationship between 1O2 production and changes in DMSO absorption spectra, eliminating the need for additional chemical probes. This method was validated by measuring the ΦΔ of rose bengal (RB) through systematic changes in absorption spectrum of DMSO under various RB concentrations and different excitation light power densities. Moreover, the ΦΔ of hematoporphyrin monomethyl ether (HMME), as determined by this method, is consistent with measurements obtained using the 1,3-diphenylisobenzofuran (DPBF) trapping probe. This consistency further validates the reliability of this method.
SIGNIFICANCE AND NOVELTY: This work presents a direct, probe-free method to determine ΦΔ, reducing potential interference and expanding the range of useable excitation wavelengths. Its ability to measure ΦΔ using only DMSO enhances the accuracy of photosensitizer measurement, and broadens the applicability of the method to a wide range of samples, thereby advancing research on the properties of photosensitizers and further promoting the development of PDT.
PMID:39396287 | DOI:10.1016/j.aca.2024.343222
Anal Chim Acta. 2024 Nov 15;1329:343171. doi: 10.1016/j.aca.2024.343171. Epub 2024 Sep 4.
ABSTRACT
BACKGROUND: Extracellular vesicles (EVs) are involved in intercellular communication and various biological processes. They hold clinical promise for the diagnosis and management of a wide range of pathologies, including cancer, cardiovascular diseases and degenerative diseases, and are of interest as regenerative therapies. Understanding the complex structure of these EVs is essential to perceive the current challenges associated with their analysis and characterization. Today, challenges remain in terms of access to high-yield, high-purity isolation methods, as well as analytical methods for characterizing and controlling the quality of these products for clinical use.
RESULTS: We isolated EVs from the same immortalized human cell culture supernatant using two commonly used approaches, namely differential ultracentrifugation and membrane affinity. Then we evaluated EV morphology, size, zeta potential, particle and protein content, as well as protein identity using cryogenic electron microscopy, nanoparticle tracking analysis, asymmetric field flow fractionation (AF4) and size exclusion chromatography (SEC) coupled to multi angle light scattering, bicinchoninic acid assay, electrophoretic light scattering, western blotting and high-resolution mass spectrometry. Compared to membrane affinity isolation, dUC is a more efficient isolation process for obtaining particles with the characteristics expected for EVs and more specifically for exosomes. To validate an isolation process, cryogenic electron microscopy is essential to confirm vesicles with membranes. High resolution mass spectrometry is powerful for understanding the mechanism of action of vesicles. Separative methods, such as AF4 and SEC, are interesting for separating vesicle subpopulations and contaminants.
SIGNIFICANCE: This study provides a critical assessment of eight different techniques for analyzing EVs, some of which are mandatory for in-depth characterization and deciphering, while others are more appropriate for routine analysis, once the production and isolation process has been validated. The strengths and limitations of the different approaches used are highlighted.
PMID:39396273 | DOI:10.1016/j.aca.2024.343171
Ann Surg Oncol. 2024 Oct 12. doi: 10.1245/s10434-024-16316-3. Online ahead of print.
ABSTRACT
INTRODUCTION: Total mesorectal excision (TME) with intersphincteric resection and handsewn coloanal anastomosis (ISR-CAA) has been shown to be oncologically safe in patients with distal rectal cancer treated with preoperative chemoradiation. The introduction of the watch-and-wait (WW) strategy for rectal cancer patients with a clinical complete response to neoadjuvant therapy is changing the profile of patients undergoing TME surgery immediately following neoadjuvant treatment. The outcomes of ISR-CAA for patients with locally advanced rectal cancers not qualifying for WW have not been investigated.
METHODS: We conducted a retrospective analysis comparing the outcomes of ISR-CAA and abdominoperineal resection (APR) in patients with distal rectal cancer treated with neoadjuvant therapy and not qualifying for WW, at a comprehensive cancer center with an established WW program. The primary outcome was local recurrence-free survival.
RESULTS: Sixty-seven patients had ISR-CAA and 79 had APR. Median follow-up was 61.1 months. The two groups were similar in sex, tumor stage, grade, and distance from the anal verge, but patients in the APR group were older on average. An R0 resection was achieved in 94% of ISR-CAA patients and 91% of APR patients. Patients in the ISR-CAA group had a lower 5-year rate of local recurrence-free survival (79% vs. 93%; p = 0.038) compared with the APR group; however, 5-year disease-free survival did not differ significantly between groups (67% for ISR-CAA and 64% for APR; p = 0.19).
CONCLUSIONS: The local recurrence rate after ISR-CAA may be higher than after APR for patients without a clinical complete response to neoadjuvant therapy requiring TME surgery.
PMID:39395915 | DOI:10.1245/s10434-024-16316-3
Eur J Surg Oncol. 2024 Oct 6;50(12):108738. doi: 10.1016/j.ejso.2024.108738. Online ahead of print.
ABSTRACT
BACKGROUND: Precise evaluation of pathological complete response (pCR) is essential for determining the prognosis of patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (NCRT) and can offer clues for the selection of subsequent treatment strategies. Most current predictive models for pCR focus primarily on pre-treatment factors, neglecting the dynamic systemic changes that occur during neoadjuvant chemoradiotherapy, and are constrained by low accuracy and lack of integrity.
PURPOSE: This study devised a novel predictor of pCR using dynamic alterations in systemic inflammation-nutritional marker indexes (SINI) during neoadjuvant therapy and developed a machine-learning model to predict pCR.
METHODS: Two cohorts of patients with LARC from center one from 2012 to 2017 and from center two from 2020 to 2023 were integrated for analysis. This study compared dynamic changes in blood indexes before and after neoadjuvant therapy and surgical operation. A least absolute shrinkage and selection operator (LASSO) regression analysis was conducted to mitigate collinearity and identify key indexes, constructing the SINI. Univariate and multiple logistic regression analyses were used to identify the independent risk factors associated with pCR. Additionally, 10 machine learning algorithms were employed to develop predictive models to assess risk. The hyperparameters of the machine learning models were optimized using a random search and 10-fold cross-validation. The models were assessed by examining various metrics, including the area under the receiver operating characteristic curves (AUC), the area under the precision-recall curve (AUPRC), decision curve analysis, calibration curves, and the precision and accuracy of the internal and external validation cohorts. Additionally, Shapley's additive explanations (SHAP) were employed to interpret the machine learning models.
RESULTS: The study cohort comprised 677 patients from the center one and 224 patients from the center two. Six key indexes were identified, and a predictive index, SINI, was constructed. Univariate and multiple logistic regression analyses revealed that SINI, clinical T-stage, clinical N-stage, tumor size, and the distance from the anal verge were independent risk factors for pCR in patients with LARC following NCRT. The mean AUC value of the extreme gradient boosting (XGB) model in the 10-fold cross-validation of the training set was 0.877. The XGB model demonstrated superior performance in the internal and external validation sets. Specifically, in the internal test set, the XGB model achieved an AUC of 0.86, AUPRC of 0.707, accuracy of 0.82, and precision of 0.80. In the external validation set, the XGB model exhibited an AUC of 0.83, AUPRC of 0.702, accuracy of 0.81, and precision of 0.81. Additionally, the predictions generated by the XGB model were analyzed using SHAP.
CONCLUSION: This study involved developing and validating an XGB model using SINI to predict pCR in patients with LARC. Besides, a SINI-based machine learning model shows promise in accurately predicting pCR following NCRT in patients with resectable LARC, offering valuable insights for personalized treatment approaches.
PMID:39395242 | DOI:10.1016/j.ejso.2024.108738
Lifetime Data Anal. 2024 Oct 12. doi: 10.1007/s10985-024-09637-8. Online ahead of print.
ABSTRACT
Recurrent event data with a terminal event arise in follow-up studies. The current literature has primarily focused on the effect of covariates on the recurrent event process using marginal estimating equation approaches or joint modeling approaches via frailties. In this article, we propose a conditional model for recurrent event data with a terminal event, which provides an intuitive interpretation of the effect of the terminal event: at an early time, the rate of recurrent events is nearly independent of the terminal event, but the dependence gets stronger as time goes close to the terminal event time. A two-stage likelihood-based approach is proposed to estimate parameters of interest. Asymptotic properties of the estimators are established. The finite-sample behavior of the proposed method is examined through simulation studies. A real data of colorectal cancer is analyzed by the proposed method for illustration.
PMID:39395077 | DOI:10.1007/s10985-024-09637-8
Anal Biochem. 2024 Oct 10;696:115686. doi: 10.1016/j.ab.2024.115686. Online ahead of print.
ABSTRACT
Prostate cancer (PC) is very common in old age and causes many deaths. Early diagnosis and monitoring of the progress of the disease and the effectiveness of PC treatment are critical. On the other hand, choosing a specific biomarker for PCs is essential. Prostate-specific antigen (PSA) is a specific biomarker secreted in the prostate epithelial cells, which increases in cancer cells. Between all employed sensing mechanism, electrochemical sensors based on nanomaterials have created many hopes. Meanwhile, graphite carbon nitride (g-C3N4) is interested in developing photoelectrochemical sensors due to its large surface area, stability, easy modification, and good photoelectronic properties. In this review, electrochemical sensors based on nanocomposites containing g-C3N4 have been investigated in PSA detection. After providing an overview of the characteristics of g-C3N4 and cancer biomarkers, it reviews the strategies and mechanisms involved in identifying PSA. Different approaches to photoelectrochemistry, impedimetric immunosensors, photocatalysis, and luminescence have been used in diagnostic mechanisms. Then, challenges and prospects for electrochemical sensors based on nanocomposites containing g-C3N4 in PSA detection have been analyzed. The recent review generally opens an efficient view in PSA diagnosis and the application of g-C3N4-based electrochemical sensors in personalized medicine diagnosis and treatment.
PMID:39393750 | DOI:10.1016/j.ab.2024.115686
Anal Chem. 2024 Oct 11. doi: 10.1021/acs.analchem.4c03055. Online ahead of print.
ABSTRACT
Herein, a novel functional DNA structure, acid-stimulated self-assembly DNA nanonetwork (ASDN), was proposed for miRNA-221 sensitive detection and high-resolution living cancer cell imaging. Significantly, the self-assembly of ASDN only occurred in the acidic extracellular environment of cancer cells, which could be endocytosed by cancer cells to eliminate the interference of noncancer cells and deliver the ASDN into cancer cells. Subsequently, endogenous miRNA-221 could trigger the catalytic hairpin assembly within ASDN, resulting in the separation of the fluorophore Cy5 and the quencher BHQ2 to recover the substantial Cy5 fluorescence signals, thus achieving signal amplification for sensitive detection of miRNA-221 with a detection limit of 5.5 pM, as well as facilitating high-resolution and low-background imaging of miRNA-221 in cancer cells. In consequence, this strategy provides an innovative DNA nanonetwork to distinguish cancer cells from other cells for sensitive detection of biomarkers, offering a meaningful reference for the application of DNA nanostructure self-assembly technology in relevant fundamental research and disease diagnosis.
PMID:39392416 | DOI:10.1021/acs.analchem.4c03055
Anal Chem. 2024 Oct 11. doi: 10.1021/acs.analchem.4c04477. Online ahead of print.
ABSTRACT
Accurate and reliable detection of uracil-DNA glycosylase (UDG) activity is crucial for clinical diagnosis and prognosis assessment. However, current techniques for accurately monitoring UDG activity still face significant challenges due to the single input or output signal modes. Here, we develop a sequentially activated-dumbbell DNA nanodevice (SEAD) that enables precise and reliable evaluation of UDG activity through primer exchange reactions (PER)-based orthogonal signal output. The SEAD incorporates a double-hairpin structure with a stem containing two deoxyuridine (dU) sites for target recognition and two preblocked primer binding regions for target amplification and signal output. Upon UDG recognition of dU, the SEAD can be cleaved by apurinic/apyrimidinic endonuclease 1 (APE1), generating two different hairpins with exposed primer binding regions. These hairpins serve as templates to initiate the parallel PER, enabling the extending of two different amplification products: a long single-stranded DNA (ssDNA) with repetitive sequences and a short ferrocene-labeled ssDNA with complementary sequences. These products further self-assemble into DNA nano-strings in an orthogonal manner that act as an electrochemiluminescence signal switch, enabling precise detection of low-abundance UDG. This work develops a sequential input and orthogonal output strategy for accurately monitoring UDG activity, highlighting the significant potential in cancer diagnosis and treatment.
PMID:39392054 | DOI:10.1021/acs.analchem.4c04477
Anal Chem. 2024 Oct 11. doi: 10.1021/acs.analchem.4c03434. Online ahead of print.
ABSTRACT
Nanolabels can enhance the detection performance of electrochemical biosensing methods, yet their practical application is hindered by complex preparation, batch-to-batch variability, and poor long-term storage stability. Herein, we present a novel electrochemical method for miRNA detection based on the just-in-time generation of zeolitic imidazolate framework-8 (ZIF-8) nanolabels initiated by nucleic acids. In this design, the target miRNA-21 is captured with magnetic beads and polyadenylated by Escherichia coli Poly(A) polymerase (EPP), producing miRNA-21 molecules with poly(A) tails (miR-21-poly(A)). These molecules are then adsorbed onto a bare gold electrode (AuE) surface via adenine-gold affinity interactions, serving as nucleation sites for the rapid in situ formation of ZIF-8 nanoparticles. The ZIF-8 nanoparticles function as signal labels, impeding electron transfer at the electrode interfaces and thereby generating a notable electrochemical signal. The developed method demonstrated exceptional sensitivity, with a detection limit (LOD) as low as 2.3 aM and a linear detection range from 10 aM to 1000 fM. The practical application of the developed method was validated by using it to evaluate miRNA-21 expression levels in various biological samples, including cell lines, tumor tissues, and clinical blood samples from non-small cell lung cancer (NSCLC) patients. This approach simplifies the detection process by eliminating the need for presynthesized nanomaterials and premodified electrodes. Its simplicity and high sensitivity make this method a promising tool for point-of-care testing and a wide range of biomedical research applications.
PMID:39391952 | DOI:10.1021/acs.analchem.4c03434
Risk Anal. 2024 Oct 10. doi: 10.1111/risa.17658. Online ahead of print.
ABSTRACT
Listeria monocytogenes is a foodborne pathogen of concern for cancer patients, who face higher morbidity and mortality rates than the general population. The neutropenic diet (ND), which excludes fresh produce, is often utilized to mitigate this risk; however, an analysis weighing the theoretical listeriosis risk reduction of produce exclusion aspects of the ND and possible negative tradeoffs has never been conducted. Consequently, this work constructed decision analytic models using disability-adjusted life years (DALYs) to compare the impacts of the ND, such as increased neutropenic enterocolitis (NEC) likelihood, with three alternative dietary practices (safe food handling [SFH], surface blanching, and refrigeration only) across five age groups, for cancer patients who consume ready-to-eat salad. Less disruptive diets had fewer negative health impacts in all scenarios, with median alternative diet DALYs per person per chemotherapy cycle having lower values in terms of negative health outcomes (0.088-0.443) than the ND (0.619-3.102). DALYs were dominated by outcomes associated with NEC, which is more common in patients following the ND than in other diets. Switchover point analysis confirmed that, because of this discrepancy, there were no feasible values of other parameters that could justify the ND. Correspondingly, the sensitivity analysis indicated that NEC mortality rate and remaining life expectancy strongly affected DALYs, further illustrating the model's strong dependence on NEC outcomes. Given these findings, and the SFH's ease of implementation and high compliance rates, the SFH diet is recommended in place of the ND.
PMID:39389932 | DOI:10.1111/risa.17658
Med Image Anal. 2024 Oct 9:103363. doi: 10.1016/j.media.2024.103363. Online ahead of print.
NO ABSTRACT
PMID:39389883 | DOI:10.1016/j.media.2024.103363
Actas Dermosifiliogr. 2024 Oct 8:S0001-7310(24)00763-4. doi: 10.1016/j.ad.2024.10.006. Online ahead of print.
ABSTRACT
High-grade anal intraepithelial squamous lesion is significantly prevalent among men who have sex with men and are infected with the human immunodeficiency virus. This condition-the precursor to anal cancer-significantly increases the risk of developing it. Conversely, low-grade anal intraepithelial squamous typically follow a benign course and usually regress spontaneously.
MATERIALS AND METHODS: To describe a population of men who have sex with men living with human immunodeficiency virus followed in a specialized anal cancer screening unit we conducted an observational, retrospective, and single-center study was.
