Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemot...Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.展开更多
BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics...BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics of cancer stem cell markers CD24 and CD133 in GC pathological tissues,and to explore their association with patients’clinicopathological parameters and postoperative survival outcomes.METHODS A total of 304 GC patients who underwent surgical treatment in our hospital from January 2018 to January 2020 were retrospectively included.Immunohistochemistry was used to detect the protein expression of CD24 and CD133 in tumor tissues,adjacent tissues,and normal gastric mucosa tissues.Based on staining intensity and the proportion of positive cells,expression levels were classified into low and high expression,while clinicopathological parameters were recorded.χ2 test was used to evaluate the correlation between expression and categorical variables,Spearman rank correlation analysis was performed to assess the correlation between the expression intensities of the two markers,and multivariate regression models were applied to identify independent risk factors influencing co-expression.Kaplan-Meier survival curves and Log-rank test were used to compare survival differences among groups with different expression patterns.RESULTS Among the 304 patients,155 cases(50.99%)were CD24 positive,including 91 low-expression and 64 highexpression;133 cases(43.75%)were CD133 positive,including 81 low-expression and 52 high-expression.There were 74 cases(24.34%)with double positivity and 81 cases(26.64%)with double negativity.Compared with tumor tissues,the positive rates of CD24 and CD133 in normal gastric tissues and adjacent tissues were significantly lower(P<0.05).Univariate analysis showed that co-expression of CD24 and CD133 in GC tissues was significantly correlated with tumor size,Lauren classification,T stage,N stage,and vascular invasion(P<0.05),but not with patient age,gender,tumor site,World Health Organization histological classification,or M stage(P>0.05).Further multivariate regression analysis suggested that tumor size,T stage,N stage,and vascular invasion were independent risk factors promoting CD24 and CD133 double positivity.Spearman rank correlation analysis indicated a moderate positive correlation between their expression intensities(r=0.420,P<0.001).During follow-up,29 of 304 patients were lost(loss rate 9.54%);146 deaths occurred.According to expression combination,there were 89 cases of CD24 single positivity(39 deaths),68 cases of CD133 single positivity(31 deaths),81 cases of double negativity(25 deaths),and 66 cases of double positivity(51 deaths).Log-rank test showed significant differences in overall survival among the four groups(χ2=20.89,P<0.001),with CD24+/CD133+group showing the worst prognosis.CONCLUSION CD24 and CD133 exhibit high positive detection rates in GC tissues,and their co-positivity is closely associated with tumor stage progression and significantly indicates unfavorable survival outcomes.The co-expression of CD24/CD133 may reflect higher aggressiveness and metastatic potential of GC,serving as a potential prognostic marker and a direction for targeted therapeutic strategies.However,as this is a single-center retrospective study with limitations such as patient loss to follow-up and sample size,further prospective,multicenter,and mechanistic studies are required to validate its clinical applicability and biological role.展开更多
BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.A...BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.AIM To determine the incidence of depression and its independent risk factors in patients with esophageal cancer and bone metastasis.METHODS A total of 100 consecutive eligible patients admitted between March 2022 and March 2025 were recruited.Depression was assessed with the Beck Depression Inventory-II;scores>4 defined the depression group(n=42)and scores≤4 the non-depression group(n=58).Demographic,clinical,and laboratory variables were compared between the groups.Multivariate logistic regression was used to identify independent risk factors.RESULTS Depression prevalence was 42.0%(42/100).Univariate analysis demonstrated significant differences in monthly per-capita household income,education level,social support,sleep disorders,and serum high-sensitivity C-reactive protein(all P<0.05);no differences were observed in sex,age,tumor characteristics,or other laboratory indices(all P>0.05).Multivariable analysis revealed the following independent risk factors for depression:Low income[odds ratio(OR)=2.66,95%confidence interval(CI):1.17-6.03],low education(OR=2.46,95%CI:1.08-5.61),low social support(OR=5.10,95%CI:1.81-14.39),sleep disorders(OR=2.79,95%CI:1.23-6.35),and elevated high-sensitivity C-reactive protein(OR=1.31 per unit increase,95%CI:1.18-1.46).CONCLUSION Depression is common among patients with esophageal cancer and bone metastasis.Low socioeconomic status,limited education,insufficient social support,sleep disturbances,and systemic inflammation were independent predictors.Interventions that address these modifiable factors may reduce depression risk in this population.展开更多
The last research focuses on the role of exosomes in cancer treatment.Exosomes are extracellular vesicles.They can be secreted by cancer cells,and they can modulate chemotherapy sensitivity.Determining exosomal conten...The last research focuses on the role of exosomes in cancer treatment.Exosomes are extracellular vesicles.They can be secreted by cancer cells,and they can modulate chemotherapy sensitivity.Determining exosomal content opens the possibility for guiding treatment strategies for cancer diseases.Exosomal microRNA are considered one of the prime candidates for exosomal biomarkers.Exosomal circular RNAs represent excellent biomarkers for liquid biopsy because of their stability in many types of cancer.Exosomal proteins remain reliable biomarkers also.Exosomes have emerged as promising therapeutic candidates.Their biological properties render them ideal vectors for drug delivery.Genetic modification of exosomes is an effective way to deliver material capable of modulating cellular pathways involved in drug resistance.Furthermore,exosomes have been explored as carriers for metal-chelating agents.Integrating exosome-based therapies with traditional anticancer agents aims to exploit the natural targeting abilities of exosomes to enhance drug delivery.Despite the dynamic development of this field,many mechanisms of exosome action remain incompletely understood.Therefore,it is necessary to conduct further studies that will allow for a better understanding of their role in the process of resistance and will enable the development of effective therapeutic strategies.展开更多
BACKGROUNDCancer stem cells(CSCs)drive recurrence and therapeutic resistance in triplenegativebreast cancer(TNBC),a highly aggressive breast cancer subtype.Intratumoralhypoxia,a common feature of solid tumors,promotes...BACKGROUNDCancer stem cells(CSCs)drive recurrence and therapeutic resistance in triplenegativebreast cancer(TNBC),a highly aggressive breast cancer subtype.Intratumoralhypoxia,a common feature of solid tumors,promotes CSCs enrichment,yet the mechanisms sustaining CSCs stemness remain poorly understood.Hypoxia-induced reactive oxygen species can oxidatively activate ataxia telangiectasiamutated(ATM)kinase(oxidized ATM,p-ATM)independently of DNA breaks.AIMTo investigate the role of hypoxia-induced oxidized ATM in sustaining TNBCCSCstemness through c-Myc-mediated regulation of one-carbon metabolism.METHODSHs578T and MDA-MB-231 TNBC cells were cultured under normoxia or hypoxia.CSC stemness was assessed by mammosphere assays and flow cytometry.ATMactivity was assessed by pharmacological inhibition(Ku60019)and short hairpinRNA knockdown.c-Myc binding to serine hydroxymethyltransferase 2(SHMT2)and methylenetetrahydrofolate dehydrogenase 2(MTHFD2)promoters was analyzedby dual-luciferase reporter assays and chromatin immunoprecipitation.NADPH/NADP+ratios were quantified,and metabolic reprogramming was profiledby liquid chromatography-tandem mass spectrometry metabolomics.RESULTSHypoxia significantly increased mammosphere formation in both Hs578T and MDA-MB-231 cells,as reflected byhigher numbers of mammospheres(Hs578T:214±18;MDA-MB-231:198±16;both P<0.01)and larger meandiameters(P<0.01).Hypoxia also elevated CD44+/CD24-cell proportions and stemness gene expression(P<0.01).Oxidized ATM was activated under hypoxia withoutγH2AX induction,confirming DNA damage independence.ATM inhibition reduced mammosphere growth and suppressed c-Myc,SHMT2,and MTHFD2.Luciferase and chromatin immunoprecipitation assays confirmed direct c-Myc binding to SHMT2 and MTHFD2promoters,while mutation of the binding sites abolished promoter activity.NADPH/NADP+ratios were significantlyelevated under hypoxia but reduced following ATM inhibition(P<0.05).Metabolomics revealed enrichmentof serine/glycine one-carbon pathways.CONCLUSIONHypoxia-induced oxidized ATM maintains TNBC-CSC stemness by promoting c-Myc-dependent upregulation ofMTHFD2 and SHMT2,linking hypoxia,redox signaling,and one-carbon metabolism.These findings suggest apotential therapeutic axis that could be exploited for TNBC treatment.展开更多
Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabo...Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabolism,in the aggressiveness and metastatic behavior of BC.Methods:A comprehensive analysis was performed using in silico transcriptomic data(n=2509 patients),immunohistochemical profiling of BC tissues(n=103),and validation through western blotting in multiple BC cell lines.Gene expression and survival analyses were conducted using Tumor Immune Estimation Resource(TIMER),Gene Expression Profiling Interactive Analysis 2(GEPIA2),and the cBioPortal for cancer genomics(cBioPortal)platforms.Correlations between PNP and key epithelial–mesenchymal transition(EMT)markers,molecular subtypes,tumor grades,and stages were examined.Results:PNP was significantly overexpressed in human epidermal growth factor receptor 2(HER-2)-positive and triple-negative BCs compared to luminal subtypes.High PNP levels were strongly associated with advanced BC stages,high-grade tumors,EMT phenotypes,and poor overall survival.Notably,HER-2 inhibition suppressed PNP expression,while PNP gene silencing induced HER-2 upregulation,revealing a reciprocal regulatory loop.Dual inhibition of PNP and HER-2 resulted in a significant reduction in cell viability compared to HER-2 inhibition alone.Conclusion:Collectively,PNP emerges as a promising biomarker of BC aggressiveness and progression.Its reciprocal interaction with HER-2 underscores its potential as a therapeutic target.Dual targeting of PNP and HER-2 may offer a novel strategy for improving outcomes in aggressive BC subtypes.展开更多
Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-through...Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.展开更多
We read with great interest the investigation of Kang et al related the applications of the multiparametric magnetic resonance imaging-based predictive model for assessing chemotherapy efficacy in colorectal cancer pa...We read with great interest the investigation of Kang et al related the applications of the multiparametric magnetic resonance imaging-based predictive model for assessing chemotherapy efficacy in colorectal cancer patients with gene mutations.The authors focused on decision-making based on the integration of tumor differentiation,signal intensity ratio,margin distance,and magnetic resonance imaging-detected lymph node metastasis.Indeed,these multiparameter predictive models could also be used for diagnosis as an alternative to invasive tissue examination methods.However,progress in this field enables us to shift the paradigm to radiology biopsies,particularly given the nonlinear effects of various radiation sources.展开更多
We read with the great interest the study by Ababneh et al in which inducedmesenchymal stem cell-derived exosomes were shown to exhibit a stronger andmore sustained anti-proliferative effect by inducing a senescence-l...We read with the great interest the study by Ababneh et al in which inducedmesenchymal stem cell-derived exosomes were shown to exhibit a stronger andmore sustained anti-proliferative effect by inducing a senescence-like state withoutapoptosis.The results obtained by the authors highlight the features of theeffects of senescent drift induction in surrounding tissues.In the light of thesefindings,the role of the properties of extracellular matrix and cellular glycocalyxin responses of human tumors to therapy remain uninvestigated.These extracellularbarriers appear to be significant obstacles to effective cancer therapy,especiallyin relation to the use of unique properties of tumor microenvironment forthe immunotherapy-resistant cancer treatment.展开更多
BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically...BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically experience a poor prognosis,highlighting an urgent need to explore novel treatment approaches.This study evaluated the overall efficacy and safety of CMT vs CMT combined with immune checkpoint inhibitors(ICIs)in the treatment of EC patients with liver metastases.Furthermore,prognostic factors influencing outcomes in this patient population were identified.AIM To evaluate the efficacy and safety of first-line chemoimmunotherapy for EC patients with liver metastases and to analyze prognostic factors.METHODS This retrospective study included 126 EC patients with liver metastases at Zhejiang Cancer Hospital between 2014 and 2024.Patients receiving CMT were compared with those receiving CMT+ICI.Analyzed variables included clinicopathological features,treatment history,characteristics of metastasis,systemic and local treatments,overall survival(OS),and treatment-related adverse events(TRAEs).Prognostic factors were evaluated using univariate and multivariate Cox proportional-hazards regression models.Finally,efficacy outcomes and TRAE profiles were compared between the two groups.RESULTS A significant difference in median OS was identified between the two groups(10.8 months in the CMT group vs 20.8 months in the CMT+ICI group,P=0.004).The CMT+ICI group also demonstrated a significantly longer median progression-free survival of 11.7 months(P<0.001).Patients receiving combination therapy exhibited significantly improved systemic objective response rate and disease control rate.Multivariate analysis identified key factors significantly influencing OS in EC patients with liver metastases:Karnofsky Performance Status score≥70,receipt of local therapy for liver metastases,and the number of cycles of CMT and immunotherapy received.Furthermore,the incidence of TRAEs did not significantly differ between the CMT+ICI and CMT groups.CONCLUSION For EC patients with liver metastases,the combination of CMT and ICIs demonstrates significantly superior efficacy compared with CMT alone,while maintaining manageable TRAEs.展开更多
Gastric cancer(GC)has high morbidity and mortality worldwide.Due to the absence of noticeable symptoms,diagnosing GC at an early stage is very difficult,which consequently leads to advanced GC and poor prognosis.Effec...Gastric cancer(GC)has high morbidity and mortality worldwide.Due to the absence of noticeable symptoms,diagnosing GC at an early stage is very difficult,which consequently leads to advanced GC and poor prognosis.Effective biomarkers are essential for prolonging patients’survival.Helicobacter pylori(H.pylori)infection represents the most significant risk factor for GC,with nearly all cases linked to this infection.Many non-coding RNAs(ncRNAs)are dysregulated in H.pylori-infected GC,indicating that ncRNAs may serve as biomarkers of early-stage GC.In this editorial,we discuss the study by Chen et al.Although previous studies have identified roles for miR-136 in gastric cancer proliferation,apoptosis,and invasion,none have specifically explored its relationship with H.pylori-associated gastric carcinogenesis.展开更多
Objectives:Ribosomal protein S6 kinase A2(RPS6KA2)has been identified as a potential prognostic biomarker in several cancers,including breast cancer,glioblastoma,and prostate cancer.However,its functional significance...Objectives:Ribosomal protein S6 kinase A2(RPS6KA2)has been identified as a potential prognostic biomarker in several cancers,including breast cancer,glioblastoma,and prostate cancer.However,its functional significance in ovarian cancer is not well characterized.This study was designed to explore the therapeutic relevance of modulating RPS6KA2 in the context of ovarian cancer,particularly in relation to cisplatin resistance.Methods:The expression levels of RPS6KA2 and key regulators involved in autophagy and ferroptosis were assessed using quantitative reverse transcription-PCR,immunofluorescence staining,immunohistochemistry,and western blotting.Prognostic associations were conducted using the Kaplan-Meier Plotter database.Autophagy flux assays and visualization of autophagosomes were performed to assess autophagy activity.Ferroptosis-related parameters,including intracellular iron content,glutathione(GSH)levels,reactive oxygen species(ROS)generation,and mitochondrial membrane potential,were measured to determine ferroptotic changes.In vivo experiments were carried out to determine the antitumor efficacy of RPS6KA2 modulation in combination with pathway-specific agents.Results:Using ovarian cancer cell lines and clinical tissue samples,we demonstrated that RPS6KA2 expression was significantly downregulated in cisplatin-resistant cells and tissues compared to their sensitive counterparts.Low RPS6KA2 expression correlated with unfavorable patient outcomes and enhanced chemoresistance.Mechanistically,RPS6KA2 inhibited autophagy by modulating the phosphatidylinositol 3-kinase-protein kinase B-mammalian target of rapamycin(PI3K-AKT-mTOR)signaling pathway,which in turn increased sensitivity to cisplatin.Additionally,RPS6KA2 facilitated ferroptosis,contributing to its tumor-suppressive function.miR-512-3p was identified as a negative regulator of RPS6KA2,driving cisplatin resistance through suppression of RPS6KA2 expression.In vivo validation confirmed that combining RPS6KA2 targeting with autophagy inhibitors or ferroptosis inducers significantly enhanced cisplatin sensitivity in ovarian cancer models.Conclusion:These results collectively indicate that targeting the miR-512-3p/RPS6KA2 regulatory axis may offer a novel and effective strategy for overcoming cisplatin resistance in ovarian cancer.展开更多
