AIM To investigate the neoadjuvant chemotherapy(NAC) effect on the survival of patients with proper stomach cancer submitted to D2 gastrectomy.METHODS We proceeded to a review of the literature with Pub Med, Embase, A...AIM To investigate the neoadjuvant chemotherapy(NAC) effect on the survival of patients with proper stomach cancer submitted to D2 gastrectomy.METHODS We proceeded to a review of the literature with Pub Med, Embase, ASCO and ESMO meeting abstracts as well as computerized use of the Cochrane Library for randomized controlled trials(RCTs) comparing NAC followed by surgery(NAC + S) with surgery alone(SA) for gastric cancer(GC). The primary outcome was the overall survival rate. Secondary outcomes were the site of the primary tumor, extension of node dissection according to Japanese Gastric Cancer Association(JGCA) performed in both arms, disease-specific(DSS) and disease-free survival(DFS) rates, clinical and pathological response rates and resectability rates after perioperative treatment. RESULTS We identified a total of 16 randomized controlled trials comparing NAC + S(n = 1089) with SA(n = 973) published in the period from January 1993-March 2017. Only 6 of these studies were well-designed, structured trials in which the type of lymph node(LN) dissection performed or at least suggested in the trial protocol was reported. Two out of three of the RCTs with D2 lymphadenectomy performed in almost all cases failed to show survival benefit in the NAC arm. Inthe third RCT, the survival rate was not even reported, and the primary end points were the clinical outcomes of surgery with and without NAC. In the remaining three RCTs, D2 lymph node dissection was performed in less than 50% of cases or only recommended in the "Study Treatment" protocol without any description in the results of the procedure really perfomed. In one of the two studies, the benefit of NAC was evident only for esophagogastric junction(EGJ) cancers. In the second study, there was no overall survival benefit of NAC. In the last trial, which documented a survival benefit for the NAC arm, the chemotherapy effect was mostly evident for EGJ cancer, and more than one-fourth of patients did not have a proper stomach cancer. Additionally, several patients did not receive resectional surgery. Furthermore, the survival rates of international reference centers that provide adequate surgery for homogeneous stomach cancer patients' populations are even higher than the survival rates reported after NAC followed by incomplete surgery.CONCLUSION NAC for GC has been rapidly introduced in international western guidelines without an evidence-based medicinerelated demonstration of its efficacy for a homogeneous population of patients with only stomach tumors submitted to adequate surgery following JGCA guidelines with extended(D2) LN dissection. Additional larger sample-size multicentre RCTs comparing the newer NAC regimens including molecular therapies followed by adequate extended surgery with surgery alone are needed.展开更多
Ulcerative colitis(UC) is a condition at increased risk for colorectal carcinoma(CRC) development. Nowadays, screening and follow-up programs are routinely performed worldwide to promote the early detection of CRCs in...Ulcerative colitis(UC) is a condition at increased risk for colorectal carcinoma(CRC) development. Nowadays, screening and follow-up programs are routinely performed worldwide to promote the early detection of CRCs in subjects with well known risk factors(extent, duration and severity of the disorder). The diffusion of these procedures is presumably the main reason for the marked reduction of cancer incidence and mortality in the course of UC. In addition, chemoprevention has been widely investigated and developed in many medical fields, and aspirin has shown a preventive effect against CRC, while mesalazine has been strongly invoked as a potential chemopreventive agent in UC. However, available studies show some limitations due to the obvious ethical implications of drug withdrawal in UC in order to design a control group. The estrogenreceptors(ER) alpha/beta balance seems to have a relevant influence on colorectal carcinogenesis and ER beta appears to parallel apoptosis, and hence an anticarcinogenic effect. Phytoestrogens are compounds acting as ER beta agonists and have shown a promising chemopreventive effect on sporadic as well as genetically inherited CRC. There is evidence suggesting a role for ERs in UC-related carcinogenesis. In this perspective, since these substances can be considered as dietary supplements and are completely free from side effects, phytoestrogens could be an interesting option for CRC prevention, even when the disease is a consequence of long-term chronic inflammation, as in the course of UC. Further studies of their effects are warranted in both the basic research and clinical fields.展开更多
Cancer is the cell fleeing from death by blocking the pathways of the intrinsic and the extrinsic program of cell death (Apoptosis). The success depends on making the programs of cell death run again.
