Introduction,Breast cancer is the most common cancer type in adolescents and young adults<40 years of age,accounting for 30%of cancers in this age group1.Breast cancer in the young presents significant challenges f...Introduction,Breast cancer is the most common cancer type in adolescents and young adults<40 years of age,accounting for 30%of cancers in this age group1.Breast cancer in the young presents significant challenges for patients and society,including more aggressive tumor biology,poor prognosis,genetic susceptibility,fertility preservation,and complex psychosocial issues.Moreover,because of the markedly younger median age of breast cancer,the proportion of young breast cancer patients in China is significantly higher than Western countries2.The first Young Breast Cancer in China(YBCC)consensus meeting was held in Guangzhou,China in December 2021 to address exclusive challenges and requirements facing young patients with breast cancer.Chinese medical experts from multiple specialties had an extensive discussion and formulated a consensus over several hot topics in young patients with breast cancer.The“Expert Consensus on the Diagnosis and Treatment of Young Breast Cancer in China(2022 edition)”published in the Chinese Medical Journal has garnered significant attention3,highlighting enormous interest in the YBCC consensus in the medical community and public.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
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
Hepatocellular carcinoma(HCC)is a pressing global health problem and is the sixth most common cancer and the third leading cause of cancer mortality worldwide.Despite continuous advances in treatment modalities,the 5-...Hepatocellular carcinoma(HCC)is a pressing global health problem and is the sixth most common cancer and the third leading cause of cancer mortality worldwide.Despite continuous advances in treatment modalities,the 5-year survival rate is low with a high propensity for recurrence and metastasis1.This clinical challenge in treating HCC is largely attributed to the heterogeneity and intrinsic therapy resistance of cancer stem cells(CSCs),which are a subpopulation of cells with self-renewal capability and multidirectional differentiation potential to induce tumorigenicity2.The behavior and maintenance of CSCs are not autonomous but critically dependent on the complex bidirectional crosstalk between CSCs and the tumor immune microenvironment(TIME)1.In this review we first summarize the recent progress in characterizing CSCs and the interactions between CSCs and the TIME in HCC.Next,we discuss the emerging therapeutic strategies targeting CSC populations with the ongoing challenges.Finally,we give our perspectives on the future directions in HCC CSC research.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:Minimally invasive distal pancreatectomy(MIDP)is increasingly being used,although its oncologic safety for pancreatic ductal adenocarcinoma(PDAC)remains controversial.In Japan,MIDP for PDAC has limited endo...Background:Minimally invasive distal pancreatectomy(MIDP)is increasingly being used,although its oncologic safety for pancreatic ductal adenocarcinoma(PDAC)remains controversial.In Japan,MIDP for PDAC has limited endorsement due to insufficient data.This study aimed to compare the perioperative and long-term outcomes of open distal pancreatectomy(ODP)and MIDP for PDAC.Methods:We retrospectively analyzed patients with resectable pancreatic body and tail cancer treated with ODP or MIDP(laparoscopic or robotic)between January 2007 and July 2022.The surgical procedures(ODP and MIDP)were compared and the patient characteristics,perioperative outcomes,and long-term outcomes were analyzed.We also compared the outcomes of patients with neoadjuvant chemotherapy(NAC)and without NAC.Results:A total of 72 distal pancreatectomies were performed(37 ODPs and 35 MIDPs).In the upfront group,MIDP resulted in significantly less blood loss than ODP(P<0.01),despite similar operative time.There was no statistically significant difference in the 2-year recurrence-free survival(RFS)rates between ODP and MIDP(39.7%vs.57.8%,P=0.60)or in the overall survival(OS)rates(66.7%vs.74.1%,P=0.43).Similarly,in the NAC group,MIDP resulted in significantly less blood loss than ODP(P=0.01);ODP and MIDP had similar 2-year RFS rates(41.7%and 60.0%,P=0.75)and OS rates(50.0%and 70.0%,P=0.36).The interval from surgery to adjuvant chemotherapy initiation did not significantly differ between the ODP and MIDP subgroups in both the upfront group(P=0.13)and the NAC group(P=0.14).The incidence of recurrence was 64.8%for ODP and 42.8%for MIDP(P=0.06).Both procedures showed similar distributions of local and distant recurrence.Conclusions:MIDP caused less blood loss and had similar oncologic safety compared with ODP.MIDP could become a feasible,minimally invasive option with sufficient oncologic safety for pancreatic body and tail cancers.展开更多