Gastrointestinal(GI)cancers remain a leading cause of cancer-related morbidity and mortality worldwide.Artificial intelligence(AI),particularly machine learning and deep learning(DL),has shown promise in enhancing can...Gastrointestinal(GI)cancers remain a leading cause of cancer-related morbidity and mortality worldwide.Artificial intelligence(AI),particularly machine learning and deep learning(DL),has shown promise in enhancing cancer detection,diagnosis,and prognostication.A narrative review of literature published from January 2015 to march 2025 was conducted using PubMed,Web of Science,and Scopus.Search terms included"gastrointestinal cancer","artificial intelligence","machine learning","deep learning","radiomics","multimodal detection"and"predictive modeling".Studies were included if they focused on clinically relevant AI applications in GI oncology.AI algorithms for GI cancer detection have achieved high performance across imaging modalities,with endoscopic DL systems reporting accuracies of 85%-97%for polyp detection and segmentation.Radiomics-based models have predicted molecular biomarkers such as programmed cell death ligand 2 expression with area under the curves up to 0.92.Large language models applied to radiology reports demonstrated diagnostic accuracy comparable to junior radiologists(78.9%vs 80.0%),though without incremental value when combined with human interpretation.Multimodal AI approaches integrating imaging,pathology,and clinical data show emerging potential for precision oncology.AI in GI oncology has reached clinically relevant accuracy levels in multiple diagnostic tasks,with multimodal approaches and predictive biomarker modeling offering new opportunities for personalized care.However,broader validation,integration into clinical workflows,and attention to ethical,legal,and social implications remain critical for widespread adoption.展开更多
BACKGROUND Chemotherapy with an immune checkpoint inhibitor is one of the standard regimens for treating advanced gastric cancer(AGC).Ascites and peritoneal dissemination are common complications and poor prognostic f...BACKGROUND Chemotherapy with an immune checkpoint inhibitor is one of the standard regimens for treating advanced gastric cancer(AGC).Ascites and peritoneal dissemination are common complications and poor prognostic factors of AGC;however,reports regarding its efficacy and safety in patients with AGC and massive ascites are limited.AIM To evaluate the safety and efficacy of nivolumab combined with chemotherapy in patients with AGC and ascites.METHODS We retrospectively collected clinical data from 124 patients with AGC who received chemotherapy plus nivolumab as first-line treatment from July 2017 to December 2024.Based on computed tomography scans,massive or moderate ascites were classified as high ascites burden(HAB),whereas mild or no ascites were classified as low ascites burden.RESULTS Ascites was detected in 47 patients(38%);26(21%)were classified into the HAB group.Patients in the HAB group exhibited a significantly poorer performance status,a higher prevalence of diffuse-type histology,and lower programmed cell death ligand 1(PD-L1)expression.Combination therapy with FOLFOX and neutropenia was significantly more common in the HAB group.Progression-free survival(PFS)(4.4 months vs 9.3 months,P=0.0012)and overall survival(OS)(7.3 months vs 21.2 months,P<0.0001)were significantly poorer in the HAB group.However,an improvement in ascites was observed in 61.5%of patients in the HAB group.PD-L1 expression did not correlate with either PFS or OS in the HAB group.CONCLUSION Nivolumab plus chemotherapy demonstrated modest efficacy and acceptable toxicity in patients with AGC and HAB.展开更多
This letter addresses challenges in the clinical translation of BIBR1532,a promising telomerase inhibitor,for the treatment of esophageal squamous cell carcinoma(ESCC).BIBR1532 exerts its anti-cancer effect by activat...This letter addresses challenges in the clinical translation of BIBR1532,a promising telomerase inhibitor,for the treatment of esophageal squamous cell carcinoma(ESCC).BIBR1532 exerts its anti-cancer effect by activating DNA damage response(ATR/CHK1 and ATM/CHK2)pathways and downregulating telomere-binding proteins.Although its therapeutic potential is limited by poor aqueous solubility,solid dispersion(SD)technology may overcome this obstacle.Systematic analysis using PubChem-derived simplified molecular input line entry system identifiers and artificial intelligence-driven FormulationDT platform evaluation(oral formulation feasibility index:0.38)revealed that the SD technology,with superior scalability(32 approved products by 2021)and lower production risks,outperforms lipid-based formulations as an optimal dissolution strategy.Material analysis revealed hydroxypropyl methylcellulose(HPMC)as the optimal carrier with lower hygroscopicity,higher temperature and no intestinal targeting,thus enabling ESCC therapy.HPMC-based SD enhances BIBR1532 solubility and bioavailability for effective ESCC treatment.Future studies should focus on pilot tests for SD fabrication.展开更多
BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning ofte...BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning often fail to capture the sparse and diagnostically critical features of metastatic potential.AIM To develop and validate a case-level multiple-instance learning(MIL)framework mimicking a pathologist's comprehensive review and improve T3/T4 CRC LNM prediction.METHODS The whole-slide images of 130 patients with T3/T4 CRC were retrospectively collected.A case-level MIL framework utilising the CONCH v1.5 and UNI2-h deep learning models was trained on features from all haematoxylin and eosinstained primary tumour slides for each patient.These pathological features were subsequently integrated with clinical data,and model performance was evaluated using the area under the curve(AUC).RESULTS The case-level framework demonstrated superior LNM prediction over slide-level training,with the CONCH v1.5 model achieving a mean AUC(±SD)of 0.899±0.033 vs 0.814±0.083,respectively.Integrating pathology features with clinical data further enhanced performance,yielding a top model with a mean AUC of 0.904±0.047,in sharp contrast to a clinical-only model(mean AUC 0.584±0.084).Crucially,a pathologist’s review confirmed that the model-identified high-attention regions correspond to known high-risk histopathological features.CONCLUSION A case-level MIL framework provides a superior approach for predicting LNM in advanced CRC.This method shows promise for risk stratification and therapy decisions,requiring further validation.展开更多
Pediatric cancers are particularly significant due to their uncommon occurrence in children,driven by a variety of underlying factors.Because of their distinct molecular and genetic makeup,which makes early detection ...Pediatric cancers are particularly significant due to their uncommon occurrence in children,driven by a variety of underlying factors.Because of their distinct molecular and genetic makeup,which makes early detection challenging,they are linked to problems.Diagnostic methods like imaging and tissue biopsy are only effective when the tumor has reached a size that can be identified.The liquid biopsy technique,the least intrusive and most convenient diagnostic method,is the subject of this review.It focuses on the significance of single cell analysis in examining uncommon cancer types.The many biomarkers found in bodily fluids and the cancer types they are linked to in children have been assessed,as has the potential route towards early detection and cancer recurrence forecasting.Combining the single cell liquid biopsy with the newest technologies,such as computational and multi-omics approaches,which have improved the efficiency of processing massive and unique genetic data,appears promising.This article discusses on a number of case reports for uncommon pediatric malignancies,such as Neuroblastoma,Medulloblastoma,Wilms Tumor,Rhabdomyosarcoma,Ewing Sarcoma,and Retinoblastoma,as well as their liquid biopsy profiles.Furthermore,the findings raise ethical questions regarding the therapeutic application of the technology as well as possible difficulties related to clinical translation.The likelihood that this single cell liquid biopsy will be clinically validated and eventually used as a routine diagnostic tool for uncommon pediatric cancers will rise with the realistic approach to sensitivity monitoring,specificity upgrading,and optimization.展开更多
