Objective: The recurrence and progression of ameloblastoma are unpredictable. Therefore, we examined the influence of clinical factors on recurrence time and analyzed the clinical factors associated with early recurre...Objective: The recurrence and progression of ameloblastoma are unpredictable. Therefore, we examined the influence of clinical factors on recurrence time and analyzed the clinical factors associated with early recurrence and cancerization. We then developed a staging system to predict early recurrence and cancerization. Methods: All of the primary craniofacial ameloblastoma patients treated in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine were recorded. There were 87 recurrent cases used to create a staging system and tested in a Cox regression analysis for risk factors associated with early recurrence or cancerization following surgery. Results: There were 890 craniofacial ameloblastoma patients, and 72 cases had recurrence. There were also 15 cases with cancerous recurrence. The overall recurrence rate was 9.78%, and the cancer rate was 1.69%. The primary cases were classified into the following 3 stages based on clinicopathological features: stage I, the maximum tumor diameter <= 6 cm; stage II, the maximum diameter of tumor >6 cm or tumor invasion to the maxilla sinus/orbital floor/soft tissue; and stage III, tumor invasion of the skull base or metastasis into regional lymph nodes. When the method of surgery was controlled by partial correlation, the staging had significance with recurrence time (P=0.004). The Cox analysis showed the tumor stage was correlated with recurrence time (P=0.027) and cancerization time (P=0.002). However, the surgical method did not influence the recurrence time when adjusted for cofounding variables. Conclusions: Tumor larger than 6 cm and invasion to soft tissues or adjacent anatomical structures are associated with early recurrence. This staging system can be used to predict the risk factors of early recurrence and cancerization in ameloblastoma patients.展开更多
Objective : To investigate the role and clinical significance of p16 protein in Condyloma Acuminatum (CA) and its cancerization. Methods: The expression of p16 protein was tested in 33 CA samples and 7 cancerized CA s...Objective : To investigate the role and clinical significance of p16 protein in Condyloma Acuminatum (CA) and its cancerization. Methods: The expression of p16 protein was tested in 33 CA samples and 7 cancerized CA samples by immunohistochemical assays. Results: There was abnormal expression of p16 protein in CA and cancerized CA, mainly major protein expression. The p16 protein expresseed in different locations in different cases was as follows: In basal layer cells in normal cuits; in spinous layer, granular layer and stratum corneum layer cells in CA;in keratin pearl peripheral and spinous layer cells in cancerized CA. Conclusion.. There was major expression of p16 protein in CA and cancerized CA, and these protein of the two groups might not naturally be the same. Our study indicated that in clinical practice, when major p16 protein expression in CA occurs, it's risk of cancerization shoud be suspected.展开更多
While actinic keratoses(AKs) have been considered precancerous until recently for being able to turn into squamous cell carcinomas(SCCs), it is now agreed that it would be more appropriate to call them cancerous. Alth...While actinic keratoses(AKs) have been considered precancerous until recently for being able to turn into squamous cell carcinomas(SCCs), it is now agreed that it would be more appropriate to call them cancerous. Although not all AKs turn into SCC and some of them may even have a spontaneous regression, there is an obvious association between SCC and AK. Approximately 90% of SCs have been reported to develop from AKs and AKs are the preinvasive form of SCCs. The presence of two or more AKs on a photodamaged skin is an indicator of field cancerization and represents an increased risk of invasive SCC. All lesions should be treated since it cannot be foreseen which of the lesions will regress and which will progress to SCC. AK can be a single lesion or it can involve multiple lesions in a field of cancerization; thus, AK treatment is grouped under two headings:(1) Lesion-specific treatment; and (2) Field-targeted treatment. Lesion-specific treatments are practicable in patients with a small number of clinically visible and isolated lesions. These treatments including cryotherapy, surgical excision, shave excision, curettage and laser are based on physical destruction of the visible lesions. Field-targeted treatments are effective in the treatment of visible lesions, subclinical lesions and keratinocyte changes in the areas surrounding the visible lesions. Field targeted treatment options are topical imiquimod cream, 5% 5-fluorouracil cream, ingenol mebutate, diclofenac gel, resimiquimod and photodynamic therapy.展开更多
