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
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
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
Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance pati...Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance patients remains limited.This study examined real-world outcomes of palbociclib plus endocrine therapy in Asian patients,with additional subgroup analyses by age and performance status.Methods:We retrospectively analyzed 46 consecutive Asian patients with recurrent or de novo HR+/HER2−breast cancer treated with first-line palbociclib plus ET between April 2021 and March 2025.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall response rate(ORR),disease control rate(DCR),and safety.Subgroup analyses were performed by age(<70 vs.≥70 years)and performance status(PS;0–1 vs.2–3).Results:The median PFS was 26.6 months(range,1.4–69.5).Stratified by age,median PFS was 26.9 months in patients<70 years and 26.2 months in those≥70 years(p=0.760).By PS,PFS was 26.9 months for PS 0–1 and 17.8 months for PS 2–3(p=0.099).ORR was 60.9%and DCR 93.5%;notably,all PS 2–3 patients achieved disease control.Hematologic toxicities were common,with neutropenia(80.4%)and leukopenia(86.7%)predominating,but grade≥3 anemia was rare(2.2%).Elderly patients experienced anemia more frequently,while overall toxicity remained manageable.Dose reductions occurred in 47.8%without loss of efficacy.Conclusions:In routine Japanese practice,palbociclib plus ET provided prolonged PFS and high disease control consistent with pivotal trials and international real-world evidence.Importantly,elderly patients tolerated treatment well,and selected PS 2–3 patients also derived clinical benefit.These findings indicate that neither age nor PS alone should preclude the use of palbociclib in carefully monitored real-world patients.展开更多
Objectives:Decades of clinical and fundamental research advancements in oncology have led to significant breakthroughs such as early screening,targeted therapies,and immunotherapy,contributing to reduced mortality rat...Objectives:Decades of clinical and fundamental research advancements in oncology have led to significant breakthroughs such as early screening,targeted therapies,and immunotherapy,contributing to reduced mortality rates in cancer patients.Despite these achievements,cancer continues to be a major public health challenge.This study employs bibliometric techniques to visually analyze the English literature on cancer prevention,screening,diagnosis,treatment,and rehabilitation.Methods:We systematically reviewed publications from 01 March 2014,to 01 March 2024,indexed in the Web of Science core collection.Tools such as VOSviewer Version 1.6.20 is characterized by its core idea of co-occurrence clustering.CiteSpace 6.3.R3 is distinguished by its powerful capabilities in bibliometric analysis,including co-citation analysis,co-occurrence analysis of keywords,author collaboration network analysis,and journal co-citation analysis,providing effective insights into research hotspots and detecting emerging trends.Bibliometrix version 3.0.3 offers rich visualization features,including collaboration network diagrams,citation distribution graphs,and keyword clouds.facilitated the analysis of the literature,helping to map out the current research landscape,identify pressing issues,and discern emerging trends,thus offering insights for future research directions.Results:The analysis revealed that major research hotspots include lung and breast cancer.Attention is predominantly concentrated on cancer treatment,subdivided into targeted therapy,immunotherapy,traditional Chinese medicine,and the development of new anticancer drugs.Significant terms identified in the study include immune checkpoint inhibitors,tumor microenvironment,and cancer stem cells.Conclusion:This bibliometric analysis highlights the evolving directions in oncology research,pinpointing nanotherapy,resistance to targeted therapies,and the integration of artificial intelligence as pivotal future research avenues in the prevention,screening,diagnosis,treatment,and rehabilitation of cancer.展开更多
Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these...Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these tumors has currently plateaued. Many investigations have assessed the role of HER2 in tumors of the digestive system in both prognostic and therapeutic settings, with heterogeneous results. Novel testing and treatment guidelines are emerging, in particular in gastric and colorectal cancers. However, further advances are needed. In this review we provide a comprehensive overview of the current state-ofknowledge of HER2 alterations in the most common tumors of the digestive system and discuss the operational implications of HER2 testing.展开更多
A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.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
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