BACKGROUND Inappropriate selection of patients with early gastric cancer(EGC)for endoscopic submucosal dissection(ESD)may lead to non-curative resection,necessitating additional gastrectomy.Conversely,inappropriate se...BACKGROUND Inappropriate selection of patients with early gastric cancer(EGC)for endoscopic submucosal dissection(ESD)may lead to non-curative resection,necessitating additional gastrectomy.Conversely,inappropriate selection for gastrectomy may result in overtreatment,adversely affecting patients’quality of life.Few have systematically evaluated the concordance between therapeutic indications under current Japanese guidelines and pathological criteria in EGC.To minimize noncurative resection risks while sparing unnecessary surgery for low-risk patients’,we specifically assess the suitability of Japanese guidelines in non-Japanese populations.This work aims to optimize clinical practice by refining endoscopic treatment criteria for adoption beyond Japan.AIM To evaluate EGC clinical decision accuracy by comparing therapeutic indication with postoperative pathological criteria and analyzing factors influencing discrepancies.METHODS A retrospective analysis was conducted on 796 EGC cases diagnosed at Peking University Third Hospital between January 2010 and December 2022.Cases were categorized into three groups:Same-estimated(preoperative therapeutic indication with postoperative pathological criteria matched),underestimated(preoperative ESD indication but postoperative surgical criteria),and overestimated(preoperative surgical indication but postoperative ESD criteria).The rate of discrepancy and associated risk factors were assessed.RESULTS The accuracy rates of preoperative evaluation for ESD and gastrectomy indications were 73.0%(321/430)and 76.0%(278/366),respectively.The overall discrepancy rate was 25.6%(204/796).Multivariate analysis identified tumor location in the upper-third stomach(odds ratio=2.158,95%confidence interval:1.373-3.390,P=0.001)was significantly associated with a higher likelihood of being underestimated and undifferentiated histologic type on preoperative biopsy(odds ratio=2.005,95%confidence interval:1.036-3.879,P=0.039)was more likely to be overestimated.Significant differences were observed in tumor diameter(P<0.001),depth of infiltration(P<0.001),ulcerative findings(P<0.001),and histologic type(P<0.001)between preoperative and postoperative evaluations.CONCLUSION The accuracy of preoperative EGC indications is 74.4%.Upper-third stomach and undifferentiated histology are primary discrepancy predictors.Upper-third tumors are prone to underestimation,while undifferentiated tumors are prone to overestimation.展开更多
Colorectal cancer(CRC)remains a major global health challenge,with high recurrence and mortality despite advances in surgery,chemotherapy,and immunotherapy.The study by He et al identifies a novel mechanism by which p...Colorectal cancer(CRC)remains a major global health challenge,with high recurrence and mortality despite advances in surgery,chemotherapy,and immunotherapy.The study by He et al identifies a novel mechanism by which peroxiredoxin 1(Prdx1)inhibits CRC progression through induction of pyroptosis,a pro-inflammatory form of programmed cell death.Traditionally viewed as an intracellular antioxidant that protects tumors from oxidative stress,Prdx1 assu-mes a paradoxical immunogenic role when released extracellularly as a damageassociated molecular pattern.Using patient samples,recombinant protein assays,and murine xenograft models,the authors demonstrate that Prdx1 activates the NOD-,LRR-and pyrin domain-containing protein 3 inflammasome/caspase-1/gasdermin D pathway,triggering membrane pore formation,tumor cell lysis,and release of interleukin-1β/interleukin-18.This cascade not only halts tumor proliferation,invasion,and migration but may also enhance anti-tumor immune surveillance.The study’s strengths include rigorous mechanistic validation,clinical cohort data,inhibitor-based causal proof,and in vivo confirmation.However,questions remain regarding the upstream receptor for Prdx1,heterogeneity across CRC subtypes,and the balance between therapeutic benefit and inflammatory toxicity.By establishing Prdx1-induced pyroptosis as a driver of tumor suppression,this work advances a promising paradigm in CRC therapy,linking cell death to immune activation and pointing toward future biomarker-driven,pyroptosis-based interventions.展开更多
BACKGROUND Perioperative anesthesia management of obese patients presents significant challenges as traditional total body weight-based dosing fails to achieve optimal anesthetic effects due to altered pharmacokinetic...BACKGROUND Perioperative anesthesia management of obese patients presents significant challenges as traditional total body weight-based dosing fails to achieve optimal anesthetic effects due to altered pharmacokinetic characteristics including abnormal drug distribution and clearance.Rocuronium exhibits markedly different distribution patterns in obese patients,with conventional weight correction methods inadequately addressing individual muscle mass variations that critically influence drug distribution.AIM To investigate the quantitative relationship between skeletal muscle index(SMI)and rocuronium distribution volume in obese colorectal cancer patients,establish a population pharmacokinetic model,and develop individualized dosing strategies based on muscle mass.METHODS A retrospective cohort study was conducted,including 100 obese patients(body mass index≥30 kg/m^(2))who underwent elective radical colorectal cancer surgery at our hospital from June 2023 to January 2025.Skeletal muscle mass was measured using InBody 260 body composition analyzer and SMI was calculated to assess muscle mass,with male SMI<7.0 kg/m^(2) and female SMI<5.7 kg/m^(2)as diagnostic criteria for sarcopenia.Plasma rocuronium concentrations were detected by liquid chromatography-tandem mass spectrometry/mass spectrometry,and nonlinear mixed-effect modeling was used to establish population pharmacokinetic modeling.Stepwise regression was used to screen covariates,and dosing regimens were optimized through Monte Carlo simulation.The primary endpoint was targeted plasma concentration achievement rate,and the secondary endpoint was postoperative residual muscle relaxation incidence.RESULTS Among 100 patients,35(35.0%)had sarcopenia and 65(65.0%)did not.Patients in the sarcopenia group were older(64.1±9.8 years vs 54.2±10.9 years,P<0.001)and had significantly lower SMI(6.2±0.8 kg/m^(2)vs 8.4±1.2 kg/m^(2),P<0.001).SMI showed strong positive correlation with rocuronium steady-state distribution volume(r=0.718,P<0.001)and moderate negative correlation with clearance(r=-0.502,P<0.001).A two-compartment population pharmacokinetic model was successfully established,with SMI being the most important covariate affecting central compartment distribution volume(△OFV=-41.2,P<0.001).Model validation showed bootstrap successful convergence rate of 92.3%,and 92.1%of observed values fell within prediction intervals in predicted concentration versus predicted concentration.The SMI-based individualized dosing regimen improved target exposure achievement rate from 82.0%in traditional regimen to 93.5%(P=0.009),and reduced postoperative residual muscle relaxation incidence from 13.0%to 3.5%(P=0.018).The sarcopenia group showed the most significant improvement in achievement rate,from 71.4%to 93.8%(P=0.017).CONCLUSION SMI shows strong correlation with rocuronium distribution volume in obese colorectal cancer patients and is a key factor affecting drug distribution.SMI-based individualized dosing strategies can significantly improve target exposure achievement rate and reduce postoperative residual muscle relaxation incidence,providing scientific evidence for precision anesthesia management in obese patients.展开更多
文摘Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.