RESULTS: Ninety-four patients were analyzed, with a mean age of 39 ± 9 years, and a 87% positivity rate for high-risk human papillomavirus (HR-HPV). At the initial visit, 47% presented with low-grade squamous intraepithelial lesions. The progression rate to high-grade squamous intraepithelial lesion was 37.2 per 100,000 patients/year. None of the patients developed anal cancer. Tobacco and alcohol consumption were associated with this progression.
DISCUSSION: In this series, longer duration of HIV infection, tobacco and alcohol use and the presence of HR-HPV were significantly associated with the occurrence of high-grade intraepithelial lesions. A lower risk of progression was seen in patients with higher education.
CONCLUSION: In men who have sex with men living with HIV, the association of factors such as smoking, alcohol, the presence of HR-HPV and an increased burden of human papillomavirus disease makes these patients more susceptible to develop high-grade anal squamous lesions.
PMID:39389343 | DOI:10.1016/j.ad.2024.10.006
Anal Chem. 2024 Oct 10. doi: 10.1021/acs.analchem.4c02984. Online ahead of print.
ABSTRACT
Aptamers are valuable tools for applications such as cell imaging, drug delivery, and therapeutics. RNA aptamers, in particular, exhibit complex structural diversity and flexibility, affording higher affinity and specificity, broader target recognition, and easier chemical modification compared with DNA aptamers. However, traditional selection methods for RNA aptamers are time-consuming and involve numerous rounds of screening, thus limiting their widespread application. To overcome this challenge, we propose an efficient truncated selection approach termed ID-SELEX. This method incorporates a molecular identification marker whereby each template is labeled with a unique molecular identifier, or UMI. Such incorporation helps mitigate biases introduced by multiple polymerase chain reaction (PCR) amplification during high-throughput sequencing, ensuring accurate identification of aptamer candidates. Utilizing ID-SELEX, we successfully identified a panel of high-quality aptamers targeting the human colon cancer cell line HCT-8 in just 2 rounds of selection. Furthermore, we demonstrated the versatility of this strategy by selecting 6 RNA aptamers targeting mouse myoblast cell line C2C12 with only one round of selection. In summary, RNA aptamer selection based on ID-SELEX utilizes high-throughput sequencing and UMI labeling to enable the rapid screening of RNA aptamers across human and murine cell lines. As such, ID-SELEX has the potential to facilitate RNA aptamer discovery, providing a novel molecular tool for biomedical research, clinical applications, and precision medicine.
PMID:39385698 | DOI:10.1021/acs.analchem.4c02984
BMC Ophthalmol. 2024 Oct 9;24(1):444. doi: 10.1186/s12886-024-03702-4.
ABSTRACT
BACKGROUND: We report two cases of fungal endophthalmitis induced by Candida species identified based on internal transcribed spacer 1 (ITS1) sequencing.
CASE PRESENTATION: In two cases, endophthalmitis was suspected, and the patients underwent pars plana vitrectomy. Case 1 was a 64-year-old woman with a history of cataract surgery 10 days prior. She had a history of anal primary melanoma, which metastasized throughout the body and subsequently relapsed. Vitreous culture and ITS-1 deep sequencing revealed the presence of the rare fungus, Candida dubliniensis. Case 2 was a 54-year-old man with a history of liver cancer and kidney failure. Culture methods and ITS1 deep sequencing both revealed the presence of Candida albicans. Both patients exhibited good visual prognoses after treatment with topical and systemic antibiotics.
CONCLUSIONS: We present two cases of fungal endophthalmitis caused by two Candida species identified by both the culture method and ITS1 deep sequencing. The fungal pathogen was identified by ITS deep sequencing three days after sample submission; the culture method yielded results after 1 week. These findings support the applicability of ITS1 sequencing for timely pathogen identification for cases of fungal endophthalmitis and provide detailed taxonomic information at the species level.
PMID:39385149 | PMC:PMC11463106 | DOI:10.1186/s12886-024-03702-4
BMC Cancer. 2024 Oct 9;24(1):1247. doi: 10.1186/s12885-024-12994-0.
ABSTRACT
BACKGROUND: Neoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer (LARC) was highly sensitive to PD-1 blockade. However, most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8 + T cells, further enhancing the responses of MSS/pMMR rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with MSS/ pMMR LARC.
METHODS: This was a open-label, single-arm, multicentre, prospective phase II trial. 32 LARC patients with MSS/pMMR will receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m2 intravenous infusion, day 1; capecitabine 1000 mg/m2 oral administration, days 1-14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be four 21-day cycles. TME will be performed at weeks 14-15. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed.
DISCUSSION: In our research, node-sparing modified radiotherapy combined with immunotherapy probably increased the responsiveness of immunotherapy for MSS/pMMR rectal cancer patients, reduced the occurrence of postoperative rectal fibrosis, and improved survival and quality of life. This is the first clinical trial to utilize a node-sparing radiation strategy combined with chemotherapy and PD-1 blockade in the neoadjuvant treatment of rectal cancer, which may result in a breakthrough in the treatment of MSS/pMMR rectal cancer.
TRIAL REGISTRATION: This study was registered at www.
CLINICALTRIALS: gov .
TRIAL REGISTRATION NUMBER: NCT05972655. Date of registration: 31 July 2023.
PMID:39385104 | PMC:PMC11463141 | DOI:10.1186/s12885-024-12994-0
Anal Chem. 2024 Oct 9. doi: 10.1021/acs.analchem.4c03334. Online ahead of print.
ABSTRACT
Circulating tumor cells (CTCs) are closely associated with cancer metastasis and recurrence, so the assessment of CTC viability is crucial for diagnosis, prognosis evaluation, and efficacy judgment of cancer. Due to the extreme scarcity of CTCs in human blood, it is difficult to accurately evaluate the viability of a single CTC. In this study, a deep learning model based on a convolutional neural network was constructed and trained to extract the morphological features of CTCs with different viabilities defined by cell counting kit-8, achieve accurate CTC identification, and assess the viability of a single CTC. Being efficient, accurate, and noninvasive, it has a broad application prospect in biomedical directions.
PMID:39384089 | DOI:10.1021/acs.analchem.4c03334
Med Image Anal. 2024 Oct 5;99:103360. doi: 10.1016/j.media.2024.103360. Online ahead of print.
ABSTRACT
Nuclear-derived morphological features and biomarkers provide relevant insights regarding the tumour microenvironment, while also allowing diagnosis and prognosis in specific cancer types. However, manually annotating nuclei from the gigapixel Haematoxylin and Eosin (H&E)-stained Whole Slide Images (WSIs) is a laborious and costly task, meaning automated algorithms for cell nuclei instance segmentation and classification could alleviate the workload of pathologists and clinical researchers and at the same time facilitate the automatic extraction of clinically interpretable features for artificial intelligence (AI) tools. But due to high intra- and inter-class variability of nuclei morphological and chromatic features, as well as H&E-stains susceptibility to artefacts, state-of-the-art algorithms cannot correctly detect and classify instances with the necessary performance. In this work, we hypothesize context and attention inductive biases in artificial neural networks (ANNs) could increase the performance and generalization of algorithms for cell nuclei instance segmentation and classification. To understand the advantages, use-cases, and limitations of context and attention-based mechanisms in instance segmentation and classification, we start by reviewing works in computer vision and medical imaging. We then conduct a thorough survey on context and attention methods for cell nuclei instance segmentation and classification from H&E-stained microscopy imaging, while providing a comprehensive discussion of the challenges being tackled with context and attention. Besides, we illustrate some limitations of current approaches and present ideas for future research. As a case study, we extend both a general (Mask-RCNN) and a customized (HoVer-Net) instance segmentation and classification methods with context- and attention-based mechanisms and perform a comparative analysis on a multicentre dataset for colon nuclei identification and counting. Although pathologists rely on context at multiple levels while paying attention to specific Regions of Interest (RoIs) when analysing and annotating WSIs, our findings suggest translating that domain knowledge into algorithm design is no trivial task, but to fully exploit these mechanisms in ANNs, the scientific understanding of these methods should first be addressed.
PMID:39383642 | DOI:10.1016/j.media.2024.103360
Anal Chem. 2024 Oct 9. doi: 10.1021/acs.analchem.4c03922. Online ahead of print.
ABSTRACT
Accurate diagnosis of highly aggressive and deadly tumors is essential for effective treatment and improved patient outcomes, and microRNAs (miRNAs) have emerged as crucial biomarkers for their roles in tumor initiation, progression, and metastasis. Herein, we present an on-site visualization colorimetric assay for tumor-associated miRNAs using ruthenium nanoparticle decorated titanium dioxide nanoribbon (Ru@TiO2) as a peroxidase-like (POD) nanozyme. Remarkably, the Ru@TiO2 nanozyme can catalyze the oxidation of chromogenic substrates through its POD-like activity, which is effectively inhibited by pyrophosphate generated during the rolling circle amplification process, thereby enabling miRNA detection through a visible colorimetric readout. This approach provides a highly sensitive and specificity assay for miRNAs in diluted human serum with a detection limit of 100 pM. It shows great potential for clinical diagnostics and biological research, offering a promising tool for early cancer diagnosis and molecular diagnostics.
PMID:39383474 | DOI:10.1021/acs.analchem.4c03922
Anal Chem. 2024 Oct 9. doi: 10.1021/acs.analchem.4c03943. Online ahead of print.
ABSTRACT
Protein-selection mass spectrometry is cost-effective for the discovery of drugs and toxics. Nuclear receptors (NRs) are major targets for pharmaceuticals and endocrine-disrupting chemicals and are, thus, widely used as "bait" proteins. However, their application is limited due to the tendency to lose protein activity during cold storage. To address this problem, we introduced a novel biomineralization-based approach to preserve activity in NRs, exemplified by human retinoic acid receptor alpha (hRARα), a target for cancer and leucocythemia therapy. Since information on the coordination chemistry of metal ion and NR protein complexes is almost unavailable, we applied peptide mapping analysis for the first time for the rational design of his-hRARα-Co phosphate nanobiomaterial with high bioactivity. This nanobiomaterial successfully captured hRARα bioactive chemicals from a Chinese herb and environmental water and discovered an unsaturated fatty acid, (±)-(9Z,11E)-13-hydroxy-9,11-octadecadienoic acid ((±)13-HODE), which exhibited strong hRARα antagonistic activity.
PMID:39383328 | DOI:10.1021/acs.analchem.4c03943
Front Oncol. 2024 Sep 24;14:1403192. doi: 10.3389/fonc.2024.1403192. eCollection 2024.
ABSTRACT
INTRODUCTION: When a gastric tube cannot be used as a substitute for the esophagus, the colon offers several advantageous features for esophageal replacement. However, this procedure remains complex and necessitates patients to have a favorable nutritional status. In this study, we investigated the viability of intrathoracic colonic interposition anastomosis through a single thoracic incision, with the goal of mitigating surgical challenges and nutritional requirements.
CASE DESCRIPTION: We conducted a colectomy and reconstructed the esophageal-colonic-gastric tract via the esophageal bed into the left thoracic cavity for a 68-year-old male patient with compromised nutritional status following 30 years post-Billroth II (BII) gastrectomy. Under normal circumstances, this patient would not have been deemed an appropriate candidate for a conventional colonic interposition procedure. The patient resumed a soft diet through the normal digestive tract two weeks after the surgery and was discharged 20 days later.
CONCLUSION: Patients who have previously received a Billroth II Gastrectomy and subsequently developed early-stage esophageal cancer, characterized by the absence of lymph node metastasis, are suitable candidates for Colon Interposition Radical Surgery via left thoracotomy.
PMID:39381042 | PMC:PMC11458370 | DOI:10.3389/fonc.2024.1403192
J Clin Lab Anal. 2024 Oct 8:e25112. doi: 10.1002/jcla.25112. Online ahead of print.
ABSTRACT
AIM: To determine the mortality rate and the predictive value of the prognostic nutritional index (PNI) for all-cause mortality during the 24 months in patients with stage IV colorectal cancer treated with capecitabine.
METHODS: We conducted a study on 87 stage IV colorectal cancer patients treated with capecitabine. Before the day of treatment, all patients were measured CEA and CRP-hs levels and calculated neutrophil/lympho ratio (NLR) and PNI. Patients were monitored and collected drug side effects and mortality for 24 months.
RESULTS: The mortality rate of study subjects was 60.9%. CRP-hs, NLR, and PNI were independent factors associated with 24-month mortality in patients with stage IV colorectal cancer (p < 0.05 to p < 0.01). At a cut-off value of 38.51, PNI was a predictor for mortality, with the area under the curve (AUC) of 0.88 and p < 0.001.
CONCLUSIONS: PNI was a good predictor of all-cause mortality in patients with stage IV colorectal cancer treated with capecitabine for 24 months.
PMID:39380366 | DOI:10.1002/jcla.25112
J Pharm Biomed Anal. 2024 Oct 5;252:116510. doi: 10.1016/j.jpba.2024.116510. Online ahead of print.
ABSTRACT
Colon adenocarcinoma(COAD) is a primary and aggressive malignancy with the fifth highest mortality rate among cancers, and it is important to discover new strategies. The online database was used to analyze the correlation between Vitamin D receptor (VDR) and COAD, and further explore the immune infiltration and related gene networks.The expression and methylation levels of VDR was analyzed by using Timer database, GEPIA platform and UALCAN database. GeneMANIA database was used to analyze and obtain gene networks that are closely linked to VDR. UALCAN database was used to score the gene effects of VDR in colorectal cancer cell lines. The cBioPortal database was used for the detection of gene mutations. The survival curve analysis was carried out using the GEPIA database. The relationship between VDR expression and immune cell infiltration was analyzed by using the timer database and TISIDB database. TISIDB database was used to obtain VDR-related drug targets.The expression of VDR was significantly lower in COAD(p<0.05). The methylation level of VDR was significantly higher in COAD (p<0.05). The gene mutation rate of VDR in COAD was 2 %. OS and DFS were not associated with changes in the VDR gene in patients with COAD. VDR expression was correlated with CD4+T cell infiltration, macrophage infiltration, neutrophil infiltration, and dendritic cell infiltration. VDR has a clear correlation with ADORA2A, BTLA, CD160, CD244, CD274, CD96, CSF1R, CTLA4, HAVCR2, IL10, IDO1, LAG3, LGALS9, PDCD1, PDCD1LG2, PVRL2, TGFB1, TGFBR1, TIGIT and VTCN1.The expression of VDR is associated with immune infiltration in patients with COAD. VDR may be a new candidate biomarker for determining the level of immune infiltration and predicting immune checkpoint inhibitor therapy.
PMID:39378759 | DOI:10.1016/j.jpba.2024.116510
Med Image Anal. 2024 Sep 30;99:103356. doi: 10.1016/j.media.2024.103356. Online ahead of print.
ABSTRACT
Breast cancer is a significant global public health concern, with various treatment options available based on tumor characteristics. Pathological examination of excision specimens after surgery provides essential information for treatment decisions. However, the manual selection of representative sections for histological examination is laborious and subjective, leading to potential sampling errors and variability, especially in carcinomas that have been previously treated with chemotherapy. Furthermore, the accurate identification of residual tumors presents significant challenges, emphasizing the need for systematic or assisted methods to address this issue. In order to enable the development of deep-learning algorithms for automated cancer detection on radiology images, it is crucial to perform radiology-pathology registration, which ensures the generation of accurately labeled ground truth data. The alignment of radiology and histopathology images plays a critical role in establishing reliable cancer labels for training deep-learning algorithms on radiology images. However, aligning these images is challenging due to their content and resolution differences, tissue deformation, artifacts, and imprecise correspondence. We present a novel deep learning-based pipeline for the affine registration of faxitron images, the x-ray representations of macrosections of ex-vivo breast tissue, and their corresponding histopathology images of tissue segments. The proposed model combines convolutional neural networks and vision transformers, allowing it to effectively capture both local and global information from the entire tissue macrosection as well as its segments. This integrated approach enables simultaneous registration and stitching of image segments, facilitating segment-to-macrosection registration through a puzzling-based mechanism. To address the limitations of multi-modal ground truth data, we tackle the problem by training the model using synthetic mono-modal data in a weakly supervised manner. The trained model demonstrated successful performance in multi-modal registration, yielding registration results with an average landmark error of 1.51 mm (±2.40), and stitching distance of 1.15 mm (±0.94). The results indicate that the model performs significantly better than existing baselines, including both deep learning-based and iterative models, and it is also approximately 200 times faster than the iterative approach. This work bridges the gap in the current research and clinical workflow and has the potential to improve efficiency and accuracy in breast cancer evaluation and streamline pathology workflow.
