Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance pati...Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance patients remains limited.This study examined real-world outcomes of palbociclib plus endocrine therapy in Asian patients,with additional subgroup analyses by age and performance status.Methods:We retrospectively analyzed 46 consecutive Asian patients with recurrent or de novo HR+/HER2−breast cancer treated with first-line palbociclib plus ET between April 2021 and March 2025.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall response rate(ORR),disease control rate(DCR),and safety.Subgroup analyses were performed by age(<70 vs.≥70 years)and performance status(PS;0–1 vs.2–3).Results:The median PFS was 26.6 months(range,1.4–69.5).Stratified by age,median PFS was 26.9 months in patients<70 years and 26.2 months in those≥70 years(p=0.760).By PS,PFS was 26.9 months for PS 0–1 and 17.8 months for PS 2–3(p=0.099).ORR was 60.9%and DCR 93.5%;notably,all PS 2–3 patients achieved disease control.Hematologic toxicities were common,with neutropenia(80.4%)and leukopenia(86.7%)predominating,but grade≥3 anemia was rare(2.2%).Elderly patients experienced anemia more frequently,while overall toxicity remained manageable.Dose reductions occurred in 47.8%without loss of efficacy.Conclusions:In routine Japanese practice,palbociclib plus ET provided prolonged PFS and high disease control consistent with pivotal trials and international real-world evidence.Importantly,elderly patients tolerated treatment well,and selected PS 2–3 patients also derived clinical benefit.These findings indicate that neither age nor PS alone should preclude the use of palbociclib in carefully monitored real-world patients.展开更多
Objective:To investigate the long-term prognosis and postoperative cosmetic outcomes of breast-conserving surgery combined with sentinel lymph node biopsy in patients with early-stage breast cancer,providing a referen...Objective:To investigate the long-term prognosis and postoperative cosmetic outcomes of breast-conserving surgery combined with sentinel lymph node biopsy in patients with early-stage breast cancer,providing a reference for the selection of clinical treatment plans.Methods:A retrospective analysis was conducted on the clinical data of 68 patients with early-stage breast cancer admitted from January 2022 to December 2025.Based on the surgical approach,patients were divided into an observation group(breast-conserving surgery+sentinel lymph node biopsy)and a control group(other surgical methods such as modified radical mastectomy/total mastectomy).Clinical and pathological characteristics,incidence of postoperative complications,follow-up prognosis,and satisfaction with cosmetic outcomes were compared between the two groups.Results:Among the 68 patients,41 were in the observation group and 27 in the control group.The average age of patients in the observation group was(54.32±8.15)years,while that in the control group was(62.45±9.76)years.The average tumor size in the observation group was(1.86±0.72)cm,compared to(3.21±1.45)cm in the control group.The incidence of postoperative complications in the observation group was 9.76%,significantly lower than that in the control group at 33.33%(P<0.05).The 6-month disease-free survival rate was 95.12%in the observation group and 88.89%in the control group,with no statistically significant difference between the two groups(P>0.05).The excellent and good rate of cosmetic outcomes in the observation group was 87.80%,significantly higher than that in the control group at 29.63%(P<0.05).Conclusion:Breast-conserving surgery combined with sentinel lymph node biopsy for early-stage breast cancer can achieve long-term prognostic outcomes comparable to those of traditional radical surgery,with the advantages of fewer postoperative complications and superior cosmetic results.This approach is worthy of clinical promotion and application,particularly for early-stage breast cancer patients who have a demand for preserving breast morphology.展开更多
BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probi...BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.展开更多
Breast cancer(BRCA)is characterized by high heterogeneity,with aggressive subtypes frequently showing poor prognosis and resistance to conventional therapies,making the discovery of new therapeutic targets and strateg...Breast cancer(BRCA)is characterized by high heterogeneity,with aggressive subtypes frequently showing poor prognosis and resistance to conventional therapies,making the discovery of new therapeutic targets and strategies imperative.Although elevated expression of discs large homolog 3(DLG3)has been reported in BRCA,its functional role in disease progression remains unclear.We performed bioinformatic analyses of clinical datasets to evaluate the prognostic significance of DLG3 expression in BRCA patients.In vitro gain-and loss-of-function experiments were conducted to assess the impact of DLG3 on BRCA cell proliferation,migration,and colony formation.Transcriptomic profiling,coupled with pharmacological inhibition,was employed to identify and validate downstream signaling pathways.Additionally,we extended our validation to an in vivo model to assess the role of DLG3 in tumor progression.We found that elevated DLG3 levels correlated with poor prognosis in breast cancer patients.Functionally,DLG3 overexpression significantly promoted cell proliferation and migration in estrogen receptor-positive MCF7 and triple-negative MDA-MB-231 breast cancer cells,whereas its knockdown suppressed these effects.Transcriptomic analyses revealed that DLG3 activates signal transducer and activator of transcription 3(STAT3)signaling,a finding further corroborated by Western blot.Critically,treatment with the STAT3 inhibitor Stattic attenuated DLG3-driven proliferation and migration,supporting a DLG3-STAT3 oncogenic axis.Furthermore,in vivo studies validated the role of DLG3 in promoting tumor growth and its correlation with elevated STAT3 signaling,consistent with our in vitro findings.Our findings establish DLG3 as a novel driver of breast cancer progression that directly activates STAT3 signaling.DLG3 thus represents both a potential prognostic biomarker and a promising therapeutic target for aggressive breast cancer subtypes,including triple-negative breast cancer.展开更多
Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabo...Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabolism,in the aggressiveness and metastatic behavior of BC.Methods:A comprehensive analysis was performed using in silico transcriptomic data(n=2509 patients),immunohistochemical profiling of BC tissues(n=103),and validation through western blotting in multiple BC cell lines.Gene expression and survival analyses were conducted using Tumor Immune Estimation Resource(TIMER),Gene Expression Profiling Interactive Analysis 2(GEPIA2),and the cBioPortal for cancer genomics(cBioPortal)platforms.Correlations between PNP and key epithelial–mesenchymal transition(EMT)markers,molecular subtypes,tumor grades,and stages were examined.Results:PNP was significantly overexpressed in human epidermal growth factor receptor 2(HER-2)-positive and triple-negative BCs compared to luminal subtypes.High PNP levels were strongly associated with advanced BC stages,high-grade tumors,EMT phenotypes,and poor overall survival.Notably,HER-2 inhibition suppressed PNP expression,while PNP gene silencing induced HER-2 upregulation,revealing a reciprocal regulatory loop.Dual inhibition of PNP and HER-2 resulted in a significant reduction in cell viability compared to HER-2 inhibition alone.Conclusion:Collectively,PNP emerges as a promising biomarker of BC aggressiveness and progression.Its reciprocal interaction with HER-2 underscores its potential as a therapeutic target.Dual targeting of PNP and HER-2 may offer a novel strategy for improving outcomes in aggressive BC subtypes.展开更多