Assessing the lethality of ‘early,’ potentially organ-confined prostate cancer （PCa） is one of the central controversies in modem-day urological clinical practice. Such cases are often considered for radical ‘cur...Assessing the lethality of ‘early,’ potentially organ-confined prostate cancer （PCa） is one of the central controversies in modem-day urological clinical practice. Such cases are often considered for radical ‘curative’ treatment, although active surveillance may be equally appropriate for many men. Moreover, the balance between judicious intervention and overtreatment can be difficult to judge. The patient＇s age, comorbidities, family history and philosophy of self-health care can be weighed against clinical features such as the palpability of disease, the number and percentage of biopsy cores involved with the disease, histological grade, presenting prostate-specific antigen （PSA） and possible previous PSA kinetics. For many years, scientists and physicians have sought additional molecular factors that may be predictive for disease stage, progression and lethality. Usually, claims for a ‘new’ unique marker fall short of true clinical value. More often than not, such molecular markers are useful only in multivariate models. This review summarizes relevant molecular markers and models reported up to and including 2008.展开更多
Background: Surgery is the treatment for early-stage cervical cancer. Radiochemotherapy is used in the treatment of locally advanced stages. But the choice of treatment can be difficult. Objective: The objective of th...Background: Surgery is the treatment for early-stage cervical cancer. Radiochemotherapy is used in the treatment of locally advanced stages. But the choice of treatment can be difficult. Objective: The objective of this work was to evaluate the therapeutic aspects of cervical cancer in the early stages IA to IIA in the oncology department of A Ledantec Hospital in Dakar. Patients and methods: This was a descriptive retrospective study, from January 2015 to December 2020, in the oncology department of A Ledantec Hospital, including all the patients who had been treated for early-stage invasive cervical cancer. Results: We included 28 patients. The average age was 49.54 years old. There were 11 patients (39.3%) with a stage ≤ IB1. Surgery was the first in 14 patients (50%). The initial approach was a midline supra and subumbilical laparotomy. The surgery was R0 in 65.22%. Postoperative complications were found in 4 patients including 1 case of operative wound suppuration, 1 case of dysuria, 1 case of postoperative eventration and 1 case of rectovaginal fistula. Concomitant Radiochemotherapy was neoadjuvant in 7 cases (25%), adjuvant in 14 cases (50%). The chemotherapy was neoadjuvant in 09 cases (56.25%) and adjuvant in 7 cases (43.75%) with minor toxicities. We had recorded 2 deaths. Conclusion: The treatment of the early stages of invasive cervical cancer is based on surgery. Neoadjuvant treatments may be useful in particular situations.展开更多
Aims:This article aims to explore the interventional and contextual components of smoking cessation support for cancer patients in the context of supportive care in cancer provided by an association,that is viable and...Aims:This article aims to explore the interventional and contextual components of smoking cessation support for cancer patients in the context of supportive care in cancer provided by an association,that is viable and effective in the French context,and to describe the partnership research process in which they were developed.Procedure:The intervention was developed from a dataset collected during a viability study for the development of a smoking cessation intervention carried out at the Ligue Contre le Cancer Gironde,a scoping review of evidence-based interventions and two narrative reviews on the determinants and ethical issues of smoking cessation in cancer.Results:The results confirmed a tangible opportunity to develop smoking cessation services within the relevant case because of the obstacles that can be overcome,the facilitators that can be mobilized,and the gaps existing in this field.In addition,they enabled the design of an intervention adapted to the context,guided by a voluntarist,multidisciplinary approach,and focused on patients’well-being.Conclusion:The associations providing supportive care in cancer can initiate and participate in the process of smoking cessation.They can play a key role in mediating between oncology and addictology.展开更多
Background: The purpose of this study was to evaluate the use of 18FDG-PET/CT in staging procedure, the pattern of failure and survival in patients with small-cell lung cancer limited disease (LD-SCLC) undergoing chem...Background: The purpose of this study was to evaluate the use of 18FDG-PET/CT in staging procedure, the pattern of failure and survival in patients with small-cell lung cancer limited disease (LD-SCLC) undergoing chemo-radiotherapy. Methods: A total of 79 LD-SCLC patients were treated with a combination of chemotherapy and chest radiotherapy. Radiotherapy of the tumour and the pathological lymph nodes was performed either as 45 Gy twice-daily or 46 - 50 Gy once-daily. 