PMID:39378568 | DOI:10.1016/j.media.2024.103356
Eur J Public Health. 2024 Oct 8:ckae152. doi: 10.1093/eurpub/ckae152. Online ahead of print.
ABSTRACT
Cancers represent the primary cause of mortality among people living with HIV (PLWH). However, comprehensive nationwide data regarding cancer incidence remains limited. Our objective was to evaluate the incidence rates of cancers, particularly those associated with human papillomavirus (HPV), within a nationwide study cohort. Using data from the Estonian Health Insurance Fund and the National Cancer Registry from 2004 to 2021, we calculated standardized incidence ratios (SIRs) for various cancer types among PLWH to compare to the general population with special emphases on HPV-associated cancers. A total of 7011 individuals (65.7% men) diagnosed with HIV were identified. HPV-associated cancers accounted for 21.4% of all incident cancer cases among PLWH. SIRs for HPV-associated cancers were 3.7 [95% confidence interval (CI) 2.2-6.2] among men living with HIV (MLWH) and 5.7 (95% CI 4.0-7.9) among women living with HIV (WLWH). In MLWH, the highest SIRs were for penile 12.5 (95% CI 4.0-38.7), followed by oropharyngeal 3.6 (95% CI 1.7-7.6) and anal-rectal cancers 2.7 (95% CI 1.1-6.4) in comparison to the general population. In WLWH, an increased incidence of cervical (SIR = 5.8, 95% CI 3.9-8.5), oropharyngeal (SIR = 6.1, 95% CI 1.5-24.3), and anal-rectal (SIR = 3.6, 95% CI 1.2-11.2) cancers was observed. A significantly increased risk of AIDS-defining and non-AIDS-defining cancers is reported. We demonstrate a substantially heightened risk of HPV-associated cancers among PLWH compared to the general population, underscoring the imperative for intensified screening and scaled-up vaccination along with improvement in adherence to antiretroviral therapy.
PMID:39378418 | DOI:10.1093/eurpub/ckae152
Anal Chem. 2024 Oct 8. doi: 10.1021/acs.analchem.4c03149. Online ahead of print.
ABSTRACT
Low-field NMR has emerged as a new analytical technique for the investigation of molecular structure and dynamics. Here, we introduce a highly integrated ultralow-frequency NMR spectrometer designed for the purpose of ultralow-field NMR polarimetry of hyperpolarized contrast media. The device measures 10 cm × 10 cm × 2.0 cm and weighs only 370 g. The spectrometer's aluminum enclosure contains all components, including an RF amplifier. The device has four ports for connecting to a high-impedance RF transmit-receive coil, a trigger input, a USB port for connectivity to a PC computer, and an auxiliary RS-485/24VDC port for system integration with other devices. The NMR spectrometer is configured for a pulse-wait-acquire-recover pulse sequence, and key sequence parameters are readily controlled by a graphical user interface (GUI) of a Windows-based PC computer. The GUI also displays the time-domain and Fourier-transformed NMR signal and allows autosaving of NMR data as a CSV file. Alternatively, the RS485 communication line allows for operating the device with sequence parameter control and data processing directly on the spectrometer board in a fully automated and integrated manner. The NMR spectrometer, equipped with a 250 ksamples/s 17-bit analog-to-digital signal converter, can perform acquisition in the 1-125 kHz frequency range. The utility of the device is demonstrated for NMR polarimetry of hyperpolarized 129Xe gas and [1-13C]pyruvate contrast media (which was compared to the 13C polarimetry using a more established technology of benchtop 13C NMR spectroscopy, and yielded similar results), allowing reproducible quantification of polarization values and relaxation dynamics. The cost of the device components is only ∼$200, offering a low-cost integrated NMR spectrometer that can be deployed as a plug-and-play device for a wide range of applications in hyperpolarized contrast media production─and beyond.
PMID:39378166 | DOI:10.1021/acs.analchem.4c03149
Surg Case Rep. 2024 Oct 8;10(1):233. doi: 10.1186/s40792-024-02037-y.
ABSTRACT
BACKGROUND: Anal fistula cancer is rare and definitive treatment has not yet been established. Laparoscopic abdominoperineal resection is generally the first choice of treatment if the cancer is determined to be resectable. However, complicated anal fistula cancer often requires extensive resection. Using a myocutaneous flap for reconstruction after resection in such cases, radical resection can be performed regardless of the size of the anal fistula cancer.
CASE PRESENTATION: We report two cases in which we performed laparoscopic abdominoperineal resection with extensive buttock resection and myocutaneous flap reconstruction for widespread anal fistula cancer. One of the cases was reconstruction with a posterior thigh flap, the other was with a bilateral expanded gluteus maximus flap. Both cases were anal fistula cancers that developed from complicated anal fistulas.
CONCLUSIONS: If the size of anal fistula cancer is large and extended buttock resection is necessary, radical resection of anal fistula cancer is possible using myocutaneous flap for reconstruction after extended abdominoperineal resection.
PMID:39377941 | PMC:PMC11461713 | DOI:10.1186/s40792-024-02037-y
Pediatr Ann. 2024 Oct;53(10):e372-e377. doi: 10.3928/19382359-20240811-02. Epub 2024 Oct 1.
ABSTRACT
Human papillomavirus (HPV) vaccine is an underutilized tool in cancer prevention. HPV vaccine completion rates in adolescents age 13 to 15 years remain low at 59%. The HPV vaccine can prevent more than 90% of cases of cancer caused by HPV, including cervical, oropharyngeal, anal, penile, vulvar, and vaginal. HPV vaccine is very safe and effective, as demonstrated by numerous large-scale studies. Practice-based strategies can improve vaccination rates, such as having providers give a strong presumptive recommendation for the vaccine, using motivational interviewing for hesitant families, and using electronic health record reminders to prompt providers to offer it, among other interventions. Offering HPV vaccine starting at age 9 years is another evidence-based strategy to improve HPV vaccine completion rates, which has been shown to be acceptable to both providers and parents. [Pediatr Ann. 2024;53(10):e372-e377.].
PMID:39377820 | DOI:10.3928/19382359-20240811-02
Front Pharmacol. 2024 Sep 23;15:1465586. doi: 10.3389/fphar.2024.1465586. eCollection 2024.
ABSTRACT
Objective: This study was aimed at exploring a specific open region of chromatin in the peripheral blood mononuclear cells (PBMCs) of patients with breast cancer and evaluating its feasibility as a biomarker for diagnosing and predicting breast cancer prognosis. Methods: We obtained PBMCs from breast cancer patients and healthy people for the assay for transposase-accessible chromatin (ATAC) sequencing (n = 3) and obtained the GSE27562 chip sequencing data for secondary analyses. Through bioinformatics analysis, we mined the pattern changes for chromatin accessibility in the PBMCs of breast cancer patients. Results: A total of 1,906 differentially accessible regions (DARs) and 1,632 differentially expressed genes (DEGs) were identified via ATAC sequencing. The upregulated DEGs in the disease group were mainly distributed in the cells, organelles, and cell-intima-related structures and were mainly responsible for biological functions such as cell nitrogen complex metabolism, macromolecular metabolism, and cell communication, in addition to functions such as nucleic acid binding, enzyme binding, hydrolase reaction, and transferase activity. Combined with microarray data analysis, the following set of nine DEGs showed intersection between the ATAC and microarray data: JUN, MSL2, CDC42, TRIB1, SERTAD3, RAB14, RHOB, RAB40B, and PRKDC. HOMER predicted and identified five transcription factors that could potentially bind to these peak sites, namely NFY, Sp 2, GFY, NRF, and ELK 1. Conclusion: Chromatin accessibility analysis of the PBMCs from patients with early-stage breast cancer underscores its potential as a significant avenue for biomarker discovery in breast cancer diagnostics and treatment. By screening the transcription factors and DEGs related to breast cancer, this study provides a comprehensive theoretical foundation that is expected to guide future clinical applications and therapeutic developments.
PMID:39376611 | PMC:PMC11456436 | DOI:10.3389/fphar.2024.1465586
Anal Cell Pathol (Amst). 2024 Sep 18;2024:6260651. doi: 10.1155/2024/6260651. eCollection 2024.
ABSTRACT
Background: Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive form of head and neck cancer, often diagnosed at advanced stages. Elucidating the molecular mechanisms involved in the malignant transformation from normal oral tissue to oral preinvasive lesions (OPL) and primary OSCC could facilitate early diagnosis and improve therapeutic strategies. Methods: Differentially expressed genes (DEGs) were identified from the GSE30784 dataset by comparing normal oral tissue, oral dysplasia, and primary OSCC samples. Cross-validation was performed using an independent RNA-seq dataset, GSE186775. Protein-protein interaction (PPI) network analysis, gene ontology annotation, and pathway enrichment analysis were conducted on the common DEGs. Hub genes were identified, and their prognostic significance was evaluated using survival analysis. Transcription factor (TF) enrichment analysis, cross-validation, and immunohistochemistry analyses were also performed. Results: A total of 226 proteins and 677 interactions were identified in the PPI network, with 34 hub genes, including FN1, SERPINE1, PLAUR, THBS1, and ITGA6. Pathways such as "Formation of the cornified envelope," "Keratinization," and "Developmental biology" were enriched. Overexpression of SERPINE1, PLAUR, THBS1, and ITGA6 correlated with poor prognosis, while upregulation of CALML5 and SPINK5 was associated with favorable outcomes. NFIB emerged as the most significant TF-regulating hub genes. Immunohistochemistry validated ITGA6 overexpression in primary OSCC. Cross-validation using the RNA-seq dataset supported the involvement of critical genes in the malignant transformation process. Conclusion: This study identified vital genes, pathways, and prognostic markers involved in the malignant transformation from normal oral tissue to OPL and primary OSCC, providing insights for early diagnosis and targeted therapy development. Cross-validation with an independent RNA-seq dataset and immunohistochemistry reinforced the findings, supporting the robustness of the identified molecular signatures.
PMID:39376501 | PMC:PMC11458300 | DOI:10.1155/2024/6260651
Anal Bioanal Chem. 2024 Oct 7. doi: 10.1007/s00216-024-05549-6. Online ahead of print.
ABSTRACT
We present a plasmonics-enhanced spikey nanorattle-based biosensor for direct surface-enhanced Raman scattering (SERS) detection of mRNA cancer biomarkers. Early detection of cancers such as head and neck squamous cell carcinoma (HNSCC) is critical for improving patient outcomes in regions with limited access to traditional diagnostic methods. Our method targets Keratin 14 (KRT14), a promising diagnostic mRNA biomarker for HNSCC, using a sandwich hybridization approach with magnetic beads and SERS spikey nanorattles (SpNR). We synthesized SpNR with a core-gap-shell structure to enhance SERS signals, achieving a limit of detection of 90 femtomolar. A pilot study using clinical samples demonstrated the efficacy of our biosensor in distinguishing between tissue with positive or negative diagnosis for HNSCC, highlighting its potential for rapid and sensitive cancer diagnostics in low-resource settings. This plasmonic assay offers a promising avenue for portable and high-specificity detection of nucleic acid biomarkers, with implications for early cancer detection and improved patient care, especially in middle and low-resource settings.
PMID:39373917 | DOI:10.1007/s00216-024-05549-6
Front Public Health. 2024 Sep 20;12:1437309. doi: 10.3389/fpubh.2024.1437309. eCollection 2024.
ABSTRACT
BACKGROUND: In this study, we characterized the HPV genotype distribution in a population of 489 adults already positive for HPV DNA. The study population was divided into two groups: 244 HIV-positive (HIV+) men who have sex with men (MSM) undergoing routine anal screening for sexually transmitted diseases (STDs) and 245 women undergoing routine cervical cancer screening. Acknowledging the fact that women and MSM represent two independent circles of sexual practices, which are-largely-exclusive of each other, we were interested in determining if particular genotypes of human papillomavirus (HPV) disproportionately predominate in one of these circles compared to the other.
RESULTS: HIV+ MSM are significantly more likely to be infected with multiple genotypes at a time, with an odds ratio (OR) of 9.30 (95% confidence interval [CI]: 3.91-22.1) and a p-value of <0.001. In addition, multivariable-adjusted logistic regression analysis showed that anal swab samples were significantly more likely to harbor lrHPV infections, with an OR of 6.67 (95% CI: 2.42-18.4) and a p-value of <0.001, in particular, HPV 6, with an OR of 8.92 (95% CI: 3.84-20.7) compared to cervical samples of screening women.
CONCLUSION: Given the significant impact of recurrent anogenital warts (AGWs) on quality of life and the accompanying predisposition to invasive anal cancer, our data underscore the critical need for HPV vaccination. This includes expanding vaccination eligibility to include both boys and adults within high-risk populations.
PMID:39371203 | PMC:PMC11449850 | DOI:10.3389/fpubh.2024.1437309
Anal Methods. 2024 Oct 7. doi: 10.1039/d4ay01625d. Online ahead of print.
ABSTRACT
Human papillomavirus 16 (HPV16) infection is the leading cause of cervical cancer. The current mainstream method for detecting HPV16 is quantitative real-time PCR (qPCR). However, due to its time-consuming nature and reliance on expensive qPCR instruments, there is growing interest in more convenient, rapid and private approaches such as recombinase polymerase amplification (RPA). In this study, we innovated an effective method for HPV16 detection by integrating a RPA system with lateral flow strip (LFS) detection. Primers with optimal efficiency and specificity were designed, and false positive signals caused by dimers were eliminated by reducing the probe concentration. The RPA-LFS method demonstrates high sensitivity and specificity, capable of detecting 230 copies per reaction of HPV16 within 25 min without cross-reactivity to other subtypes. It exhibits good tolerance, remaining unaffected by 1.0% miconazole, 0.5% tioconazole and 1.0% hemoglobin. The results of clinical samples detected by this method were consistent with those of qPCR. The method provides a practical reference for HPV16 diagnosis and can be valuable in home and resource-limited settings, contributing to the reduction of cervical cancer incidence.
PMID:39371011 | DOI:10.1039/d4ay01625d
Sci Rep. 2024 Sep 2;14(1):20446. doi: 10.1038/s41598-024-71465-5.
ABSTRACT
Colorectal cancer (CRC) is a wide-spread gastrointestinal cancer that is associated with augmented morbidity and mortality, and we do not yet have a deep understanding of its epidemiology and carcinogenicity. The transcriptome can reveal the complexity and heterogeneity of tumors and uncover new biomarkers or treatment options. In this study, we identified messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), round RNAs (circRNAs), and microRNAs (miRNAs) using whole-transcriptome sequencing and generated competing endogenous RNA (ceRNA) modulatory axes. We conducted whole transcriptome sequencing on 10 CRC and para-cancer (CRCP) samples and discovered 2465 differentially expressed (DE) mRNAs (DEmRNAs), 77 DE miRNAs (DEmiRNAs). 2852 DE lncRNAs (DElncRNAs) and 1477 DE circRNAs (DEcircRNAs). In addition, utilizing co-DE analysis, we generated the ceRNA axis. Subsequently, we employed the ceRNA axis to identify essential genes and corresponding associations with lncRNAs, circRNAs, and miRNAs in CRC. ceRNA regulatory network including mRNA-miRNA-lncRNA and mRNA-miRNA-circRNA. These modulatory axes potentially modulate the positive regulation of smooth muscle contraction, melanosome, plasma membrane, integral plasma membrane component and so on. Finally, the results of RNA sequencing (RNA-SEQ) were combined with the TCGA and GEO databases, and the DEGs strongly correlated with the TCGA-COAD overall survival (OS) as estimated by univariate cox and logarithmic rank analyses were cross-analyzed, and the co-upregulated DEGs were screened. Among the many DEs, KPNA2 was chosen for additional analysis. Using invitro experimentations, western blot, CCK8, EdU and other experiments were performed to verify the results. We found siRNA-based KPNA2 depletion reduces bladder cancer cells' viability, migratory, and proliferative activities, which showed that the DEmRNA profiles were comparable to the sequencing information, confirming that the sequencing data were very reliable. These evidences highlight the ceRNA regulatory mechanisms in CRC and will aid future research into the molecular mechanisms behind colorectal cancer prevention and treatment.
PMID:39227669 | DOI:10.1038/s41598-024-71465-5
Anal Chem. 2024 Sep 3. doi: 10.1021/acs.analchem.4c03766. Online ahead of print.
