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
Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly can...Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly cancer-associated fibroblasts(CAFs),as a critical determinant of disease behavior.CAFs constitute a heterogeneous population originating from fibroblasts,mesenchymal stem cells,endothelial cells,epithelial cells undergoing epithelial-mesenchymal transition(EMT),and adipose tissue.Through dynamic crosstalk with tumor,immune,endothelial,and adipocyte compartments,CAFs orchestrate oncogenic processes including tumor proliferation,invasion,immune evasion,extracellular matrix remodeling,angiogenesis,and metabolic reprogramming.This review comprehensively summarizes the cellular origins,phenotypic and functional heterogeneity,and spatial distribution of CAFs within the prostate TME.We further elucidate the molecular mechanisms by which CAFs regulate PCa progression and therapeutic resistance,and critically evaluate emerging strategies to therapeutically target CAFmediated signaling,metabolic,and immune pathways.By integrating recent advances from single-cell and spatial transcriptomics(ST),our objective is to provide a holistic framework for understanding CAF biology and to highlight potential avenues for stromal reprogramming as an adjunct to current PCa therapies.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
Lung cancer is the most common but fatal malignant tumor worldwide.Patients with lung cancer experienced a relatively low 5-year overall survival rate,and issues such as metastasis and drug resistance remain prominent...Lung cancer is the most common but fatal malignant tumor worldwide.Patients with lung cancer experienced a relatively low 5-year overall survival rate,and issues such as metastasis and drug resistance remain prominent challenges in its clinical management.Neddylation,a novel type of post-translational modification,was overactivated in lung cancer and was closely associated with its occurrence,development,metastasis,and drug resistance.This review systematically summarizes the biological process of neddylation and deeply explores the latest research progress on how neddylation affects lung cancer cell proliferation,metastasis,and drug resistance mechanisms,with a focus on its regulation of key molecules such as Cullin-RING E3 ligases and the SCCRO family.Meanwhile,it concludes the current advances in potential therapeutic agents targeting neddylation-related targets,including small-molecule compounds(such as Pevonedistat)and natural extracts(such as arctigenin).Finally,the review prospectively evaluates the application potential and questions requiring further exploration of neddylation in lung cancer treatment.In conclusion,we aim to systematically summarize the biological process of neddylation,critically explore its roles in lung cancer proliferation,metastasis,and drug resistance,and evaluate the therapeutic potential of neddylation-targeting agents.展开更多
Realistic models for cancer research representing disease progression that commensurately respond to therapeutics consistent with clinical observation are the holy grail for pre-clinical research and screening.Althoug...Realistic models for cancer research representing disease progression that commensurately respond to therapeutics consistent with clinical observation are the holy grail for pre-clinical research and screening.Although such an ideal is elusive,well-characterized in vivo models facilitate our understanding of disease,progression,and therapeutic opportunities.Here,we characterize a commonly used syngeneic BALB/c mouse model of triple negative breast cancer(4T1)after establishing tumors in their flanks.Tumors developed at the subcutaneous injection site for all experimental mice and their volumes were monitored.We quantified a rare subset of breast cancer stemlike cells(CSCs),classified as CD44^(+)/CD24^(−)phenotypes in in vitro and ex vivo cell populations.Chromosome numbers in ex vivo metaphase cells were greater than cells cultured in vitro(89.4±3.4,range of 70-132 and 82.6±1.1,range of 70-128;respectively).Further,we observed different types of chromosome aberrations,including gap,deletion,exchange,interstitial deletion,terminal deletion,ring,dicentric,and Robertsonian translocations.For both sources of cells,the number of aberrations was dominated by deletions,terminal deletions,and Robertsonian translocations.Ex vivo cells exhibited greater prevalence of deletions and terminal deletions,whereas in vitro cells displayed more ring aberrations and Robertsonian translocations.In conclusion,we successfully characterized cancer cells from a syngeneic mouse model of breast cancer in terms of rare CSC proportion and a variety of chromosomal aberrations,which is useful for understanding tumor traits associated with cancer development and therapeutic action.The data act as a valuable resource for other studies using the 4T1 BALB/c model.展开更多
Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of ...Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.展开更多
For decades,the central dogma of oncology has been that a cancer’s identity is inextricably linked to its anatomical origin.This principle underpins the entire diagnostic and therapeutic framework,from histology-base...For decades,the central dogma of oncology has been that a cancer’s identity is inextricably linked to its anatomical origin.This principle underpins the entire diagnostic and therapeutic framework,from histology-based classification to site-specific treatment guidelines.Yet,this framework catastrophically fails for a substantial population of patients diagnosed with cancer of unknown primary(CUP).These patients present metastatic disease,yet their primary tumors remain elusive despite exhaustive clinical workup1.CUP,accounting for 1%-3%of all cancer diagnoses,is an enigma with devastating consequences;the median overall survival is only 2-12 months2-4.The inability to pinpoint an origin forces clinicians to rely on broad-spectrum empirical chemotherapy,such as taxane-carboplatin regimens,which have limited efficacy and exclude patients from the promise of targeted therapies and clinical trials5.CUP is not only a diagnostic challenge but also an indictment of the siloed approach to understanding malignancy:this cancer highlights the limitations of origin-based diagnostic frameworks.However,the confluence of high-dimensional biological data and advanced artificial intelligence(AI)is now poised to address this long-standing diagnostic limitation and to herald a new era for not only CUP but also oncology as a whole(Figure 1).展开更多
Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations...Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations,and functional implications of RIPK family members across various cancers.Methods:We collected multi-omics data from The Cancer Genome Atlas and other public databases,including gene expression,copy number variation(CNV),mutation,methylation,tumor mutation burden(TMB),and microsatellite instability(MSI).Differential expression and survival analyses were performed using DESeq2 and Cox proportional hazards models.CNV and mutation data were analyzed with GISTIC2 and Mutect2,and methylation data with the ChAMP package.Correlations with TMB and MSI were assessed using Pearson coefficients,and gene set enrichment analysis was conducted with the MSigDB Hallmark gene sets.Results:RIPK family members show significant differential expression in various cancers,with RIPK1 and RIPK4 frequently altered.Survival analysis reveals heterogeneous impacts on overall survival.CNV and mutation analyses identify high alteration frequencies for RIPK2 and RIPK7,affecting gene expression.RIPK1 and RIPK7 are hypermethylated in several cancers,inversely correlating with RIPK3 expression.RIPK1,RIPK2,RIPK5,RIPK6,and RIPK7 correlate positively with TMB,while RIPK3 shows negative correlations in some cancers.MSI analysis indicates associations with DNA mismatch repair.G ene set enrichment analysis highlights immune-related pathway enrichment for RIPK1,RIPK2,RIPK3,and RIPK6,and cell proliferation and DNA repair pathways for RIPK4 and RIPK5.RIPK family members showed heterogeneous alterations across cancers:for example,RIPK7 was mutated in up to~15%of u terine c orpus e ndometrial c arcinoma and l ung s quamous c ell c arcinoma cases,and RIPK1 and RIPK7 exhibited frequent promoter hypermethylation in multiple tumor types.Several genes displayed context-dependent associations with overall survival and with TMB/MSI.Conclusion:This pan-cancer analysis of the RIPK family reveals their diverse roles and potential as biomarkers and therapeutic targets.The findings emphasize the importance of RIPK genes in tumorigenesis and suggest context-dependent functions across cancer types.Further studies are needed to explore their mechanisms in cancer development and clinical applications.展开更多
Objective:To determine whether immunotherapy can bring new hope for patients with limited-stage small-cell lung cancer(LS-SCLC).We conducted this retrospective study to evaluate whether immunotherapy can achieve bette...Objective:To determine whether immunotherapy can bring new hope for patients with limited-stage small-cell lung cancer(LS-SCLC).We conducted this retrospective study to evaluate whether immunotherapy can achieve better efficacy in LS-SCLC patients.Methods:We evaluated 122 LS-SCLC patients who received concurrent chemoradiotherapy(CCRT)or sequential chemoradiotherapy(SCRT)(Group A)and immunotherapy combined with CCRT/SCRT followed by immunotherapy(Group B),to assess the objective response rate(ORR),disease control rate(DCR),and progression-free survival(PFS).Factors affecting prognosis were also explored using Cox analysis.The prognosis of patients with type 2 diabetes and patients with different TNM stages was compared to guide the selection of clinical regimens.Results:The overall ORR was 55.93%.The overall DCR was 98.31%.The DCR was 100%in Group A and 96.61%in Group B.There was no statistical difference in ORR and DCR.The overall median PFS was 9.86 months(95%CI,8.62-11.10),and the difference in median PFS between the two groups was statistically significant(8.94 vs.11.89 months,p=0.03).The Cox regression analysis showed type 2 diabetes was associated with the survival prognosis.Patients with type 2 diabetes tended to choose immunotherapy combined with CCRT/SCRT.Patients in TNM stage IIIB had a significantly worse prognosis than those in stage I+II+IIIA.Conclusion:We suggest that LS-SCLC patients who receive immunotherapy combined with CCRT/SCRT can achieve longer PFS than those with CCRT/SCRT.Type 2 diabetes and TNM stage affect the survival prognosis.Patients with type 2 diabetes may benefit from immunotherapy combination treatments.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
Objectives:Gastric cancer(GC)remains a major global health concern,and Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1),a regulatory subunit of the PI3K signaling pathway,may play a critical yet underexplored ro...Objectives:Gastric cancer(GC)remains a major global health concern,and Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1),a regulatory subunit of the PI3K signaling pathway,may play a critical yet underexplored role in GC progression.This study aimed to investigate the prognostic significance of PIK3R1 in GC and its association with the tumor immune microenvironment.Methods:PIK3R1 expression and its clinical relevance were analyzed using datasets from GC patients who underwent gastrectomy,including cohorts from The Cancer Genome Atlas(TCGA)and the Sun Yat-sen University Cancer Center(SYSUCC).Prognostic models integrating PIK3R1 expression with clinical parameters were constructed for both cohorts.The immune microenvironment associated with PIK3R1 expression was assessed through immunohistochemistry and single-cell RNA sequencing.In vitro assays were conducted to evaluate the effects of PIK3R1 on GC cell proliferation and migration.Results:PIK3R1 was significantly overexpressed in GC tissues and was closely associated with aggressive tumor characteristics and poor clinical outcomes.A nomogram combining PIK3R1 expression with clinicopathological features effectively predicted patient prognosis.Knockdown of PIK3R1 in GC cells reduced proliferation and migration in vitro.Immunological profiling revealed that high PIK3R1 expression correlated with increased infiltration of forkhead box protein P3(Foxp3^(+))and cluster of differentiation 73(CD73^(+))T cells.Patients with low PIK3R1 expression and low CD73^(+)T cell infiltration had significantly better survival.Conclusions:PIK3R1 overexpression is linked to poor prognosis in GC and influences the extent of immune cell infiltration within the tumor microenvironment.A novel prognostic model integrating PIK3R1 and CD73 expression with clinical parameters was established to stratify GC patients into distinct risk groups,offering potential value for personalized therapeutic strategies.展开更多