18Fluro-2-deoxy-D-glucose (18FDG)-PET/CT was performed in 35 patients as part of the staging procedure. Results: With a median follow-up time of 17 months 6% developed isolated loco-regional failures while 57% developed distant metastases. No isolated regional failures were seen. Median overall survival was 22 months. Patients staged with a 18FDG-PET/CT had a significantly lower incidence of distant failures and a significantly improved overall survival compared with patients only staged with a CT scan (p = 0.03) (median overall survival of 34 versus 17 months, respectively). Conclusion: The pattern of failure showed a high risk of distant metastases but a low incidence of isolated loco-regional failures. Patients staged with an 18FDG-PET/CT had a significantly lower incidence of distant failures and better overall survival, indicating that 18FDG-PET could be beneficial in patients with LD-SCLC before deciding on treatment regimen.展开更多
Objective To investigate the therapeutic efficacy and its influencing factors of ultrasoundguided percutaneous radiofrequency ablation (PRFA) in the treatment of liver carcinoma. Methods With a temperature-controlled ...Objective To investigate the therapeutic efficacy and its influencing factors of ultrasoundguided percutaneous radiofrequency ablation (PRFA) in the treatment of liver carcinoma. Methods With a temperature-controlled multi-electrode needle, ultrasound-guided PRFA was employed to treat forty-seven patients with 67 tumor nodules, with a diameterof 2.6 ± 1.1 cm (1.0 - 5.5 cm). Results A complete ablation (CA) rate of 80. 6% was achieved in the present series, with a CA rate of 91.7 % in the tumors ≤3 cm in diameter,75. 0% in tumors from 3.1 to 4. 0 cm,and 14. 3% in tumors 】4 cm. The CA rate was significantly greater in tumors with a temperature rising up to 70℃ within the initial 2 minutes at ablation as compared with that longer than 2 minutes (P 【 0.05). A markedly higher CA rate was obtained in tumors with an ablation-maintaining temperature of over 80℃ than that between 70℃ and 80℃ ( P 【 0. 01). All patients were followed up with a mean time of 11. 3 months. The local recurrence rate was 9.3% (5/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
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
A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.展开更多
Background: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
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
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 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 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
文摘AIM To investigate the neoadjuvant chemotherapy(NAC) effect on the survival of patients with proper stomach cancer submitted to D2 gastrectomy.METHODS We proceeded to a review of the literature with Pub Med, Embase, ASCO and ESMO meeting abstracts as well as computerized use of the Cochrane Library for randomized controlled trials(RCTs) comparing NAC followed by surgery(NAC + S) with surgery alone(SA) for gastric cancer(GC). The primary outcome was the overall survival rate. Secondary outcomes were the site of the primary tumor, extension of node dissection according to Japanese Gastric Cancer Association(JGCA) performed in both arms, disease-specific(DSS) and disease-free survival(DFS) rates, clinical and pathological response rates and resectability rates after perioperative treatment. RESULTS We identified a total of 16 randomized controlled trials comparing NAC + S(n = 1089) with SA(n = 973) published in the period from January 1993-March 2017. Only 6 of these studies were well-designed, structured trials in which the type of lymph node(LN) dissection performed or at least suggested in the trial protocol was reported. Two out of three of the RCTs with D2 lymphadenectomy performed in almost all cases failed to show survival benefit in the NAC arm. Inthe third RCT, the survival rate was not even reported, and the primary end points were the clinical outcomes of surgery with and without NAC. In the remaining three RCTs, D2 lymph node dissection was performed in less than 50% of cases or only recommended in the "Study Treatment" protocol without any description in the results of the procedure really perfomed. In one of the two studies, the benefit of NAC was evident only for esophagogastric junction(EGJ) cancers. In the second study, there was no overall survival benefit of NAC. In the last trial, which documented a survival benefit for the NAC arm, the chemotherapy effect was mostly evident for EGJ cancer, and more than one-fourth of patients did not have a proper stomach cancer. Additionally, several patients did not receive resectional surgery. Furthermore, the survival rates of international reference centers that provide adequate surgery for homogeneous stomach cancer patients' populations are even higher than the survival rates reported after NAC followed by incomplete surgery.CONCLUSION NAC for GC has been rapidly introduced in international western guidelines without an evidence-based medicinerelated demonstration of its efficacy for a homogeneous population of patients with only stomach tumors submitted to adequate surgery following JGCA guidelines with extended(D2) LN dissection. Additional larger sample-size multicentre RCTs comparing the newer NAC regimens including molecular therapies followed by adequate extended surgery with surgery alone are needed.