ABSTRACT
In this work, by ingeniously integrating catalytic hairpin assembly (CHA), double-end Mg2+-dependent DNAzyme, and hybridization chain reaction (HCR) as a triple cascade signal amplifier, an efficient concatenated CHA-DNAzyme-HCR (CDH) system was constructed to develop an ultrasensitive electrochemical biosensor with a low-background signal for the detection of microRNA-221 (miRNA-221). In the presence of the target miRNA-221, the CHA cycle was initiated by reacting with hairpins H1 and H2 to form DNAzyme structure H1-H2, which catalyzed the cleavage of the substrate hairpin H0 to release two output DNAs (output 1 and output 2). Subsequently, the double-loop hairpin H fixed on the electrode plate was opened by the output DNAs, to trigger the HCR with the assistance of hairpins Ha and Hb. Finally, methylene blue was intercalated into the long dsDNA polymer of the HCR product, resulting in a significant electrochemical signal. Surprisingly, the double-loop structure of the hairpin H could prominently reduce the background signal for enhancing the signal-to-noise ratio (S/N). As a proof of concept, an ultrasensitive electrochemical biosensor was developed using the CDH system with a detection limit as low as 9.25 aM, achieving favorable application for the detection of miRNA-221 in various cancer cell lysates. Benefiting from its enzyme-free, label-free, low-background, and highly sensitive characteristics, the CDH system showed widespread application potential for analyzing trace amounts of biomarkers in various clinical research studies.
PMID:39225442 | DOI:10.1021/acs.analchem.4c03766
Anal Methods. 2024 Sep 3. doi: 10.1039/d4ay01410c. Online ahead of print.
ABSTRACT
Accurate detection of tumor biomarkers in blood is crucial for diagnosing and treating tumor disease. In this study, a metal enzyme-linked immunosorbent assay (MeLISA) was fabricated for the ultrasensitive and naked-eye detection of tumor biomarker alpha-fetoprotein (AFP) in clinical serum samples. Herein, novel copper metal-organic frameworks and gold platinum nanoparticle composites (Cu-MOFs@AuPtNPs) were synthesized for the first time by an in situ method, which showed an enormous specific surface area and excellent peroxidase (POx) mimicking properties. Cu-MOFs@AuPtNPs linked with antibodies targeting AFP served as a signal nanoprobe to amplify the detection signal. Additionally, the specificity of MeLISA was significantly enhanced through a conventional antigen-antibody reaction and efficient blocking of non-specific sites with BSA. Under optimal conditions, the sandwich-type MeLISA exhibited a wide range from 0.001 to 1000 ng mL-1 (R2 = 0.997) and a low detection limit of 0.86 pg mL-1 (S/N = 3) with acceptable stability, selectivity, and reproducibility. It is noteworthy that the suggested MeLISA performed exceptionally well in detecting clinical serum samples, which were visible to the naked eye and did not require complex platforms. To sum up, the innovative MeLISA based on Cu-MOFs@AuPtNPs provides an alternative method for early cancer diagnosis, particularly in economically backward areas where simple diagnostic apparatus is extremely desirable.
PMID:39225244 | DOI:10.1039/d4ay01410c
BMC Cancer. 2024 Sep 2;24(1):1089. doi: 10.1186/s12885-024-12858-7.
ABSTRACT
BACKGROUND: The aim of this study is to investigate the impact of arginine on immune function and postoperative complications in colorectal cancer (CRC) patients.
METHODS: We conducted a comprehensive search to identify eligible RCTs in various databases, such as PubMed, Cochrane Library, EMBASE, Web of Science, MEDLINE, China National Knowledge Infrastructure (CNKI), Wanfang, VIP Medicine Information System (VIP), and Chinese Biomedical Database (CBM). This study aimed to examine IgA, IgG, and IgM levels as well as CD4+ and CD8+ counts as well as the CD4+/CD8+ ratio. Anastomotic leaking, length of stay (LOS), and surgical site infection (SSI) were included as secondary outcomes. Stata (StataCorp, version 14.0) was utilized for data analysis. To ensure the results were reliable, we used meta-regression, sensitivity analysis, and publication bias analysis.
RESULTS: A total of 24 publications (including 1883 patients) out of 681 that were retrieved fulfilled the inclusion criteria. The arginine group showed notable improvements in humoral immunity, with gains in IgA (SMD=0.45, 95% CI: 0.30-0.60), IgG (SMD=0.80, 95% CI: 0.64-0.96), and IgM (SMD=0.66, 95% CI: 0.39-0.93). With regards to cellular immunity, the arginine group exhibited a substantial increase in the CD4+ T cell count (SMD = 1.03, 95% CI: 0.67-1.38) compared to the control group. However, the CD4+/CD8+ ratio decreased significantly (SMD=1.37, 95% CI: 0.88-1.86) in the same arginine group, indicating a change in the balance between these two cell types. Additionally, the CD8+ T cell count showed a notable decrease (SMD=-0.70, 95% CI: -1.09 to -0.32) in the arginine group when compared to the control group. Anastomotic leakage was also considerably lower in the arginine group (SMD=-0.05, 95% CI: -0.08 to -0.02), the rate of SSIs was lower (RR = -0.02, 95% CI: -0.05-0), and the length of time patients spent in the hospital was shorter (SMD=-0.15, 95% CI: -0.38 to -0.08).
CONCLUSIONS: After radiation treatment for CRC, arginine improves immune function and decreases the risk of infection problems.
TRIAL REGISTRATION: Registration with PROSPERO for this meta-analysis is number CRD42024520509.
PMID:39223466 | DOI:10.1186/s12885-024-12858-7
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2024 Aug;46(4):528-538. doi: 10.3881/j.issn.1000-503X.15899.
ABSTRACT
Objective To analyze the sensitivity of ARHGAP8 in predicting the efficacy of neoadjuvant chemotherapy in the patients with locally advanced mid-low colorectal cancer and provide accurate evidence for the treatment of advanced colorectal cancer. Methods The differentially expressed gene ARHGAP8 was screened out by bioinformatics analysis.Cancer tissue and rectal tissue of 68 patients with primary rectal cancer were selected.The rectal cancer tissue samples and the rectal tissue samples were collected for clinical validation of ARHGAP8 expression by quantitative real-time PCR,Western blotting,and immunohistochemistry.The clinical and pathological features such as gender,age,tumor stage,differentiation degree,and pathological type of the patients were collected for functional validation.Forty-four patients with locally advanced mid-low rectal cancer who received neoadjuvant chemotherapy were selected for immunohistochemical examination of ARHGAP8 expression.The expression level of ARHGAP8 was compared between before and after chemotherapy and among different efficacy groups. Results The bioinformatics analysis revealed differences in the expression level of ARHGAP8 between the cancer tissue and rectal tissue (P<0.001).The expression level of ARHGAP8 was correlated with tumor stage (P=0.024),lymph node metastasis (P=0.007),and age (P=0.005).Quantitative real-time PCR results showed that the mRNA level of ARHGAP8 in the cancer tissue was higher than that in the rectal tissue (P<0.001).Western blotting and immunohistochemistry results demonstrated that the protein level of ARHGAP8 in the cancer tissue was higher than that in the rectal tissue (P=0.011).The expression of ARHGAP8 was correlated with tumor size (P=0.010) and pathological stage (P=0.005),while it showed no significant association with tumor differentiation degree,lymph node metastasis,liver metastasis,Ki-67,or microsatellite instability expression level.The 44 patients receiving neoadjuvant chemotherapy included 13,8,8,and 15 patients of tumor regression grades 0,1,2,and 3,respectively.Among them,65.91% (29/44) patients showed responses to the treatment.After neoadjuvant chemotherapy,the expression of ARHGAP8 in the cancer tissue was down-regulated in the patients who responded to the chemotherapy (P<0.001).The response rate in the patients with low protein level of ARHGAP8 was 92.86%,which was higher than that (53.33%) in the patients with high protein level of ARHGAP8 (P=0.033). Conclusion ARHGAP8 is highly expressed in the rectal cancer tissue.The patients with locally advanced mid-low rectal cancer and low ARHGAP8 expression are more sensitive to neoadjuvant chemotherapy with the XELOX protocol.ARHGAP8 can serve as a potential biomarker for the occurrence and development of rectal cancer and an important index for evaluating the efficacy of neoadjuvant chemotherapy with the XELOX protocol in the patients with locally advanced mid-low rectal cancer.
PMID:39223018 | DOI:10.3881/j.issn.1000-503X.15899
Cir Esp (Engl Ed). 2024 Aug 31:S2173-5077(24)00193-5. doi: 10.1016/j.cireng.2024.07.005. Online ahead of print.
ABSTRACT
We present a first in human clinical trial of a new rectoscope that shows, by means of transillumination, the optimal point of transection of the rectum in oncologic surgery. The device was developed together with a team of engineers and was manufactured by 3D printing. Eighteen patients with a mean age of 71 years and a mean distance from the tumor to the anal margin measured by colonoscopy of 10.4 ± 3.9 cm and by MRI of 10 ± 2.4 cm were included in the trial. Transillumination was feasible in all cases, and the use of the rectoscope was safe, as no adverse events due to its use were recorded.
PMID:39222746 | DOI:10.1016/j.cireng.2024.07.005
World J Gastrointest Surg. 2024 Aug 27;16(8):2528-2537. doi: 10.4240/wjgs.v16.i8.2528.
ABSTRACT
BACKGROUND: The abdominal perineal resection (APR), historically referred to as Mile's procedure, stands as a time-honored surgical intervention for rectal cancer management. Advancements in surgical techniques and the advent of neoadjuvant therapies have significantly improved the rate of sphincter preservation among patients afflicted with rectal cancer, including those with ultralow rectal cancer. Despite these improvements, APR maintains its irreplaceable role in the clinical landscape, particularly for cases involving low rectal cancer with encroachment on the external anal sphincter or levator ani muscles. Optimal perineal exposure stands as a pivotal phase in APR, given that the precision of this maneuver is directly correlated with both the safety of the surgery and the patient's subsequent long-term prognosis.
AIM: To evaluate the value of Lone-Star retractor (LSR) perineal exposure method in the treatment for laparoscopic APR of rectal cancer.
METHODS: We reviewed the records of 38 patients with rectal cancer at Anqing Municipal Hospital from January 2020 to December 2023, including 20 patients who underwent the APR procedure with a LSR perineal exposure method (LSR group) and 18 patients who underwent the APR procedure with a conventional perineal exposure method (control group). In the LSR group, following incision of the skin and subcutaneous tissue, the LSR was placed and dynamically adjusted according to the surgical plane to fully expose the perineal operative field.
RESULTS: A total of 38 patients underwent laparoscopic APR, none of whom were found to have distant metastasis upon intraoperative exploration. Perineal blood loss, the postoperative hospital stays and the wound pain scores in the LSR group were significantly lower than those in the control group. A single surgeon completed the perineal operation significantly more often in the LSR group than in the control group (P < 0.05). The incidence of infection via the perineal incision in the LSR group was significantly lower than that in the control group (P < 0.05). No cases of distant metastasis or local recurrence were found among the patients at the postoperative follow-up.
CONCLUSION: The application of the LSR technique might be helpful for performing perineal exposure during APR for rectal cancer and could reduce the incidence of perineal complications, shorten the postoperative hospital stay, improve postoperative pain, and allow one surgeon to perform the perineal operation.
PMID:39220070 | PMC:PMC11362942 | DOI:10.4240/wjgs.v16.i8.2528
Anal Methods. 2024 Sep 2. doi: 10.1039/d4ay00905c. Online ahead of print.
ABSTRACT
Temperature-responsive yeast cell-imprinted sensors (CIPs/AuNPs/Ti3C2Tx/AuNPs/Au) were prepared based on fluorescein isothiocyanate labeled yeast cells (FITC-yeast) via metal-free visible-light-induced atom transfer radical polymerization (MVL ATRP). Here, N-isopropyl acrylamide (NIPAM) was used as a temperature-responsive functional monomer, α-methacrylic acid (MAA) was chosen as an auxiliary functional monomer, N,N'-methylene bisacrylamide (MBA) was used as a cross-linker, and FITC-yeast was selected as both a template and photocatalyst. Under the optimal conditions, the detection range of the yeast cell-imprinted sensor toward yeast cells was 1.0 × 102 to 1.0 × 109 cells per mL, and the detection limit was 11 cells per mL (S/N = 3), with a linear equation of ΔI (μA) = 8.44 log[C (cells per mL)] + 7.62 (R2 = 0.993). The sensor showed good selective recognition in the presence of interfering substances such as autolyzed yeast cells (AY), dead yeast cells (DY), human mammary epithelial cells (MCF-10A), human breast cancer cells (MCF-7) and Escherichia coli (EC). The sensor also had good consistency and reproducibility. Finally, spiked recovery experiments were performed to investigate the recognition of yeast cells in the actual sample using the yeast cell-imprinted sensor. The spiked recoveries were all in the range of 98.5-108.0%, and the RSD values were all less than 4%, indicating that the sensor had good application prospects.
PMID:39219465 | DOI:10.1039/d4ay00905c
Colorectal Dis. 2024 Sep 1. doi: 10.1111/codi.17153. Online ahead of print.
NO ABSTRACT
PMID:39219037 | DOI:10.1111/codi.17153
Anal Chim Acta. 2024 Oct 2;1324:343040. doi: 10.1016/j.aca.2024.343040. Epub 2024 Jul 31.
ABSTRACT
BACKGROUND: Persistent infection with human papillomavirus (HPV) significantly contributes to the development of cervical cancer. Thus, it is urgent to develop rapid and accurate methods for HPV detection. Herein, we present an ultrasensitive CRISPR/Cas12a-based electrochemiluminescent (ECL) imaging technique for the detection of HPV-18 DNA.
RESULT: The ECL DNA sensor array is constructed by applying black hole quencher (BHQ) and polymer dots (Pdots) co-labeled hairpin DNA (hpDNA) onto a gold-coated indium tin oxide slide (Au-ITO). The ECL imaging method involves an incubation process of target HPV-18 with a mixture of crRNA and Cas12a to activate Cas12a, followed by an incubation of the active Cas12a with the ECL sensor. This interaction causes the indiscriminate cleavage of BHQ from Pdots by digesting hpDNA on the sensor surface, leading to the restoration of the ECL signal of Pdots. The ECL brightness readout demonstrates superior performance of the ECL imaging technique, with a linear detection range of 10 fM-500 pM and a limit-of-detection (LOD) of 5.3 fM.
SIGNIFICANCE: The Cas12a-based ECL imaging approach offers high sensitivity and a broad detection range, making it highly promising for nucleic acid detection applications.
PMID:39218584 | DOI:10.1016/j.aca.2024.343040
Anal Chim Acta. 2024 Oct 2;1324:343103. doi: 10.1016/j.aca.2024.343103. Epub 2024 Aug 13.
ABSTRACT
BACKGROUND: Recently, various techniques have been developed to accurately and sensitively detect tumor biomarkers for the early diagnosis and effective therapy of cancer. The electrochemiluminescence (ECL) method holding outstanding features including high sensitivity, ease of operation, and spatiotemporal controllability exhibited great potential for DNA/RNA detection, immunoassay, cancer cell detection, and environmental analysis. However, a glaring problem of ECL approaches is that the layer-by-layer modification on the electrode leads to poor stability and sensitivity of the sensors. Therefore, new simple and efficient methods for electrode modification which can effectively improve the ECL signal have attracted more and more research interests.
RESULTS: Based on the dual amplification strategy of target-induced CHA and nanocomposite probes leading to self-generated co-reactant (H2O2), we proposed a highly sensitive miRNA-ECL detection system. The introduction of the target miRNA-21 triggers the CHA cycle amplification of DNA1 and biotin-modified DNA2, releasing the target miRNA-21 sequence for the target cycle reaction. After the reaction, the newly introduced DNA2 was combined with Au NPs modified with SA and Glucose oxidase (GOD). In the presence of oxygen, glucose was decomposed by GOD to produce H2O2, and then H2O2 was immediately catalyzed by the Hemin/G-quadruplex at the double-stranded end of the CHA product to produce a large amount of O2-•. As a co-reactant of luminol, the ECL signal was significantly enhanced, thereby achieving highly sensitive detection of miRNA-21 content and obtaining a low detection limit of 0.65 fM. The high specificity of the ECL biosensor was also proved by base mismatch.
SIGNIFICANCE: Compared with other current detection methods, this sensor can achieve quantitative analysis of other target analytes by flexibly changing the probe DNA sequence, and provide a new feasible solution for the detection of tumor-associated markers. Benefiting from the improved sensitivity and selectivity, the proposed biosensing platform is expected to provide a new strategy for biomarkers analysis and outstanding prospect for further clinical application.
