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
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
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
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
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
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 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
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
In the era of precision medicine,the breast cancer surgical treatment field is gradually moving toward a de-escalation model.Through precise preoperative assessments and multidisciplinary decision-making,surgical trau...In the era of precision medicine,the breast cancer surgical treatment field is gradually moving toward a de-escalation model.Through precise preoperative assessments and multidisciplinary decision-making,surgical trauma can be decreased,and patients’quality of life can be improved by ensuring safety.Herein,we explore the axillary de-escalation surgery model for breast cancer.展开更多
In order to solve the challenge of breast cancer region segmentation,we improved the U-Net.The convolutional block attention module with prioritized attention(CBAM-PA)and dilated transformer(Dformer)modules were desig...In order to solve the challenge of breast cancer region segmentation,we improved the U-Net.The convolutional block attention module with prioritized attention(CBAM-PA)and dilated transformer(Dformer)modules were designed to replace the convolutional layers at the encoding side in the base U-Net,the input logic of the U-Net was improved by dynamically adjusting the input size of each layer,and the short connections in the U-Net were replaced with crosslayer connections to enhance the image restoration capability at the decoding side.On the breast ultrasound images(BUSI)dataset,we obtain a Dice coefficient of 0.8031 and an intersection-over-union(IoU)value of 0.7362.The experimental results show that the proposed enhancement method effectively improves the accuracy and quality of breast cancer lesion region segmentation.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
Triple-negative breast cancer(TNBC)is currently the most heterogeneous and aggressive breast cancer type.It has a high recurrence rate,poor clinical prospects,and lack of predictive markers and potential treatment opt...Triple-negative breast cancer(TNBC)is currently the most heterogeneous and aggressive breast cancer type.It has a high recurrence rate,poor clinical prospects,and lack of predictive markers and potential treatment options.Dysregulated microRNAs(miRNAs)are involved in various cellular processes in TNBC.Moreover,variations in the miRNA levels in TNBC may act as a dependable indicator for predicting the effectiveness and specificity of treatments.Currently,the application of miRNAs for breast cancer therapy is primarily in the preclinical stage,with a focus on identifying highly specific and sensitive miRNAs that could offer new possibilities for early diagnosis,clinical treat-ment,and prognostic monitoring of TNBC.展开更多
BACKGROUND Breast cancer(BC)continues to occupy a leading position in terms of morbidity and mortality from malignant neoplasms among the female population.One of the promising markers associated with BC progression i...BACKGROUND Breast cancer(BC)continues to occupy a leading position in terms of morbidity and mortality from malignant neoplasms among the female population.One of the promising markers associated with BC progression is programmed death ligand 1(PD-L1).Previously,we investigated PD-L1 expression in BC via a new antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)and reported that high PDCD1 LG1 expression in tumor cells is an independent factor for a high risk of regional metastasis in patients with BC.However,the prognostic significance of PDCD1 LG1 expression in BC stromal cells has not been adequately studied.AIM To study the features of PDCD1 LG1 expression in BC stromal cells and its relationship with BC clinicopathological characteristics.METHODS In a prospective single-center observational study,tumor samples from 148 patients with newly diagnosed BC were examined.The tumor sections were immunohistochemically stained with antibodies against PDCD1 LG1.In the tumor samples,the PDCD1 LG1-positive lymphocyte(PDCD1 LG1+LF)score,presence of nuclear PDCD1 LG1 expression in the LFs,PDCD1 LG1 expression in polymorphic cell infiltrates(PDCD1 LG1+polymorphic cell infiltrates[PCIs]),and cells of the fibroblastic stroma and endothelial cells of the tumor microvessels were assessed.Statistical analyses were performed using Statistica 10.0 software.RESULTS A PDCD1 LG1+LF score≥3 was detected more often at stages N0 and N3 than at N1 and N2(P=0.03).Moderate and pronounced PDCD1 LG1+PCIs and the presence of PDCD1 LG1+fibroblastic stroma were associated with negative estrogen receptor status(P=0.0008 and P=0.03,respectively),human epidermal growth factor receptor 2-positive(HER2+)BC(P<0.00001 and P=0.0005),and luminal B HER2+,non-luminal HER2+and triple-negative BC(P<0.00001 and P=0.004).The risk of metastasis to regional lymph nodes(RLNs)depend on lymphovascular invasion(LVI)and the PDCD1 LG1+LF score.In the absence of LVI and a PDCD1 LG1+LF score<3 or≥3,metastases in RLNs were absent in 66.6%and 93.9%of patients with BC,respectively.In the presence of LVI and a PDCD1 LG1+LF score<3 or≥3,metastases in RLNs were detected in 82.6%and 92.7%of patients with BC,respectively.CONCLUSION The results indicated that the combined assessment of the PDCD1 LG1+LF score and LVI can improve the accuracy of predicting the risk of metastasis to RLNs in patients with BC.展开更多