The global burden of cancer,with over 19 million new cases annually,underscores the urgent need for effective therapies.Among the most promising anticancer compounds is camptothecin(CPT),a monoterpene alkaloid predomi...The global burden of cancer,with over 19 million new cases annually,underscores the urgent need for effective therapies.Among the most promising anticancer compounds is camptothecin(CPT),a monoterpene alkaloid predominantly derived from Nothapodytes species.Despite its significantpharmaceutical value,the exploitation of such Threatened Plant Species with Widespread Distribution(TPSWD),particularly driven by the global demand for natural compounds in anticancer therapies,presents a paradox in which their widespread distribution fails to ensure their secure conservation status.Furthermore,the lack of in-depth biogeographic and systematic studies complicates efforts to balance resource utilization with biodiversity preservation.The asymmetric distribution of CPT within plant taxa,along with limited knowledge of its biosynthetic pathways and the enzymes and genes involved,further hampers sustainable production.Here,we review the current knowledge on the production and protection of Nothapodytes,focusing on their plant resources,active ingredients,and natural drug derivatives.We also explore strategies for rescuing and sustainably utilizing Nothapodytes,including biotechnological advancements and integrated conservation practices.Finally,we propose future directions to address conservation challenges,ensuring a sustainable supply of CPT while safeguarding these TPSWD species.展开更多
The metastatic pattern of colon cancer is typically well characterized,with initial dissemination occurring through regional lymphatics,followed by hematogenous spread.The most frequent sites of metastasis in colorect...The metastatic pattern of colon cancer is typically well characterized,with initial dissemination occurring through regional lymphatics,followed by hematogenous spread.The most frequent sites of metastasis in colorectal cancer(CRC)include regional lymph nodes(50%–70%),liver(35%–50%),lungs(21%),peritoneum(15%),and ovaries(13%).1 Isolated distant lymph node metastasis,particularly in the absence of concurrent systemic disease,is exceedingly rare in CRC.To date,only six cases of isolated axillary lymph node metastasis(ALNM)from colorectal primaries have been documented in the literature.1–6 Even more uncommon is the incidental discovery of malignant cells in anastomotic doughnuts following stoma reversal procedures.Herein,we report a rare case involving both the incidental histopathological detection of tumor cells within doughnuts during stoma closure and the subsequent development of isolated ALNM after curative resection of sigmoid colon carcinoma.展开更多
Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling res...Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling results in mucosal impairment and the initiation of cancer.Banxia Xiexin Decoction(BXD),a well-known formula in traditional Chinese medicine(TCM),shows promise in treating gastric disorders,but its mechanisms in gastric restoration remain unclear.Methods:Using MNNG-induced CAG and PLGC rat models,BXD was administered for 12 weeks.Gastric mucosal pathology was assessed via hematoxylin-eosin staining.Proliferation(Ki-67)and angiogenesis(VEGFA)markers were evaluated by immunohistochemistry.Network pharmacology identified BXD’s targets and pathways.Notch pathway components(Notch1,Jagged1,Dll4,Hes1)were analyzed via qPCR,Western blot,and immunohistochemistry.Results:BXD significantly ameliorated mucosal atrophy,glandular structural disorder,and dysplasia in CAG and PLGC rats.Network pharmacology revealed 323 overlapping targets between BXD and PLGC,with Notch signaling as a central pathway.BXD downregulated Notch1,Jagged1,Dll4,and Hes1 expression at transcriptional and protein levels,suppressed Ki-67(proliferation)and VEGFA(angiogenesis)overexpression,and restored gastric mucosal integrity.Conclusion:BXD inhibits Notch signaling,reduces aberrant proliferation and angiogenesis,and interrupts Correa’s gastric carcinogenesis cascade.This study provides mechanistic evidence supporting BXD as a TCM-based intervention for gastric precancerous lesions.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
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