PMID:39218582 | DOI:10.1016/j.aca.2024.343103
Anal Chim Acta. 2024 Oct 2;1324:343068. doi: 10.1016/j.aca.2024.343068. Epub 2024 Aug 6.
ABSTRACT
BACKGROUND: Live single-cell metabolomic studies encounter inherent difficulties attributed to the limited sample volume, minimal compound quantity, and insufficient sensitivity in the Mass Spectrometry (MS) method used to obtain single-cell data. However, understanding cellular heterogeneity, functional diversity, and metabolic processes within individual cells is essential. Exploring how individual cells respond to stimuli, including drugs, environmental changes, or signaling molecules, offers insights into biology, oncology, and drug discovery. Efficient release of cell contents (lysis) is vital for accurate metabolite detection at the single-cell level. Despite this, traditional approaches in live single cell metabolomics methods do not emphasize efficient lysis to prevent sample dilution. Instead, current live single cell metabolomics methods use direct infusion to introduce the cell into the mass spectrometry without prior chromatographic separation or a lysis step, which adversely affects sensitivity and metabolic coverage.
RESULTS: To address this, we developed an integrated single-cell electrical lysis and nano spray (SCEL-nS) platform coupled to an Orbitrap MS capable of efficiently lysing a single cell after being sampled with specially manufactured micropipettes. Lysis efficiency was validated by comparing live cell stain fluorescent intensities of intact and electrically lysed cells through microscopy imaging. The SCEL-nS platform successfully induced the breakdown of a single cell, significantly reducing the live cell stain's fluorescent intensity indicating cell membrane breakdown. Additionally, SCEL-nS was validated by measuring single cells spiked with the anti-cancer drug tamoxifen by MS. SCEL-nS use resulted in statistically significant increase in the peak measured by the method compared to the traditional non-lysis method.
SIGNIFICANCE: Overall, our results demonstrate that the newly incorporated SCEL-nS platform achieved higher sensitivities compared to traditional live single cell analysis methods.
PMID:39218570 | DOI:10.1016/j.aca.2024.343068
J Pharm Biomed Anal. 2024 Aug 22;251:116445. doi: 10.1016/j.jpba.2024.116445. Online ahead of print.
ABSTRACT
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as icotinib, osimertinib, and aumolertinib have emerged as promising treatment options for EGFR mutated Non-small cell lung cancer (NSCLC) patients. Additionally, anlotinib, an anti-angiogenic agent targeting VEGFR, FGFR, and PDGFR, has been used in combination with EGFR-TKIs in NSCLC cases. A method utilizing ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated for quantifying icotinib, osimertinib, aumolertinib and anlotinib simultaneously in clinical TDM. The chromatographic separation was performed using a Kinetex C18 column (100 mm × 2.1 mm) and an elution gradient of ammonium acetate in water acidified with 0.1 % formic acid and in acetonitrile. The assay was validated over a linear range of 4-2000 ng/mL for icotinib, 2-1000 ng/mL for osimertinib, 1-500 ng/mL for aumolertinib, and 0.8-400 ng/mL for anlotinib, following the guidelines on bioanalytical methods by FDA. The quantification method exhibited satisfactory performance in terms of selectivity, accuracy (from 91.3 % to 107 %), precision (intra- and inter-day coeffficients of variation ranged from 0.944 % to 7.48 %), linearity, recovery (from 86.0 % to 91.9 %), matrix effect (IS-normalized matrix factors were from 96.7 % to 102 %), and stability. Overall, the method proved to be sensitive, reliable, and straightforward, enabling successful simultaneous determination of blood concentrations of icotinib, osimertinib, aumolertinib, and anlotinib in patients. The validity of the method has been confirmed across various instruments.
PMID:39214029 | DOI:10.1016/j.jpba.2024.116445
Anal Chem. 2024 Aug 30. doi: 10.1021/acs.analchem.4c02364. Online ahead of print.
ABSTRACT
Mitochondrial polarity is a critical indicator of numerous pathological and biological processes; thus, the development of fluorescent probes capable of targeting mitochondria and visually monitoring its polarity is of great significance. In this study, fluorescent probes were designed with a N, N-dialkylamino rhodol scaffold as the fluorophore sensitive to polarity environments, in which the alkyl chain length was adjusted rationally to obtain distinct polarity recognition modes. By integrating mitochondria targeting groups, three fluorogenic chemical probes ROML-1, ROML-2, and ROML-3 have been obtained, featuring the capability to target mitochondria and monitor its polarity precisely, dynamically and visually. The probes displayed a distinctive response to the alterations in polarity. ROML-1 and ROML-2 followed a turn-on pattern while ROML-3 was ratiometric. It has been demonstrated that the hypersensitivity to polarity and ratio fluorescence property of ROML-3 was attributed to methyl groups rather than ethyl or butyl groups. The introduction of short methyl chains made the dihedral angle between the dialkylamino substituent and fluorophore of ROML-3 (spirocyclic form) rotatable and enlarged the energy gap between the ground state and excited state, which has been validated by the results of density functional theory (DFT) calculations. Furthermore, ROML-3 was used to monitor mitochondrial polarity via confocal microscopy imaging, which revealed that compared to healthy cells the polarity of mitochondria in cancer cells was enhanced; meanwhile, the polarity of mitochondria in senescent cells was higher in contrast with young cells. The present probe ROML-3 has been proven to be an efficient tool to monitor mitochondrial polarity dynamics, which demonstrated potential significance in biomedical research and disease diagnosis.
PMID:39213642 | DOI:10.1021/acs.analchem.4c02364
Cancer Treat Res. 2024;192:277-303. doi: 10.1007/978-3-031-61238-1_14.
ABSTRACT
Immunotherapy has revolutionised cancer treatment over the past decade. Long-term durable responses can be achieved in some cancer patient populations that were previously facing terminal disease. In this chapter, we summarise current phase 3 clinical trial evidence for the use of immunotherapy in gastrointestinal cancers (oesophageal squamous cell carcinoma, oesophago-gastric adenocarcinoma, pancreatic cancer, biliary cancer, hepatocellular carcinoma, colorectal cancer, and squamous cell cancer of the anus). We discuss meaningful biomarkers used in clinical trials to select patients most likely to benefit from immunotherapy, such as mismatch-repair deficiency (MMRd)/microsatellite instability (MSI) and programmed-death-ligand-1 (PD-L1) immunohistochemistry (IHC) expression. Clinical questions are arising regarding the role of immunotherapy in the adjuvant/perioperative setting, optimal timing of surgery in patients who respond to immunotherapy, and toxicities specific to patients with gastrointestinal malignancies. We outline the current landscape and future horizon of immunotherapy in gastrointestinal cancers, such as strategies to increase effectiveness of checkpoint blockade through combinations with other checkpoint inhibitors, cytotoxic chemotherapy, targeted agents, radiotherapy, CAR-T therapy, and cancer vaccines.
PMID:39212926 | DOI:10.1007/978-3-031-61238-1_14
Cancer Treat Res. 2024;192:233-263. doi: 10.1007/978-3-031-61238-1_12.
ABSTRACT
In USA, colorectal cancer is the third most commonly diagnosed cancer in men, second in women, as well as the third leading cause of cancer deaths (Siegel et al. in Cancer J Clin 73:1-112, 2023 [109]). Worldwide, colorectal cancer is the second leading cause of death and causes almost 916,000 deaths each year (Ferlay in Global cancer observatory: cancer today. International Agency for Research on Cancer, Lyon, 2020 [28]). Fortunately, due to the colon's surgical and endoscopic accessibility and functional redundancy, colorectal cancer is very treatable. Colonoscopic surveillance has the potential for not only providing tissue for the diagnosis of precancerous polyps and invasive carcinoma, but also preventing development of invasive carcinoma by the removal of precancerous lesions. This chapter discusses the clinical and pathologic features of the spectrum of epithelial, hematolymphoid, and mesenchymal malignant tumors of the colon, rectum, appendix, and anus.
PMID:39212924 | DOI:10.1007/978-3-031-61238-1_12
Clin Exp Dermatol. 2024 Aug 30:llae362. doi: 10.1093/ced/llae362. Online ahead of print.
ABSTRACT
BACKGROUND: In the UK, few (12%) anal squamous cell carcinomas (aSCC) are diagnosed early at stage 1 (T1N0M0). The Homerton Anogenital Neoplasia Service (HANS) is a highly specialised tertiary centre where high resolution anoscopy (HRA) is performed to diagnose and treat anal intraepithelial neoplasia (AIN), a precursor to cancer. In some cases, aSCC (here defined as anal canal cancers and perianal cancers up to 5cm from the anal verge) is found on referral for AIN; in others, aSCC may develop while undergoing AIN management. We reviewed aSCC diagnoses at our specialist unit to establish whether HRA offers added value in the early detection of aSCC in a high-risk cohort.
METHODS: A cross-sectional analysis was performed of all primary aSCC diagnoses at HANS between January 2016 and June 2021. Patient records, histopathology and radiology reports were reviewed to define anal cancer stage per TNM classification (AJCC version 8). Results were compared with national anal cancer data published by the Office for National Statistics (AJCC version 8).
RESULTS: Fifty-three aSCC diagnoses were made at HANS; 35 (66%) were stage 1 (14 prevalent, 21 incident), 11 (21%) stage 2 (9 prevalent, 2 incident) and 6 (11%) stage 3 (5 prevalent, 1 incident). None were stage 4; 1 cancer was unstageable due to further management at another unit. By comparison, 5836 aSCCs were diagnosed in the UK between 2013-2017; of these, 12.0% were stage 1, 22.8% stage 2, 33.0% stage 3 and 8.46% stage 4; 23.8% were unknown or unstageable. There was a statistically significant difference in the proportion of early (i.e. stage 1) HRA-detected cancers (HDCs) compared with national statistics (p < 0.001).
CONCLUSION: Our results suggest that surveillance and examination within an HRA programme may lead to detection of aSCC at an earlier stage allowing for less morbid treatment and potentially a lower mortality.
PMID:39212481 | DOI:10.1093/ced/llae362
Anal Methods. 2024 Aug 30. doi: 10.1039/d4ay01135j. Online ahead of print.
ABSTRACT
Cancer is one of the most important causes of human death and poses a serious threat to human health. As a cancer biomarker, microRNA-155 (miRNA-155) is highly expressed in various types of cancer tissues and is involved in the proliferation of tumor cells. Therefore, developing a miRNA-155 detection technology with high specificity and sensitivity is of great significance for the early detection, accurate treatment and prognostic evaluation of tumors. Here, we developed a fluorescence detection method using exonuclease III-assisted target cycling and catalytic hairpin assembly (CHA) as a signal amplification technique. This study developed a biosensor for the detection of miRNA-155, utilizing a DNA hairpin (Hp) for target recognition and generating double-stranded DNA (dual-Hp-T). The 3' flat end of the double-stranded DNA can be cleaved by exonuclease III to achieve the target cycle, and a large amount of single-stranded DNA (fuel) can trigger CHA to achieve signal amplification. Simultaneously, the fluorescence resonance energy transfer (FRET) of signal probes with different fluorescence labels on H1 and H2 ends occurs with the CHA reaction. The two fluorescence signals obtained can be used to cross-validate the experimental results. The biosensor exhibits excellent performance of high recovery, high sensitivity and high operability, which can achieve the specific detection of miRNA-155 with a detection limit as low as 8.3 pM. Additionally, the detection efficacy in a human serum environment is also highly satisfactory. This technology provides strong technical support for the development of nucleic acid probes and the diagnosis and treatment of cancer, demonstrating significant practical application value.
PMID:39211941 | DOI:10.1039/d4ay01135j
J Pharm Anal. 2024 Oct;14(10):100997. doi: 10.1016/j.jpha.2024.100997. Epub 2024 May 8.
ABSTRACT
miR-135 is a highly conserved miRNA in mammals and includes miR-135a and miR-135b. Recent studies have shown that miR-135b is a key regulatory factor in cardio-cerebrovascular diseases. It is involved in regulating the pathological process of myocardial infarction, myocardial ischemia/reperfusion injury, cardiac hypertrophy, atrial fibrillation, diabetic cardiomyopathy, atherosclerosis, pulmonary hypertension, cerebral ischemia/reperfusion injury, Parkinson's disease, and Alzheimer's disease. Obviously, miR-135b is an emerging player in cardio-cerebrovascular diseases and is expected to be an important target for the treatment of cardio-cerebrovascular diseases. However, the crucial role of miR-135b in cardio-cerebrovascular diseases and its underlying mechanism of action has not been reviewed. Therefore, in this review, we aimed to comprehensively summarize the role of miR-135b and the signaling pathway mediated by miR-135b in cardio-cerebrovascular diseases. Drugs targeting miR-135b for the treatment of diseases and related patents, highlighting the importance of this target and its utility as a therapeutic target for cardio-cerebrovascular diseases, have been discussed.
PMID:39211791 | PMC:PMC11350494 | DOI:10.1016/j.jpha.2024.100997
J Surg Case Rep. 2024 Aug 28;2024(8):rjae554. doi: 10.1093/jscr/rjae554. eCollection 2024 Aug.
ABSTRACT
Anal cancer is uncommon, comprising 2.2% of gastrointestinal cancers. Squamous cell carcinoma (SCC) is the most common; while perianal basal cell carcinoma (BCC) is rare, representing only 0.2% of anorectal malignancies. BCC, associated with sun exposure and immunosuppression, often resembles benign conditions and manifests as perianal ulcers or masses. Histologically, BCC exhibits basaloid tumor cells with distinct patterns. Despite its rarity, accurate diagnosis is crucial. We expose a case study of a 59-year-old male, previously healthy, that presented with hematochezia and perianal pain, leading to a diagnosis of lower gastrointestinal bleeding. Colonoscopy was needed, and a biopsy revealed an ulcerated, indurated lesion involving the left lateral hemorrhoidal bundle, diagnosed as pigmented basaloid carcinoma. Microscopic examination showed malignant nests of cells with peripheral nuclear palisading, melanocytes, and melanin pigment. Immunohistochemistry confirmed positivity for p63, CK5/6, and BCL2. Respect the treatment, due to the involvement of the anal sphincteric muscle, radiotherapy was chosen.
PMID:39211371 | PMC:PMC11358057 | DOI:10.1093/jscr/rjae554
J Pharm Biomed Anal. 2024 Aug 15;251:116421. doi: 10.1016/j.jpba.2024.116421. Online ahead of print.
ABSTRACT
In India, ginger is highly valued for cultural and medicinal purposes. Besides traditional uses, ginger has been proven for its efficacy in cancer, chemotherapy-induced nausea, bacterial infections, neuroinflammation, and oxidative stress. This study focuses on Zingiber sianginensis, a rare ginger species in the Siang region of Arunachal Pradesh, India. This study studied pharmacognostical evaluation, phytometabolomics analysis, and its effect on oxidative stress biomarkers. Microscopic and chemical tests were employed for pharmacognostical evaluation, revealing distinctive characteristics of Zingiber sianginensis, such as non-close collateral vascular bundles and unique cork layers. Chemical tests, including the phloroglucinol and hydrochloric acid test, differentiated Zingiber sianginensis from Zingiber officinale Roscoe. Phytometabolomics analysis, using Gas Chromatography-Mass Spectrometry (GC/MS) and Liquid Chromatography-Electrospray Ionisation-Quadrupole Time of Flight-Mass Spectrometry (LC-ESI-QTOF-MS/MS) techniques, identified a diverse range of metabolites in Zingiber sianginensis, including polyphenols, monoterpenoids, diterpenoids, sesquiterpenoids, and organic compounds. The LC-ESI-QTOF-MS/MS analysis revealed 158 compounds, verified through cross-referencing with established databases. Heavy metal analysis by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) confirmed that Zingiber sianginensis complies with safety standards, showing concentrations of heavy metals within acceptable limits. The isolation and characterization of compounds from Zingiber sianginensis identified natural products such as (R)-(-)- alpha-Curcumene (1), 1-Dehydro-[10]-gingerdione (2), 6-Shogaol (3), and 6-Gingerol (4). Quantification of 6-gingerol revealed that Zingiber sianginensis contains approximately twice the amount compared to Zingiber officinale Roscoe's, suggesting its potential as a source for higher 6-gingerol content. The hydroalcoholic extract of Zingiber sianginensis exhibited antioxidant properties, reducing oxidative stress biomarkers in human dermal fibroblast cells treated with rotenone. Allantoin and 3-bromotyrosine levels significantly decreased, indicating the extract's potential in combating oxidative stress-related disorders. Overall, this comprehensive study provides valuable insights into the pharmacognostical, phytometabolomic, and safety aspects of Zingiber sianginensis, highlighting its potential as a source of bioactive compounds with health benefits.