Accurate segmentation of breast cancer in mammogram images plays a critical role in early diagnosis and treatment planning.As research in this domain continues to expand,various segmentation techniques have been propo...Accurate segmentation of breast cancer in mammogram images plays a critical role in early diagnosis and treatment planning.As research in this domain continues to expand,various segmentation techniques have been proposed across classical image processing,machine learning(ML),deep learning(DL),and hybrid/ensemble models.This study conducts a systematic literature review using the PRISMA methodology,analyzing 57 selected articles to explore how these methods have evolved and been applied.The review highlights the strengths and limitations of each approach,identifies commonly used public datasets,and observes emerging trends in model integration and clinical relevance.By synthesizing current findings,this work provides a structured overview of segmentation strategies and outlines key considerations for developing more adaptable and explainable tools for breast cancer detection.Overall,our synthesis suggests that classical and ML methods are suitable for limited labels and computing resources,while DL models are preferable when pixel-level annotations and resources are available,and hybrid pipelines are most appropriate when fine-grained clinical precision is required.展开更多
The integration of machine learning(ML)technology with Internet of Things(IoT)systems produces essential changes in healthcare operations.Healthcare personnel can track patients around the clock thanks to healthcare I...The integration of machine learning(ML)technology with Internet of Things(IoT)systems produces essential changes in healthcare operations.Healthcare personnel can track patients around the clock thanks to healthcare IoT(H-IoT)technology,which also provides proactive statistical findings and precise medical diagnoses that enhance healthcare performance.This study examines how ML might support IoT-based health care systems,namely in the areas of prognostic systems,disease detection,patient tracking,and healthcare operations control.The study looks at the benefits and drawbacks of several machine learning techniques for H-IoT applications.It also examines the fundamental problems,such as data security and cyberthreats,as well as the high processing demands that these systems face.Alongside this,the essay discusses the advantages of all the technologies,including machine learning,deep learning,and the Internet of Things,as well as the significant difficulties and problems that arise when integrating the technology into healthcare forecasts.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
Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor ...Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor(ER)-positive,and lacks routine screening,leading to delayed diagnosis and advanced disease.Major risk factors include hormonal imbalance,radiation exposure,obesity,alcohol use,and Breast Cancer Gene 1 and 2(BRCA1/2)mutations.Clinically,it may resemble gynecomastia but usually appears as a unilateral,painless mass or nipple discharge.Advances in imaging and liquid biopsy have enhanced early detection.Molecular mechanisms involve hormonal signaling,HER2/epidermal growth factor receptor(EGFR)pathways,tumor suppressor gene alterations,and epigenetic changes.While standard treatments mirror those for female breast cancer,emerging options such as cyclin-dependent kinase 4 and 6(CDK4/6),and poly(ADP-ribose)polymerase(PARP)inhibitors,immunotherapy,and precision medicine are reshaping management.Incorporating artificial intelligence,molecular profiling,and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.展开更多
Objective:To evaluate the clinical efficacy of blood-letting cupping combined with manual lymphatic drainage in treating breast cancer-related lymphedema(BCRL)and explore its mechanism of action from both traditional ...Objective:To evaluate the clinical efficacy of blood-letting cupping combined with manual lymphatic drainage in treating breast cancer-related lymphedema(BCRL)and explore its mechanism of action from both traditional Chinese medicine and modern medical perspectives,providing a scientific basis and novel therapeutic approaches for clinical management of BCRL.Methods:Patients with BCRL admitted to the outpatient and inpatient departments of Hebei University Affiliated Hospital were enrolled.A prospective randomized controlled trial design was adopted,with eligible patients randomly assigned to a treatment group and a control group.The control group received manual lymphatic drainage alone,while the treatment group received manual lymphtic drainage combined with blood-letting cupping therapy.Posttreatment comparisons evaluated upper limb circumference reduction,edema severity grading,and upper limb functional scores.Vital signs and adverse reactions during treatment were recorded for both groups.Statistical software analyzed the data.Results:The treatment group demonstrated significantly greater reduction in upper limb circumference,improvement in edema severity,and higher upper limb function scores compared to the control group(P<0.05).Vital signs remained stable throughout treatment in both groups.No severe adverse reactions occurred in the treatment group;only isolated cases of mild skin itching were reported,which resolved after symptomatic management.Conclusion:The combination of bloodletting cupping and manual lymphatic drainage demonstrates reliable efficacy in treating BCRL,effectively alleviating edema symptoms and improving upper limb function with high safety.Its mechanism may relate to traditional Chinese medicine principles of“unblocking meridians,promoting blood circulation,and resolving stasis”and modern medical concepts of“enhancing local blood circulation,facilitating lymphatic drainage,and reducing inflammatory responses”.展开更多
Introduction:Chemotherapy-induced gastrointestinal symptom clusters in breast cancer impair quality of life and treatment adherence,yet lack effective interventions.While acupuncture mitigates isolated chemotherapy-in...Introduction:Chemotherapy-induced gastrointestinal symptom clusters in breast cancer impair quality of life and treatment adherence,yet lack effective interventions.While acupuncture mitigates isolated chemotherapy-induced symptoms,its mechanisms for multi-symptom clusters remain unclear.This study evaluates electroacupuncture's efficacy and explores its biological mechanisms in managing these clusters.Methods:This prospective,multicenter,block-randomized,double-blind,sham-controlled trial will enroll 388 patients with breast cancer undergoing neoadjuvant/adjuvant chemotherapy,to be randomly assigned(1:1)to electroacupuncture or sham electro-acupuncture groups.Both groups will receive the standard quadruple antiemetic regimen combined with electroacupuncture or sham intervention.The primary endpoint is the incidence of chemotherapy-induced gastrointestinal symptom clusters within 120 h after chemotherapy.Secondary endpoints include improvement in gastrointestinal symptom clusters post-first chemotherapy cycle,nausea-free rates during acute and delayed phases,vomiting-free rates during overall,acute,and delayed phases,complete response rate,complete protection rate,and quality of life.Adverse events will be documented throughout the study.Discussion:This study will assess the efficacy and safety of electroacupuncture in alleviating chemotherapy-induced gastro-intestinal symptom clusters in patients with breast cancer.By integrating multi-omics analyses,we aim to elucidate the biological mechanisms underlying its therapeutic effects.The findings may offer a robust clinical foundation for optimizing symptom cluster management in cancer care.Trial Registration:Clinical Trials ID:NCT06952920.Date of registration:April 16,2025.Prospectively registered.URL of Trial Registry Record:https://clinicaltrials.gov/study/NCT06952920cond=NCT06952920&rank=1.展开更多
Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual pat...Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual patient responses towards different drugs.This study aimed to investigate the patient-derived breast cancer culture models for drug sensitivity evaluations.Methods:Tumor and adjacent tissues from female breast cancer patients were collected during surgery.Patient-derived breast cancer cells were cultured using the conditional reprogramming technique to establish 2D models.The obtained patient-derived conditional reprogramming breast cancer(CRBC)cells were subsequently embedded in alginate-gelatin methacryloyl hydrogel microspheres to form 3D culture models.Comparisons between 2D and 3D models were made using immunohistochemistry(tumor markers),MTS assays(cell viability),flow cytometry(apoptosis),transwell assays(migration),and Western blotting(protein expression).Drug sensitivity tests were conducted to evaluate patient-specific responses to anti-cancer agents.Results:2D and 3D culture models were successfully established using samples from eight patients.The 3D models retained histological and marker characteristics of the original tumors.Compared to 2D cultures,3D models exhibited increased apoptosis,enhanced drug resistance,elevated stem cell marker expression,and greater migration ability—features more reflective of in vivo tumor behavior.Conclusion:Patient-derived 3D CRBC models effectively mimic the in vivo tumor microenvironment and demonstrate stronger resistance to anti-cancer drugs than 2D models.These hydrogel-based models offer a cost-effective and clinically relevant platform for drug screening and personalized breast cancer treatment.展开更多
critical for guiding treatment and improving patient outcomes.Traditional molecular subtyping via immuno-histochemistry(IHC)test is invasive,time-consuming,and may not fully represent tumor heterogeneity.This study pr...critical for guiding treatment and improving patient outcomes.Traditional molecular subtyping via immuno-histochemistry(IHC)test is invasive,time-consuming,and may not fully represent tumor heterogeneity.This study proposes a non-invasive approach using digital mammography images and deep learning algorithm for classifying breast cancer molecular subtypes.Four pretrained models,including two Convolutional Neural Networks(MobileNet_V3_Large and VGG-16)and two Vision Transformers(ViT_B_16 and ViT_Base_Patch16_Clip_224)were fine-tuned to classify images into HER2-enriched,Luminal,Normal-like,and Triple Negative subtypes.Hyperparameter tuning,including learning rate adjustment and layer freezing strategies,was applied to optimize performance.Among the evaluated models,ViT_Base_Patch16_Clip_224 achieved the highest test accuracy(94.44%),with equally high precision,recall,and F1-score of 0.94,demonstrating excellent generalization.MobileNet_V3_Large achieved the same accuracy but showed less training stability.In contrast,VGG-16 recorded the lowest performance,indicating a limitation in its generalizability for this classification task.The study also highlighted the superior performance of the Vision Transformer models over CNNs,particularly due to their ability to capture global contextual features and the benefit of CLIP-based pretraining in ViT_Base_Patch16_Clip_224.To enhance clinical applicability,a graphical user interface(GUI)named“BCMS Dx”was developed for streamlined subtype prediction.Deep learning applied to mammography has proven effective for accurate and non-invasive molecular subtyping.The proposed Vision Transformer-based model and supporting GUI offer a promising direction for augmenting diagnostic workflows,minimizing the need for invasive procedures,and advancing personalized breast cancer management.展开更多
BACKGROUND Breast cancer is one of the most prevalent malignancies affecting women worldwide,with approximately 2.3 million new cases diagnosed annually.Breast cancer stem cells(BCSCs)play pivotal roles in tumor initi...BACKGROUND Breast cancer is one of the most prevalent malignancies affecting women worldwide,with approximately 2.3 million new cases diagnosed annually.Breast cancer stem cells(BCSCs)play pivotal roles in tumor initiation,progression,metastasis,therapeutic resistance,and disease recurrence.Cancer stem cells possess selfrenewal capacity,multipotent differentiation potential,and enhanced tumorigenic activity,but their molecular characteristics and regulatory mechanisms require further investigation.AIM To comprehensively characterize the molecular features of BCSCs through multiomics approaches,construct a prognostic prediction model based on stem cellrelated genes,reveal cell-cell communication networks within the tumor microenvironment,and provide theoretical foundation for personalized treatment strategies.METHODS Flow cytometry was employed to detect the expression of BCSC surface markers(CD34,CD45,CD29,CD90,CD105).Transcriptomic analysis was performed to identify differentially expressed genes.Least absolute shrinkage and selection operator regression analysis was utilized to screen key prognostic genes and construct a risk scoring model.Single-cell RNA sequencing and spatial transcriptomics were applied to analyze tumor heterogeneity and spatial gene expression patterns.Cell-cell communication network analysis was conducted to reveal interactions between stem cells and the microenvironment.RESULTS Flow cytometric analysis revealed the highest expression of CD105(96.30%),followed by CD90(68.43%)and CD34(62.64%),while CD29 showed lower expression(7.16%)and CD45 exhibited the lowest expression(1.19%).Transcriptomic analysis identified 3837 significantly differentially expressed genes(1478 upregulated and 2359 downregulated).Least absolute shrinkage and selection operator regression analysis selected 10 key prognostic genes,and the constructed risk scoring model effectively distinguished between high-risk and low-risk patient groups(P<0.001).Single-cell analysis revealed tumor cellular heterogeneity,and spatial transcriptomics demonstrated distinct spatial expression gradients of stem cell-related genes.MED18 gene showed significantly higher expression in malignant tissues(P<0.001)and occupied a central position in cell-cell communication networks,exhibiting significant correlations with tumor cells,macrophages,fibroblasts,and endothelial cells.CONCLUSION This study comprehensively characterized the molecular features of BCSCs through multi-omics approaches,identified reliable surface markers and key regulatory genes,and constructed a prognostic prediction model with clinical application value.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
Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containin...Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containing 2(ZMIZ2)and minichromosome maintenance complex component 3(MCM3)in TNBC progression.Methods:The relationship between ZMIZ2 expression and clinical characteristics of TNBC was investigated.In vitro and in vivo experiments were performed to investigate the role of ZMIZ2 dysregulation in TNBC cell malignant behaviors.The regulatory relationship between ZMIZ2 and MCM3 was also explored.Transcriptome sequencing was performed to elucidate possible mechanisms underlying the ZMIZ2/MCM3 axis in TNBC.Results:High ZMIZ2 expression levels were associated with the malignant degree of TNBC.ZMIZ2 overexpression promoted TNBC cell proliferation,migration,and invasion;inhibited apoptosis;and induced G1 phase cell cycle arrest,whereas knockdown of ZMIZ2 had the opposite effect.ZMIZ2 directly targeted and positively regulated MCM3 expression.MCM3 knockdown reversed the effect of ZMIZ2 overexpression on TNBC tumor growth both in vitro and in vivo.High MCM3 expression levels were linked to the degree of malignancy and poor prognosis in TNBC.The differentially expressed genes associated with the ZMIZ2/MCM3 axis were significantly enriched in multiple pathways,such as the mitogen-activated protein kinase(MAPK),mechanistic target of rapamycin(mTOR),Wnt,and Ras signaling pathways,as verified by The Cancer Genome Atlas data.Conclusions:ZMIZ2 and MCM3 were highly expressed in TNBC.ZMIZ2 promoted the development by positively regulating MCM3 expression.Key pathways,such as the Ras/MAPK,phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mTOR,and Wnt signaling pathways,may be key downstreammechanisms.展开更多
“Ruyong(breast abscess)”has a high incidence rate.Traditional Chinese medicine(TCM)diagnosis and treatment of this condition demonstrate significant advantages,including diverse therapeuticmethods,outstanding effica...“Ruyong(breast abscess)”has a high incidence rate.Traditional Chinese medicine(TCM)diagnosis and treatment of this condition demonstrate significant advantages,including diverse therapeuticmethods,outstanding efficacy,and high safety.Based on TCM theory and combining relevant ancient texts and modern research,this paper systematically summarizes the different understandings of“Ruyong(breast abscess)”by physicians throughout history in terms of disease names,etiology,pathogenesis,and treatment.The ancient names for Ruyong(breast abscess)were varied,also referred to as“Duru(stagnation in breast)”or“Naichuang(breast sore)”.Its symptoms are diverse,with the main clinical manifestations being localized redness,swelling,heat,pain,and poor milk discharge in the affected breast.The etiology is primarily attributed to“milk stasis”“liver qi stagnation and stomach heat”and“exposure to external pathogens”.Additionally,this paper summarizes the treatment experiences from ancient and modern medical texts and highlights the complementary effects of internal and external therapies.This study provides a reference for modern clinical understanding and treatment of“Ruyong(breast abscess)”in the hope of further improvement of clinical efficacy.展开更多
Mammary stem cells(MaSCs),endowed with self-renewal and multilineage differentiation capabilities,are crucial for mammary gland development,function,and disease initiation.Recent advances in MaSCs biology research enc...Mammary stem cells(MaSCs),endowed with self-renewal and multilineage differentiation capabilities,are crucial for mammary gland development,function,and disease initiation.Recent advances in MaSCs biology research encompass molecular marker identification,regulatory pathway dissection,and microenvironmental crosstalk.This review synthesizes key progress and remaining challenges in MaSC research.Molecular profiling advances have identified key markers recently,such as Procr,DII1,Bcl11b,and PD-L1.Central to their regulatory logic are evolutionarily conserved pathways,including Wnt,Notch,Hedgehog,and Hippo,which exhibit context-dependent thresholds to balance self-renewal and differentiation.Beyond intrinsic signaling,the dynamic interplay between MaSCs and their microenvironment,such as luminalderived Wnt4,macrophage-mediated TNF-α signaling,and adrenergic inputs from sympathetic nerves,spatially orchestrates stem cell behavior.In addition,this review also discusses the roles of breast cancer stem cells(BCSCs) in tumorigenesis and therapeutic resistance,focusing on the molecular mechanisms underlying MaSC transformation into BCSCs.Despite progress,challenges remain:human MaSCs functional assays lack standardization,pathway inhibitors risk off-target effects,and delivery systems lack precision.Emerging tools like spatial multi-omics,organoids,and biomimetic scaffolds address these gaps.By integrating MaSCs and BCSCs biology,this review links mechanisms to breast cancer and outlines strategies to target malignancy to accelerate clinical translation.展开更多
The principal breast cancer treatment approach has long been surgical removal of the primary breast lesions and regional lymph nodes,particularly the axillary lymph nodes.However,the advent of minimally invasive diagn...The principal breast cancer treatment approach has long been surgical removal of the primary breast lesions and regional lymph nodes,particularly the axillary lymph nodes.However,the advent of minimally invasive diagnostic techniques,such as sentinel lymph node biopsy(SLNB),has markedly diminished the extent of surgery required for regional lymph nodes.展开更多
Mammographic screening has been pivotal in early breast cancer detection,significantly reducing mortality by enabling timely detection for interventions.1 Mammography remains the gold standard for breast cancer screen...Mammographic screening has been pivotal in early breast cancer detection,significantly reducing mortality by enabling timely detection for interventions.1 Mammography remains the gold standard for breast cancer screening due to its proven ability to detect early-stage cancers and its accessibility for large-scale population screening.Unlike ultrasound,which is typically used as a supplementary tool for dense breast tissue,or MRI,which is often reserved for high-risk cases due to its high cost and longer procedure time,mammography provides a standardized,cost-effective modality suitable for widespread use.By applying artificial intelligence(AI)in mammography,healthcare systems can enhance the accuracy and efficiency of screening programs,particularly in high-volume settings.However,interpreting mammograms requires highly trained specialists,and training radiologists is both time consuming and resource-intensive.展开更多
文摘Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance patients remains limited.This study examined real-world outcomes of palbociclib plus endocrine therapy in Asian patients,with additional subgroup analyses by age and performance status.Methods:We retrospectively analyzed 46 consecutive Asian patients with recurrent or de novo HR+/HER2−breast cancer treated with first-line palbociclib plus ET between April 2021 and March 2025.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall response rate(ORR),disease control rate(DCR),and safety.Subgroup analyses were performed by age(<70 vs.≥70 years)and performance status(PS;0–1 vs.2–3).Results:The median PFS was 26.6 months(range,1.4–69.5).Stratified by age,median PFS was 26.9 months in patients<70 years and 26.2 months in those≥70 years(p=0.760).By PS,PFS was 26.9 months for PS 0–1 and 17.8 months for PS 2–3(p=0.099).ORR was 60.9%and DCR 93.5%;notably,all PS 2–3 patients achieved disease control.Hematologic toxicities were common,with neutropenia(80.4%)and leukopenia(86.7%)predominating,but grade≥3 anemia was rare(2.2%).Elderly patients experienced anemia more frequently,while overall toxicity remained manageable.Dose reductions occurred in 47.8%without loss of efficacy.Conclusions:In routine Japanese practice,palbociclib plus ET provided prolonged PFS and high disease control consistent with pivotal trials and international real-world evidence.Importantly,elderly patients tolerated treatment well,and selected PS 2–3 patients also derived clinical benefit.These findings indicate that neither age nor PS alone should preclude the use of palbociclib in carefully monitored real-world patients.