文摘Ulcerative colitis(UC) is a condition at increased risk for colorectal carcinoma(CRC) development. Nowadays, screening and follow-up programs are routinely performed worldwide to promote the early detection of CRCs in subjects with well known risk factors(extent, duration and severity of the disorder). The diffusion of these procedures is presumably the main reason for the marked reduction of cancer incidence and mortality in the course of UC. In addition, chemoprevention has been widely investigated and developed in many medical fields, and aspirin has shown a preventive effect against CRC, while mesalazine has been strongly invoked as a potential chemopreventive agent in UC. However, available studies show some limitations due to the obvious ethical implications of drug withdrawal in UC in order to design a control group. The estrogenreceptors(ER) alpha/beta balance seems to have a relevant influence on colorectal carcinogenesis and ER beta appears to parallel apoptosis, and hence an anticarcinogenic effect. Phytoestrogens are compounds acting as ER beta agonists and have shown a promising chemopreventive effect on sporadic as well as genetically inherited CRC. There is evidence suggesting a role for ERs in UC-related carcinogenesis. In this perspective, since these substances can be considered as dietary supplements and are completely free from side effects, phytoestrogens could be an interesting option for CRC prevention, even when the disease is a consequence of long-term chronic inflammation, as in the course of UC. Further studies of their effects are warranted in both the basic research and clinical fields.
文摘Cancer is the cell fleeing from death by blocking the pathways of the intrinsic and the extrinsic program of cell death (Apoptosis). The success depends on making the programs of cell death run again.
文摘Assessing the lethality of ‘early,’ potentially organ-confined prostate cancer （PCa） is one of the central controversies in modem-day urological clinical practice. Such cases are often considered for radical ‘curative’ treatment, although active surveillance may be equally appropriate for many men. Moreover, the balance between judicious intervention and overtreatment can be difficult to judge. The patient＇s age, comorbidities, family history and philosophy of self-health care can be weighed against clinical features such as the palpability of disease, the number and percentage of biopsy cores involved with the disease, histological grade, presenting prostate-specific antigen （PSA） and possible previous PSA kinetics. For many years, scientists and physicians have sought additional molecular factors that may be predictive for disease stage, progression and lethality. Usually, claims for a ‘new’ unique marker fall short of true clinical value. More often than not, such molecular markers are useful only in multivariate models. This review summarizes relevant molecular markers and models reported up to and including 2008.