BACKGROUND Breast cancer is one of the most prevalent causes of morbidity and mortality worldwide,presenting an increasing public health challenge,particularly in lowincome and middle-income countries.However,data on ...BACKGROUND Breast cancer is one of the most prevalent causes of morbidity and mortality worldwide,presenting an increasing public health challenge,particularly in lowincome and middle-income countries.However,data on the knowledge,attitudes,and preventive practices regarding breast cancer and the associated factors among females in Wollo,Ethiopia,remain limited.AIM To assess the impact of family history(FH)of breast disease on knowledge,attitudes,and breast cancer preventive practices among reproductive-age females.METHODS A community-based cross-sectional study was conducted in May and June 2022 in Northeast Ethiopia and involved 143 reproductive-age females with FH of breast diseases and 209 without such a history.We selected participants using the systematic random sampling technique.We analyzed the data using Statistical Package for Social Science version 25 software,and logistic regression analysis was employed to determine odds ratios for variable associations,with statistical significance set at P<0.05.RESULTS Among participants with FH of breast diseases,the levels of knowledge,attitudes,and preventive practices were found to be 83.9%[95%confidence interval(CI):77.9-89.9],49.0%(95%CI:40.8-57.1),and 74.1%(95%CI:66.9-81.3),respectively.In contrast,among those without FH of breast diseases,these levels were significantly decreased to 10.5%(95%CI:6.4-14.7),32.1%(95%CI:25.7-38.4),and 16.7%(95%CI:11.7-21.8),respectively.This study also indicated that knowledge,attitudes,and preventive practices related to breast cancer are significantly higher among participants with FH of breast diseases compared to those without HF breast diseases.CONCLUSION Educational status,monthly income,and community health insurance were identified as significant factors associated with the levels of knowledge,attitudes,and preventive practices regarding breast cancer among reproductive-age females.展开更多
Objectives This study aimed to develop and preliminarily assess the quality of a Mindfulness Breast Care(MBC)App to reduce body image distress and stigma among breast cancer survivors(BCSs).Methods The development pro...Objectives This study aimed to develop and preliminarily assess the quality of a Mindfulness Breast Care(MBC)App to reduce body image distress and stigma among breast cancer survivors(BCSs).Methods The development process of the MBC App involved:1)establishing a research group;2)determining of the content of the MBC App based on Mindfulness-Based Cognitive Therapy and 3)technical exploitation and maintenance.A mixed-methods study was conducted.We selected ten BCSs by a convenience sampling method.After using the APP for three months,five assessed the quality using the Mobile App Rating Scale:User Version(uMARS)and another five were interviewed for process evaluation.Results The MBC App was developed with three modules:1)Library to provide health education information on body image,stigma,mindfulness,recovery and etc;2)Mindfulness Yoga to offer 12 Hatha yoga videos for daily practice;and 3)Mindfulness Practices to have 12 sessions of mindfulness videoconferences.Based on the uMARS data,the MBC App received high ratings for functionality(4.10±0.34),aesthetics(3.93±0.55),information quality(4.10±0.72),and perceived impact(4.03±0.96),as well as moderate ratings for engagement(3.72±0.94)and subjective quality(3.87±0.77).Participants indicated that the MBC App provided reliable knowledge,information,and emotional support.Recommendations from participants included categorizing knowledge in the Library Module,recording videoconferences of mindfulness practice,and adding discussion sessions in the videoconference.Afterward,we optimized the MBC App to enhance the user experience accordingly.Conclusions The MBC App offers online mindfulness interventions specifically for BCSs in China.The preliminary quality assessment indicates that the MBC App may be a promising tool for delivering mindfulness interventions to BCSs.展开更多