Cancer pain is one of the most prevalent and debilitating symptoms in patients with advanced malignancies,arising from multifactorial mechanisms involving peripheral,central,and systemic pathways.Conventional analgesi...Cancer pain is one of the most prevalent and debilitating symptoms in patients with advanced malignancies,arising from multifactorial mechanisms involving peripheral,central,and systemic pathways.Conventional analgesics,including opioids and nonsteroidal anti-inflammatory drugs,are often limited by their insufficient efficacy,tolerance,and risk of dependence.Traditional Chinese Medicine(TCM),characterized by its multi-component,multi-target,and systemic regulatory properties,has shown promising potential in cancer pain management.This review provides a comprehensive overview of the clinical classification and underlying mechanisms of cancer pain(including nerve infiltration,dysregulation of inflammatory mediators and ion channels,central sensitization,neuro-immune crosstalk,metabolic reprogramming,and gut-brain axis impairment),as well as the analgesic effects of representative TCM agents in cancer pain management.For example,bioactive components such as tetrahydroberberine,levo-tetrahydropalmatine,and piperine exert analgesic effects,thereby improving the quality of life of patients by inhibiting inflammatory cascades,regulating neurotransmitter systems,and preserving neural integrity.Commonly used preclinical models,including bone cancer pain,pancreatic cancer pain,and chemotherapy-induced peripheral neuropathy models,are summarized for their utility in mechanistic studies and efficacy evaluations.This review also discusses the current limitations of clinical evidence,such as small sample sizes,short follow-up periods,and limited translation from animal models,alongside major challenges in standardization,mechanistic elucidation,and clinical trial design.Future directions should focus on precise pain phenotyping,integrated multi-target interventions,rigorous efficacy safety validation,and innovations in drug delivery to facilitate the standardization and global adoption of TCM in cancer pain management.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
According to the 2024 global cancer data from GLOBOCAN,liver cancer ranks the 6th most common malignancy and the 3rd leading cause of cancer-related mortality worldwide[1].Among these cases,hepatocellular carcinoma(HC...According to the 2024 global cancer data from GLOBOCAN,liver cancer ranks the 6th most common malignancy and the 3rd leading cause of cancer-related mortality worldwide[1].Among these cases,hepatocellular carcinoma(HCC)accounts for approximately 85%−90%[2,3].Its incidence and mortality rates remain persistently high worldwide.However,China has the highest incidence and mortality rates of the disease in the world[4].And the majority of patients are diagnosed at intermediate or advanced stages.Thus,identifying novel tumor biomarkers for early detection and implementing precision therapy has long been a key focus of research.展开更多
Artificial intelligence(AI)is transforming the diagnostic landscape of malignant tumors in the urinary system,including prostate cancer,bladder cancer,and renal cell carcinoma(RCC).By integrating imaging,pathology,and...Artificial intelligence(AI)is transforming the diagnostic landscape of malignant tumors in the urinary system,including prostate cancer,bladder cancer,and renal cell carcinoma(RCC).By integrating imaging,pathology,and molecular data,AI enhances the precision and reproducibility of tumor detection,grading,and risk stratification.In prostate cancer,AI-assisted multiparametric Magnetic resonance imaging(MRI)and digital pathology systems improve lesion localization and Gleason scoring.For bladder cancer,deep learning-based cystoscopy and radiomics models from Computed tomography/magnetic resonance imaging(CT/MRI)enable real-time lesion segmentation and non-invasive biomarker prediction,such as Programmed Cell Death-Ligand 1(PD-L1)expression.In RCC,AI,combined with CT/MRI and multi-omics data,aids in subtype classification and prognostic prediction,supporting personalized therapy.However,despite these promising advances,challenges such as data standardization,model generalizability,interpretability,and regulatory compliance hinder AI’s clinical translation.This review outlines the current state of AI in urological cancer diagnosis and prognosis,its technological innovations,and the clinical challenges and opportunities that lie ahead.展开更多