文摘Background: Surgery is the treatment for early-stage cervical cancer. Radiochemotherapy is used in the treatment of locally advanced stages. But the choice of treatment can be difficult. Objective: The objective of this work was to evaluate the therapeutic aspects of cervical cancer in the early stages IA to IIA in the oncology department of A Ledantec Hospital in Dakar. Patients and methods: This was a descriptive retrospective study, from January 2015 to December 2020, in the oncology department of A Ledantec Hospital, including all the patients who had been treated for early-stage invasive cervical cancer. Results: We included 28 patients. The average age was 49.54 years old. There were 11 patients (39.3%) with a stage ≤ IB1. Surgery was the first in 14 patients (50%). The initial approach was a midline supra and subumbilical laparotomy. The surgery was R0 in 65.22%. Postoperative complications were found in 4 patients including 1 case of operative wound suppuration, 1 case of dysuria, 1 case of postoperative eventration and 1 case of rectovaginal fistula. Concomitant Radiochemotherapy was neoadjuvant in 7 cases (25%), adjuvant in 14 cases (50%). The chemotherapy was neoadjuvant in 09 cases (56.25%) and adjuvant in 7 cases (43.75%) with minor toxicities. We had recorded 2 deaths. Conclusion: The treatment of the early stages of invasive cervical cancer is based on surgery. Neoadjuvant treatments may be useful in particular situations.
文摘Aims:This article aims to explore the interventional and contextual components of smoking cessation support for cancer patients in the context of supportive care in cancer provided by an association,that is viable and effective in the French context,and to describe the partnership research process in which they were developed.Procedure:The intervention was developed from a dataset collected during a viability study for the development of a smoking cessation intervention carried out at the Ligue Contre le Cancer Gironde,a scoping review of evidence-based interventions and two narrative reviews on the determinants and ethical issues of smoking cessation in cancer.Results:The results confirmed a tangible opportunity to develop smoking cessation services within the relevant case because of the obstacles that can be overcome,the facilitators that can be mobilized,and the gaps existing in this field.In addition,they enabled the design of an intervention adapted to the context,guided by a voluntarist,multidisciplinary approach,and focused on patients’well-being.Conclusion:The associations providing supportive care in cancer can initiate and participate in the process of smoking cessation.They can play a key role in mediating between oncology and addictology.
文摘Background: The purpose of this study was to evaluate the use of 18FDG-PET/CT in staging procedure, the pattern of failure and survival in patients with small-cell lung cancer limited disease (LD-SCLC) undergoing chemo-radiotherapy. Methods: A total of 79 LD-SCLC patients were treated with a combination of chemotherapy and chest radiotherapy. Radiotherapy of the tumour and the pathological lymph nodes was performed either as 45 Gy twice-daily or 46 - 50 Gy once-daily. 18Fluro-2-deoxy-D-glucose (18FDG)-PET/CT was performed in 35 patients as part of the staging procedure. Results: With a median follow-up time of 17 months 6% developed isolated loco-regional failures while 57% developed distant metastases. No isolated regional failures were seen. Median overall survival was 22 months. Patients staged with a 18FDG-PET/CT had a significantly lower incidence of distant failures and a significantly improved overall survival compared with patients only staged with a CT scan (p = 0.03) (median overall survival of 34 versus 17 months, respectively). Conclusion: The pattern of failure showed a high risk of distant metastases but a low incidence of isolated loco-regional failures. Patients staged with an 18FDG-PET/CT had a significantly lower incidence of distant failures and better overall survival, indicating that 18FDG-PET could be beneficial in patients with LD-SCLC before deciding on treatment regimen.
文摘Objective To investigate the therapeutic efficacy and its influencing factors of ultrasoundguided percutaneous radiofrequency ablation (PRFA) in the treatment of liver carcinoma. Methods With a temperature-controlled multi-electrode needle, ultrasound-guided PRFA was employed to treat forty-seven patients with 67 tumor nodules, with a diameterof 2.6 ± 1.1 cm (1.0 - 5.5 cm). Results A complete ablation (CA) rate of 80. 6% was achieved in the present series, with a CA rate of 91.7 % in the tumors ≤3 cm in diameter,75. 0% in tumors from 3.1 to 4. 0 cm,and 14. 3% in tumors 】4 cm. The CA rate was significantly greater in tumors with a temperature rising up to 70℃ within the initial 2 minutes at ablation as compared with that longer than 2 minutes (P 【 0.05). A markedly higher CA rate was obtained in tumors with an ablation-maintaining temperature of over 80℃ than that between 70℃ and 80℃ ( P 【 0. 01). All patients were followed up with a mean time of 11. 3 months. The local recurrence rate was 9.3% (5/
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.
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 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(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 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.
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-2022-00010)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.
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 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.