Neoadjuvant therapy(NAT)has become the standard treatment for patients with locally advanced breast cancer and stage II-III HER2-positive(HER2+)or triple-negative breast cancer(TNBC)1,2.It is essential to accurately m...Neoadjuvant therapy(NAT)has become the standard treatment for patients with locally advanced breast cancer and stage II-III HER2-positive(HER2+)or triple-negative breast cancer(TNBC)1,2.It is essential to accurately mark the primary breast tumor and positive axillary lymph nodes(ALNs)prior to NAT to ensure precise surgical excision,guide axillary downstaging,and guarantee reliable lesion retrieval for pathologic evaluation3.The false-negative rate of sentinel lymph node biopsy(SLNB)after NAT can be reduced to<10%by applying modalities,such as the identification of≥3 sentinel lymph nodes(SLNs)with dual-mapping techniques or removal of the marked lymph node with target axillary dissection(TAD)according to the ASCO,NCCN,and CBCS guidelines3-5.However,there is a lack of consensus regarding the optimal methods and materials for accurate marking6,7.Conventional techniques include clip placement,guidewire localization,and carbon or ink tattooing,whereas wireless technologies,such as MagseedR,radiofrequency identification tags,SAVI SCOUTR,and radioactive iodine-125(125I)seeds,have also been adopted.Traditional marking techniques have a localization failure rate of approximately 10%.In contrast,the use of 125I seeds(with a radiation dose of 0.1-0.3 mCi)has significantly improved localization accuracy8,9.Nevertheless,owing to radioactive properties,concerns have been raised regarding the potential impact of 125I seed marking on assessing the pathologic complete response(pCR)after NAT10.Moreover,whether the influence of 125I seed marking on pCR could lead to suboptimal adjuvant treatment decisions and potentially compromise long-term oncologic outcomes has not been established.To investigate the potential impact of 125I seed placement on the pCR rate and long-term outcomes in breast cancer patients receiving NAT,we conducted a retrospective cohort study utilizing propensity score matching(PSM).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
Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 tr...Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 trial)showed no additional advantage.The PD-RAD study was set up to understand the immunological effects of RT on the tumor microenvironment(TME)to aid in optimizing sequencing of combination therapies.Methods:The PD-RAD trial(ClinicalTrials.gov identifier:NCT03258788)aimed to enroll thirty NSCLC patients receiving radical-intent RT.Tumor biopsies and blood samples were collected pre-RT and at week 2 during RT and analyzed using multiplex immunohistochemistry(mIHC)and high-dimensional mass cytometry(CyTOF),respectively.Results:Paired biopsies were collected from only three patients(Pts 1,3&4)and blood from four patients(Pts 1-4)before the study was closed early during the COVID-19 pandemic.Programmed Death-Ligand 1(PD-L1)expression in the TME was raised in Patient 1,who responded well to treatment,and unaltered in two patients with progressive disease.CyTOF analysis revealed elevated circulating classical monocytes,highest in the patient with a good response.Conclusions:This study underscores the challenges of integrating advanced immune monitoring during RT delivery and did not meet its primary endpoint.The hypothesis-generating findings highlight PD-L1+macrophages in the TME and classical monocytes in the blood as potential immune biomarkers of RT response,but larger studies are needed to validate these observations and characterize the immune changes following curative-intent RT in patients with NSCLC.展开更多
Objectives:Cancer treatment relies heavily on accurate diagnosis and effective monitoring of the disease.These processes often involve invasive procedures,such as colonoscopy,to detect malignant tissues,followed by mo...Objectives:Cancer treatment relies heavily on accurate diagnosis and effective monitoring of the disease.These processes often involve invasive procedures,such as colonoscopy,to detect malignant tissues,followed by molecular analyses to determine relevant biomarkers.This study aimed to evaluate the clinical performance of droplet digital PCR(ddPCR)for detecting Kirsten Rat Sarcoma Viral Proto-Oncogene(KRAS),Neuroblastoma RAS Viral Oncogene Homolog(NRAS),and B-Raf Murine Sarcoma Viral Oncogene Homolog B(BRAF)mutations in circulating tumor DNA(ctDNA)from colorectal cancer patients using liquid biopsy.Methods:ctDNA was isolated from colorectal cancer(CRC)patients(n=110)and analyzed for KRAS,BRAF,and NRAS mutations.The ctDNA obtained through liquid biopsy was analyzed using ddPCR,and the findings were compared with sequencing data from tumor DNA archived in formalin-fixed paraffin-embedded(FFPE)blocks.Results:For KRAS mutations,ddPCR achieved a sensitivity of 72.0%and a specificity of 71.4%.However,when pooling all target mutations(KRAS,NRAS and BRAF),the overall sensitivity and specificity were lower,at 48.3%and 51.1%,respectively.Conclusion:The results of this study indicate that the ddPCR analysis of ctDNA may provide complementary information for the molecular diagnosis of CRC patients.展开更多
Colorectal cancer(CRC), one of the leading causes of cancer-related mortality globally, urgently requires complementary and alternative therapies. Ferroptosis, an iron-dependent form of regulated cell death driven by ...Colorectal cancer(CRC), one of the leading causes of cancer-related mortality globally, urgently requires complementary and alternative therapies. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising anticancer strategy. Dendrobium officinale(D. officinale), a renowned traditional Chinese medicinal herb, is widely used in several Asian countries for its nutritional and therapeutic benefits.Although D. officinale has demonstrated anti-tumor effects, the molecular mechanisms underlying its action against CRC remain incompletely characterized. This study aimed to elucidate the role of D. officinale in suppressing CRC through the induction of ferroptosis and its regulatory effects on glutathione peroxidase 4(GPX4), a key suppressor of ferroptosis. In vitro assays were conducted using HCT116 and SW480 CRC cell lines, and in vivo efficacy was evaluated in BALB/c nude mice bearing CRC xenografts. D. officinale significantly reduced CRC cell viability and proliferation in vitro and suppressed tumor growth in vivo. Induction of ferroptosis was evidenced by elevated levels of Fe^(2+), malondialdehyde(MDA), and lipid peroxidation, along with a depleted glutathione/oxidized glutathione disulfide(GSH/GSSG) ratio. Notably, these effects were reversed by ferroptosis inhibitors, including ferrostatin-1(Fer-1) and deferoxamine. Consistently, D. officinale markedly downregulated GPX4 expression. Overexpression of GPX4 rescued D. officinale-induced ferroptosis, whereas GPX4 silencing exacerbated this effect. D. officinale suppresses CRC by triggering GPX4-dependent ferroptosis,providing a novel, naturally derived therapeutic approach. These findings bridge traditional medicine and modern oncology, establishing a foundation for developing targeted CRC treatments.展开更多