基金National Natural Science Foundation of China,No.82003223and China Postdoctoral Science Foundation,No.2020M671398.
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics of cancer stem cell markers CD24 and CD133 in GC pathological tissues,and to explore their association with patients’clinicopathological parameters and postoperative survival outcomes.METHODS A total of 304 GC patients who underwent surgical treatment in our hospital from January 2018 to January 2020 were retrospectively included.Immunohistochemistry was used to detect the protein expression of CD24 and CD133 in tumor tissues,adjacent tissues,and normal gastric mucosa tissues.Based on staining intensity and the proportion of positive cells,expression levels were classified into low and high expression,while clinicopathological parameters were recorded.χ2 test was used to evaluate the correlation between expression and categorical variables,Spearman rank correlation analysis was performed to assess the correlation between the expression intensities of the two markers,and multivariate regression models were applied to identify independent risk factors influencing co-expression.Kaplan-Meier survival curves and Log-rank test were used to compare survival differences among groups with different expression patterns.RESULTS Among the 304 patients,155 cases(50.99%)were CD24 positive,including 91 low-expression and 64 highexpression;133 cases(43.75%)were CD133 positive,including 81 low-expression and 52 high-expression.There were 74 cases(24.34%)with double positivity and 81 cases(26.64%)with double negativity.Compared with tumor tissues,the positive rates of CD24 and CD133 in normal gastric tissues and adjacent tissues were significantly lower(P<0.05).Univariate analysis showed that co-expression of CD24 and CD133 in GC tissues was significantly correlated with tumor size,Lauren classification,T stage,N stage,and vascular invasion(P<0.05),but not with patient age,gender,tumor site,World Health Organization histological classification,or M stage(P>0.05).Further multivariate regression analysis suggested that tumor size,T stage,N stage,and vascular invasion were independent risk factors promoting CD24 and CD133 double positivity.Spearman rank correlation analysis indicated a moderate positive correlation between their expression intensities(r=0.420,P<0.001).During follow-up,29 of 304 patients were lost(loss rate 9.54%);146 deaths occurred.According to expression combination,there were 89 cases of CD24 single positivity(39 deaths),68 cases of CD133 single positivity(31 deaths),81 cases of double negativity(25 deaths),and 66 cases of double positivity(51 deaths).Log-rank test showed significant differences in overall survival among the four groups(χ2=20.89,P<0.001),with CD24+/CD133+group showing the worst prognosis.CONCLUSION CD24 and CD133 exhibit high positive detection rates in GC tissues,and their co-positivity is closely associated with tumor stage progression and significantly indicates unfavorable survival outcomes.The co-expression of CD24/CD133 may reflect higher aggressiveness and metastatic potential of GC,serving as a potential prognostic marker and a direction for targeted therapeutic strategies.However,as this is a single-center retrospective study with limitations such as patient loss to follow-up and sample size,further prospective,multicenter,and mechanistic studies are required to validate its clinical applicability and biological role.
文摘BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.AIM To determine the incidence of depression and its independent risk factors in patients with esophageal cancer and bone metastasis.METHODS A total of 100 consecutive eligible patients admitted between March 2022 and March 2025 were recruited.Depression was assessed with the Beck Depression Inventory-II;scores>4 defined the depression group(n=42)and scores≤4 the non-depression group(n=58).Demographic,clinical,and laboratory variables were compared between the groups.Multivariate logistic regression was used to identify independent risk factors.RESULTS Depression prevalence was 42.0%(42/100).Univariate analysis demonstrated significant differences in monthly per-capita household income,education level,social support,sleep disorders,and serum high-sensitivity C-reactive protein(all P<0.05);no differences were observed in sex,age,tumor characteristics,or other laboratory indices(all P>0.05).Multivariable analysis revealed the following independent risk factors for depression:Low income[odds ratio(OR)=2.66,95%confidence interval(CI):1.17-6.03],low education(OR=2.46,95%CI:1.08-5.61),low social support(OR=5.10,95%CI:1.81-14.39),sleep disorders(OR=2.79,95%CI:1.23-6.35),and elevated high-sensitivity C-reactive protein(OR=1.31 per unit increase,95%CI:1.18-1.46).CONCLUSION Depression is common among patients with esophageal cancer and bone metastasis.Low socioeconomic status,limited education,insufficient social support,sleep disturbances,and systemic inflammation were independent predictors.Interventions that address these modifiable factors may reduce depression risk in this population.
文摘The last research focuses on the role of exosomes in cancer treatment.Exosomes are extracellular vesicles.They can be secreted by cancer cells,and they can modulate chemotherapy sensitivity.Determining exosomal content opens the possibility for guiding treatment strategies for cancer diseases.Exosomal microRNA are considered one of the prime candidates for exosomal biomarkers.Exosomal circular RNAs represent excellent biomarkers for liquid biopsy because of their stability in many types of cancer.Exosomal proteins remain reliable biomarkers also.Exosomes have emerged as promising therapeutic candidates.Their biological properties render them ideal vectors for drug delivery.Genetic modification of exosomes is an effective way to deliver material capable of modulating cellular pathways involved in drug resistance.Furthermore,exosomes have been explored as carriers for metal-chelating agents.Integrating exosome-based therapies with traditional anticancer agents aims to exploit the natural targeting abilities of exosomes to enhance drug delivery.Despite the dynamic development of this field,many mechanisms of exosome action remain incompletely understood.Therefore,it is necessary to conduct further studies that will allow for a better understanding of their role in the process of resistance and will enable the development of effective therapeutic strategies.
文摘BACKGROUNDCancer stem cells(CSCs)drive recurrence and therapeutic resistance in triplenegativebreast cancer(TNBC),a highly aggressive breast cancer subtype.Intratumoralhypoxia,a common feature of solid tumors,promotes CSCs enrichment,yet the mechanisms sustaining CSCs stemness remain poorly understood.Hypoxia-induced reactive oxygen species can oxidatively activate ataxia telangiectasiamutated(ATM)kinase(oxidized ATM,p-ATM)independently of DNA breaks.AIMTo investigate the role of hypoxia-induced oxidized ATM in sustaining TNBCCSCstemness through c-Myc-mediated regulation of one-carbon metabolism.METHODSHs578T and MDA-MB-231 TNBC cells were cultured under normoxia or hypoxia.CSC stemness was assessed by mammosphere assays and flow cytometry.ATMactivity was assessed by pharmacological inhibition(Ku60019)and short hairpinRNA knockdown.c-Myc binding to serine hydroxymethyltransferase 2(SHMT2)and methylenetetrahydrofolate dehydrogenase 2(MTHFD2)promoters was analyzedby dual-luciferase reporter assays and chromatin immunoprecipitation.NADPH/NADP+ratios were quantified,and metabolic reprogramming was profiledby liquid chromatography-tandem mass spectrometry metabolomics.RESULTSHypoxia significantly increased mammosphere formation in both Hs578T and MDA-MB-231 cells,as reflected byhigher numbers of mammospheres(Hs578T:214±18;MDA-MB-231:198±16;both P<0.01)and larger meandiameters(P<0.01).Hypoxia also elevated CD44+/CD24-cell proportions and stemness gene expression(P<0.01).Oxidized ATM was activated under hypoxia withoutγH2AX induction,confirming DNA damage independence.ATM inhibition reduced mammosphere growth and suppressed c-Myc,SHMT2,and MTHFD2.Luciferase and chromatin immunoprecipitation assays confirmed direct c-Myc binding to SHMT2 and MTHFD2promoters,while mutation of the binding sites abolished promoter activity.NADPH/NADP+ratios were significantlyelevated under hypoxia but reduced following ATM inhibition(P<0.05).Metabolomics revealed enrichmentof serine/glycine one-carbon pathways.CONCLUSIONHypoxia-induced oxidized ATM maintains TNBC-CSC stemness by promoting c-Myc-dependent upregulation ofMTHFD2 and SHMT2,linking hypoxia,redox signaling,and one-carbon metabolism.These findings suggest apotential therapeutic axis that could be exploited for TNBC treatment.