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:In clinical practice,approximately 80%of prostate cancer(PC)cases are localized and can achieve favorable outcomes with appropriate treatment.Conversely,some remaining cases exhibit an aggressive phenotype ...Background:In clinical practice,approximately 80%of prostate cancer(PC)cases are localized and can achieve favorable outcomes with appropriate treatment.Conversely,some remaining cases exhibit an aggressive phenotype or develop resistance to therapeutic interventions,leading to tumor metastasis and a poorer prognosis.When PC metastasizes to distant sites,the bone remains the predominant location,and brain metastases are regarded as exceedingly rare.Case Description:The current study focused on a rare clinical PC case that presented multiple brain metastases after prostate surgery.The patient was initially diagnosed with PC through prostate biopsy and subsequently underwent prostate debulking surgery while continuing androgen deprivation therapy,which maintained low prostatespecific antigen(PSA)levels for 4 years.However,a sudden PSA surge to 7.858 ng/mL led to the emergence of two brain metastatic tumors,which were confirmed to have originated from the prostate.Conclusions:Patients with advanced PC require comprehensive evaluations to detect rare metastatic sites,such as the brain,to avoid missed diagnoses.For patients with brain metastases,a multimodal approach combining surgical resection,postoperative radiotherapy,and endocrine therapy can effectively alleviate symptoms and enhance survival.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
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 is the third most common cancer worldwide and arises secondary to the progressive accumulation of genetic and epigenetic alterations in normal colon cells,which results in a polyp-to-cancer progressi...Colorectal cancer is the third most common cancer worldwide and arises secondary to the progressive accumulation of genetic and epigenetic alterations in normal colon cells,which results in a polyp-to-cancer progression sequence.It is known that individuals with a personal history of colon adenomas or cancer are at increased risk for metachronous colon neoplasms.One explanation for this increased risk could be field cancerization,which is a phenomenon in which the histologically normal tissue in an organ is primed to undergo transformation.Epigenetic alterations appear to be promising markers for field cancerization.In this review,we discuss field cancerization in the colon and the data supporting the use of methylated DNA as a biomarker for this phenomenon.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
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
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
BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.A...BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.AIM To determine the incidence of depression and its independent risk factors in patients with esophageal cancer and bone metastasis.METHODS A total of 100 consecutive eligible patients admitted between March 2022 and March 2025 were recruited.Depression was assessed with the Beck Depression Inventory-II;scores>4 defined the depression group(n=42)and scores≤4 the non-depression group(n=58).Demographic,clinical,and laboratory variables were compared between the groups.Multivariate logistic regression was used to identify independent risk factors.RESULTS Depression prevalence was 42.0%(42/100).Univariate analysis demonstrated significant differences in monthly per-capita household income,education level,social support,sleep disorders,and serum high-sensitivity C-reactive protein(all P<0.05);no differences were observed in sex,age,tumor characteristics,or other laboratory indices(all P>0.05).Multivariable analysis revealed the following independent risk factors for depression:Low income[odds ratio(OR)=2.66,95%confidence interval(CI):1.17-6.03],low education(OR=2.46,95%CI:1.08-5.61),low social support(OR=5.10,95%CI:1.81-14.39),sleep disorders(OR=2.79,95%CI:1.23-6.35),and elevated high-sensitivity C-reactive protein(OR=1.31 per unit increase,95%CI:1.18-1.46).CONCLUSION Depression is common among patients with esophageal cancer and bone metastasis.Low socioeconomic status,limited education,insufficient social support,sleep disturbances,and systemic inflammation were independent predictors.Interventions that address these modifiable factors may reduce depression risk in this population.展开更多
Objectives:Tamoxifen is a key drug that provides endocrine therapy for estrogen receptor(ER)α-positive breast cancer;however,resistance remains a significant clinical challenge.This study aims to investigate the mole...Objectives:Tamoxifen is a key drug that provides endocrine therapy for estrogen receptor(ER)α-positive breast cancer;however,resistance remains a significant clinical challenge.This study aims to investigate the molecular mechanisms of tamoxifen resistance in ERα-positive breast cancer,with particular focus on the role of SET Domain Containing 1A(SETD1A)-driven forkhead box A2(FOXA2)as a key regulator of this resistance.Methods:FOXA2 expression and its regulation by SETD1A were assessed via(quantitative polymerase chain reaction),western blotting,transcriptome profiling,and chromatin immunoprecipitation analyses.The effects of FOXA2 on cell proliferation,migration,invasion,and cancer stem cell traits were evaluated using small interfering RNA(siRNA)-mediated silencing.Clinical