文摘Objective:To investigate the long-term prognosis and postoperative cosmetic outcomes of breast-conserving surgery combined with sentinel lymph node biopsy in patients with early-stage breast cancer,providing a reference for the selection of clinical treatment plans.Methods:A retrospective analysis was conducted on the clinical data of 68 patients with early-stage breast cancer admitted from January 2022 to December 2025.Based on the surgical approach,patients were divided into an observation group(breast-conserving surgery+sentinel lymph node biopsy)and a control group(other surgical methods such as modified radical mastectomy/total mastectomy).Clinical and pathological characteristics,incidence of postoperative complications,follow-up prognosis,and satisfaction with cosmetic outcomes were compared between the two groups.Results:Among the 68 patients,41 were in the observation group and 27 in the control group.The average age of patients in the observation group was(54.32±8.15)years,while that in the control group was(62.45±9.76)years.The average tumor size in the observation group was(1.86±0.72)cm,compared to(3.21±1.45)cm in the control group.The incidence of postoperative complications in the observation group was 9.76%,significantly lower than that in the control group at 33.33%(P<0.05).The 6-month disease-free survival rate was 95.12%in the observation group and 88.89%in the control group,with no statistically significant difference between the two groups(P>0.05).The excellent and good rate of cosmetic outcomes in the observation group was 87.80%,significantly higher than that in the control group at 29.63%(P<0.05).Conclusion:Breast-conserving surgery combined with sentinel lymph node biopsy for early-stage breast cancer can achieve long-term prognostic outcomes comparable to those of traditional radical surgery,with the advantages of fewer postoperative complications and superior cosmetic results.This approach is worthy of clinical promotion and application,particularly for early-stage breast cancer patients who have a demand for preserving breast morphology.
文摘BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.
文摘Breast cancer(BRCA)is characterized by high heterogeneity,with aggressive subtypes frequently showing poor prognosis and resistance to conventional therapies,making the discovery of new therapeutic targets and strategies imperative.Although elevated expression of discs large homolog 3(DLG3)has been reported in BRCA,its functional role in disease progression remains unclear.We performed bioinformatic analyses of clinical datasets to evaluate the prognostic significance of DLG3 expression in BRCA patients.In vitro gain-and loss-of-function experiments were conducted to assess the impact of DLG3 on BRCA cell proliferation,migration,and colony formation.Transcriptomic profiling,coupled with pharmacological inhibition,was employed to identify and validate downstream signaling pathways.Additionally,we extended our validation to an in vivo model to assess the role of DLG3 in tumor progression.We found that elevated DLG3 levels correlated with poor prognosis in breast cancer patients.Functionally,DLG3 overexpression significantly promoted cell proliferation and migration in estrogen receptor-positive MCF7 and triple-negative MDA-MB-231 breast cancer cells,whereas its knockdown suppressed these effects.Transcriptomic analyses revealed that DLG3 activates signal transducer and activator of transcription 3(STAT3)signaling,a finding further corroborated by Western blot.Critically,treatment with the STAT3 inhibitor Stattic attenuated DLG3-driven proliferation and migration,supporting a DLG3-STAT3 oncogenic axis.Furthermore,in vivo studies validated the role of DLG3 in promoting tumor growth and its correlation with elevated STAT3 signaling,consistent with our in vitro findings.Our findings establish DLG3 as a novel driver of breast cancer progression that directly activates STAT3 signaling.DLG3 thus represents both a potential prognostic biomarker and a promising therapeutic target for aggressive breast cancer subtypes,including triple-negative breast cancer.
基金funded by Al Jalila Foundation-Research Grant(AJF2023-078)to SSMS.
文摘Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabolism,in the aggressiveness and metastatic behavior of BC.Methods:A comprehensive analysis was performed using in silico transcriptomic data(n=2509 patients),immunohistochemical profiling of BC tissues(n=103),and validation through western blotting in multiple BC cell lines.Gene expression and survival analyses were conducted using Tumor Immune Estimation Resource(TIMER),Gene Expression Profiling Interactive Analysis 2(GEPIA2),and the cBioPortal for cancer genomics(cBioPortal)platforms.Correlations between PNP and key epithelial–mesenchymal transition(EMT)markers,molecular subtypes,tumor grades,and stages were examined.Results:PNP was significantly overexpressed in human epidermal growth factor receptor 2(HER-2)-positive and triple-negative BCs compared to luminal subtypes.High PNP levels were strongly associated with advanced BC stages,high-grade tumors,EMT phenotypes,and poor overall survival.Notably,HER-2 inhibition suppressed PNP expression,while PNP gene silencing induced HER-2 upregulation,revealing a reciprocal regulatory loop.Dual inhibition of PNP and HER-2 resulted in a significant reduction in cell viability compared to HER-2 inhibition alone.Conclusion:Collectively,PNP emerges as a promising biomarker of BC aggressiveness and progression.Its reciprocal interaction with HER-2 underscores its potential as a therapeutic target.Dual targeting of PNP and HER-2 may offer a novel strategy for improving outcomes in aggressive BC subtypes.
基金funded by BK21 FOUR(Fostering Outstanding Universities for Research)(No.:5199990914048).
文摘Accurate segmentation of breast cancer in mammogram images plays a critical role in early diagnosis and treatment planning.As research in this domain continues to expand,various segmentation techniques have been proposed across classical image processing,machine learning(ML),deep learning(DL),and hybrid/ensemble models.This study conducts a systematic literature review using the PRISMA methodology,analyzing 57 selected articles to explore how these methods have evolved and been applied.The review highlights the strengths and limitations of each approach,identifies commonly used public datasets,and observes emerging trends in model integration and clinical relevance.By synthesizing current findings,this work provides a structured overview of segmentation strategies and outlines key considerations for developing more adaptable and explainable tools for breast cancer detection.Overall,our synthesis suggests that classical and ML methods are suitable for limited labels and computing resources,while DL models are preferable when pixel-level annotations and resources are available,and hybrid pipelines are most appropriate when fine-grained clinical precision is required.