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:This study aimed to determine the role and mechanism underlying migration and invasion inhibitory protein(MIIP)modulation in M2 macrophages within the tumor microenvironment and the potential of targeting t...Objectives:This study aimed to determine the role and mechanism underlying migration and invasion inhibitory protein(MIIP)modulation in M2 macrophages within the tumor microenvironment and the potential of targeting the MIIP-stimulator of interferon genes(STING)pathway in colorectal cancer(CRC)therapy.Methods:MIIP expression was analyzed for associations with the STING pathway and M2 macrophage infiltration using public datasets and clinical CRC samples.CRC cells were genetically modified using lentiviral vectors to overexpress or silence MIIP and STING.The interactions of genetically modified CRC cells with macrophages were studied in co-culture systems.Techniques,including immunofluorescence staining,RT‒qPCR,western blot,ELISA,flow cytometry,and Transwell migration and invasion assays,were used to evaluate the crosstalk between CRC cells and macrophages.An orthotopic mouse CRC model was developed to study the effects of MIIP on M2 macrophage polarization and tumor metastasis through the STING-NFκB2-IL10 axis.The therapeutic significance of a STING antagonist was also assessed in vivo.Results:Analyses of The Cancer Genome Atlas(TCGA)cohort and our CRC cohort revealed low MIIP expression is associated with STING pathway activation,increased M2 macrophage infiltration,and poor clinical outcomes.The results of functional experiments demonstrated that MIIP inhibits IL10 production via the STING-TRAF3-NFκB2 axis in CRC cells,suppressing M2 macrophage polarization in co-culture systems.Conversely,M2 macrophages promoted CRC cell migration and invasion in an IL10-dependent manner.In vitro and in vivo studies confirmed that the MIIP-mediated feedback loop between CRC cells and macrophages depends on the STING-NFκB2-IL10 axis.Furthermore,inhibition of STING expression in a mouse model reduced M2 macrophage polarization and tumor metastasis.Conclusions:This study established MIIP as a crucial regulator of macrophage polarization in the CRC tumor microenvironment,providing new insights into the role in suppressing CRC progression and immune-tumor crosstalk.These findings highlight the potential of targeting the STING pathway as a therapeutic strategy for CRC patients who respond poorly to immune checkpoint inhibitors.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.82230057 and 82272859)the National Key R&D Program of China(Grant No.2022YFC2505101).
文摘Introduction,Breast cancer is the most common cancer type in adolescents and young adults<40 years of age,accounting for 30%of cancers in this age group1.Breast cancer in the young presents significant challenges for patients and society,including more aggressive tumor biology,poor prognosis,genetic susceptibility,fertility preservation,and complex psychosocial issues.Moreover,because of the markedly younger median age of breast cancer,the proportion of young breast cancer patients in China is significantly higher than Western countries2.The first Young Breast Cancer in China(YBCC)consensus meeting was held in Guangzhou,China in December 2021 to address exclusive challenges and requirements facing young patients with breast cancer.Chinese medical experts from multiple specialties had an extensive discussion and formulated a consensus over several hot topics in young patients with breast cancer.The“Expert Consensus on the Diagnosis and Treatment of Young Breast Cancer in China(2022 edition)”published in the Chinese Medical Journal has garnered significant attention3,highlighting enormous interest in the YBCC consensus in the medical community and public.
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.
基金supported by the Hong Kong Research Grants Council Theme-based Research Scheme(Grant No.T12-716/22-R)Innovation and Technology Commission grant for State Key Laboratory of Liver Research(Grant No.ITC PD/17-9)University Development Fund of The University of Hong Kong,and Loke Yew Endowed Professorship award.I.O.L.Ng is Loke Yew Professor in Pathology.
文摘Hepatocellular carcinoma(HCC)is a pressing global health problem and is the sixth most common cancer and the third leading cause of cancer mortality worldwide.Despite continuous advances in treatment modalities,the 5-year survival rate is low with a high propensity for recurrence and metastasis1.This clinical challenge in treating HCC is largely attributed to the heterogeneity and intrinsic therapy resistance of cancer stem cells(CSCs),which are a subpopulation of cells with self-renewal capability and multidirectional differentiation potential to induce tumorigenicity2.The behavior and maintenance of CSCs are not autonomous but critically dependent on the complex bidirectional crosstalk between CSCs and the tumor immune microenvironment(TIME)1.In this review we first summarize the recent progress in characterizing CSCs and the interactions between CSCs and the TIME in HCC.Next,we discuss the emerging therapeutic strategies targeting CSC populations with the ongoing challenges.Finally,we give our perspectives on the future directions in HCC CSC research.