Introduction:Chemotherapy-induced gastrointestinal symptom clusters in breast cancer impair quality of life and treatment adherence,yet lack effective interventions.While acupuncture mitigates isolated chemotherapy-in...Introduction:Chemotherapy-induced gastrointestinal symptom clusters in breast cancer impair quality of life and treatment adherence,yet lack effective interventions.While acupuncture mitigates isolated chemotherapy-induced symptoms,its mechanisms for multi-symptom clusters remain unclear.This study evaluates electroacupuncture's efficacy and explores its biological mechanisms in managing these clusters.Methods:This prospective,multicenter,block-randomized,double-blind,sham-controlled trial will enroll 388 patients with breast cancer undergoing neoadjuvant/adjuvant chemotherapy,to be randomly assigned(1:1)to electroacupuncture or sham electro-acupuncture groups.Both groups will receive the standard quadruple antiemetic regimen combined with electroacupuncture or sham intervention.The primary endpoint is the incidence of chemotherapy-induced gastrointestinal symptom clusters within 120 h after chemotherapy.Secondary endpoints include improvement in gastrointestinal symptom clusters post-first chemotherapy cycle,nausea-free rates during acute and delayed phases,vomiting-free rates during overall,acute,and delayed phases,complete response rate,complete protection rate,and quality of life.Adverse events will be documented throughout the study.Discussion:This study will assess the efficacy and safety of electroacupuncture in alleviating chemotherapy-induced gastro-intestinal symptom clusters in patients with breast cancer.By integrating multi-omics analyses,we aim to elucidate the biological mechanisms underlying its therapeutic effects.The findings may offer a robust clinical foundation for optimizing symptom cluster management in cancer care.Trial Registration:Clinical Trials ID:NCT06952920.Date of registration:April 16,2025.Prospectively registered.URL of Trial Registry Record:https://clinicaltrials.gov/study/NCT06952920cond=NCT06952920&rank=1.展开更多
Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated signi...Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.展开更多
Traditional Chinese medicine(TCM)has garnered increasing attention globally,with its modernization becoming a prominent research focus both within China and internationally.However,the lack of a precise definition for...Traditional Chinese medicine(TCM)has garnered increasing attention globally,with its modernization becoming a prominent research focus both within China and internationally.However,the lack of a precise definition for TCM modernization has hindered clear guidance for its development.Additionally,cancer remains a significant global public health challenge,largely untreatable with current methods.Therefore,a comprehensive understanding of TCM modernization is crucial for its evolution,revolution,drug discovery,and cancer therapy.This study provides an overview of the history,theory,characteristics,and evolution of TCM,highlighting its potential in cancer prevention and treatment.We propose a definition for TCM modernization,innovative Chinese medicine(ICM),and elucidate strategies to elevate TCM from a supporting role to a leading one.Electronic databases such as PubMed,Web of Science,ScienceDirect,and Clinical Trials were utilized to retrieve relevant literature spanning from 1979 to 2024,with most publications being from the last five years,using keywords like“Traditional Chinese medicine”,“Cancer”,“Mechanism”,and“Clinical trial”.In this study,we introduce the theory of TCM modernization following target identification and initial compound screening:ICM,defined by“3 D”elements:definite active ingredient composition and content,determined functional mechanism,and detection through evidence-based medicine.Overall,the“3 D”definition of ICM will establish a standard for ICM,accelerate TCM modernization,enhance drug discovery targeting cancer and various human diseases,and benefit patients worldwide.展开更多
Although the combination of chemotherapy and immunotherapy can improve the treatment of breast cancer,traditional drugs are highly toxic because they do not specifically target tumors.In this study,we developed a self...Although the combination of chemotherapy and immunotherapy can improve the treatment of breast cancer,traditional drugs are highly toxic because they do not specifically target tumors.In this study,we developed a self-driving bacteria/nanoparticle biohybrid called Bif@PDA-aPD1/DOX-Lip by attaching polydopamine(PDA)coated doxorubicin(DOX)liposomes and the immune checkpoint inhibitor anti-programmed cell death protein 1 antibody(aPD-1)to Bifidobacterium infantis(B.infantis,Bif).Using the homing abilities of bacteria,Bif@PDA-aPD1/DOX-Lip could actively accumulate in tumor tissue,releasing DOX and aPD-1 in the acidic environment to have a synergistic anti-tumor effect.Results show that the concentration of DOX in tumors of the Bif@PDA-aPD1/DOX-Lip group was 6.31 times higher than in the free DOX group.The combination of DOX and aPD-1 not only killed tumor cells but also promoted immune normalization by maturing dendritic cells(DCs),increasing M1 macrophage ratio,and enhancing infiltration of CD8+and CD4+T cells in tumors and spleen.Therefore,Bif@PDA-aPD1/DOX-Lip therapy significantly inhibited tumor growth and increased the average survival time of mice to over 80 days.The Bif@PDA-aPD1/DOX-Lip biomotors offer a highly effective method for enhancing chemo-immunotherapy in solid tumors.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Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly cancer-associated fibroblasts(CAFs),as a critical determinant of disease behavior.CAFs constitute a heterogeneous population originating from fibroblasts,mesenchymal stem cells,endothelial cells,epithelial cells undergoing epithelial-mesenchymal transition(EMT),and adipose tissue.Through dynamic crosstalk with tumor,immune,endothelial,and adipocyte compartments,CAFs orchestrate oncogenic processes including tumor proliferation,invasion,immune evasion,extracellular matrix remodeling,angiogenesis,and metabolic reprogramming.This review comprehensively summarizes the cellular origins,phenotypic and functional heterogeneity,and spatial distribution of CAFs within the prostate TME.We further elucidate the molecular mechanisms by which CAFs regulate PCa progression and therapeutic resistance,and critically evaluate emerging strategies to therapeutically target CAFmediated signaling,metabolic,and immune pathways.By integrating recent advances from single-cell and spatial transcriptomics(ST),our objective is to provide a holistic framework for understanding CAF biology and to highlight potential avenues for stromal reprogramming as an adjunct to current PCa therapies.
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(No.82574683)the National Natural Science Foundation of Science and Technology Department of Sichuan Province(Nos.2023NSFSC1928 and 2023NSFSC1992)+2 种基金Project of State Administration of Traditional Chinese Medicine of China(No.ZYYCXTD-D-202209)Project of Sichuan Provincial Administration of Traditional Chinese Medicine(No.2022C001)Fundamental Research Funds for the Central Universities(No.YJ201880).