基金funded by Al Jalila Foundation-Research Grant(AJF2023-078)to SSMS.
文摘Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabolism,in the aggressiveness and metastatic behavior of BC.Methods:A comprehensive analysis was performed using in silico transcriptomic data(n=2509 patients),immunohistochemical profiling of BC tissues(n=103),and validation through western blotting in multiple BC cell lines.Gene expression and survival analyses were conducted using Tumor Immune Estimation Resource(TIMER),Gene Expression Profiling Interactive Analysis 2(GEPIA2),and the cBioPortal for cancer genomics(cBioPortal)platforms.Correlations between PNP and key epithelial–mesenchymal transition(EMT)markers,molecular subtypes,tumor grades,and stages were examined.Results:PNP was significantly overexpressed in human epidermal growth factor receptor 2(HER-2)-positive and triple-negative BCs compared to luminal subtypes.High PNP levels were strongly associated with advanced BC stages,high-grade tumors,EMT phenotypes,and poor overall survival.Notably,HER-2 inhibition suppressed PNP expression,while PNP gene silencing induced HER-2 upregulation,revealing a reciprocal regulatory loop.Dual inhibition of PNP and HER-2 resulted in a significant reduction in cell viability compared to HER-2 inhibition alone.Conclusion:Collectively,PNP emerges as a promising biomarker of BC aggressiveness and progression.Its reciprocal interaction with HER-2 underscores its potential as a therapeutic target.Dual targeting of PNP and HER-2 may offer a novel strategy for improving outcomes in aggressive BC subtypes.
基金the Deanship of Research and Graduate Studies at King Khalid University,KSA,for funding this work through the Large Research Project under grant number RGP2/164/46.
文摘Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.
基金Supported by Russian Science Foundation,No.24-64-00028.
文摘We read with great interest the investigation of Kang et al related the applications of the multiparametric magnetic resonance imaging-based predictive model for assessing chemotherapy efficacy in colorectal cancer patients with gene mutations.The authors focused on decision-making based on the integration of tumor differentiation,signal intensity ratio,margin distance,and magnetic resonance imaging-detected lymph node metastasis.Indeed,these multiparameter predictive models could also be used for diagnosis as an alternative to invasive tissue examination methods.However,progress in this field enables us to shift the paradigm to radiology biopsies,particularly given the nonlinear effects of various radiation sources.
文摘We read with the great interest the study by Ababneh et al in which inducedmesenchymal stem cell-derived exosomes were shown to exhibit a stronger andmore sustained anti-proliferative effect by inducing a senescence-like state withoutapoptosis.The results obtained by the authors highlight the features of theeffects of senescent drift induction in surrounding tissues.In the light of thesefindings,the role of the properties of extracellular matrix and cellular glycocalyxin responses of human tumors to therapy remain uninvestigated.These extracellularbarriers appear to be significant obstacles to effective cancer therapy,especiallyin relation to the use of unique properties of tumor microenvironment forthe immunotherapy-resistant cancer treatment.
基金Supported by National Natural Science Foundation of China,No.82303672Zhejiang Provincial Health Commission and Zhejiang Provincial Administration of Traditional Chinese Medicine through the Targeted Project for Medical and Health Research,No.2025ZL017and China Primary Health Care Foundation,No.ZLMY20240311001ZJ.
文摘BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically experience a poor prognosis,highlighting an urgent need to explore novel treatment approaches.This study evaluated the overall efficacy and safety of CMT vs CMT combined with immune checkpoint inhibitors(ICIs)in the treatment of EC patients with liver metastases.Furthermore,prognostic factors influencing outcomes in this patient population were identified.AIM To evaluate the efficacy and safety of first-line chemoimmunotherapy for EC patients with liver metastases and to analyze prognostic factors.METHODS This retrospective study included 126 EC patients with liver metastases at Zhejiang Cancer Hospital between 2014 and 2024.Patients receiving CMT were compared with those receiving CMT+ICI.Analyzed variables included clinicopathological features,treatment history,characteristics of metastasis,systemic and local treatments,overall survival(OS),and treatment-related adverse events(TRAEs).Prognostic factors were evaluated using univariate and multivariate Cox proportional-hazards regression models.Finally,efficacy outcomes and TRAE profiles were compared between the two groups.RESULTS A significant difference in median OS was identified between the two groups(10.8 months in the CMT group vs 20.8 months in the CMT+ICI group,P=0.004).The CMT+ICI group also demonstrated a significantly longer median progression-free survival of 11.7 months(P<0.001).Patients receiving combination therapy exhibited significantly improved systemic objective response rate and disease control rate.Multivariate analysis identified key factors significantly influencing OS in EC patients with liver metastases:Karnofsky Performance Status score≥70,receipt of local therapy for liver metastases,and the number of cycles of CMT and immunotherapy received.Furthermore,the incidence of TRAEs did not significantly differ between the CMT+ICI and CMT groups.CONCLUSION For EC patients with liver metastases,the combination of CMT and ICIs demonstrates significantly superior efficacy compared with CMT alone,while maintaining manageable TRAEs.
基金Supported by The Joint Fund of Zhejiang Provincial Natural Science Foundation of China,No.LKLY25H160002.
文摘Gastric cancer(GC)has high morbidity and mortality worldwide.Due to the absence of noticeable symptoms,diagnosing GC at an early stage is very difficult,which consequently leads to advanced GC and poor prognosis.Effective biomarkers are essential for prolonging patients’survival.Helicobacter pylori(H.pylori)infection represents the most significant risk factor for GC,with nearly all cases linked to this infection.Many non-coding RNAs(ncRNAs)are dysregulated in H.pylori-infected GC,indicating that ncRNAs may serve as biomarkers of early-stage GC.In this editorial,we discuss the study by Chen et al.Although previous studies have identified roles for miR-136 in gastric cancer proliferation,apoptosis,and invasion,none have specifically explored its relationship with H.pylori-associated gastric carcinogenesis.
基金supported by the Academic Leader Training Programof Pudong New Area Health System in Shanghai(Grant No.PWRd2021-13)Shanghai Municipal Health Commission(Grant No.202340094).