PMID:39208650 | DOI:10.1016/j.jpba.2024.116421
Anal Methods. 2024 Aug 29. doi: 10.1039/d4ay01030b. Online ahead of print.
ABSTRACT
Oral squamous cell carcinoma (OSCC) is the most common type of head and neck cancers. OSCC constitutes 90% of the head and neck malignancies. The delayed identification of oral cancer is the primary cause of ineffective medical treatment. To address this issue, low-cost, reliable point-of-care devices that can be utilized for large-scale screening, even in low-resource settings, including rural areas and primary healthcare centers, are of great interest. Herein, a comprehensive analysis of numerous salivary biomarkers that exhibit significant variations in concentration between individuals with oral cancer and those without is given. Furthermore, the article explores several point-of-care devices that exhibit potential in the realm of oral cancer detection. The biomarkers are discussed with a focus on their structural characteristics and role in oral cancer progression. The devices based on colorimetry and microfluidics are discussed in detail, considering their compliance with the 'REASSURED' criteria given by the World Health Organization (WHO) and suitability for mass screening in low-resource settings. Finally, the discourse revolves around the fundamental aspects pertaining to the advancement of multiplex, cost-effective point-of-care devices designed for widespread screening purposes.
PMID:39206589 | DOI:10.1039/d4ay01030b
ANZ J Surg. 2024 Aug 28. doi: 10.1111/ans.19194. Online ahead of print.
ABSTRACT
BACKGROUND: The demographics and geography of Australia and New Zealand (ANZ), with few metropolitan centres and vast, sparsely populated rural areas, represent a challenge to providing equal care to all patients. This study aimed to compare rectal cancer care at rural and urban hospitals in ANZ.
METHODS: From the Bowel Cancer Outcomes Registry (BCOR, formerly known as the Bi-National Colorectal Cancer Audit; BCCA), rectal cancer patients treated between 2007 and 2020 were compared based on hospital location (urban versus rural). Propensity-score matching was performed to correct for differences in baseline characteristics between groups.
RESULTS: A total of 9385 rectal cancer patients were identified from the BCOR: 1329 (14.2%) were treated at rural hospitals and 8056 (85.8%) at urban hospitals. Propensity-score matching resulted in 889 patients in each group, matched for age, ASA score, hospital type (public/private), tumour height from the anal verge, and pre-treatment cT- and cAJCC-stage. Rural patients had fewer pre-treatment MRIs (67.9% versus 74.7%; P = 0.002), and underwent less neoadjuvant therapy (44.7% versus 50.9%; P = 0.01). Rural patients underwent fewer ULARs (39.4% versus 45.6%; P = 0.03), and fewer anastomoses were formed (67.9% versus 74.4%; P = 0.05). CRM rates and postoperative AJCC stages (P = 0.19) were similar between groups (P = 0.87). Fewer rural patients received adjuvant chemotherapy (37.8% versus 43.3%; P = 0.02).
CONCLUSION: There are significant differences in pre-treatment MRI rates, (neo)adjuvant treatment rates and surgical procedures performed between rectal cancer patients treated at rural and urban hospitals in ANZ, while CRM rates and postoperative AJCC stages are similar.
PMID:39205431 | DOI:10.1111/ans.19194
Vaccines (Basel). 2024 Jul 25;12(8):838. doi: 10.3390/vaccines12080838.
ABSTRACT
BACKGROUND: The objectives were to evaluate the safety and immunogenicity of the nonavalent human papillomavirus (nHPV) vaccine in adult Spanish women living with HIV (WLHIV); the prevalence of anal and cervical dysplasia and nHPV vaccine genotypes in the anus and cervix; and risk factors for high-risk HPV (HR-HPV) infection in anal mucosa.
METHODS: In this single-center, open-arm, non-randomized clinical trial, the nHPV vaccine was administered at 0, 2, and 6 months to WLHIV enrolled between February 2020 and November 2023, measuring vaccine antibody titers pre-vaccination and at 2, 6, and 7 months after the first dose. Cervical and anal cytology and HPV PCR genotyping studies were performed. Women with abnormal cytology and/or anal or cervical HPV infection at baseline underwent high-resolution anoscopy and/or colposcopy.
RESULTS: A total of 122 participants were included with mean age of 49.6 years: 52.5% smoked; 10.7% had anal-genital condylomatosis; 38.5% were infected by HR-HPV in the anus and 25.4% in the cervix, most frequently HPV 16; 19.1% had anal intraepithelial neoplasia 1-(AIN1); and 3.1% had cervical intraepithelial neoplasia 1 and 2 (CIN1/CIN2). Vaccine administration did not modify viral-immunological status (CD4 [809 ± 226.8 cells/uL vs. 792.35 ± 349.95; p = 0.357]) or plasma HIV load (3.38 ± 4.41 vs. 1.62 ± 2.55 cop/uL [log]; p = 0.125). Anti-HPV antibodies ([IQR: 0-0] vs. 7.63 nm [IQR: 3.46-19.7]; p = 0.0001) and seroconversion rate (8.2% vs. 96.7% [p = 0.0001]) were increased at 7 versus 0 months. There were no severe vaccine-related adverse reactions; injection-site pain was reported by around half of the participants. HR-HPV infection in the anus was solely associated with a concomitant cervix infection (HR 5.027; 95% CI: 1.009-25.042).
CONCLUSIONS: nHPV vaccine in adult WLHIV is immunogenic and safe.
PMID:39203964 | PMC:PMC11359547 | DOI:10.3390/vaccines12080838
Life (Basel). 2024 Aug 12;14(8):1000. doi: 10.3390/life14081000.
ABSTRACT
(1) Background: Familial adenomatous polyposis (FAP) is a hereditary condition characterized by the development of numerous adenomas in the large intestine, often necessitating colectomy due to an elevated risk of colorectal cancer. Despite surgical intervention, adenomas frequently recur, underscoring the importance of ongoing surveillance. This study evaluates the outcomes of a 12-year endoscopic follow-up after colectomy and gastrointestinal reconstruction for FAP. (2) Methods: A retrospective analysis was conducted on 41 FAP patients who underwent at least one postoperative endoscopic examination. Assessments of the pouch or rectum were performed every 12-18 months following ileorectal anastomosis and every 18-24 months after ileal pouch-anal anastomosis. Follow-up biopsies were assessed using the adopted Spigelman classification. (3) Results: Postoperative pathology revealed invasive colorectal cancer in three patients. Abdominoperineal resection was performed in two cases due to secondary invasive carcinoma, and one T1 tumor was radically removed with ESD. One patient underwent radical pouch excision following a nodal pelvic recurrence of rectal cancer. Over a 12-year observation period, the mean Spigelman score increased by 2 points, and the proportion of patients with low-grade polypoid lesions decreased. The quantity or size of polyps increased in 24 patients, decreased in 8 patients, and remained stable in 9 patients. In four patients, granular, laterally spreading tumors were discovered in the rectal stump. (4) Conclusions: Regular endoscopic surveillance in FAP patients facilitates early identification of neoplastic and inflammatory changes. The downstaging potential highlights the effectiveness of early interventions. While the Spigelman classification assessed polyps well, it did not predict cancer occurrence. A notable number of patients had invasive cancer at the time of surgery, underscoring the importance of early surgical qualification, which is particularly crucial for identifying upstaging or secondary cancer.
PMID:39202742 | PMC:PMC11355371 | DOI:10.3390/life14081000
Biomedicines. 2024 Aug 13;12(8):1838. doi: 10.3390/biomedicines12081838.
ABSTRACT
BACKGROUND: Human papillomavirus (HPV) infection is linked to several cancers, including anal and oral cancers. The incidence of anal cancer is particularly high among HIV-positive men who have sex with men (MSM). DNA methylation markers have shown promise as biomarkers for identifying precancerous lesions and cancer in HPV-infected individuals. The aim of this study was to investigate the correlation of DNA methylation with HPV infection in oral samples and the correlation of DNA methylation with lesion degree in the anal samples of HIV-positive MSM.
METHODS: This study investigated DNA methylation in oral and anal samples from HIV-positive MSM at the National Institute for Infectious Diseases (INMI) in Rome, Italy. Exfoliated oral epithelial cells and anal samples were collected and analyzed for 28 HPV genotypes using the Allplex 28 HPV assay. DNA methylation was assessed with the PrecursorM+ kit for oral samples and the AnoGyn kit for anal samples, focusing on the promoter regions of specific genes.
RESULTS: The study included 63 participants, with a median age of 49 and a median CD4+ count of 705 cells/µL. The oral samples showed HPV16 as the most common type, with 22% testing positive for DNA methylation. The anal samples exhibited HPV-related methylation changes linked to cytological lesions, with a 30% increase in the observed ddCt ratio. Significant differences were found in both ASCL1 and ZNF582 genes, particularly for HSILvsNILM and HSILvsLSIL lesions. Of the samples with an increased ddCt ratio, 80% were from patients over 35 years old, and multiple HPV infections were common.
CONCLUSIONS: DNA methylation markers could be valuable in identifying high-risk HPV infections in oral samples and detecting potential precancerous lesions in anal samples. These markers may enhance the early detection and prevention strategies for HPV-related cancers in high-risk populations, with follow-up data indicating potential for monitoring lesion progression.
PMID:39200302 | PMC:PMC11352028 | DOI:10.3390/biomedicines12081838
Cancers (Basel). 2024 Aug 8;16(16):2799. doi: 10.3390/cancers16162799.
ABSTRACT
BACKGROUND: Managing patients with obstructing rectal cancer is challenging due to the risks of gastrointestinal obstruction and perforation. This study evaluates the outcomes of pre-emptive laparoscopic colostomy creation in patients with locally advanced rectal and anal cancer to prevent symptoms and facilitate therapy initiation.
METHODS: This retrospective cohort study includes patients with locally advanced rectal or anal cancer assessed by our Colorectal Multidisciplinary Team from January 2017 to February 2024. Patients who underwent pre-emptive laparoscopic colostomy were compared to a control group of non-obstructing rectal cancer patients who started direct oncological treatment. The primary endpoint was the time from diagnosis to the initiation of oncological treatments. The secondary endpoints were the rate and timing of subsequent radical resection, surgical morbidity and hospital stay. A Weibull regression was used to evaluate the time differences between the groups.
RESULTS: There were 37 patients who received pre-emptive laparoscopic colostomy, compared to 207 control patients. The mean time from diagnosis to the start of neoadjuvant therapy was 38.3 ± 2.3 days. Despite higher rates of malnutrition and more advanced stages in the colostomy group, no significant differences were observed in the time to start therapy (p = 0.083) or time to radical resection (p = 0.187) between the groups. The laparoscopic procedure showed low rates of postoperative complications and acceptable lengths of stay.
DISCUSSION AND CONCLUSIONS: Pre-emptive laparoscopic colostomy is a feasible approach for managing obstructing rectal or anal cancer. Treatment timelines were not extended compared to timelines for non-obstructing cases, despite differences in nutritional status and staging. Further prospective studies with larger cohorts are needed to validate these findings and refine treatment protocols for obstructing gastrointestinal malignancies.
PMID:39199572 | PMC:PMC11352586 | DOI:10.3390/cancers16162799
Anal Chem. 2024 Aug 28. doi: 10.1021/acs.analchem.4c03462. Online ahead of print.
ABSTRACT
Liquid biopsy provides a convenient and safer procedure for the diagnosis and genomic profiling of tumors that are inaccessible to biopsy by analyzing exfoliated tumor cells (ETCs) or tumor-derived cell-free DNA (cfDNA). However, its primary challenge lies in its limited accuracy in comparison to tissue-based approaches. We report a parallel single-ETC genomic sequencing (Past-Seq) method for the accurate diagnosis and genomic profiling of hard-to-biopsy tumors such as cholangiocarcinoma (CCA) and upper tract urothelial carcinoma (UTUC). For CCA, a prospective cohort of patients with suspicious biliary strictures (n = 36) was studied. Parallel single-cell whole genome sequencing and whole exome sequencing were performed on bile ETCs for CCA diagnosis and resolving mutational profiles, respectively, along with bile cfDNA sequenced for comparison. Concordant single-cell copy number alteration (CNA) profiles in multiple ETCs provided compelling evidence for generating a malignant diagnosis. Past-Seq yielded bile-based accurate CCA diagnosis (96% sensitivity, 100% specificity, and positive predictive value), surpassing pathological evaluation (56% sensitivity) and bile cfDNA CNA analysis (13% sensitivity), and generated the best performance in the retrieval tissue mutations. To further explore the applicability of Past-Seq, 10 suspicious UTUC patients were investigated with urine specimens, and Past-Seq exhibited 90% sensitivity in diagnosing UTUC, demonstrating its broad applicability across various liquid biopsies and cancer types.
PMID:39197101 | DOI:10.1021/acs.analchem.4c03462
Anal Bioanal Chem. 2024 Aug 28. doi: 10.1007/s00216-024-05502-7. Online ahead of print.
ABSTRACT
A capillary zone electrophoresis (CZE) system was coupled to an Orbitrap mass spectrometer operating in a data-independent acquisition (DIA) mode for in-depth proteomics analysis. The performance of this CZE-DIA-MS system was systemically evaluated and optimized under different operating conditions. The performance of the fully optimized CZE-DIA-MS system was subsequently compared to the one by using the same CZE-MS system operating in a data-dependent acquisition (DDA) mode. The experimental results show that the numbers of identified peptides and proteins acquired in the DIA mode are much higher than the ones acquired in the DDA mode, especially with the small sample loading amount. Specifically, the numbers of identified peptides and proteins acquired in the DIA mode are 1.8-fold and 2-fold higher than the ones acquired in the DDA mode by using 12.5 ng Hela digests. The proteins identified in the DIA mode also cover almost all the proteins identified in the DDA mode. In addition, a potential cancer biomarker protein, carbohydrate antigen 125, undetected in the DDA mode, can be easily identified in the DIA mode even with 12.5 ng Hela digests. The performance of the CZE-DIA-MS system for in-depth proteomics analysis with a limited sample amount has been fully demonstrated for the first time through this study.
PMID:39196334 | DOI:10.1007/s00216-024-05502-7
Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2024 Aug 28:1-22. doi: 10.1080/19440049.2024.2386143. Online ahead of print.
ABSTRACT
Contrary to the initial hypothesis, Flemish adolescents who reported consuming organic food at least 7.5 times per week did not exhibit reduced internal exposure to the tested recently used pesticides. After adjustment for gender, age, country of origin, socioeconomic status, body mass index, consumption of high-fat foods and foods linked to organic food consumption, and concerning organochlorine derivatives and lead, additional adjustment for the duration of breastfeeding expressed in weeks, they displayed slightly elevated internal exposure to organochlorine derivatives, lead, methyl arsenate, and toxic relevant arsenic. A comparison was also made between the correlation of internal exposure to pollutants with the frequency of organic food consumption on one hand and the total consumption of equivalent products from all sources on the other. Regarding potatoes, vegetables, and fruits, no clear trends were observed. Regarding eggs, there was a trend towards higher internal exposures with organic food consumption, significant for trans-nonachlor, PCB118, and 2,4-dichlorophenoxyacetic acid, and marginally significant for glyphosate. For dairy, there was a trend towards higher internal exposures with organic food consumption, significant for perfluorononanoic acid and marginally significant for PCB153. Regarding nuts and seeds, the higher internal exposure to dichlorophenoxyacetic acid and the lower exposure to 3-phenoxybenzoic acid were marginally significant, while there was also a trend towards higher internal exposure to other pollutants with organic food consumption, significant for PCB118, PCB153, and sum PCBs, and marginally significant for trans-nonachlor. Concerning breakfast cereals and muesli, no clear trends were observed.
PMID:39196262 | DOI:10.1080/19440049.2024.2386143
World J Clin Oncol. 2024 Aug 24;15(8):1048-1060. doi: 10.5306/wjco.v15.i8.1048.
ABSTRACT
BACKGROUND: Celiac disease (CeD) is an autoimmune disorder triggered by the immune response to gluten in genetically predisposed individuals. Recent research has unveiled a heightened risk of developing specific malignant neoplasms (MN) and various malignancies, including gastrointestinal, lymphomas, skin, and others, in individuals with CeD.
AIM: To investigate the prevalence of MN in hospitalized CeD patients in the United States.