relevance was examined by analyzing patient datasets and tumor tissue microarrays.Results:FOXA2 expression was significantly elevated in tamoxifen-resistant(TamR)and ERα-negative breast cancer cells compared to that in ERα-positive MCF-7 cells,regardless of tamoxifen treatment or ERαdepletion.Transcriptome and chromatin immunoprecipitation analyses revealed that SETD1A,a histone methyltransferase,directly regulated FOXA2 expression.Functionally,FOXA2 knockdown inhibited the proliferation,migration,invasion,and cancer stem cell properties of TamR cells while restoring tamoxifen sensitivity.High FOXA2 expression was correlated with poor survival and reduced responsiveness to tamoxifen in patients with ER-positive breast cancer.Conclusion:Our findings identified FOXA2 as a key mediator of tamoxifen resistance regulated by SETD1A and suggested that targeting the SETD1A-FOXA2 axis may offer a novel strategy for overcoming endocrine resistance in breast cancer.展开更多
Parasitic infections are increasingly recognized as contributors to cancer development,yet the underlying oncogenic mechanisms remain insufficiently understood.Growing evidence from molecular oncology,immunology,and m...Parasitic infections are increasingly recognized as contributors to cancer development,yet the underlying oncogenic mechanisms remain insufficiently understood.Growing evidence from molecular oncology,immunology,and microbiome research suggests that chronic parasitic infections may drive tumorigenesis through sustained inflammation,deregulated signaling pathways,genomic instability,and the release of parasite-derived exosomes that reshape the tumor microenvironment.These insights underscore the need to integrate parasitology with cancer biology to understand infection-associated malignancies better.The aim of this narrative review is to synthesize current knowledge on how selected parasites contribute to cancer development and to highlight emerging therapeutic and diagnostic opportunities.We examine pathogens such as Schistosoma haematobium,Opisthorchis viverrini,Toxoplasma gondii,Plasmodium falciparum,and Leishmania spp.,detailing their roles in chronic inflammation,immune modulation,and interactions with tumor-associated immune cells.The review further discusses parasite-induced immunosuppression,coinfections,and their cumulative impact on cancer risk.Additionally,we explore novel therapeutic approaches,including pathway inhibitors,epigenetic drugs,microbiome modulation,and engineered parasites.Future perspectives emphasize parasite-based immunotherapies,long-term epigenetic consequences of infection,and AI-driven multiomics strategies for identifying oncogenic signatures.This review integrates advances from parasitology and oncology to provide new insights into biomarkers,targeted therapies,and mechanisms of infection-induced tumorigenesis.The literature search covered studies indexed in PubMed,Scopus,and Web of Science up to July 2025.展开更多
基金supported by grants from the National Natural Science Foundation of China (No. 81672745, 81671009)projects of the Shanghai Natural Science Foundation (No. 15ZR1424600)Shanghai Summit & Plateau Disciplines
文摘Objective: The recurrence and progression of ameloblastoma are unpredictable. Therefore, we examined the influence of clinical factors on recurrence time and analyzed the clinical factors associated with early recurrence and cancerization. We then developed a staging system to predict early recurrence and cancerization. Methods: All of the primary craniofacial ameloblastoma patients treated in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine were recorded. There were 87 recurrent cases used to create a staging system and tested in a Cox regression analysis for risk factors associated with early recurrence or cancerization following surgery. Results: There were 890 craniofacial ameloblastoma patients, and 72 cases had recurrence. There were also 15 cases with cancerous recurrence. The overall recurrence rate was 9.78%, and the cancer rate was 1.69%. The primary cases were classified into the following 3 stages based on clinicopathological features: stage I, the maximum tumor diameter <= 6 cm; stage II, the maximum diameter of tumor >6 cm or tumor invasion to the maxilla sinus/orbital floor/soft tissue; and stage III, tumor invasion of the skull base or metastasis into regional lymph nodes. When the method of surgery was controlled by partial correlation, the staging had significance with recurrence time (P=0.004). The Cox analysis showed the tumor stage was correlated with recurrence time (P=0.027) and cancerization time (P=0.002). However, the surgical method did not influence the recurrence time when adjusted for cofounding variables. Conclusions: Tumor larger than 6 cm and invasion to soft tissues or adjacent anatomical structures are associated with early recurrence. This staging system can be used to predict the risk factors of early recurrence and cancerization in ameloblastoma patients.