文摘Lung cancer is the most common but fatal malignant tumor worldwide.Patients with lung cancer experienced a relatively low 5-year overall survival rate,and issues such as metastasis and drug resistance remain prominent challenges in its clinical management.Neddylation,a novel type of post-translational modification,was overactivated in lung cancer and was closely associated with its occurrence,development,metastasis,and drug resistance.This review systematically summarizes the biological process of neddylation and deeply explores the latest research progress on how neddylation affects lung cancer cell proliferation,metastasis,and drug resistance mechanisms,with a focus on its regulation of key molecules such as Cullin-RING E3 ligases and the SCCRO family.Meanwhile,it concludes the current advances in potential therapeutic agents targeting neddylation-related targets,including small-molecule compounds(such as Pevonedistat)and natural extracts(such as arctigenin).Finally,the review prospectively evaluates the application potential and questions requiring further exploration of neddylation in lung cancer treatment.In conclusion,we aim to systematically summarize the biological process of neddylation,critically explore its roles in lung cancer proliferation,metastasis,and drug resistance,and evaluate the therapeutic potential of neddylation-targeting agents.
基金National Research,Development and Innovation Fund of the Ministry of Culture and Innovation under the National Laboratories Program(National Tumor Biology Laboratory,Grant/Award Number:2022-2.1.1-NL-2022-00010)Senior Research Fellowship from National Health and Medical Research Council of Australia,Grant/Award Number:1156693+1 种基金Hungarian Thematic Excellence Program,Grant/Award Number:TKP2021-EGA-44Tour de Cure,Pioneering Grant,Grant/Award Number:RSP-253-18/19。
文摘Realistic models for cancer research representing disease progression that commensurately respond to therapeutics consistent with clinical observation are the holy grail for pre-clinical research and screening.Although such an ideal is elusive,well-characterized in vivo models facilitate our understanding of disease,progression,and therapeutic opportunities.Here,we characterize a commonly used syngeneic BALB/c mouse model of triple negative breast cancer(4T1)after establishing tumors in their flanks.Tumors developed at the subcutaneous injection site for all experimental mice and their volumes were monitored.We quantified a rare subset of breast cancer stemlike cells(CSCs),classified as CD44^(+)/CD24^(−)phenotypes in in vitro and ex vivo cell populations.Chromosome numbers in ex vivo metaphase cells were greater than cells cultured in vitro(89.4±3.4,range of 70-132 and 82.6±1.1,range of 70-128;respectively).Further,we observed different types of chromosome aberrations,including gap,deletion,exchange,interstitial deletion,terminal deletion,ring,dicentric,and Robertsonian translocations.For both sources of cells,the number of aberrations was dominated by deletions,terminal deletions,and Robertsonian translocations.Ex vivo cells exhibited greater prevalence of deletions and terminal deletions,whereas in vitro cells displayed more ring aberrations and Robertsonian translocations.In conclusion,we successfully characterized cancer cells from a syngeneic mouse model of breast cancer in terms of rare CSC proportion and a variety of chromosomal aberrations,which is useful for understanding tumor traits associated with cancer development and therapeutic action.The data act as a valuable resource for other studies using the 4T1 BALB/c model.
文摘Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.
基金supported by the National Natural Science Foundation of China(Grant Nos.32270688,31801117,and 82430107 to X.L.,and 32500589 to H.S.)the China Postdoctoral Science Foundation(Grant Nos.BX20240253 and 2024M762384 to H.S.)+1 种基金the Natural Science Foundation of Tianjin(Grant No.24JCQNJC01280 to H.S.)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-3-003A).
文摘For decades,the central dogma of oncology has been that a cancer’s identity is inextricably linked to its anatomical origin.This principle underpins the entire diagnostic and therapeutic framework,from histology-based classification to site-specific treatment guidelines.Yet,this framework catastrophically fails for a substantial population of patients diagnosed with cancer of unknown primary(CUP).These patients present metastatic disease,yet their primary tumors remain elusive despite exhaustive clinical workup1.CUP,accounting for 1%-3%of all cancer diagnoses,is an enigma with devastating consequences;the median overall survival is only 2-12 months2-4.The inability to pinpoint an origin forces clinicians to rely on broad-spectrum empirical chemotherapy,such as taxane-carboplatin regimens,which have limited efficacy and exclude patients from the promise of targeted therapies and clinical trials5.CUP is not only a diagnostic challenge but also an indictment of the siloed approach to understanding malignancy:this cancer highlights the limitations of origin-based diagnostic frameworks.However,the confluence of high-dimensional biological data and advanced artificial intelligence(AI)is now poised to address this long-standing diagnostic limitation and to herald a new era for not only CUP but also oncology as a whole(Figure 1).
基金supported by grants from the Tianjin Health Technology Project(Grant no.2022QN106).
文摘Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations,and functional implications of RIPK family members across various cancers.Methods:We collected multi-omics data from The Cancer Genome Atlas and other public databases,including gene expression,copy number variation(CNV),mutation,methylation,tumor mutation burden(TMB),and microsatellite instability(MSI).Differential expression and survival analyses were performed using DESeq2 and Cox proportional hazards models.CNV and mutation data were analyzed with GISTIC2 and Mutect2,and methylation data with the ChAMP package.Correlations with TMB and MSI were assessed using Pearson coefficients,and gene set enrichment analysis was conducted with the MSigDB Hallmark gene sets.Results:RIPK family members show significant differential expression in various cancers,with RIPK1 and RIPK4 frequently altered.Survival analysis reveals heterogeneous impacts on overall survival.CNV and mutation analyses identify high alteration frequencies for RIPK2 and RIPK7,affecting gene expression.RIPK1 and RIPK7 are hypermethylated in several cancers,inversely correlating with RIPK3 expression.RIPK1,RIPK2,RIPK5,RIPK6,and RIPK7 correlate positively with TMB,while RIPK3 shows negative correlations in some cancers.MSI analysis indicates associations with DNA mismatch repair.G ene set enrichment analysis highlights immune-related pathway enrichment for RIPK1,RIPK2,RIPK3,and RIPK6,and cell proliferation and DNA repair pathways for RIPK4 and RIPK5.RIPK family members showed heterogeneous alterations across cancers:for example,RIPK7 was mutated in up to~15%of u terine c orpus e ndometrial c arcinoma and l ung s quamous c ell c arcinoma cases,and RIPK1 and RIPK7 exhibited frequent promoter hypermethylation in multiple tumor types.Several genes displayed context-dependent associations with overall survival and with TMB/MSI.Conclusion:This pan-cancer analysis of the RIPK family reveals their diverse roles and potential as biomarkers and therapeutic targets.The findings emphasize the importance of RIPK genes in tumorigenesis and suggest context-dependent functions across cancer types.Further studies are needed to explore their mechanisms in cancer development and clinical applications.