METHODS: Using data from the National Inpatient Sample spanning two decades, from January 2000 to December 2019, we identified 529842 CeD patients, of which 78128 (14.75%) had MN. Propensity score matching, based on age, sex, race, and calendar year, was employed to compare CeD patients with the general non-CeD population at a 1:1 ratio.
RESULTS: Positive associations were observed for several malignancies, including small intestine, lymphoma, nonmelanoma skin, liver, melanoma skin, pancreas myelodysplastic syndrome, biliary, stomach, and other neuroendocrine tumors (excluding small and large intestine malignant carcinoid), leukemia, uterus, and testis. Conversely, CeD patients exhibited a reduced risk of respiratory and secondary malignancies. Moreover, certain malignancies showed null associations with CeD, including head and neck, nervous system, esophagus, colorectal, anus, breast, malignant carcinoids, bone and connective tissues, myeloma, cervix, and ovary cancers.
CONCLUSION: Our study is unique in highlighting the detailed results of positive, negative, or null associations between different hematologic and solid malignancies and CeD. Furthermore, it offers insights into evolving trends in CeD hospital outcomes, shedding light on advancements in its management over the past two decades. These findings contribute valuable information to the understanding of CeD's impact on health and healthcare utilization.
PMID:39193153 | PMC:PMC11346075 | DOI:10.5306/wjco.v15.i8.1048
Anal Chem. 2024 Aug 28. doi: 10.1021/acs.analchem.4c00932. Online ahead of print.
ABSTRACT
Highly abundant proteins present in biological fluids and tissues significantly interfere with low-abundance protein identification by mass spectrometry (MS), limiting proteomic depth and hindering protein biomarker discovery. Herein, to enhance the coverage of tissue proteomics, we developed a nanoparticle-protein corona (NP-PC)-based method for the aging mouse proteome atlas. Based on this method, we investigated the complexity of life process of 5 major organs, including the heart, liver, spleen, lungs, and kidneys, from 4 groups of mice at different ages. Compared with the conventional strategy, NP-PC-based proteomics significantly increased the number of identified protein groups in the heart (from 3007 to 3927; increase of 30.6%), liver (from 2982 to 4610; increase of 54.6%), spleen (from 5047 to 7351; increase of 45.7%), lungs (from 4984 to 6903; increase of 38.5%), and kidneys (from 3550 to 5739; increase of 61.7%), and we identified a total of 10 104 protein groups. The overall data indicated that 3-week-old mice showed more differences compared with the other three age groups. The proteins of amino acid-related metabolism were increased in aged mice compared with those in the 3-week-old mice. Protein-related infections were increased in the spleen of the aged mice. Interestingly, the spliceosome-related pathway significantly changed from youth to elders in the liver, spleen, and lungs, indicating the vital role of the spliceosome during the aging process. Our established aging mouse organ proteome atlas provides comprehensive insights into understanding the aging process, and it may help in prevention and treatment of age-related diseases.
PMID:39192740 | DOI:10.1021/acs.analchem.4c00932
Anal Chem. 2024 Aug 27. doi: 10.1021/acs.analchem.4c02271. Online ahead of print.
ABSTRACT
Cell surface proteins participate in many important biological processes, such as cell-to-cell interaction, signal transduction, cell adhesion, and protein transportation. In-depth study of the cell surface protein group is of great significance. Nevertheless, detection and analysis of the surfaceome remain a significant challenge due to their low abundance and hydrophobicity. Herein, we reported an ultrafast and chemoselective labeling method using our newly developed trifunctional probe, the OPA-S-S-alkyne, which labeled cell surface lysine residues, and then established a novel cell surfaceome profiling approach. According to our experimental results, the OPA-S-S-alkyne probe can react extremely fast with living cells, labeling cells in only 1 min, while traditional NHS (labeling cell surface lysine with N-hydroxysuccinimide ester probe) and CSC (labeling cell surface glycan with hydrazide biotin probe) methods normally take longer time of more than 30 min and 1 h, respectively. Taking advantage of this ultrafast property of the method, we highlight the utility of this method by exploring the temporal dynamic changes of surfaceome upon EGF stimulation in living Hela cells and reported "early" and "late" EGF-regulated cell surface proteins, which are difficult to be distinguished by the current cell surface profiling approaches.
PMID:39192718 | DOI:10.1021/acs.analchem.4c02271
Anal Chem. 2024 Aug 27. doi: 10.1021/acs.analchem.4c01094. Online ahead of print.
ABSTRACT
In this work, SiO2/CNTs photonic crystal beads were constructed by doping CNTs into SiO2 photonic crystals, which have an angle-independent responsive structural color and can be used as bipolar electrodes due to their good electrical conductivity. In addition, the bipolar electrode-electrochemiluminescence (BPE-ECL) experiments and finite element simulation prove that the low driving voltage can trigger the bipolar electrode electrochemical reactions by confinement effect. Inspired by this, it is the first to combine the SiO2/CNTs structural color coding scheme with low-drive voltage induced wireless BPE-ECL imaging based on the confinement effect of microchannels to achieve simultaneous immune detection of ovarian cancer biomarkers (CA125, CEA, AFP). The detection limits of successfully constructed high-throughput BPE-ECL biosensor for AFP, CEA, and CA125 are 0.72 ng/mL, 0.95 ng/mL, and 1.03 U/mL, respectively, and have good stability and specificity, which expands the application of electrochemiluminescence and lays a foundation for the development of electrochemiluminescence coding technology.
PMID:39190788 | DOI:10.1021/acs.analchem.4c01094
Cancer Med. 2024 Aug;13(16):e70133. doi: 10.1002/cam4.70133.
ABSTRACT
BACKGROUND: While cervical cancer incidence rates (IR) in the United States have dropped in the last 20 years, non-cervical human papillomavirus (HPV) associated cancers increased. Many people in Texas (TX) live in medically underserved areas and have higher risk of developing HPV-associated cancers. Since previous studies of these regions focused on cervical cancer, we included other HPV-associated cancers in our analysis of IR in East TX and the TX-Mexico Border compared to other TX regions.
METHODS: Cancer data from 2006 to 2019 were obtained from the TX Cancer Registry. Cases of HPV-associated cervical, vaginal, vulvar, penile, anal, and oropharyngeal cancers and corresponding patient-level demographic data were included. We calculated IR per 100,000 and drew heat maps to visualize cancer IR by county. To control potential confounders, we added county-level risk factors: rates for smoking, excessive drinking, obesity, STIs, primary care provider availability and dentist availability, from the County Health Rankings and Roadmaps program. We reported IRs by region and time and estimated unadjusted and adjusted risk ratio (RR) for association of each type of cancer and region. Lastly, we created adjusted models for each cancer by period to see time trends of regional differences.
RESULTS: Risk of anal, cervical, and oropharyngeal cancer was lower at parts of the Border than in the rest of TX in the adjusted model. We also observed increasing anal and oropharyngeal cancer risk and decreasing cervical and vaginal cancer risk over time.
CONCLUSION: Patient sociodemographics, behavioral risk factors, and access to care may contribute to some observed differences in cancer IR across regions. This indicates that targeted prevention efforts towards these regions, especially in low socioeconomic status communities, may benefit future generations.
PMID:39190562 | PMC:PMC11348903 | DOI:10.1002/cam4.70133
Anal Bioanal Chem. 2024 Aug 27. doi: 10.1007/s00216-024-05488-2. Online ahead of print.
ABSTRACT
The use of pesticides is often regarded as a fundamental aspect of conventional agriculture. However, these compounds have gained recognition as some of the oldest and most widely employed xenobiotic contaminants, necessitating effective strategies for human biomonitoring. In this context, a method was developed for the determination of 16 legacy organochlorine pesticides, 6 metabolites of current pesticides (2,4-D, malathion, parathion, fipronil, pyraclostrobin, cypermethrin, permethrin, cyfluthrin), and 1 triazine herbicide (atrazine) in serum. Samples were prepared with water, formic acid, acetonitrile, and ultrasound irradiation, followed by solid-phase extraction with Oasis Prime HLB. Subsequently, metabolites from current pesticides underwent derivatization using MTBSTFA with 1% TBDMSCl for analysis via gas chromatography-tandem mass spectrometry (GC-MS/MS), employing an SLB-5MS fused silica capillary column. Analytical curves were generated with limits of quantification from 0.3 to 4.0 ng.mL-1. Accuracy ranged from 69 to 124%, and the coefficient of variation from 2 to 28%. Moreover, determining 1-(4-chlorophenyl)-1H-pyrazol-3-ol was suggested as a biomarker for pyraclostrobin biomonitoring. This analytical approach facilitated the determination of both legacy and metabolites of current pesticides in the same serum sample, presenting an interesting and cost-effective option for large cohorts, and multi-omics studies that evaluate time-dependent biomarkers in blood samples, thereby enabling biomonitoring within the same matrix. Furthermore, a proof-of-concept involving 10 volunteers demonstrated exposure to 9 pesticides at mean concentrations measured in ng mL-1, consistent with findings from various biomonitoring initiatives.
PMID:39190144 | DOI:10.1007/s00216-024-05488-2
Anal Methods. 2024 Aug 27. doi: 10.1039/d4ay01432d. Online ahead of print.
ABSTRACT
Carbohydrate antigen 19-9 (CA19-9) is an important marker for pancreatic cancer, ovarian cancer and other tumors, and its rapid and stable detection is the basis for early diagnosis and treatment. In this paper, a label-free electrochemical immunosensor for the sensitive detection of CA19-9 has been developed. First, the synthesis of two novel core-shell bimetallic nanomaterials, namely Ce-MOF-on-Fe-MOF and Fe-MOF-on-Ce-MOF, was accomplished using the MOF-on-MOF approach. The poor electrical conductivity of MOF materials was addressed by incorporating polyethylenimide (PEI) functionalized rGO with Ce-MOF-on-Fe-MOF and Fe-MOF-on-Ce-MOF nanomaterials. Simultaneously, toluidine blue (Tb) was employed as a redox probe and physically adsorbed onto the synthesized materials, resulting in the formation of two nanomaterials: rGO@Ce-MOF-on-Fe-MOF@Tb and rGO@Fe-MOF-on-Ce-MOF@Tb. The fundamental characterization reveals that the sensing performance of the rGO@Ce-MOF-on-Fe-MOF@TB-based immune sensor surpasses that of the rGO@Fe-MOF-on-Ce-MOF@TB-based immune sensor, which is attributed to the fact that, unlike the interlayer-constrained structure of Fe-MOF-on-Ce-MOF, in Ce-MOF-on-Fe-MOF, Ce-MOF penetrates into Fe-MOF to form a heterogeneous structure due to the relatively large pore size of Fe-MOF, which better combines the excellent biocompatibility and strong anchoring effect of Fe MOFs on antibodies, as well as the high electrochemical activity and conductivity of Ce-MOF, to enhance sensing performance. The proposed label-free immunosensor based on rGO@Ce-MOF-on-Fe-MOF@Tb has a wide linear range (1-100 000 mU mL-1), a low detection limit (0.34 mU mL-1), good stability, reproducibility, and repeatability, and satisfactory applicability, which provides a potential platform for clinical applications.
PMID:39189647 | DOI:10.1039/d4ay01432d
Anal Methods. 2024 Aug 27. doi: 10.1039/d4ay01359j. Online ahead of print.
ABSTRACT
Re-discovery of known metabolites is a common challenge in natural product-based drug discovery, and to avoid re-discovery, dereplication has been proposed for identifying known metabolites at the early stage of isolation. A majority of methods use LCMS to profile the extract and ignore the known mass. LC-HRMS profiling may generate a long mass list of metabolites. The identification of a new metabolite is difficult within the mass list. To overcome this, it was hypothesized that identifying a 'new metabolite' in the whole metabolome is more difficult than identifying it within the class of metabolites. A prioritization strategy was proposed to focus on the elimination of unknown and uncommon metabolites first using the designed bias filters and to prioritize the known secondary metabolites. The study employed Murraya paniculata root for the identification of new metabolites. The LC-HRMS-generated mass list of 509 metabolites was subjected to various filters, which resulted in 93 metabolites. Subsequently, it was subjected to regular dereplication, resulting in 10 coumarins, among which 3 were identified as new. Further, chromatographic efforts led to the isolation of a new coumarin, named ghosalin (1). The structure of the new compound was established through 2D NMR and X-ray crystallography. Cytotoxicity studies revealed that ghosalin has significant cytotoxicity against cancer cell lines. The proposed prioritization strategy demonstrates an alternative way for the rapid annotation of a particular set of metabolites to isolate a new metabolite from the whole metabolome of a plant extract.
PMID:39189121 | DOI:10.1039/d4ay01359j
Phys Imaging Radiat Oncol. 2024 Jul 31;31:100618. doi: 10.1016/j.phro.2024.100618. eCollection 2024 Jul.
ABSTRACT
BACKGROUND AND PURPOSE: Squamous cell carcinoma of the anus (SCCA) can recur after chemoradiotherapy (CRT). Early prediction of treatment response is crucial for individualising treatment. Existing data on radiological biomarkers is limited and contradictory. We performed an individual patient data meta-analysis (IPM) of four prospective trials investigating whether diffusion-weighted (DW) magnetic resonance imaging (MRI) in weeks two to three of CRT predicts treatment failure in SCCA.
MATERIAL AND METHODS: Individual patient data from four trials, including paired DW-MRI at baseline and during CRT, were combined into one dataset. The association between ADC volume histogram parameters and treatment failure (locoregional and any failure) was assessed using logistic regression. Pre-defined analysis included categorising patients into a change in the mean ADC of the delineated tumour volume above and below 20%.
RESULTS: The study found that among all included 142 patients, 11.3 % (n = 16) had a locoregional treatment failure. An ADC mean change of <20 % and >20 % resulted in a locoregional failure rate of 16.7 % and 8.0 %, respectively. However, no other ADC-based histogram parameter was associated with locoregional or any treatment failure.
CONCLUSIONS: DW-MRI standard parameters, as an isolated biomarker, were not found to be associated with increased odds of treatment failure in SCCA in this IPM. Radiological biomarker investigations involve multiple steps and can result in heterogeneous data. In future, it is crucial to include radiological biomarkers in large prospective trials to minimize heterogeneity and maximize learning.
PMID:39188809 | PMC:PMC11345337 | DOI:10.1016/j.phro.2024.100618
World J Clin Cases. 2024 Aug 26;12(24):5483-5491. doi: 10.12998/wjcc.v12.i24.5483.
ABSTRACT
BACKGROUND: Radical surgery is a preferred treatment for colorectal carcinoma, wherein nursing intervention is essential for postoperative recovery and prevention of complications. Recently, the application of humanistic care in medical care has attracted attention. Humanistic care emphasizes comprehensive care, with importance attached to patients' physical needs as well as psychological and emotional support to provide more humane and personalized care services. However, no clinical reports have examined the use of humanistic care in patients undergoing radical surgery for colorectal carcinoma.
AIM: To investigate the influence of humanistic care-based operating room nursing on the safety, postoperative recovery, and nursing satisfaction of patients who have undergone radical surgery for colorectal carcinoma.
METHODS: In total, 120 patients with rectal cancer who underwent surgery in Zhongnan Hospital of Wuhan University between August 2023 and March 2024 were selected and grouped based on the nursing methods employed. Of these patients, 55 were treated with routine nursing intervention (control group) and 65 were provided humanistic care-based operating room nursing (research group). The patients' vital signs were recorded, including systolic/diastolic blood pressure (SBP/DBP) and heart beats per minute (BPM), as well as serum stress indices, including norepinephrine (NE), adrenal hormone (AD), and cortisol (Cor). Postoperative recovery and complications were also recorded. Patients' negative emotions, life hope, and nursing satisfaction were evaluated using the Self-rating Depression/Anxiety Scale (SDS/SAS), Herth Hope Index (HHI), and self-developed nursing satisfaction questionnaire, respectively.
RESULTS: During emergence from anesthesia, SBP, DBP, and BPM levels were found to be lower in the research group than those in the control group, also serum Cor, AD, and NE levels were lower. In addition, the research group had shorter operative, awakening, anal exhaust, first postoperative ambulation, drainage tube removal, intestinal recovery, and hospital times. The total complication rate and the SDS and SAS scores were lower in the research group than those in the control group. The HHI and nursing satisfaction scores were higher in the research group.
CONCLUSION: Humanistic care-based operating room nursing can mitigate physiological stress responses, reduce postoperative complications, promote postoperative recovery, relieve adverse psychological emotions, and enhance life hope and nursing satisfaction in patients undergoing radical surgery for colorectal carcinoma, which can be popularized in clinical practice.