文摘Objective : To investigate the role and clinical significance of p16 protein in Condyloma Acuminatum (CA) and its cancerization. Methods: The expression of p16 protein was tested in 33 CA samples and 7 cancerized CA samples by immunohistochemical assays. Results: There was abnormal expression of p16 protein in CA and cancerized CA, mainly major protein expression. The p16 protein expresseed in different locations in different cases was as follows: In basal layer cells in normal cuits; in spinous layer, granular layer and stratum corneum layer cells in CA;in keratin pearl peripheral and spinous layer cells in cancerized CA. Conclusion.. There was major expression of p16 protein in CA and cancerized CA, and these protein of the two groups might not naturally be the same. Our study indicated that in clinical practice, when major p16 protein expression in CA occurs, it's risk of cancerization shoud be suspected.
文摘While actinic keratoses(AKs) have been considered precancerous until recently for being able to turn into squamous cell carcinomas(SCCs), it is now agreed that it would be more appropriate to call them cancerous. Although not all AKs turn into SCC and some of them may even have a spontaneous regression, there is an obvious association between SCC and AK. Approximately 90% of SCs have been reported to develop from AKs and AKs are the preinvasive form of SCCs. The presence of two or more AKs on a photodamaged skin is an indicator of field cancerization and represents an increased risk of invasive SCC. All lesions should be treated since it cannot be foreseen which of the lesions will regress and which will progress to SCC. AK can be a single lesion or it can involve multiple lesions in a field of cancerization; thus, AK treatment is grouped under two headings:(1) Lesion-specific treatment; and (2) Field-targeted treatment. Lesion-specific treatments are practicable in patients with a small number of clinically visible and isolated lesions. These treatments including cryotherapy, surgical excision, shave excision, curettage and laser are based on physical destruction of the visible lesions. Field-targeted treatments are effective in the treatment of visible lesions, subclinical lesions and keratinocyte changes in the areas surrounding the visible lesions. Field targeted treatment options are topical imiquimod cream, 5% 5-fluorouracil cream, ingenol mebutate, diclofenac gel, resimiquimod and photodynamic therapy.
基金supported by the National Natural Science Foundation of China(No.82360238,82071245)。
文摘Cancer pain is one of the most prevalent and debilitating symptoms in patients with advanced malignancies,arising from multifactorial mechanisms involving peripheral,central,and systemic pathways.Conventional analgesics,including opioids and nonsteroidal anti-inflammatory drugs,are often limited by their insufficient efficacy,tolerance,and risk of dependence.Traditional Chinese Medicine(TCM),characterized by its multi-component,multi-target,and systemic regulatory properties,has shown promising potential in cancer pain management.This review provides a comprehensive overview of the clinical classification and underlying mechanisms of cancer pain(including nerve infiltration,dysregulation of inflammatory mediators and ion channels,central sensitization,neuro-immune crosstalk,metabolic reprogramming,and gut-brain axis impairment),as well as the analgesic effects of representative TCM agents in cancer pain management.For example,bioactive components such as tetrahydroberberine,levo-tetrahydropalmatine,and piperine exert analgesic effects,thereby improving the quality of life of patients by inhibiting inflammatory cascades,regulating neurotransmitter systems,and preserving neural integrity.Commonly used preclinical models,including bone cancer pain,pancreatic cancer pain,and chemotherapy-induced peripheral neuropathy models,are summarized for their utility in mechanistic studies and efficacy evaluations.This review also discusses the current limitations of clinical evidence,such as small sample sizes,short follow-up periods,and limited translation from animal models,alongside major challenges in standardization,mechanistic elucidation,and clinical trial design.Future directions should focus on precise pain phenotyping,integrated multi-target interventions,rigorous efficacy safety validation,and innovations in drug delivery to facilitate the standardization and global adoption of TCM in cancer pain management.
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 a grant from the Central Level Public Welfare Research Institutes Basic Research Expenses of Chinese Academy of Medical Sciences(No.2023-RW320-05)。
文摘According to the 2024 global cancer data from GLOBOCAN,liver cancer ranks the 6th most common malignancy and the 3rd leading cause of cancer-related mortality worldwide[1].Among these cases,hepatocellular carcinoma(HCC)accounts for approximately 85%−90%[2,3].Its incidence and mortality rates remain persistently high worldwide.However,China has the highest incidence and mortality rates of the disease in the world[4].And the majority of patients are diagnosed at intermediate or advanced stages.Thus,identifying novel tumor biomarkers for early detection and implementing precision therapy has long been a key focus of research.