文摘The integration of machine learning(ML)technology with Internet of Things(IoT)systems produces essential changes in healthcare operations.Healthcare personnel can track patients around the clock thanks to healthcare IoT(H-IoT)technology,which also provides proactive statistical findings and precise medical diagnoses that enhance healthcare performance.This study examines how ML might support IoT-based health care systems,namely in the areas of prognostic systems,disease detection,patient tracking,and healthcare operations control.The study looks at the benefits and drawbacks of several machine learning techniques for H-IoT applications.It also examines the fundamental problems,such as data security and cyberthreats,as well as the high processing demands that these systems face.Alongside this,the essay discusses the advantages of all the technologies,including machine learning,deep learning,and the Internet of Things,as well as the significant difficulties and problems that arise when integrating the technology into healthcare forecasts.
基金National Research,Development and Innovation Fund of the Ministry of Culture and Innovation under the National Laboratories Program(National Tumor Biology Laboratory,Grant/Award Number:2022-2.1.1-NL-2022-00010)Senior Research Fellowship from National Health and Medical Research Council of Australia,Grant/Award Number:1156693+1 种基金Hungarian Thematic Excellence Program,Grant/Award Number:TKP2021-EGA-44Tour de Cure,Pioneering Grant,Grant/Award Number:RSP-253-18/19。
文摘Realistic models for cancer research representing disease progression that commensurately respond to therapeutics consistent with clinical observation are the holy grail for pre-clinical research and screening.Although such an ideal is elusive,well-characterized in vivo models facilitate our understanding of disease,progression,and therapeutic opportunities.Here,we characterize a commonly used syngeneic BALB/c mouse model of triple negative breast cancer(4T1)after establishing tumors in their flanks.Tumors developed at the subcutaneous injection site for all experimental mice and their volumes were monitored.We quantified a rare subset of breast cancer stemlike cells(CSCs),classified as CD44^(+)/CD24^(−)phenotypes in in vitro and ex vivo cell populations.Chromosome numbers in ex vivo metaphase cells were greater than cells cultured in vitro(89.4±3.4,range of 70-132 and 82.6±1.1,range of 70-128;respectively).Further,we observed different types of chromosome aberrations,including gap,deletion,exchange,interstitial deletion,terminal deletion,ring,dicentric,and Robertsonian translocations.For both sources of cells,the number of aberrations was dominated by deletions,terminal deletions,and Robertsonian translocations.Ex vivo cells exhibited greater prevalence of deletions and terminal deletions,whereas in vitro cells displayed more ring aberrations and Robertsonian translocations.In conclusion,we successfully characterized cancer cells from a syngeneic mouse model of breast cancer in terms of rare CSC proportion and a variety of chromosomal aberrations,which is useful for understanding tumor traits associated with cancer development and therapeutic action.The data act as a valuable resource for other studies using the 4T1 BALB/c model.
文摘Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor(ER)-positive,and lacks routine screening,leading to delayed diagnosis and advanced disease.Major risk factors include hormonal imbalance,radiation exposure,obesity,alcohol use,and Breast Cancer Gene 1 and 2(BRCA1/2)mutations.Clinically,it may resemble gynecomastia but usually appears as a unilateral,painless mass or nipple discharge.Advances in imaging and liquid biopsy have enhanced early detection.Molecular mechanisms involve hormonal signaling,HER2/epidermal growth factor receptor(EGFR)pathways,tumor suppressor gene alterations,and epigenetic changes.While standard treatments mirror those for female breast cancer,emerging options such as cyclin-dependent kinase 4 and 6(CDK4/6),and poly(ADP-ribose)polymerase(PARP)inhibitors,immunotherapy,and precision medicine are reshaping management.Incorporating artificial intelligence,molecular profiling,and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.
文摘Objective:To evaluate the clinical efficacy of blood-letting cupping combined with manual lymphatic drainage in treating breast cancer-related lymphedema(BCRL)and explore its mechanism of action from both traditional Chinese medicine and modern medical perspectives,providing a scientific basis and novel therapeutic approaches for clinical management of BCRL.Methods:Patients with BCRL admitted to the outpatient and inpatient departments of Hebei University Affiliated Hospital were enrolled.A prospective randomized controlled trial design was adopted,with eligible patients randomly assigned to a treatment group and a control group.The control group received manual lymphatic drainage alone,while the treatment group received manual lymphtic drainage combined with blood-letting cupping therapy.Posttreatment comparisons evaluated upper limb circumference reduction,edema severity grading,and upper limb functional scores.Vital signs and adverse reactions during treatment were recorded for both groups.Statistical software analyzed the data.Results:The treatment group demonstrated significantly greater reduction in upper limb circumference,improvement in edema severity,and higher upper limb function scores compared to the control group(P<0.05).Vital signs remained stable throughout treatment in both groups.No severe adverse reactions occurred in the treatment group;only isolated cases of mild skin itching were reported,which resolved after symptomatic management.Conclusion:The combination of bloodletting cupping and manual lymphatic drainage demonstrates reliable efficacy in treating BCRL,effectively alleviating edema symptoms and improving upper limb function with high safety.Its mechanism may relate to traditional Chinese medicine principles of“unblocking meridians,promoting blood circulation,and resolving stasis”and modern medical concepts of“enhancing local blood circulation,facilitating lymphatic drainage,and reducing inflammatory responses”.
基金Noncommunicable Chronic Diseases-National Science and Technology Major Project,Grant/Award Numbers:2024ZD0521400,2024ZD0521404Affiliated Hospital of Qinghai University。
文摘Introduction:Chemotherapy-induced gastrointestinal symptom clusters in breast cancer impair quality of life and treatment adherence,yet lack effective interventions.While acupuncture mitigates isolated chemotherapy-induced symptoms,its mechanisms for multi-symptom clusters remain unclear.This study evaluates electroacupuncture's efficacy and explores its biological mechanisms in managing these clusters.Methods:This prospective,multicenter,block-randomized,double-blind,sham-controlled trial will enroll 388 patients with breast cancer undergoing neoadjuvant/adjuvant chemotherapy,to be randomly assigned(1:1)to electroacupuncture or sham electro-acupuncture groups.Both groups will receive the standard quadruple antiemetic regimen combined with electroacupuncture or sham intervention.The primary endpoint is the incidence of chemotherapy-induced gastrointestinal symptom clusters within 120 h after chemotherapy.Secondary endpoints include improvement in gastrointestinal symptom clusters post-first chemotherapy cycle,nausea-free rates during acute and delayed phases,vomiting-free rates during overall,acute,and delayed phases,complete response rate,complete protection rate,and quality of life.Adverse events will be documented throughout the study.Discussion:This study will assess the efficacy and safety of electroacupuncture in alleviating chemotherapy-induced gastro-intestinal symptom clusters in patients with breast cancer.By integrating multi-omics analyses,we aim to elucidate the biological mechanisms underlying its therapeutic effects.The findings may offer a robust clinical foundation for optimizing symptom cluster management in cancer care.Trial Registration:Clinical Trials ID:NCT06952920.Date of registration:April 16,2025.Prospectively registered.URL of Trial Registry Record:https://clinicaltrials.gov/study/NCT06952920cond=NCT06952920&rank=1.