文摘Objectives:Ribosomal protein S6 kinase A2(RPS6KA2)has been identified as a potential prognostic biomarker in several cancers,including breast cancer,glioblastoma,and prostate cancer.However,its functional significance in ovarian cancer is not well characterized.This study was designed to explore the therapeutic relevance of modulating RPS6KA2 in the context of ovarian cancer,particularly in relation to cisplatin resistance.Methods:The expression levels of RPS6KA2 and key regulators involved in autophagy and ferroptosis were assessed using quantitative reverse transcription-PCR,immunofluorescence staining,immunohistochemistry,and western blotting.Prognostic associations were conducted using the Kaplan-Meier Plotter database.Autophagy flux assays and visualization of autophagosomes were performed to assess autophagy activity.Ferroptosis-related parameters,including intracellular iron content,glutathione(GSH)levels,reactive oxygen species(ROS)generation,and mitochondrial membrane potential,were measured to determine ferroptotic changes.In vivo experiments were carried out to determine the antitumor efficacy of RPS6KA2 modulation in combination with pathway-specific agents.Results:Using ovarian cancer cell lines and clinical tissue samples,we demonstrated that RPS6KA2 expression was significantly downregulated in cisplatin-resistant cells and tissues compared to their sensitive counterparts.Low RPS6KA2 expression correlated with unfavorable patient outcomes and enhanced chemoresistance.Mechanistically,RPS6KA2 inhibited autophagy by modulating the phosphatidylinositol 3-kinase-protein kinase B-mammalian target of rapamycin(PI3K-AKT-mTOR)signaling pathway,which in turn increased sensitivity to cisplatin.Additionally,RPS6KA2 facilitated ferroptosis,contributing to its tumor-suppressive function.miR-512-3p was identified as a negative regulator of RPS6KA2,driving cisplatin resistance through suppression of RPS6KA2 expression.In vivo validation confirmed that combining RPS6KA2 targeting with autophagy inhibitors or ferroptosis inducers significantly enhanced cisplatin sensitivity in ovarian cancer models.Conclusion:These results collectively indicate that targeting the miR-512-3p/RPS6KA2 regulatory axis may offer a novel and effective strategy for overcoming cisplatin resistance in ovarian cancer.
文摘Gastrointestinal(GI)cancers remain a leading cause of cancer-related morbidity and mortality worldwide.Artificial intelligence(AI),particularly machine learning and deep learning(DL),has shown promise in enhancing cancer detection,diagnosis,and prognostication.A narrative review of literature published from January 2015 to march 2025 was conducted using PubMed,Web of Science,and Scopus.Search terms included"gastrointestinal cancer","artificial intelligence","machine learning","deep learning","radiomics","multimodal detection"and"predictive modeling".Studies were included if they focused on clinically relevant AI applications in GI oncology.AI algorithms for GI cancer detection have achieved high performance across imaging modalities,with endoscopic DL systems reporting accuracies of 85%-97%for polyp detection and segmentation.Radiomics-based models have predicted molecular biomarkers such as programmed cell death ligand 2 expression with area under the curves up to 0.92.Large language models applied to radiology reports demonstrated diagnostic accuracy comparable to junior radiologists(78.9%vs 80.0%),though without incremental value when combined with human interpretation.Multimodal AI approaches integrating imaging,pathology,and clinical data show emerging potential for precision oncology.AI in GI oncology has reached clinically relevant accuracy levels in multiple diagnostic tasks,with multimodal approaches and predictive biomarker modeling offering new opportunities for personalized care.However,broader validation,integration into clinical workflows,and attention to ethical,legal,and social implications remain critical for widespread adoption.
文摘BACKGROUND Chemotherapy with an immune checkpoint inhibitor is one of the standard regimens for treating advanced gastric cancer(AGC).Ascites and peritoneal dissemination are common complications and poor prognostic factors of AGC;however,reports regarding its efficacy and safety in patients with AGC and massive ascites are limited.AIM To evaluate the safety and efficacy of nivolumab combined with chemotherapy in patients with AGC and ascites.METHODS We retrospectively collected clinical data from 124 patients with AGC who received chemotherapy plus nivolumab as first-line treatment from July 2017 to December 2024.Based on computed tomography scans,massive or moderate ascites were classified as high ascites burden(HAB),whereas mild or no ascites were classified as low ascites burden.RESULTS Ascites was detected in 47 patients(38%);26(21%)were classified into the HAB group.Patients in the HAB group exhibited a significantly poorer performance status,a higher prevalence of diffuse-type histology,and lower programmed cell death ligand 1(PD-L1)expression.Combination therapy with FOLFOX and neutropenia was significantly more common in the HAB group.Progression-free survival(PFS)(4.4 months vs 9.3 months,P=0.0012)and overall survival(OS)(7.3 months vs 21.2 months,P<0.0001)were significantly poorer in the HAB group.However,an improvement in ascites was observed in 61.5%of patients in the HAB group.PD-L1 expression did not correlate with either PFS or OS in the HAB group.CONCLUSION Nivolumab plus chemotherapy demonstrated modest efficacy and acceptable toxicity in patients with AGC and HAB.
基金Supported by“Continuation”Project of Excellent Doctors,Guangdong Basic and Applied Basic Research Foundation,No.2025A04J5082Guangdong Basic and Applied Basic Research Foundation,No.2024A1515011236.
文摘This letter addresses challenges in the clinical translation of BIBR1532,a promising telomerase inhibitor,for the treatment of esophageal squamous cell carcinoma(ESCC).BIBR1532 exerts its anti-cancer effect by activating DNA damage response(ATR/CHK1 and ATM/CHK2)pathways and downregulating telomere-binding proteins.Although its therapeutic potential is limited by poor aqueous solubility,solid dispersion(SD)technology may overcome this obstacle.Systematic analysis using PubChem-derived simplified molecular input line entry system identifiers and artificial intelligence-driven FormulationDT platform evaluation(oral formulation feasibility index:0.38)revealed that the SD technology,with superior scalability(32 approved products by 2021)and lower production risks,outperforms lipid-based formulations as an optimal dissolution strategy.Material analysis revealed hydroxypropyl methylcellulose(HPMC)as the optimal carrier with lower hygroscopicity,higher temperature and no intestinal targeting,thus enabling ESCC therapy.HPMC-based SD enhances BIBR1532 solubility and bioavailability for effective ESCC treatment.Future studies should focus on pilot tests for SD fabrication.
基金Supported by Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau),No.2023MSXM060.
文摘BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning often fail to capture the sparse and diagnostically critical features of metastatic potential.AIM To develop and validate a case-level multiple-instance learning(MIL)framework mimicking a pathologist's comprehensive review and improve T3/T4 CRC LNM prediction.METHODS The whole-slide images of 130 patients with T3/T4 CRC were retrospectively collected.A case-level MIL framework utilising the CONCH v1.5 and UNI2-h deep learning models was trained on features from all haematoxylin and eosinstained primary tumour slides for each patient.These pathological features were subsequently integrated with clinical data,and model performance was evaluated using the area under the curve(AUC).RESULTS The case-level framework demonstrated superior LNM prediction over slide-level training,with the CONCH v1.5 model achieving a mean AUC(±SD)of 0.899±0.033 vs 0.814±0.083,respectively.Integrating pathology features with clinical data further enhanced performance,yielding a top model with a mean AUC of 0.904±0.047,in sharp contrast to a clinical-only model(mean AUC 0.584±0.084).Crucially,a pathologist’s review confirmed that the model-identified high-attention regions correspond to known high-risk histopathological features.CONCLUSION A case-level MIL framework provides a superior approach for predicting LNM in advanced CRC.This method shows promise for risk stratification and therapy decisions,requiring further validation.