Lipids serve as fundamental constituents of cell membranes and organelles.Recent studies have highlighted the significance of lipids as biomarkers in the diagnosis of breast cancer.Although liquid chromatography coupl...Lipids serve as fundamental constituents of cell membranes and organelles.Recent studies have highlighted the significance of lipids as biomarkers in the diagnosis of breast cancer.Although liquid chromatography coupled with tandem mass spectrometry(LC-MS/MS)is widely employed for lipid analysis in complex samples,it suffers from limitations such as complexity and time-consuming procedures.In this study,we have developed dopamine-modified TiO_(2)nanoparticles(TiO_(2)-DA)and applied the materials to assist the analysis of lipids by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS).The TiO_(2)-DA can provide large specific surface area and acidic environment,well suited for lipid analysis.The method was initially validated using standard lipid molecules.Good sensitivity,reproducibility and quantification performance was observed.Then,the method was applied to the analysis of 90 serum samples from 30 patients with breast cancer,30 patients with benign breast disease and 30 healthy controls.Five lipid molecules were identified as potential biomarkers for breast cancer.We constructed a classification model based on the MALDI-TOF MS signal of the 5 lipid molecules,and achieved high sensitivity,specificity and accuracy for the differentiation of breast cancer from benign breast disease and healthy control.We further collected another 60 serum samples from 20 healthy controls,20 patients with benign breast disease and 20 patients with breast cancer for MALDITOF MS analysis to verify the accuracy of the classification model.This advancement holds great promise for the development of diagnostic models for other lipid metabolism-related diseases.展开更多
Objective:Triple-negative breast cancer(TNBC)is a highly aggressive subtype that lacks targeted therapies,leading to a poorer prognosis.However,some patients achieve long-term recurrence-free survival(RFS),offering va...Objective:Triple-negative breast cancer(TNBC)is a highly aggressive subtype that lacks targeted therapies,leading to a poorer prognosis.However,some patients achieve long-term recurrence-free survival(RFS),offering valuable insights into tumor biology and potential treatment strategies.Methods:We conducted a comprehensive multi-omics analysis of 132 patients with American Joint Committee on Cancer(AJCC)stage III TNBC,comprising 36 long-term survivors(RFS≥8 years),62 moderate-term survivors(RFS:3-8 years),and 34 short-term survivors(RFS<3 years).Analyses investigated clinicopathological factors,whole-exome sequencing,germline mutations,copy number alterations(CNAs),RNA sequences,and metabolomic profiles.Results:Long-term survivors exhibited fewer metastatic regional lymph nodes,along with tumors showing reduced stromal fibrosis and lower Ki67 index.Molecularly,these tumors exhibited multiple alterations in genes related to homologous recombination repair,with higher frequencies of germline mutations and somatic CNAs.Additionally,tumors from long-term survivors demonstrated significant downregulation of the RTK-RAS signaling pathway.Metabolomic profiling revealed decreased levels of lipids and carbohydrate,particularly those involved in glycerophospholipid,fructose,and mannose metabolism,in long-term survival group.Multivariate Cox analysis identified fibrosis[hazard ratio(HR):12.70,95%confidence interval(95%CI):2.19-73.54,P=0.005]and RAC1copy number loss/deletion(HR:0.22,95%CI:0.06-0.83,P=0.026)as independent predictors of RFS.Higher fructose/mannose metabolism was associated with worse overall survival(HR:1.30,95%CI:1.01-1.68,P=0.045).Our findings emphasize the association between biological determinants and prolonged survival in patients with TNBC.Conclusions:Our study systematically identified the key molecular and metabolic features associated with prolonged survival in AJCC stage III TNBC,suggesting potential therapeutic targets to improve patient outcomes.展开更多
Objective:Early predicting response before neoadjuvant chemotherapy(NAC)is crucial for personalized treatment plans for locally advanced breast cancer patients.We aim to develop a multi-task model using multiscale who...Objective:Early predicting response before neoadjuvant chemotherapy(NAC)is crucial for personalized treatment plans for locally advanced breast cancer patients.We aim to develop a multi-task model using multiscale whole slide images(WSIs)features to predict the response to breast cancer NAC more finely.Methods:This work collected 1,670 whole slide images for training and validation sets,internal testing sets,external testing sets,and prospective testing sets of the weakly-supervised deep learning-based multi-task model(DLMM)in predicting treatment response and pCR to NAC.Our approach models two-by-two feature interactions across scales by employing concatenate fusion of single-scale feature representations,and controls the expressiveness of each representation via a gating-based attention mechanism.Results:In the retrospective analysis,DLMM exhibited excellent predictive performance for the prediction of treatment response,with area under the receiver operating characteristic curves(AUCs)of 0.869[95%confidence interval(95%CI):0.806−0.933]in the internal testing set and 0.841(95%CI:0.814−0.867)in the external testing sets.For the pCR prediction task,DLMM reached AUCs of 0.865(95%CI:0.763−0.964)in the internal testing and 0.821(95%CI:0.763−0.878)in the pooled external testing set.In the prospective testing study,DLMM also demonstrated favorable predictive performance,with AUCs of 0.829(95%CI:0.754−0.903)and 0.821(95%CI:0.692−0.949)in treatment response and pCR prediction,respectively.DLMM significantly outperformed the baseline models in all testing sets(P<0.05).Heatmaps were employed to interpret the decision-making basis of the model.Furthermore,it was discovered that high DLMM scores were associated with immune-related pathways and cells in the microenvironment during biological basis exploration.Conclusions:The DLMM represents a valuable tool that aids clinicians in selecting personalized treatment strategies for breast cancer patients.展开更多