Objectives This review aimed to systematically synthesize the available research on the disclosure of diagnosis and related issues in childhood cancer from the perspectives of healthcare professionals,with the goal of...Objectives This review aimed to systematically synthesize the available research on the disclosure of diagnosis and related issues in childhood cancer from the perspectives of healthcare professionals,with the goal of informing the optimization of disclosure processes and meeting the communication needs of affected families.Methods In accordance with the Joanna Briggs Institute(JBI)methodology for mixed methods systematic reviews,the convergent segregated approach was used in this review.Articles were retrieved from 11 databases,including PubMed,Web of Science,CINAHL,CENTRAL,Embase,Ovid/Medline,PsycINFO,PsycArticles,Scopus,ERIC,and China National Knowledge Infrastructure(CNKI).The quality of the selected articles was assessed using the Mixed Method Appraisal Tool(MMAT).The review protocol was registered on PROSPERO(CRD42024542746).Results A total of 21 studies from 10 countries were included.Their methodological quality was generally medium to high,with MMAT scores ranging from 60%to 100%.The synthesis yielded three core themes:1)the spectrum of professional and societal attitudes toward disclosure;2)the dynamic practices of navigating disclosure amid uncertainty,including timing and environment,stakeholders,and content of disclosure;and 3)factors influencing disclosure,including children’s,parental,healthcare professionals’,and socio-cultural factors.Conclusions This review synthesized the perspectives and experiences of healthcare professionals regarding disclosure in childhood cancer,highlighting the complexity and multidimensional nature of this process in clinical practice.Future research should further investigate the experiences and needs of children and their parents,explore cultural variations in disclosure practices,develop context-appropriate assessment tools,and construct multidimensional intervention strategies to enhance the humanistic care and professional effectiveness of the disclosure process.展开更多
Breast cancer(BRCA)is characterized by high heterogeneity,with aggressive subtypes frequently showing poor prognosis and resistance to conventional therapies,making the discovery of new therapeutic targets and strateg...Breast cancer(BRCA)is characterized by high heterogeneity,with aggressive subtypes frequently showing poor prognosis and resistance to conventional therapies,making the discovery of new therapeutic targets and strategies imperative.Although elevated expression of discs large homolog 3(DLG3)has been reported in BRCA,its functional role in disease progression remains unclear.We performed bioinformatic analyses of clinical datasets to evaluate the prognostic significance of DLG3 expression in BRCA patients.In vitro gain-and loss-of-function experiments were conducted to assess the impact of DLG3 on BRCA cell proliferation,migration,and colony formation.Transcriptomic profiling,coupled with pharmacological inhibition,was employed to identify and validate downstream signaling pathways.Additionally,we extended our validation to an in vivo model to assess the role of DLG3 in tumor progression.We found that elevated DLG3 levels correlated with poor prognosis in breast cancer patients.Functionally,DLG3 overexpression significantly promoted cell proliferation and migration in estrogen receptor-positive MCF7 and triple-negative MDA-MB-231 breast cancer cells,whereas its knockdown suppressed these effects.Transcriptomic analyses revealed that DLG3 activates signal transducer and activator of transcription 3(STAT3)signaling,a finding further corroborated by Western blot.Critically,treatment with the STAT3 inhibitor Stattic attenuated DLG3-driven proliferation and migration,supporting a DLG3-STAT3 oncogenic axis.Furthermore,in vivo studies validated the role of DLG3 in promoting tumor growth and its correlation with elevated STAT3 signaling,consistent with our in vitro findings.Our findings establish DLG3 as a novel driver of breast cancer progression that directly activates STAT3 signaling.DLG3 thus represents both a potential prognostic biomarker and a promising therapeutic target for aggressive breast cancer subtypes,including triple-negative breast cancer.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
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 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
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
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
The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierar...The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierarchy are emerging as versatile building blocks for engineered drug delivery systems,showing a promising prospect in cancer therapy.CDs enable precise synthesis of functionalized polymers with tailored architectures,endowing their excellent stability and large surface area to prolong drug circulation,enhance solubility,and increase targeting efficiency.Recently,CD-based nanotherapeutics has shown transformative potential in chemotherapy,phototherapy,immunotherapy,gene therapy and other codelivery systems of combination therapy.This review will introduce the types of CD-based nanotherapeutics,systematically summarize their design methods and anticancer application,and further discuss the prospects and challenges,providing a roadmap for advancing CD nanotechnology toward cancer therapeutics.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
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.
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.