基金supported by grants from the Hangzhou Key Project for Agricultural and Social Development under Grant No.20231203A12(JZ)the General Program of the Scientific Research Special Project for Post-Marketing Clinical Research of Innovative Drugs,Development Center for Medical Science&Technology,National Health Commission of the People’s Republic of China under Grant No.WKZX2024CX104202(JZ).
文摘Artificial intelligence(AI)is transforming the diagnostic landscape of malignant tumors in the urinary system,including prostate cancer,bladder cancer,and renal cell carcinoma(RCC).By integrating imaging,pathology,and molecular data,AI enhances the precision and reproducibility of tumor detection,grading,and risk stratification.In prostate cancer,AI-assisted multiparametric Magnetic resonance imaging(MRI)and digital pathology systems improve lesion localization and Gleason scoring.For bladder cancer,deep learning-based cystoscopy and radiomics models from Computed tomography/magnetic resonance imaging(CT/MRI)enable real-time lesion segmentation and non-invasive biomarker prediction,such as Programmed Cell Death-Ligand 1(PD-L1)expression.In RCC,AI,combined with CT/MRI and multi-omics data,aids in subtype classification and prognostic prediction,supporting personalized therapy.However,despite these promising advances,challenges such as data standardization,model generalizability,interpretability,and regulatory compliance hinder AI’s clinical translation.This review outlines the current state of AI in urological cancer diagnosis and prognosis,its technological innovations,and the clinical challenges and opportunities that lie ahead.
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supported by the National Natural Science Foundation[Grant Number:82102788]Anhui Province Key Project for Clinical Medical Research Translation and Advancement[202204295107020031,202204295107020007]Anhui Provincial University Excellent Scientific Research and Innovation Team Project[2022AH010071].
文摘Background:In clinical practice,approximately 80%of prostate cancer(PC)cases are localized and can achieve favorable outcomes with appropriate treatment.Conversely,some remaining cases exhibit an aggressive phenotype or develop resistance to therapeutic interventions,leading to tumor metastasis and a poorer prognosis.When PC metastasizes to distant sites,the bone remains the predominant location,and brain metastases are regarded as exceedingly rare.Case Description:The current study focused on a rare clinical PC case that presented multiple brain metastases after prostate surgery.The patient was initially diagnosed with PC through prostate biopsy and subsequently underwent prostate debulking surgery while continuing androgen deprivation therapy,which maintained low prostatespecific antigen(PSA)levels for 4 years.However,a sudden PSA surge to 7.858 ng/mL led to the emergence of two brain metastatic tumors,which were confirmed to have originated from the prostate.Conclusions:Patients with advanced PC require comprehensive evaluations to detect rare metastatic sites,such as the brain,to avoid missed diagnoses.For patients with brain metastases,a multimodal approach combining surgical resection,postoperative radiotherapy,and endocrine therapy can effectively alleviate symptoms and enhance survival.
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 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.
基金This manuscript was supported by National Institutes of Health(NIH)National Cancer Institute(NCI)NIH awards RO1CA115513,P30CA15704,UO1CA152756,U54CA143862,and P01CA077852(WMG)Burroughs Wellcome Fund Translational Research Award for Clinician Scientist(WMG).
文摘Colorectal cancer is the third most common cancer worldwide and arises secondary to the progressive accumulation of genetic and epigenetic alterations in normal colon cells,which results in a polyp-to-cancer progression sequence.It is known that individuals with a personal history of colon adenomas or cancer are at increased risk for metachronous colon neoplasms.One explanation for this increased risk could be field cancerization,which is a phenomenon in which the histologically normal tissue in an organ is primed to undergo transformation.Epigenetic alterations appear to be promising markers for field cancerization.In this review,we discuss field cancerization in the colon and the data supporting the use of methylated DNA as a biomarker for this phenomenon.
文摘Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.
基金National 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-2022-00010Senior 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.
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.