基金funded by the National Natural Science Foundation of China(grant no.82273162)the National Natural Science Foundation of China(grant no.82203272)the Science and Technology Development Foundation of Nanjing Medical University(grant NMUB20240119)。
文摘Objective:To determine whether immunotherapy can bring new hope for patients with limited-stage small-cell lung cancer(LS-SCLC).We conducted this retrospective study to evaluate whether immunotherapy can achieve better efficacy in LS-SCLC patients.Methods:We evaluated 122 LS-SCLC patients who received concurrent chemoradiotherapy(CCRT)or sequential chemoradiotherapy(SCRT)(Group A)and immunotherapy combined with CCRT/SCRT followed by immunotherapy(Group B),to assess the objective response rate(ORR),disease control rate(DCR),and progression-free survival(PFS).Factors affecting prognosis were also explored using Cox analysis.The prognosis of patients with type 2 diabetes and patients with different TNM stages was compared to guide the selection of clinical regimens.Results:The overall ORR was 55.93%.The overall DCR was 98.31%.The DCR was 100%in Group A and 96.61%in Group B.There was no statistical difference in ORR and DCR.The overall median PFS was 9.86 months(95%CI,8.62-11.10),and the difference in median PFS between the two groups was statistically significant(8.94 vs.11.89 months,p=0.03).The Cox regression analysis showed type 2 diabetes was associated with the survival prognosis.Patients with type 2 diabetes tended to choose immunotherapy combined with CCRT/SCRT.Patients in TNM stage IIIB had a significantly worse prognosis than those in stage I+II+IIIA.Conclusion:We suggest that LS-SCLC patients who receive immunotherapy combined with CCRT/SCRT can achieve longer PFS than those with CCRT/SCRT.Type 2 diabetes and TNM stage affect the survival prognosis.Patients with type 2 diabetes may benefit from immunotherapy combination treatments.
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.
基金supported by the National Natural Science Foundation of China(grant no.81602426).
文摘Objectives:Gastric cancer(GC)remains a major global health concern,and Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1),a regulatory subunit of the PI3K signaling pathway,may play a critical yet underexplored role in GC progression.This study aimed to investigate the prognostic significance of PIK3R1 in GC and its association with the tumor immune microenvironment.Methods:PIK3R1 expression and its clinical relevance were analyzed using datasets from GC patients who underwent gastrectomy,including cohorts from The Cancer Genome Atlas(TCGA)and the Sun Yat-sen University Cancer Center(SYSUCC).Prognostic models integrating PIK3R1 expression with clinical parameters were constructed for both cohorts.The immune microenvironment associated with PIK3R1 expression was assessed through immunohistochemistry and single-cell RNA sequencing.In vitro assays were conducted to evaluate the effects of PIK3R1 on GC cell proliferation and migration.Results:PIK3R1 was significantly overexpressed in GC tissues and was closely associated with aggressive tumor characteristics and poor clinical outcomes.A nomogram combining PIK3R1 expression with clinicopathological features effectively predicted patient prognosis.Knockdown of PIK3R1 in GC cells reduced proliferation and migration in vitro.Immunological profiling revealed that high PIK3R1 expression correlated with increased infiltration of forkhead box protein P3(Foxp3^(+))and cluster of differentiation 73(CD73^(+))T cells.Patients with low PIK3R1 expression and low CD73^(+)T cell infiltration had significantly better survival.Conclusions:PIK3R1 overexpression is linked to poor prognosis in GC and influences the extent of immune cell infiltration within the tumor microenvironment.A novel prognostic model integrating PIK3R1 and CD73 expression with clinical parameters was established to stratify GC patients into distinct risk groups,offering potential value for personalized therapeutic strategies.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82573747,82172873,W2421095,and 82503888)National Science and Technology Major Project(Grant No.2025ZD0543900)+2 种基金Natural Science Foundation of Shandong Province(Grant Nos.ZR2024LMB011 and ZR2024QH058)Taishan Scholars Program of Shandong Province(Grant No.tsqn202211337)Collaborative Academic Innovation Project of Shandong Cancer Hospital(Grant No.GF003).
文摘Neoadjuvant therapy(NAT)has become the standard treatment for patients with locally advanced breast cancer and stage II-III HER2-positive(HER2+)or triple-negative breast cancer(TNBC)1,2.It is essential to accurately mark the primary breast tumor and positive axillary lymph nodes(ALNs)prior to NAT to ensure precise surgical excision,guide axillary downstaging,and guarantee reliable lesion retrieval for pathologic evaluation3.The false-negative rate of sentinel lymph node biopsy(SLNB)after NAT can be reduced to<10%by applying modalities,such as the identification of≥3 sentinel lymph nodes(SLNs)with dual-mapping techniques or removal of the marked lymph node with target axillary dissection(TAD)according to the ASCO,NCCN,and CBCS guidelines3-5.However,there is a lack of consensus regarding the optimal methods and materials for accurate marking6,7.Conventional techniques include clip placement,guidewire localization,and carbon or ink tattooing,whereas wireless technologies,such as MagseedR,radiofrequency identification tags,SAVI SCOUTR,and radioactive iodine-125(125I)seeds,have also been adopted.Traditional marking techniques have a localization failure rate of approximately 10%.In contrast,the use of 125I seeds(with a radiation dose of 0.1-0.3 mCi)has significantly improved localization accuracy8,9.Nevertheless,owing to radioactive properties,concerns have been raised regarding the potential impact of 125I seed marking on assessing the pathologic complete response(pCR)after NAT10.Moreover,whether the influence of 125I seed marking on pCR could lead to suboptimal adjuvant treatment decisions and potentially compromise long-term oncologic outcomes has not been established.To investigate the potential impact of 125I seed placement on the pCR rate and long-term outcomes in breast cancer patients receiving NAT,we conducted a retrospective cohort study utilizing propensity score matching(PSM).