文摘Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance patients remains limited.This study examined real-world outcomes of palbociclib plus endocrine therapy in Asian patients,with additional subgroup analyses by age and performance status.Methods:We retrospectively analyzed 46 consecutive Asian patients with recurrent or de novo HR+/HER2−breast cancer treated with first-line palbociclib plus ET between April 2021 and March 2025.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall response rate(ORR),disease control rate(DCR),and safety.Subgroup analyses were performed by age(<70 vs.≥70 years)and performance status(PS;0–1 vs.2–3).Results:The median PFS was 26.6 months(range,1.4–69.5).Stratified by age,median PFS was 26.9 months in patients<70 years and 26.2 months in those≥70 years(p=0.760).By PS,PFS was 26.9 months for PS 0–1 and 17.8 months for PS 2–3(p=0.099).ORR was 60.9%and DCR 93.5%;notably,all PS 2–3 patients achieved disease control.Hematologic toxicities were common,with neutropenia(80.4%)and leukopenia(86.7%)predominating,but grade≥3 anemia was rare(2.2%).Elderly patients experienced anemia more frequently,while overall toxicity remained manageable.Dose reductions occurred in 47.8%without loss of efficacy.Conclusions:In routine Japanese practice,palbociclib plus ET provided prolonged PFS and high disease control consistent with pivotal trials and international real-world evidence.Importantly,elderly patients tolerated treatment well,and selected PS 2–3 patients also derived clinical benefit.These findings indicate that neither age nor PS alone should preclude the use of palbociclib in carefully monitored real-world patients.
基金supported by the grants from the Scientific and Technological Innovation Project of Information Traditional Chinese Medicine,China Academy of Chinese Medical Sciences(No.CI2021 B002).
文摘Objectives:Decades of clinical and fundamental research advancements in oncology have led to significant breakthroughs such as early screening,targeted therapies,and immunotherapy,contributing to reduced mortality rates in cancer patients.Despite these achievements,cancer continues to be a major public health challenge.This study employs bibliometric techniques to visually analyze the English literature on cancer prevention,screening,diagnosis,treatment,and rehabilitation.Methods:We systematically reviewed publications from 01 March 2014,to 01 March 2024,indexed in the Web of Science core collection.Tools such as VOSviewer Version 1.6.20 is characterized by its core idea of co-occurrence clustering.CiteSpace 6.3.R3 is distinguished by its powerful capabilities in bibliometric analysis,including co-citation analysis,co-occurrence analysis of keywords,author collaboration network analysis,and journal co-citation analysis,providing effective insights into research hotspots and detecting emerging trends.Bibliometrix version 3.0.3 offers rich visualization features,including collaboration network diagrams,citation distribution graphs,and keyword clouds.facilitated the analysis of the literature,helping to map out the current research landscape,identify pressing issues,and discern emerging trends,thus offering insights for future research directions.Results:The analysis revealed that major research hotspots include lung and breast cancer.Attention is predominantly concentrated on cancer treatment,subdivided into targeted therapy,immunotherapy,traditional Chinese medicine,and the development of new anticancer drugs.Significant terms identified in the study include immune checkpoint inhibitors,tumor microenvironment,and cancer stem cells.Conclusion:This bibliometric analysis highlights the evolving directions in oncology research,pinpointing nanotherapy,resistance to targeted therapies,and the integration of artificial intelligence as pivotal future research avenues in the prevention,screening,diagnosis,treatment,and rehabilitation of cancer.
文摘Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these tumors has currently plateaued. Many investigations have assessed the role of HER2 in tumors of the digestive system in both prognostic and therapeutic settings, with heterogeneous results. Novel testing and treatment guidelines are emerging, in particular in gastric and colorectal cancers. However, further advances are needed. In this review we provide a comprehensive overview of the current state-ofknowledge of HER2 alterations in the most common tumors of the digestive system and discuss the operational implications of HER2 testing.
文摘A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.
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.
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 the Fuxing Nursing Research Foundation of Fudan University[FNF202352].