基金supported by the Natural Science Foundation of Guangdong Province(No.2021B1515120053)Guangdong Basic and Applied Basic Research Foundation(Grant No.2024A1515140166).
文摘Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual patient responses towards different drugs.This study aimed to investigate the patient-derived breast cancer culture models for drug sensitivity evaluations.Methods:Tumor and adjacent tissues from female breast cancer patients were collected during surgery.Patient-derived breast cancer cells were cultured using the conditional reprogramming technique to establish 2D models.The obtained patient-derived conditional reprogramming breast cancer(CRBC)cells were subsequently embedded in alginate-gelatin methacryloyl hydrogel microspheres to form 3D culture models.Comparisons between 2D and 3D models were made using immunohistochemistry(tumor markers),MTS assays(cell viability),flow cytometry(apoptosis),transwell assays(migration),and Western blotting(protein expression).Drug sensitivity tests were conducted to evaluate patient-specific responses to anti-cancer agents.Results:2D and 3D culture models were successfully established using samples from eight patients.The 3D models retained histological and marker characteristics of the original tumors.Compared to 2D cultures,3D models exhibited increased apoptosis,enhanced drug resistance,elevated stem cell marker expression,and greater migration ability—features more reflective of in vivo tumor behavior.Conclusion:Patient-derived 3D CRBC models effectively mimic the in vivo tumor microenvironment and demonstrate stronger resistance to anti-cancer drugs than 2D models.These hydrogel-based models offer a cost-effective and clinically relevant platform for drug screening and personalized breast cancer treatment.
基金funded by the Ministry of Higher Education(MoHE)Malaysia through the Fundamental Research Grant Scheme—Early Career Researcher(FRGS-EC),grant number FRGSEC/1/2024/ICT02/UNIMAP/02/8.
文摘critical for guiding treatment and improving patient outcomes.Traditional molecular subtyping via immuno-histochemistry(IHC)test is invasive,time-consuming,and may not fully represent tumor heterogeneity.This study proposes a non-invasive approach using digital mammography images and deep learning algorithm for classifying breast cancer molecular subtypes.Four pretrained models,including two Convolutional Neural Networks(MobileNet_V3_Large and VGG-16)and two Vision Transformers(ViT_B_16 and ViT_Base_Patch16_Clip_224)were fine-tuned to classify images into HER2-enriched,Luminal,Normal-like,and Triple Negative subtypes.Hyperparameter tuning,including learning rate adjustment and layer freezing strategies,was applied to optimize performance.Among the evaluated models,ViT_Base_Patch16_Clip_224 achieved the highest test accuracy(94.44%),with equally high precision,recall,and F1-score of 0.94,demonstrating excellent generalization.MobileNet_V3_Large achieved the same accuracy but showed less training stability.In contrast,VGG-16 recorded the lowest performance,indicating a limitation in its generalizability for this classification task.The study also highlighted the superior performance of the Vision Transformer models over CNNs,particularly due to their ability to capture global contextual features and the benefit of CLIP-based pretraining in ViT_Base_Patch16_Clip_224.To enhance clinical applicability,a graphical user interface(GUI)named“BCMS Dx”was developed for streamlined subtype prediction.Deep learning applied to mammography has proven effective for accurate and non-invasive molecular subtyping.The proposed Vision Transformer-based model and supporting GUI offer a promising direction for augmenting diagnostic workflows,minimizing the need for invasive procedures,and advancing personalized breast cancer management.
基金the Natural Science Foundation of Yongchuan District,No.2023yc-jckx20021.
文摘BACKGROUND Breast cancer is one of the most prevalent malignancies affecting women worldwide,with approximately 2.3 million new cases diagnosed annually.Breast cancer stem cells(BCSCs)play pivotal roles in tumor initiation,progression,metastasis,therapeutic resistance,and disease recurrence.Cancer stem cells possess selfrenewal capacity,multipotent differentiation potential,and enhanced tumorigenic activity,but their molecular characteristics and regulatory mechanisms require further investigation.AIM To comprehensively characterize the molecular features of BCSCs through multiomics approaches,construct a prognostic prediction model based on stem cellrelated genes,reveal cell-cell communication networks within the tumor microenvironment,and provide theoretical foundation for personalized treatment strategies.METHODS Flow cytometry was employed to detect the expression of BCSC surface markers(CD34,CD45,CD29,CD90,CD105).Transcriptomic analysis was performed to identify differentially expressed genes.Least absolute shrinkage and selection operator regression analysis was utilized to screen key prognostic genes and construct a risk scoring model.Single-cell RNA sequencing and spatial transcriptomics were applied to analyze tumor heterogeneity and spatial gene expression patterns.Cell-cell communication network analysis was conducted to reveal interactions between stem cells and the microenvironment.RESULTS Flow cytometric analysis revealed the highest expression of CD105(96.30%),followed by CD90(68.43%)and CD34(62.64%),while CD29 showed lower expression(7.16%)and CD45 exhibited the lowest expression(1.19%).Transcriptomic analysis identified 3837 significantly differentially expressed genes(1478 upregulated and 2359 downregulated).Least absolute shrinkage and selection operator regression analysis selected 10 key prognostic genes,and the constructed risk scoring model effectively distinguished between high-risk and low-risk patient groups(P<0.001).Single-cell analysis revealed tumor cellular heterogeneity,and spatial transcriptomics demonstrated distinct spatial expression gradients of stem cell-related genes.MED18 gene showed significantly higher expression in malignant tissues(P<0.001)and occupied a central position in cell-cell communication networks,exhibiting significant correlations with tumor cells,macrophages,fibroblasts,and endothelial cells.CONCLUSION This study comprehensively characterized the molecular features of BCSCs through multi-omics approaches,identified reliable surface markers and key regulatory genes,and constructed a prognostic prediction model with clinical application value.