文摘Pediatric cancers are particularly significant due to their uncommon occurrence in children,driven by a variety of underlying factors.Because of their distinct molecular and genetic makeup,which makes early detection challenging,they are linked to problems.Diagnostic methods like imaging and tissue biopsy are only effective when the tumor has reached a size that can be identified.The liquid biopsy technique,the least intrusive and most convenient diagnostic method,is the subject of this review.It focuses on the significance of single cell analysis in examining uncommon cancer types.The many biomarkers found in bodily fluids and the cancer types they are linked to in children have been assessed,as has the potential route towards early detection and cancer recurrence forecasting.Combining the single cell liquid biopsy with the newest technologies,such as computational and multi-omics approaches,which have improved the efficiency of processing massive and unique genetic data,appears promising.This article discusses on a number of case reports for uncommon pediatric malignancies,such as Neuroblastoma,Medulloblastoma,Wilms Tumor,Rhabdomyosarcoma,Ewing Sarcoma,and Retinoblastoma,as well as their liquid biopsy profiles.Furthermore,the findings raise ethical questions regarding the therapeutic application of the technology as well as possible difficulties related to clinical translation.The likelihood that this single cell liquid biopsy will be clinically validated and eventually used as a routine diagnostic tool for uncommon pediatric cancers will rise with the realistic approach to sensitivity monitoring,specificity upgrading,and optimization.
基金Supported by China Health&Medical Development Foundation,No.M2021551.
文摘BACKGROUND Inappropriate selection of patients with early gastric cancer(EGC)for endoscopic submucosal dissection(ESD)may lead to non-curative resection,necessitating additional gastrectomy.Conversely,inappropriate selection for gastrectomy may result in overtreatment,adversely affecting patients’quality of life.Few have systematically evaluated the concordance between therapeutic indications under current Japanese guidelines and pathological criteria in EGC.To minimize noncurative resection risks while sparing unnecessary surgery for low-risk patients’,we specifically assess the suitability of Japanese guidelines in non-Japanese populations.This work aims to optimize clinical practice by refining endoscopic treatment criteria for adoption beyond Japan.AIM To evaluate EGC clinical decision accuracy by comparing therapeutic indication with postoperative pathological criteria and analyzing factors influencing discrepancies.METHODS A retrospective analysis was conducted on 796 EGC cases diagnosed at Peking University Third Hospital between January 2010 and December 2022.Cases were categorized into three groups:Same-estimated(preoperative therapeutic indication with postoperative pathological criteria matched),underestimated(preoperative ESD indication but postoperative surgical criteria),and overestimated(preoperative surgical indication but postoperative ESD criteria).The rate of discrepancy and associated risk factors were assessed.RESULTS The accuracy rates of preoperative evaluation for ESD and gastrectomy indications were 73.0%(321/430)and 76.0%(278/366),respectively.The overall discrepancy rate was 25.6%(204/796).Multivariate analysis identified tumor location in the upper-third stomach(odds ratio=2.158,95%confidence interval:1.373-3.390,P=0.001)was significantly associated with a higher likelihood of being underestimated and undifferentiated histologic type on preoperative biopsy(odds ratio=2.005,95%confidence interval:1.036-3.879,P=0.039)was more likely to be overestimated.Significant differences were observed in tumor diameter(P<0.001),depth of infiltration(P<0.001),ulcerative findings(P<0.001),and histologic type(P<0.001)between preoperative and postoperative evaluations.CONCLUSION The accuracy of preoperative EGC indications is 74.4%.Upper-third stomach and undifferentiated histology are primary discrepancy predictors.Upper-third tumors are prone to underestimation,while undifferentiated tumors are prone to overestimation.
文摘Colorectal cancer(CRC)remains a major global health challenge,with high recurrence and mortality despite advances in surgery,chemotherapy,and immunotherapy.The study by He et al identifies a novel mechanism by which peroxiredoxin 1(Prdx1)inhibits CRC progression through induction of pyroptosis,a pro-inflammatory form of programmed cell death.Traditionally viewed as an intracellular antioxidant that protects tumors from oxidative stress,Prdx1 assu-mes a paradoxical immunogenic role when released extracellularly as a damageassociated molecular pattern.Using patient samples,recombinant protein assays,and murine xenograft models,the authors demonstrate that Prdx1 activates the NOD-,LRR-and pyrin domain-containing protein 3 inflammasome/caspase-1/gasdermin D pathway,triggering membrane pore formation,tumor cell lysis,and release of interleukin-1β/interleukin-18.This cascade not only halts tumor proliferation,invasion,and migration but may also enhance anti-tumor immune surveillance.The study’s strengths include rigorous mechanistic validation,clinical cohort data,inhibitor-based causal proof,and in vivo confirmation.However,questions remain regarding the upstream receptor for Prdx1,heterogeneity across CRC subtypes,and the balance between therapeutic benefit and inflammatory toxicity.By establishing Prdx1-induced pyroptosis as a driver of tumor suppression,this work advances a promising paradigm in CRC therapy,linking cell death to immune activation and pointing toward future biomarker-driven,pyroptosis-based interventions.
文摘BACKGROUND Perioperative anesthesia management of obese patients presents significant challenges as traditional total body weight-based dosing fails to achieve optimal anesthetic effects due to altered pharmacokinetic characteristics including abnormal drug distribution and clearance.Rocuronium exhibits markedly different distribution patterns in obese patients,with conventional weight correction methods inadequately addressing individual muscle mass variations that critically influence drug distribution.AIM To investigate the quantitative relationship between skeletal muscle index(SMI)and rocuronium distribution volume in obese colorectal cancer patients,establish a population pharmacokinetic model,and develop individualized dosing strategies based on muscle mass.METHODS A retrospective cohort study was conducted,including 100 obese patients(body mass index≥30 kg/m^(2))who underwent elective radical colorectal cancer surgery at our hospital from June 2023 to January 2025.Skeletal muscle mass was measured using InBody 260 body composition analyzer and SMI was calculated to assess muscle mass,with male SMI<7.0 kg/m^(2) and female SMI<5.7 kg/m^(2)as diagnostic criteria for sarcopenia.Plasma rocuronium concentrations were detected by liquid chromatography-tandem mass spectrometry/mass spectrometry,and nonlinear mixed-effect modeling was used to establish population pharmacokinetic modeling.Stepwise regression was used to screen covariates,and dosing regimens were optimized through Monte Carlo simulation.The primary endpoint was targeted plasma concentration achievement rate,and the secondary endpoint was postoperative residual muscle relaxation incidence.RESULTS Among 100 patients,35(35.0%)had sarcopenia and 65(65.0%)did not.Patients in the sarcopenia group were older(64.1±9.8 years vs 54.2±10.9 years,P<0.001)and had significantly lower SMI(6.2±0.8 kg/m^(2)vs 8.4±1.2 kg/m^(2),P<0.001).SMI showed strong positive correlation with rocuronium steady-state distribution volume(r=0.718,P<0.001)and moderate negative correlation with clearance(r=-0.502,P<0.001).A two-compartment population pharmacokinetic model was successfully established,with SMI being the most important covariate affecting central compartment distribution volume(△OFV=-41.2,P<0.001).Model validation showed bootstrap successful convergence rate of 92.3%,and 92.1%of observed values fell within prediction intervals in predicted concentration versus predicted concentration.The SMI-based individualized dosing regimen improved target exposure achievement rate from 82.0%in traditional regimen to 93.5%(P=0.009),and reduced postoperative residual muscle relaxation incidence from 13.0%to 3.5%(P=0.018).The sarcopenia group showed the most significant improvement in achievement rate,from 71.4%to 93.8%(P=0.017).CONCLUSION SMI shows strong correlation with rocuronium distribution volume in obese colorectal cancer patients and is a key factor affecting drug distribution.SMI-based individualized dosing strategies can significantly improve target exposure achievement rate and reduce postoperative residual muscle relaxation incidence,providing scientific evidence for precision anesthesia management in obese patients.