PMID:39188612 | PMC:PMC11269985 | DOI:10.12998/wjcc.v12.i24.5483
Anal Chem. 2024 Aug 26. doi: 10.1021/acs.analchem.4c02592. Online ahead of print.
ABSTRACT
The architecture of cell culture, two-dimensional (2D) versus three-dimensional (3D), significantly impacts various cellular factors, including cell-cell interactions, nutrient and oxygen gradients, metabolic activity, and gene expression profiles. This can result in different cellular responses during cancer drug treatment, with 3D-cultured cells often exhibiting higher resistance to chemotherapeutic drugs. While various genetic and proteomic analyses have been employed to investigate the underlying mechanisms of this increased resistance, complementary techniques that provide experimental evidence of spatial molecular profiling data are limited. Stimulated Raman scattering (SRS) microscopy has demonstrated its capability to measure both intracellular drug uptake and growth inhibition. In this work, we applied three-band (C-D, C-H, and fingerprint regions) SRS imaging to 2D and 3D cell cultures and performed a comparative analysis of drug uptake and response with the goal of understanding whether the difference in drug uptake explains the drug resistance in 3D culture compared to 2D. Our investigations revealed that despite similar intracellular drug levels in 2D and 3D A549 cells during lapatinib treatment, the growth of 3D spheroids was less impacted, supporting an enhanced drug tolerance in the 3D microenvironment. We further elucidated drug penetration patterns and the resulting heterogeneous cellular responses across different spheroid layers. Additionally, we investigated the role of the extracellular matrix in modulating drug delivery and cell response and discovered that limited drug penetration in 3D could also contribute to lower drug response. Our study provides valuable insights into the intricate mechanisms of increased drug resistance in 3D tumor models during cancer drug treatments.
PMID:39186736 | DOI:10.1021/acs.analchem.4c02592
Anal Chem. 2024 Aug 26. doi: 10.1021/acs.analchem.4c02355. Online ahead of print.
ABSTRACT
A triple signal amplification strategy was integrated with a built-in double electrode and external energy storage device to fabricate a novel self-powered biosensor for ultrasensitive detection of miRNA-21. Specifically, DNA tetrahedra and haripin2-glucose oxidase are modified on the surface of the biocathode and bioanode by catalytic hairpin assembly (CHA) to achieve dual signal amplification. Moreover, triple signal amplification is realized by including an external capacitor. Consequently, the as-constructed self-powered biosensor demonstrates a low detection limit of 0.06 fM toward the miRNA-21 assay within the range of 0.1 fM to 10 pM. This study presents a practical and sensitive approach to timely cancer detection.
PMID:39186685 | DOI:10.1021/acs.analchem.4c02355
Anal Chem. 2024 Aug 26. doi: 10.1021/acs.analchem.4c02565. Online ahead of print.
ABSTRACT
The spatial constraints imposed by the DNA structure have significant implications for the walking efficiency of three-dimensional DNA walkers. However, accurately quantifying and manipulating steric hindrance remains a challenging task. This study presents a steric hindrance-controlled DNA walker utilizing an enzymatic strand displacement amplification (ESDA) strategy for detecting microRNA-21 (miR-21) with tunable dynamic range and sensitivity. The steric hindrance of the DNA walker was precisely manipulated by varying the length of empty bases from 6.5 Å to 27.4 Å at the end of the track strand and adjusting the volumetric dimensions of the hairpin structure from 9.13 nm3 to 26.2 nm3 at the terminus of the single-foot DNA walking strand. This method demonstrated a tunable limit of detection for miR-21 ranging from 3.6 aM to 35.6 nM, along with a dynamic range from ∼100-fold to ∼166 000-fold. Impressively, it exhibited successful identification of cancer cells and clinical serum samples with high miR-21 expression. The proposed novel strategy not only enables tunable detection of miRNA through the regulation of steric hindrance but also achieves accurate and quantitative analysis of the steric hindrance effect, promising broader applications in personalized medicine, early disease detection, and drug development.
PMID:39185581 | DOI:10.1021/acs.analchem.4c02565
Anal Cell Pathol (Amst). 2024 Aug 17;2024:6217134. doi: 10.1155/2024/6217134. eCollection 2024.
ABSTRACT
BACKGROUND: Gastric cancer (GC) is the most common malignant tumor and ranks third in the world. LncRNA H19 (H19), one of the members of lncRNA, is overexpressed in various tumors. However, many undetermined molecular mechanisms by which H19 promotes GC progression still need to be further investigated. Methodology. A series of experiments was used to confirm the undetermined molecular mechanism including wound healing and transwell assays. Key Results. In this study, a significant upregulation of H19 expression was detected in GC cells and tissues. The poor overall survival was observed in GC patient with high H19 expression. Overexpression of H19 promoted the migration of GC cells, while knockdown of H19 significantly inhibited cell migration. Moreover, miR-148a-3p had a certain negative correlation with H19. Luciferase reporter assay confirmed that H19 could directly bind to miR-148a-3p. As expected, miR-148a mimics inhibited cell migration and invasion induced by H19 overexpression. The above findings proved that H19 functions as a miRNA sponge and verified that miR-148a-3p is the H19-associated miRNA in GC. We also confirmed that SOX-12 expression was upregulated in GC patient's samples. SOX-12 expression was positively correlated with expression of H19 and was able to directly bind to miR-148a-3p. Importantly, in vitro wound healing assay showed that knockout of SOX-12 could reverse the promoting effect of H19 overexpression on cell migration.
CONCLUSION: In conclusion, H19 has certain application value in the diagnosis and prognosis of GC. Specifically, H19 accelerates GCs to migration and metastasis by miR-138a-3p/SOX-12 axis.
PMID:39184399 | PMC:PMC11344645 | DOI:10.1155/2024/6217134
Bayesian Anal. 2024 Jun;19(2):623-647. doi: 10.1214/23-ba1366. Epub 2024 Jun 28.
ABSTRACT
Current protocols to estimate the number, size, and location of cancerous lesions in the prostate using multiparametric magnetic resonance imaging (mpMRI) are highly dependent on reader experience and expertise. Automatic voxel-wise cancer classifiers do not directly provide estimates of number, location, and size of cancerous lesions that are clinically important. Existing spatial partitioning methods estimate linear or piecewise-linear boundaries separating regions of local stationarity in spatially registered data and are inadequate for the application of lesion detection. Frequentist segmentation and clustering methods often require pre-specification of the number of clusters and do not quantify uncertainty. Previously, we developed a novel Bayesian functional spatial partitioning method to estimate the boundary surrounding a single cancerous lesion using data derived from mpMRI. We propose a Bayesian functional spatial partitioning method for multiple lesion detection with an unknown number of lesions. Our method utilizes functional estimation to model the smooth boundary curves surrounding each cancerous lesion. In a Reversible Jump Markov Chain Monte Carlo (RJ-MCMC) framework, we develop novel jump steps to jointly estimate and quantify uncertainty in the number of lesions, their boundaries, and the spatial parameters in each lesion. Through simulation we show that our method is robust to the shape of the lesions, number of lesions, and region-specific spatial processes. We illustrate our method through the detection of prostate cancer lesions using MRI.
PMID:39183822 | PMC:PMC11343089 | DOI:10.1214/23-ba1366
Anal Chem. 2024 Aug 25. doi: 10.1021/acs.analchem.4c02653. Online ahead of print.
ABSTRACT
Metabolic abnormalities play a pivotal role in various pathological conditions, necessitating the quantification of specific metabolites for diagnosis. While mass spectrometry remains the primary method for metabolite measurement, its limited throughput underscores the need for biosensors capable of rapid detection. Previously, we reported that pillar[6]arene with 12 carboxylate groups (P6AC) forms host-guest complexes with 1-methylnicotinamide (1-MNA), which is produced in vivo by nicotinamide N-methyltransferase (NNMT). P6AC acts as a biosensor by measuring the fluorescence quenching caused by photoinduced electron transfer upon 1-MNA binding. However, the low sensitivity of P6AC makes it impractical for detecting 1-MNA in unpurified biological samples. In this study, we found that P6A with 12 sulfonate groups (P6AS) is a specific and potent supramolecular host for 1-MNA interactions even in biological samples. The 1-MNA binding affinity of P6AS in water was found to be (5.68 ± 1.02) × 106 M-1, which is approximately 700-fold higher than that of P6AC. Moreover, the 1-MNA detection limit of P6AS was determined to be 2.84 × 10-7 M, which is substantially lower than that of P6AC. Direct addition of P6AS to culture medium was sufficient to quantify 1-MNA produced by cancer cells. Furthermore, this sensor was able to specifically detect 1-MNA even in unpurified human urine. P6AS therefore enables rapid and high-throughput quantification of 1-MNA, and further improvement of our strategy will contribute to the establishment of high-throughput screening of NNMT inhibitors, diagnosis of liver diseases, and imaging of human cancer cells in vivo.
PMID:39183562 | DOI:10.1021/acs.analchem.4c02653
Zhonghua Wai Ke Za Zhi. 2024 Aug 26;62(10):954-960. doi: 10.3760/cma.j.cn112139-20240406-00167. Online ahead of print.
ABSTRACT
Objective: To investigate functional outcomes and condition-specific quality-of-life (CSQoL) after intersphincteric resection (ISR) in patients with low rectal cancer using traditional and exploratory questionnaires. Methods: A prospective observational study was conducted in the Characteristic Medical Center of the People's Liberation Army Rocket Force. Totally 90 patients with low rectal cancer who underwent ISR with ileostomy reversal from May 2020 to April 2023 were enrolled. There were 64 males and 26 females, aged(58.6±10.4) years (range: 28 to 79 years). The median distance from the distal tumor margin to the anal verge(M(IQR)) was 3.0 (1.5) cm (range: 1.0 to 5.0 cm). An electronic self-assessment survey was sent to enrolled patients at 3 to 6, 12, and 24 to 36 months after reversal, and differences in functional and CSQoL results between the 3 groups were analyzed with generalized estimation equations. Functional outcomes were determined by the Wexner incontinence score (WIS) and the low anterior resection syndrome (LARS) score. In line with the five frequency responses ranging from never (score 0) to always (score 4) defined by the WIS, an exploratory survey was used to measure the severity of 16 LARS-specific variables confirmed by the latest international Delphi consensus. Furthermore, CSQoL was evaluated using the Fecal Incontinence Quality-of-life Scale (FIQL) and the visual analog scale (VAS). Results: There were 55 patients who completed the questionnaires at 3 to 6 months, 59 patients at 12 months, and 40 patients at 24 to 36 months of follow-up, respectively. The summary score of FIQL and VAS improved significantly after reversal (2.33±0.69 vs. 2.40±0.66 vs. 2.79±0.76, P=0.003; 5.31±1.65 vs. 5.61±1.9 vs. 6.58±1.92, P=0.002), but the differences in the WIS and LARS score did not reach statistical significance (both P>0.05). The survey responses for the LARS-specific variables indicated that "emptying difficulties" and "dissatisfaction with the bowels" were the most frequent symptom and consequence after ISR, respectively. The exploratory severity score for LARS improved significantly among the 3 time periods(34 (14) vs. 31 (13) vs. 23 (17), P=0.001). Furthermore, the FIQL summary score was strongly correlated with the LARS severity score (rs=-0.72, P<0.01), but weakly or moderately associated with the WIS and LARS score. Conclusions: Although a high prevalence of LARS may persist for years, patients reported an improvement in CSQoL and functional outcomes after ISR. The highest priorities recommended by the international consensus might provide better assessments the severity of LARS.
PMID:39183021 | DOI:10.3760/cma.j.cn112139-20240406-00167
Anal Chim Acta. 2024 Sep 15;1322:343066. doi: 10.1016/j.aca.2024.343066. Epub 2024 Aug 6.
ABSTRACT
For hepatocellular carcinoma (HCC), N-glycosylation has been proved to be widely involved in various aspects of the disease, including development, metastasis, subtyping, diagnosis and prognosis. The common practice is to discover biomarkers in situ of cancer occurrence (i.e., cancer vs. adjacent tissues) yet to clinically monitor in sera because of non-invasiveness. This study benchmarks N-glycoproteomics characterization of common differential tissue and serum N-glycoproteins of patients with HCC. Differential N-glycosylation in matched tissue and serum samples from the same patients were quantitatively characterized at the intact N-glycopeptide molecular level, and 29 common N-glycoproteins were found. Subcellular localization analysis was carried out to confirm the tissue originality. Secreted N-glycoprotein APOH was up-regulated, and transmembrane and intracellular N-glycoproteins including OSMR, GAT2, CSF-1 and MAGI3 were down-regulated.
PMID:39182988 | DOI:10.1016/j.aca.2024.343066
Anal Chim Acta. 2024 Sep 22;1323:343085. doi: 10.1016/j.aca.2024.343085. Epub 2024 Aug 8.
ABSTRACT
BACKGROUND: Aflatoxin B1 (AFB1), is a potent hepatic carcinogen which causes cancer by inducing DNA changes in the liver cells. Variety of methods have been developed for detection of AFB1 which are based on single mode detection strategy. Fabrication of novel platform which are compatible for multimodal detection of AFB1 provide robust performance for reliable detection of AFB1. In this study, we aimed to develop a robust biosensing platform that combines electrochemical and fluorescence techniques for the sensitive and specific detection of Aflatoxin B1.
RESULTS: The sensing platform includes the magnetic core-shell Fe3O4@AuNPs and zeolitic imidazolate framework-8 (ZIF-8). In electrochemical mode, the applied voltametric approach was used through functionalization of glassy carbon electrode and exhibited a linear range between 0.5 and 10000 pg mL-1 with LOD of 0.32 pg mL-1. Fluorescence analysis was based on the FRET on/off status of FAM-functionalized aptamer deposited on the same platform. The FAM emission recovered by the addition of AFB1 concentration in the range of 6-60 fg mL-1 with the LOD of 0.20 fg mL-1. The real sample analysis demonstrated satisfactory relative recoveries in the range of 92.81-105.32 % and 91.66-106.66 % using the electrochemical and fluorescence methods, respectively, and its reliability was confirmed by the HPLC technique.
SIGNIFICANCE: The experimental results affirm that the proposed aptasensor serves as a sensitive, efficient, and precise platform for monitoring AFB1 in both electrochemical and fluorescence detection approaches. Proposed strategy showed efficient selectivity among different analytes and was reproducible. Furthermore, the applicability of biosensor was confirmed in food and biological samples.
PMID:39182978 | DOI:10.1016/j.aca.2024.343085
Anal Chim Acta. 2024 Sep 22;1323:343070. doi: 10.1016/j.aca.2024.343070. Epub 2024 Aug 8.
ABSTRACT
BACKGROUND: Rapid and sensitive colorimetric detection methods are crucial for diseases diagnosis, particularly those involving proteases like furin, which are implicated in various conditions, including cancer. Traditional detection methods for furin suffer from limitations in sensitivity and practicality for on-site detection, motivating the development of novel detection strategies. Therefore, developing a simple, enzyme-free, and rapid colorimetric analysis method with high sensitivity for furin detection is imperative.
RESULTS: Herein, we have proposed a colorimetric method in this work for the first time to detect furin, leveraging the assembly of G-quadruplex/hemin DNAzyme with enhanced catalytic activity. Specifically, a peptide-DNA conjugate (PDC) comprising a furin-recognition peptide and flanking DNA sequences for signal amplification is designed to facilitate the DNAzyme assembly. Upon furin treatment, PDC cleavage triggers a cyclic catalytic hairpin assembly reaction to form the complementary double-stranded structures by hairpin 1 (HP1) and hairpin 2 (HP2), bringing the G-quadruplex sequence in HP1 closer to hemin on HP2. Moreover, the resulting G-quadruplex/hemin DNAzymes exhibit robust peroxidase-like activity, enabling the catalysis of the colorimetric reaction of ABTS2- for furin detection. Our method demonstrates high sensitivity, rapid response, and compatibility with complex sample matrices, achieving a detection limit as low as 1.1 pM.
SIGNIFICANCE: The DNAzyme reported in this work exhibits robust catalytic activity, enabling high sensitivity and good efficiency for the detection. By eliminating the requirement for exogenous enzymes, our approach enables visual furin detection without expensive instrumentation and reagents, promising significant utility in biomedical and clinical diagnostic applications. Given the various design of peptide sequence and the programmability of DNA, it can be readily applied to analyzing other useful tumor biomarkers.
PMID:39182972 | DOI:10.1016/j.aca.2024.343070