Objective ZW10 interacting kinetochore protein(ZWINT)has been demonstrated to play a pivotal role in the growth,invasion,and migration of cancers.Nevertheless,whether the expression levels of ZWINT are significantly c...Objective ZW10 interacting kinetochore protein(ZWINT)has been demonstrated to play a pivotal role in the growth,invasion,and migration of cancers.Nevertheless,whether the expression levels of ZWINT are significantly correlated with clinicopathological characteristics and prognostic outcomes of patients with breast cancer remains elusive.This study systematically investigated the clinical significance of ZWINT expression in breast cancer through integrated molecular subtyping and survival analysis.Methods We systematically characterized the spatial expression pattern of ZWINT across various breast cancer subtypes and assessed its prognostic significance using an integrated bioinformatics approach that involved multi-omics analysis.The approach included the Breast Cancer Gene-Expression Miner v5.1(bc-GenExMiner v5.1),TNMplot,MuTarget,PrognoScan database,and Database for Annotation,Visualization,and Integrated Discovery(DAVID).Results Our analysis revealed consistent upregulation of ZWINT mRNA and protein expression across distinct clinicopathological subtypes of breast cancer.ZWINT overexpression demonstrated significant co-occurrence with truncating mutations in cadherin 1(CDH1)and tumor protein p53(TP53),suggesting potential functional crosstalk in tumor progression pathways.The overexpression of ZWINT correlated with adverse clinical outcomes,showing 48%increased mortality risk(overall survival:HR 1.48,95%CI 1.23–1.79),66%higher recurrence probability(relapse-free survival:1.66,95%CI 1.50–1.84),and 63%elevated metastasis risk(distant metastasis-free survival:HR 1.63,95%CI 1.39–1.90).Multivariate Cox regression incorporating TNM staging and molecular subtypes confirmed ZWINT as an independent prognostic determinant(P<0.001,Harrell’s C-index=0.7827),which was validated through bootstrap resampling(1000 iterations).Conclusion ZWINT may serve as a potential biomarker for prognosis and a possible therapeutic target alongside TP53/CDH1 in breast cancer.展开更多
Background:Cisplatin(DDP)has been used in the treatment of various human cancers.However,DDP alone lacks efficacy in treating triple-negative breast cancer(TNBC),and its clinical application is often hampered by side ...Background:Cisplatin(DDP)has been used in the treatment of various human cancers.However,DDP alone lacks efficacy in treating triple-negative breast cancer(TNBC),and its clinical application is often hampered by side effects.Astragalus polysaccharide(APS)is one of the active components extracted from Astragalus membranaceus and has gained attention for its various biological properties.This research is aimed to evaluate the effectiveness of a combination of APS and DDP on TNBC and explore the potential mechanisms.Methods:The efficacy and mechanisms of single or combined treatment were evaluated using Cell Counting Kit-8(CCK8)assay,Annexin V-fluorescein isothiocyanate(FITC)/propidium iodide(PI)staining,wound healing assay,trans-well invasion/migration assay,hematoxylin-eosin(HE)staining,immunohistochemical(IHC)staining,Western Blot(WB)analysis,and fluorescence-activated cell sorting(FACS).An orthotopic model of TNBC was used to assess the in vivo treatment efficacy of single or combination treatment.Results:APS significantly enhanced the anti-proliferative,anti-migratory,and anti-invasive effects of DDP on TNBC cells.The combination of APS and DDP downregulated anti-apoptotic genes(Bcl2 and Bcl-xL)while upregulating pro-apoptotic genes(Puma,Cle-Caspase3,Cle-PARP),leading to enhanced apoptosis.This combination treatment increased E-cadherin levels,decreased Vimentin,Snail,Slug,and Twist levels,and effectively suppressed epithelial-mesenchymal transition(EMT)-associated cell invasion.In the orthotopic model of TNBC,a synergistic reduction in tumor growth was observed in mice treated with APS and DDP.Additionally,the combination of APS and DDP induced the infiltration of CD8+T lymphocytes into the tumor immune microenvironment.Conclusion:The combination of APS and DDP exhibits more potent tumor inhibition and anti-tumor immunity than either agent alone,representing a novel approach to enhance therapeutic efficacy without increasing the side effects of DDP.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.