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:Minimally invasive distal pancreatectomy(MIDP)is increasingly being used,although its oncologic safety for pancreatic ductal adenocarcinoma(PDAC)remains controversial.In Japan,MIDP for PDAC has limited endorsement due to insufficient data.This study aimed to compare the perioperative and long-term outcomes of open distal pancreatectomy(ODP)and MIDP for PDAC.Methods:We retrospectively analyzed patients with resectable pancreatic body and tail cancer treated with ODP or MIDP(laparoscopic or robotic)between January 2007 and July 2022.The surgical procedures(ODP and MIDP)were compared and the patient characteristics,perioperative outcomes,and long-term outcomes were analyzed.We also compared the outcomes of patients with neoadjuvant chemotherapy(NAC)and without NAC.Results:A total of 72 distal pancreatectomies were performed(37 ODPs and 35 MIDPs).In the upfront group,MIDP resulted in significantly less blood loss than ODP(P<0.01),despite similar operative time.There was no statistically significant difference in the 2-year recurrence-free survival(RFS)rates between ODP and MIDP(39.7%vs.57.8%,P=0.60)or in the overall survival(OS)rates(66.7%vs.74.1%,P=0.43).Similarly,in the NAC group,MIDP resulted in significantly less blood loss than ODP(P=0.01);ODP and MIDP had similar 2-year RFS rates(41.7%and 60.0%,P=0.75)and OS rates(50.0%and 70.0%,P=0.36).The interval from surgery to adjuvant chemotherapy initiation did not significantly differ between the ODP and MIDP subgroups in both the upfront group(P=0.13)and the NAC group(P=0.14).The incidence of recurrence was 64.8%for ODP and 42.8%for MIDP(P=0.06).Both procedures showed similar distributions of local and distant recurrence.Conclusions:MIDP caused less blood loss and had similar oncologic safety compared with ODP.MIDP could become a feasible,minimally invasive option with sufficient oncologic safety for pancreatic body and tail cancers.
基金supported by the National Key R&D Program of China(2024YFF1306700)the Key Project of Basic Research of Yunnan Province,China(202301AS070001)the Regional Innovative Development Joint Fund of NSFC(U23A20149).
文摘The global burden of cancer,with over 19 million new cases annually,underscores the urgent need for effective therapies.Among the most promising anticancer compounds is camptothecin(CPT),a monoterpene alkaloid predominantly derived from Nothapodytes species.Despite its significantpharmaceutical value,the exploitation of such Threatened Plant Species with Widespread Distribution(TPSWD),particularly driven by the global demand for natural compounds in anticancer therapies,presents a paradox in which their widespread distribution fails to ensure their secure conservation status.Furthermore,the lack of in-depth biogeographic and systematic studies complicates efforts to balance resource utilization with biodiversity preservation.The asymmetric distribution of CPT within plant taxa,along with limited knowledge of its biosynthetic pathways and the enzymes and genes involved,further hampers sustainable production.Here,we review the current knowledge on the production and protection of Nothapodytes,focusing on their plant resources,active ingredients,and natural drug derivatives.We also explore strategies for rescuing and sustainably utilizing Nothapodytes,including biotechnological advancements and integrated conservation practices.Finally,we propose future directions to address conservation challenges,ensuring a sustainable supply of CPT while safeguarding these TPSWD species.
文摘The metastatic pattern of colon cancer is typically well characterized,with initial dissemination occurring through regional lymphatics,followed by hematogenous spread.The most frequent sites of metastasis in colorectal cancer(CRC)include regional lymph nodes(50%–70%),liver(35%–50%),lungs(21%),peritoneum(15%),and ovaries(13%).1 Isolated distant lymph node metastasis,particularly in the absence of concurrent systemic disease,is exceedingly rare in CRC.To date,only six cases of isolated axillary lymph node metastasis(ALNM)from colorectal primaries have been documented in the literature.1–6 Even more uncommon is the incidental discovery of malignant cells in anastomotic doughnuts following stoma reversal procedures.Herein,we report a rare case involving both the incidental histopathological detection of tumor cells within doughnuts during stoma closure and the subsequent development of isolated ALNM after curative resection of sigmoid colon carcinoma.