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.
基金the National Institute for Health and Care Research(NHR)Manchester Biomedical Research Centre(BRC)(NIHR203308,NIHR-BRC-1215-20007)Astra-Zeneca(ESR-14-10711)+2 种基金CRUK RadNet(C19941/A27801)TMI and CFF are the recipient of an NIHR Senior Investigator Award(NIHR205054 and NIHR205061)CTH is supported by the NIHR University College London Hospitals NHS Foundation Trust BRC,the City of London CRUK RadNet and the CRUK Lung Cancer Centre of Excellence.
文摘Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 trial)showed no additional advantage.The PD-RAD study was set up to understand the immunological effects of RT on the tumor microenvironment(TME)to aid in optimizing sequencing of combination therapies.Methods:The PD-RAD trial(ClinicalTrials.gov identifier:NCT03258788)aimed to enroll thirty NSCLC patients receiving radical-intent RT.Tumor biopsies and blood samples were collected pre-RT and at week 2 during RT and analyzed using multiplex immunohistochemistry(mIHC)and high-dimensional mass cytometry(CyTOF),respectively.Results:Paired biopsies were collected from only three patients(Pts 1,3&4)and blood from four patients(Pts 1-4)before the study was closed early during the COVID-19 pandemic.Programmed Death-Ligand 1(PD-L1)expression in the TME was raised in Patient 1,who responded well to treatment,and unaltered in two patients with progressive disease.CyTOF analysis revealed elevated circulating classical monocytes,highest in the patient with a good response.Conclusions:This study underscores the challenges of integrating advanced immune monitoring during RT delivery and did not meet its primary endpoint.The hypothesis-generating findings highlight PD-L1+macrophages in the TME and classical monocytes in the blood as potential immune biomarkers of RT response,but larger studies are needed to validate these observations and characterize the immune changes following curative-intent RT in patients with NSCLC.
基金funded by the Ministry of Health of the Czech Republic—conceptual development of research organization(MMCI,00209805)Czech Science Foundation(No.25-15990S)+1 种基金the project 7D241003 EUREKA EUROSTARS35897,project SALVAGE(P JAC,reg.No.CZ.02.01.01/00/22_008/0004644)—funded by the European Unionby the State Budget of the Czech Republic,and by the LRI project BBMRI.cz(Nos.LM2023033 and CZ.02.1.01/0.0/0.0/16_013/0001674.).
文摘Objectives:Cancer treatment relies heavily on accurate diagnosis and effective monitoring of the disease.These processes often involve invasive procedures,such as colonoscopy,to detect malignant tissues,followed by molecular analyses to determine relevant biomarkers.This study aimed to evaluate the clinical performance of droplet digital PCR(ddPCR)for detecting Kirsten Rat Sarcoma Viral Proto-Oncogene(KRAS),Neuroblastoma RAS Viral Oncogene Homolog(NRAS),and B-Raf Murine Sarcoma Viral Oncogene Homolog B(BRAF)mutations in circulating tumor DNA(ctDNA)from colorectal cancer patients using liquid biopsy.Methods:ctDNA was isolated from colorectal cancer(CRC)patients(n=110)and analyzed for KRAS,BRAF,and NRAS mutations.The ctDNA obtained through liquid biopsy was analyzed using ddPCR,and the findings were compared with sequencing data from tumor DNA archived in formalin-fixed paraffin-embedded(FFPE)blocks.Results:For KRAS mutations,ddPCR achieved a sensitivity of 72.0%and a specificity of 71.4%.However,when pooling all target mutations(KRAS,NRAS and BRAF),the overall sensitivity and specificity were lower,at 48.3%and 51.1%,respectively.Conclusion:The results of this study indicate that the ddPCR analysis of ctDNA may provide complementary information for the molecular diagnosis of CRC patients.
基金supported by the Department of Education of Guangdong Province (No.2023KTSCX024)the Project of Traditional Chinese Medicine Bureau of Guangdong Province(No.20251091)+3 种基金the Joint Funds of the National Natural Science Foundation of China (No.U22A20368)the Key-Area Research and Development Program of Guangdong Province (No.2020B1111100004)Guangdong Basic and Applied Basic Research Foundation (No.2020B1515130005)Shenzhen Baoan District Science and Technology Innovation Bureau Project(Nos.2022JD226 and 2023JD252)。
文摘Colorectal cancer(CRC), one of the leading causes of cancer-related mortality globally, urgently requires complementary and alternative therapies. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising anticancer strategy. Dendrobium officinale(D. officinale), a renowned traditional Chinese medicinal herb, is widely used in several Asian countries for its nutritional and therapeutic benefits.Although D. officinale has demonstrated anti-tumor effects, the molecular mechanisms underlying its action against CRC remain incompletely characterized. This study aimed to elucidate the role of D. officinale in suppressing CRC through the induction of ferroptosis and its regulatory effects on glutathione peroxidase 4(GPX4), a key suppressor of ferroptosis. In vitro assays were conducted using HCT116 and SW480 CRC cell lines, and in vivo efficacy was evaluated in BALB/c nude mice bearing CRC xenografts. D. officinale significantly reduced CRC cell viability and proliferation in vitro and suppressed tumor growth in vivo. Induction of ferroptosis was evidenced by elevated levels of Fe^(2+), malondialdehyde(MDA), and lipid peroxidation, along with a depleted glutathione/oxidized glutathione disulfide(GSH/GSSG) ratio. Notably, these effects were reversed by ferroptosis inhibitors, including ferrostatin-1(Fer-1) and deferoxamine. Consistently, D. officinale markedly downregulated GPX4 expression. Overexpression of GPX4 rescued D. officinale-induced ferroptosis, whereas GPX4 silencing exacerbated this effect. D. officinale suppresses CRC by triggering GPX4-dependent ferroptosis,providing a novel, naturally derived therapeutic approach. These findings bridge traditional medicine and modern oncology, establishing a foundation for developing targeted CRC treatments.