文摘Objectives This review aimed to systematically synthesize the available research on the disclosure of diagnosis and related issues in childhood cancer from the perspectives of healthcare professionals,with the goal of informing the optimization of disclosure processes and meeting the communication needs of affected families.Methods In accordance with the Joanna Briggs Institute(JBI)methodology for mixed methods systematic reviews,the convergent segregated approach was used in this review.Articles were retrieved from 11 databases,including PubMed,Web of Science,CINAHL,CENTRAL,Embase,Ovid/Medline,PsycINFO,PsycArticles,Scopus,ERIC,and China National Knowledge Infrastructure(CNKI).The quality of the selected articles was assessed using the Mixed Method Appraisal Tool(MMAT).The review protocol was registered on PROSPERO(CRD42024542746).Results A total of 21 studies from 10 countries were included.Their methodological quality was generally medium to high,with MMAT scores ranging from 60%to 100%.The synthesis yielded three core themes:1)the spectrum of professional and societal attitudes toward disclosure;2)the dynamic practices of navigating disclosure amid uncertainty,including timing and environment,stakeholders,and content of disclosure;and 3)factors influencing disclosure,including children’s,parental,healthcare professionals’,and socio-cultural factors.Conclusions This review synthesized the perspectives and experiences of healthcare professionals regarding disclosure in childhood cancer,highlighting the complexity and multidimensional nature of this process in clinical practice.Future research should further investigate the experiences and needs of children and their parents,explore cultural variations in disclosure practices,develop context-appropriate assessment tools,and construct multidimensional intervention strategies to enhance the humanistic care and professional effectiveness of the disclosure process.
文摘Breast cancer(BRCA)is characterized by high heterogeneity,with aggressive subtypes frequently showing poor prognosis and resistance to conventional therapies,making the discovery of new therapeutic targets and strategies imperative.Although elevated expression of discs large homolog 3(DLG3)has been reported in BRCA,its functional role in disease progression remains unclear.We performed bioinformatic analyses of clinical datasets to evaluate the prognostic significance of DLG3 expression in BRCA patients.In vitro gain-and loss-of-function experiments were conducted to assess the impact of DLG3 on BRCA cell proliferation,migration,and colony formation.Transcriptomic profiling,coupled with pharmacological inhibition,was employed to identify and validate downstream signaling pathways.Additionally,we extended our validation to an in vivo model to assess the role of DLG3 in tumor progression.We found that elevated DLG3 levels correlated with poor prognosis in breast cancer patients.Functionally,DLG3 overexpression significantly promoted cell proliferation and migration in estrogen receptor-positive MCF7 and triple-negative MDA-MB-231 breast cancer cells,whereas its knockdown suppressed these effects.Transcriptomic analyses revealed that DLG3 activates signal transducer and activator of transcription 3(STAT3)signaling,a finding further corroborated by Western blot.Critically,treatment with the STAT3 inhibitor Stattic attenuated DLG3-driven proliferation and migration,supporting a DLG3-STAT3 oncogenic axis.Furthermore,in vivo studies validated the role of DLG3 in promoting tumor growth and its correlation with elevated STAT3 signaling,consistent with our in vitro findings.Our findings establish DLG3 as a novel driver of breast cancer progression that directly activates STAT3 signaling.DLG3 thus represents both a potential prognostic biomarker and a promising therapeutic target for aggressive breast cancer subtypes,including triple-negative breast cancer.
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.
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.
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.
基金financially supported by National Natural Science Foundation of China (No.3240117,X.S)Sichuan Science and Technology Program (No.2024YFFK0345,Z.X)+3 种基金Natural Science Foundation of Chongqing (No.CSTB2024NSCQ-MSX0046,F.R)Startup Fund of Chongqing Normal University (No.23XLB036,F.R)National College Student Innovation and Entrepreneurship Program of Southwest University (No.202410635109,Y.Z)Guangdong High-level Hospital Construction Fund。
文摘The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierarchy are emerging as versatile building blocks for engineered drug delivery systems,showing a promising prospect in cancer therapy.CDs enable precise synthesis of functionalized polymers with tailored architectures,endowing their excellent stability and large surface area to prolong drug circulation,enhance solubility,and increase targeting efficiency.Recently,CD-based nanotherapeutics has shown transformative potential in chemotherapy,phototherapy,immunotherapy,gene therapy and other codelivery systems of combination therapy.This review will introduce the types of CD-based nanotherapeutics,systematically summarize their design methods and anticancer application,and further discuss the prospects and challenges,providing a roadmap for advancing CD nanotechnology toward cancer therapeutics.
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.