基金supported by the National Natural Science Foundation of China(Grant No.82274442)the Key Research Project in Traditional Chinese Medicine of Tianjin Municipal Health Commission(Grant No.202007)the Integrated Traditional Chinese and Western Medicine Research Project of Tianjin Municipal Health Commission(Grant No.2023134).
文摘Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling results in mucosal impairment and the initiation of cancer.Banxia Xiexin Decoction(BXD),a well-known formula in traditional Chinese medicine(TCM),shows promise in treating gastric disorders,but its mechanisms in gastric restoration remain unclear.Methods:Using MNNG-induced CAG and PLGC rat models,BXD was administered for 12 weeks.Gastric mucosal pathology was assessed via hematoxylin-eosin staining.Proliferation(Ki-67)and angiogenesis(VEGFA)markers were evaluated by immunohistochemistry.Network pharmacology identified BXD’s targets and pathways.Notch pathway components(Notch1,Jagged1,Dll4,Hes1)were analyzed via qPCR,Western blot,and immunohistochemistry.Results:BXD significantly ameliorated mucosal atrophy,glandular structural disorder,and dysplasia in CAG and PLGC rats.Network pharmacology revealed 323 overlapping targets between BXD and PLGC,with Notch signaling as a central pathway.BXD downregulated Notch1,Jagged1,Dll4,and Hes1 expression at transcriptional and protein levels,suppressed Ki-67(proliferation)and VEGFA(angiogenesis)overexpression,and restored gastric mucosal integrity.Conclusion:BXD inhibits Notch signaling,reduces aberrant proliferation and angiogenesis,and interrupts Correa’s gastric carcinogenesis cascade.This study provides mechanistic evidence supporting BXD as a TCM-based intervention for gastric precancerous lesions.
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.
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.
文摘Objectives:This study aimed to determine the role and mechanism underlying migration and invasion inhibitory protein(MIIP)modulation in M2 macrophages within the tumor microenvironment and the potential of targeting the MIIP-stimulator of interferon genes(STING)pathway in colorectal cancer(CRC)therapy.Methods:MIIP expression was analyzed for associations with the STING pathway and M2 macrophage infiltration using public datasets and clinical CRC samples.CRC cells were genetically modified using lentiviral vectors to overexpress or silence MIIP and STING.The interactions of genetically modified CRC cells with macrophages were studied in co-culture systems.Techniques,including immunofluorescence staining,RT‒qPCR,western blot,ELISA,flow cytometry,and Transwell migration and invasion assays,were used to evaluate the crosstalk between CRC cells and macrophages.An orthotopic mouse CRC model was developed to study the effects of MIIP on M2 macrophage polarization and tumor metastasis through the STING-NFκB2-IL10 axis.The therapeutic significance of a STING antagonist was also assessed in vivo.Results:Analyses of The Cancer Genome Atlas(TCGA)cohort and our CRC cohort revealed low MIIP expression is associated with STING pathway activation,increased M2 macrophage infiltration,and poor clinical outcomes.The results of functional experiments demonstrated that MIIP inhibits IL10 production via the STING-TRAF3-NFκB2 axis in CRC cells,suppressing M2 macrophage polarization in co-culture systems.Conversely,M2 macrophages promoted CRC cell migration and invasion in an IL10-dependent manner.In vitro and in vivo studies confirmed that the MIIP-mediated feedback loop between CRC cells and macrophages depends on the STING-NFκB2-IL10 axis.Furthermore,inhibition of STING expression in a mouse model reduced M2 macrophage polarization and tumor metastasis.Conclusions:This study established MIIP as a crucial regulator of macrophage polarization in the CRC tumor microenvironment,providing new insights into the role in suppressing CRC progression and immune-tumor crosstalk.These findings highlight the potential of targeting the STING pathway as a therapeutic strategy for CRC patients who respond poorly to immune checkpoint inhibitors.