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.
基金supported by the Jilin Province Health Science and Technology Ability Improvement Project(2023JL057).
文摘Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containing 2(ZMIZ2)and minichromosome maintenance complex component 3(MCM3)in TNBC progression.Methods:The relationship between ZMIZ2 expression and clinical characteristics of TNBC was investigated.In vitro and in vivo experiments were performed to investigate the role of ZMIZ2 dysregulation in TNBC cell malignant behaviors.The regulatory relationship between ZMIZ2 and MCM3 was also explored.Transcriptome sequencing was performed to elucidate possible mechanisms underlying the ZMIZ2/MCM3 axis in TNBC.Results:High ZMIZ2 expression levels were associated with the malignant degree of TNBC.ZMIZ2 overexpression promoted TNBC cell proliferation,migration,and invasion;inhibited apoptosis;and induced G1 phase cell cycle arrest,whereas knockdown of ZMIZ2 had the opposite effect.ZMIZ2 directly targeted and positively regulated MCM3 expression.MCM3 knockdown reversed the effect of ZMIZ2 overexpression on TNBC tumor growth both in vitro and in vivo.High MCM3 expression levels were linked to the degree of malignancy and poor prognosis in TNBC.The differentially expressed genes associated with the ZMIZ2/MCM3 axis were significantly enriched in multiple pathways,such as the mitogen-activated protein kinase(MAPK),mechanistic target of rapamycin(mTOR),Wnt,and Ras signaling pathways,as verified by The Cancer Genome Atlas data.Conclusions:ZMIZ2 and MCM3 were highly expressed in TNBC.ZMIZ2 promoted the development by positively regulating MCM3 expression.Key pathways,such as the Ras/MAPK,phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mTOR,and Wnt signaling pathways,may be key downstreammechanisms.
基金supported by 2024 Henan Provincial Special Research Project on Traditional Chinese Medicine(2024ZY2158)Henan Provincial Key Discipline Construction Project of Traditional Chinese Medicine{Yuwei Traditional Chinese Medicine Science and Education[2024]No.1}+1 种基金Key Disciplines of History and Literature of Chinese Medicine in Henan University of Chinese Medicine for the Year 2025{Henan Traditional Chinese Medicine Office[2025]No.13}National Chinese Medicine Advantage Specialty Construction Project{Chinese Traditional Chinese Medicine Political Letter(2024)No.90}.
文摘“Ruyong(breast abscess)”has a high incidence rate.Traditional Chinese medicine(TCM)diagnosis and treatment of this condition demonstrate significant advantages,including diverse therapeuticmethods,outstanding efficacy,and high safety.Based on TCM theory and combining relevant ancient texts and modern research,this paper systematically summarizes the different understandings of“Ruyong(breast abscess)”by physicians throughout history in terms of disease names,etiology,pathogenesis,and treatment.The ancient names for Ruyong(breast abscess)were varied,also referred to as“Duru(stagnation in breast)”or“Naichuang(breast sore)”.Its symptoms are diverse,with the main clinical manifestations being localized redness,swelling,heat,pain,and poor milk discharge in the affected breast.The etiology is primarily attributed to“milk stasis”“liver qi stagnation and stomach heat”and“exposure to external pathogens”.Additionally,this paper summarizes the treatment experiences from ancient and modern medical texts and highlights the complementary effects of internal and external therapies.This study provides a reference for modern clinical understanding and treatment of“Ruyong(breast abscess)”in the hope of further improvement of clinical efficacy.
基金supported by the National Natural Science Foundation of China(32270837 and 32470849 to C.C.32400661 to M.Z.)the Key Research Project of Hangzhou Institute for Advanced Study(B04006C023001 to C.C.).
文摘Mammary stem cells(MaSCs),endowed with self-renewal and multilineage differentiation capabilities,are crucial for mammary gland development,function,and disease initiation.Recent advances in MaSCs biology research encompass molecular marker identification,regulatory pathway dissection,and microenvironmental crosstalk.This review synthesizes key progress and remaining challenges in MaSC research.Molecular profiling advances have identified key markers recently,such as Procr,DII1,Bcl11b,and PD-L1.Central to their regulatory logic are evolutionarily conserved pathways,including Wnt,Notch,Hedgehog,and Hippo,which exhibit context-dependent thresholds to balance self-renewal and differentiation.Beyond intrinsic signaling,the dynamic interplay between MaSCs and their microenvironment,such as luminalderived Wnt4,macrophage-mediated TNF-α signaling,and adrenergic inputs from sympathetic nerves,spatially orchestrates stem cell behavior.In addition,this review also discusses the roles of breast cancer stem cells(BCSCs) in tumorigenesis and therapeutic resistance,focusing on the molecular mechanisms underlying MaSC transformation into BCSCs.Despite progress,challenges remain:human MaSCs functional assays lack standardization,pathway inhibitors risk off-target effects,and delivery systems lack precision.Emerging tools like spatial multi-omics,organoids,and biomimetic scaffolds address these gaps.By integrating MaSCs and BCSCs biology,this review links mechanisms to breast cancer and outlines strategies to target malignancy to accelerate clinical translation.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.81672638 and W2421095)National Natural Science Foundation of Shandong Province(Grant No.ZR2024LMB011)Collaborative Academic Innovation Project of Shandong Cancer Hospital(Grant No.GF003)。
文摘The principal breast cancer treatment approach has long been surgical removal of the primary breast lesions and regional lymph nodes,particularly the axillary lymph nodes.However,the advent of minimally invasive diagnostic techniques,such as sentinel lymph node biopsy(SLNB),has markedly diminished the extent of surgery required for regional lymph nodes.
基金supported by the NUHS Clinician Scientist Program 2.0(NCSP 2.0)under Department of Surgery,National University Hospital.The study design,data collection,data analysis and interpretation were conducted by the study team independently.
文摘Mammographic screening has been pivotal in early breast cancer detection,significantly reducing mortality by enabling timely detection for interventions.1 Mammography remains the gold standard for breast cancer screening due to its proven ability to detect early-stage cancers and its accessibility for large-scale population screening.Unlike ultrasound,which is typically used as a supplementary tool for dense breast tissue,or MRI,which is often reserved for high-risk cases due to its high cost and longer procedure time,mammography provides a standardized,cost-effective modality suitable for widespread use.By applying artificial intelligence(AI)in mammography,healthcare systems can enhance the accuracy and efficiency of screening programs,particularly in high-volume settings.However,interpreting mammograms requires highly trained specialists,and training radiologists is both time consuming and resource-intensive.