文摘BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.AIM To determine the incidence of depression and its independent risk factors in patients with esophageal cancer and bone metastasis.METHODS A total of 100 consecutive eligible patients admitted between March 2022 and March 2025 were recruited.Depression was assessed with the Beck Depression Inventory-II;scores>4 defined the depression group(n=42)and scores≤4 the non-depression group(n=58).Demographic,clinical,and laboratory variables were compared between the groups.Multivariate logistic regression was used to identify independent risk factors.RESULTS Depression prevalence was 42.0%(42/100).Univariate analysis demonstrated significant differences in monthly per-capita household income,education level,social support,sleep disorders,and serum high-sensitivity C-reactive protein(all P<0.05);no differences were observed in sex,age,tumor characteristics,or other laboratory indices(all P>0.05).Multivariable analysis revealed the following independent risk factors for depression:Low income[odds ratio(OR)=2.66,95%confidence interval(CI):1.17-6.03],low education(OR=2.46,95%CI:1.08-5.61),low social support(OR=5.10,95%CI:1.81-14.39),sleep disorders(OR=2.79,95%CI:1.23-6.35),and elevated high-sensitivity C-reactive protein(OR=1.31 per unit increase,95%CI:1.18-1.46).CONCLUSION Depression is common among patients with esophageal cancer and bone metastasis.Low socioeconomic status,limited education,insufficient social support,sleep disturbances,and systemic inflammation were independent predictors.Interventions that address these modifiable factors may reduce depression risk in this population.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF),funded by the Ministry of Education(RS-2023-00248378 and NRF-2020R1A6A1A03043708).
文摘Objectives:Tamoxifen is a key drug that provides endocrine therapy for estrogen receptor(ER)α-positive breast cancer;however,resistance remains a significant clinical challenge.This study aims to investigate the molecular mechanisms of tamoxifen resistance in ERα-positive breast cancer,with particular focus on the role of SET Domain Containing 1A(SETD1A)-driven forkhead box A2(FOXA2)as a key regulator of this resistance.Methods:FOXA2 expression and its regulation by SETD1A were assessed via(quantitative polymerase chain reaction),western blotting,transcriptome profiling,and chromatin immunoprecipitation analyses.The effects of FOXA2 on cell proliferation,migration,invasion,and cancer stem cell traits were evaluated using small interfering RNA(siRNA)-mediated silencing.Clinical relevance was examined by analyzing patient datasets and tumor tissue microarrays.Results:FOXA2 expression was significantly elevated in tamoxifen-resistant(TamR)and ERα-negative breast cancer cells compared to that in ERα-positive MCF-7 cells,regardless of tamoxifen treatment or ERαdepletion.Transcriptome and chromatin immunoprecipitation analyses revealed that SETD1A,a histone methyltransferase,directly regulated FOXA2 expression.Functionally,FOXA2 knockdown inhibited the proliferation,migration,invasion,and cancer stem cell properties of TamR cells while restoring tamoxifen sensitivity.High FOXA2 expression was correlated with poor survival and reduced responsiveness to tamoxifen in patients with ER-positive breast cancer.Conclusion:Our findings identified FOXA2 as a key mediator of tamoxifen resistance regulated by SETD1A and suggested that targeting the SETD1A-FOXA2 axis may offer a novel strategy for overcoming endocrine resistance in breast cancer.
文摘Parasitic infections are increasingly recognized as contributors to cancer development,yet the underlying oncogenic mechanisms remain insufficiently understood.Growing evidence from molecular oncology,immunology,and microbiome research suggests that chronic parasitic infections may drive tumorigenesis through sustained inflammation,deregulated signaling pathways,genomic instability,and the release of parasite-derived exosomes that reshape the tumor microenvironment.These insights underscore the need to integrate parasitology with cancer biology to understand infection-associated malignancies better.The aim of this narrative review is to synthesize current knowledge on how selected parasites contribute to cancer development and to highlight emerging therapeutic and diagnostic opportunities.We examine pathogens such as Schistosoma haematobium,Opisthorchis viverrini,Toxoplasma gondii,Plasmodium falciparum,and Leishmania spp.,detailing their roles in chronic inflammation,immune modulation,and interactions with tumor-associated immune cells.The review further discusses parasite-induced immunosuppression,coinfections,and their cumulative impact on cancer risk.Additionally,we explore novel therapeutic approaches,including pathway inhibitors,epigenetic drugs,microbiome modulation,and engineered parasites.Future perspectives emphasize parasite-based immunotherapies,long-term epigenetic consequences of infection,and AI-driven multiomics strategies for identifying oncogenic signatures.This review integrates advances from parasitology and oncology to provide new insights into biomarkers,targeted therapies,and mechanisms of infection-induced tumorigenesis.The literature search covered studies indexed in PubMed,Scopus,and Web of Science up to July 2025.