基金Noncommunicable Chronic Diseases-National Science and Technology Major Project,Grant/Award Numbers:2024ZD0521400,2024ZD0521404Affiliated Hospital of Qinghai University。
文摘Introduction:Chemotherapy-induced gastrointestinal symptom clusters in breast cancer impair quality of life and treatment adherence,yet lack effective interventions.While acupuncture mitigates isolated chemotherapy-induced symptoms,its mechanisms for multi-symptom clusters remain unclear.This study evaluates electroacupuncture's efficacy and explores its biological mechanisms in managing these clusters.Methods:This prospective,multicenter,block-randomized,double-blind,sham-controlled trial will enroll 388 patients with breast cancer undergoing neoadjuvant/adjuvant chemotherapy,to be randomly assigned(1:1)to electroacupuncture or sham electro-acupuncture groups.Both groups will receive the standard quadruple antiemetic regimen combined with electroacupuncture or sham intervention.The primary endpoint is the incidence of chemotherapy-induced gastrointestinal symptom clusters within 120 h after chemotherapy.Secondary endpoints include improvement in gastrointestinal symptom clusters post-first chemotherapy cycle,nausea-free rates during acute and delayed phases,vomiting-free rates during overall,acute,and delayed phases,complete response rate,complete protection rate,and quality of life.Adverse events will be documented throughout the study.Discussion:This study will assess the efficacy and safety of electroacupuncture in alleviating chemotherapy-induced gastro-intestinal symptom clusters in patients with breast cancer.By integrating multi-omics analyses,we aim to elucidate the biological mechanisms underlying its therapeutic effects.The findings may offer a robust clinical foundation for optimizing symptom cluster management in cancer care.Trial Registration:Clinical Trials ID:NCT06952920.Date of registration:April 16,2025.Prospectively registered.URL of Trial Registry Record:https://clinicaltrials.gov/study/NCT06952920cond=NCT06952920&rank=1.
文摘Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.
基金supported by the National Natural Science Foundation of China(No.82203343)the National Postdoctoral Program for Innovative Talents of China(No.BX20220273)+3 种基金China Postdoctoral Science Foundation(No.2022M712874)Henan Province Key Research and Development Promotion Special Project(Science and Technology)in 2023(No.232102311007)Henan Province Key Scientific Research Project of Colleges and Universities in 2023(No.23A310007)the Outstanding Youth Project of Henan Provincial Natural Science Foundation(No.252300421123)。
文摘Traditional Chinese medicine(TCM)has garnered increasing attention globally,with its modernization becoming a prominent research focus both within China and internationally.However,the lack of a precise definition for TCM modernization has hindered clear guidance for its development.Additionally,cancer remains a significant global public health challenge,largely untreatable with current methods.Therefore,a comprehensive understanding of TCM modernization is crucial for its evolution,revolution,drug discovery,and cancer therapy.This study provides an overview of the history,theory,characteristics,and evolution of TCM,highlighting its potential in cancer prevention and treatment.We propose a definition for TCM modernization,innovative Chinese medicine(ICM),and elucidate strategies to elevate TCM from a supporting role to a leading one.Electronic databases such as PubMed,Web of Science,ScienceDirect,and Clinical Trials were utilized to retrieve relevant literature spanning from 1979 to 2024,with most publications being from the last five years,using keywords like“Traditional Chinese medicine”,“Cancer”,“Mechanism”,and“Clinical trial”.In this study,we introduce the theory of TCM modernization following target identification and initial compound screening:ICM,defined by“3 D”elements:definite active ingredient composition and content,determined functional mechanism,and detection through evidence-based medicine.Overall,the“3 D”definition of ICM will establish a standard for ICM,accelerate TCM modernization,enhance drug discovery targeting cancer and various human diseases,and benefit patients worldwide.
基金supported by the Science and Technology Strategic Cooperation Programs of Luzhou Municipal People's Government and Southwest Medical University(No.2024LZXNYDJ017)the Project Program of the Science and Technology Department of Sichuan Province(No.2025zNSFSC0679)the Project Program of Chongqing Science and Technology Bureau(No.cstc2020jcyjmsxmX1037).
文摘Although the combination of chemotherapy and immunotherapy can improve the treatment of breast cancer,traditional drugs are highly toxic because they do not specifically target tumors.In this study,we developed a self-driving bacteria/nanoparticle biohybrid called Bif@PDA-aPD1/DOX-Lip by attaching polydopamine(PDA)coated doxorubicin(DOX)liposomes and the immune checkpoint inhibitor anti-programmed cell death protein 1 antibody(aPD-1)to Bifidobacterium infantis(B.infantis,Bif).Using the homing abilities of bacteria,Bif@PDA-aPD1/DOX-Lip could actively accumulate in tumor tissue,releasing DOX and aPD-1 in the acidic environment to have a synergistic anti-tumor effect.Results show that the concentration of DOX in tumors of the Bif@PDA-aPD1/DOX-Lip group was 6.31 times higher than in the free DOX group.The combination of DOX and aPD-1 not only killed tumor cells but also promoted immune normalization by maturing dendritic cells(DCs),increasing M1 macrophage ratio,and enhancing infiltration of CD8+and CD4+T cells in tumors and spleen.Therefore,Bif@PDA-aPD1/DOX-Lip therapy significantly inhibited tumor growth and increased the average survival time of mice to over 80 days.The Bif@PDA-aPD1/DOX-Lip biomotors offer a highly effective method for enhancing chemo-immunotherapy in solid tumors.