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.
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 grants from the Natural Science Foundation of Shandong Province(Grant No.ZR2024QH058).
文摘In the era of precision medicine,the breast cancer surgical treatment field is gradually moving toward a de-escalation model.Through precise preoperative assessments and multidisciplinary decision-making,surgical trauma can be decreased,and patients’quality of life can be improved by ensuring safety.Herein,we explore the axillary de-escalation surgery model for breast cancer.
基金supported by the National Natural Science Foundation of China(No.61961037)the Industrial Support Plan of Education Department of Gansu Province(No.2021CYZC-30)。
文摘In order to solve the challenge of breast cancer region segmentation,we improved the U-Net.The convolutional block attention module with prioritized attention(CBAM-PA)and dilated transformer(Dformer)modules were designed to replace the convolutional layers at the encoding side in the base U-Net,the input logic of the U-Net was improved by dynamically adjusting the input size of each layer,and the short connections in the U-Net were replaced with crosslayer connections to enhance the image restoration capability at the decoding side.On the breast ultrasound images(BUSI)dataset,we obtain a Dice coefficient of 0.8031 and an intersection-over-union(IoU)value of 0.7362.The experimental results show that the proposed enhancement method effectively improves the accuracy and quality of breast cancer lesion region segmentation.
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 Shandong Provincial Natural Science Foundation(no.ZR2020MH319).
文摘Triple-negative breast cancer(TNBC)is currently the most heterogeneous and aggressive breast cancer type.It has a high recurrence rate,poor clinical prospects,and lack of predictive markers and potential treatment options.Dysregulated microRNAs(miRNAs)are involved in various cellular processes in TNBC.Moreover,variations in the miRNA levels in TNBC may act as a dependable indicator for predicting the effectiveness and specificity of treatments.Currently,the application of miRNAs for breast cancer therapy is primarily in the preclinical stage,with a focus on identifying highly specific and sensitive miRNAs that could offer new possibilities for early diagnosis,clinical treat-ment,and prognostic monitoring of TNBC.
基金Supported by Russian Science Foundation,No.23-25-00183.
文摘BACKGROUND Breast cancer(BC)continues to occupy a leading position in terms of morbidity and mortality from malignant neoplasms among the female population.One of the promising markers associated with BC progression is programmed death ligand 1(PD-L1).Previously,we investigated PD-L1 expression in BC via a new antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)and reported that high PDCD1 LG1 expression in tumor cells is an independent factor for a high risk of regional metastasis in patients with BC.However,the prognostic significance of PDCD1 LG1 expression in BC stromal cells has not been adequately studied.AIM To study the features of PDCD1 LG1 expression in BC stromal cells and its relationship with BC clinicopathological characteristics.METHODS In a prospective single-center observational study,tumor samples from 148 patients with newly diagnosed BC were examined.The tumor sections were immunohistochemically stained with antibodies against PDCD1 LG1.In the tumor samples,the PDCD1 LG1-positive lymphocyte(PDCD1 LG1+LF)score,presence of nuclear PDCD1 LG1 expression in the LFs,PDCD1 LG1 expression in polymorphic cell infiltrates(PDCD1 LG1+polymorphic cell infiltrates[PCIs]),and cells of the fibroblastic stroma and endothelial cells of the tumor microvessels were assessed.Statistical analyses were performed using Statistica 10.0 software.RESULTS A PDCD1 LG1+LF score≥3 was detected more often at stages N0 and N3 than at N1 and N2(P=0.03).Moderate and pronounced PDCD1 LG1+PCIs and the presence of PDCD1 LG1+fibroblastic stroma were associated with negative estrogen receptor status(P=0.0008 and P=0.03,respectively),human epidermal growth factor receptor 2-positive(HER2+)BC(P<0.00001 and P=0.0005),and luminal B HER2+,non-luminal HER2+and triple-negative BC(P<0.00001 and P=0.004).The risk of metastasis to regional lymph nodes(RLNs)depend on lymphovascular invasion(LVI)and the PDCD1 LG1+LF score.In the absence of LVI and a PDCD1 LG1+LF score<3 or≥3,metastases in RLNs were absent in 66.6%and 93.9%of patients with BC,respectively.In the presence of LVI and a PDCD1 LG1+LF score<3 or≥3,metastases in RLNs were detected in 82.6%and 92.7%of patients with BC,respectively.CONCLUSION The results indicated that the combined assessment of the PDCD1 LG1+LF score and LVI can improve the accuracy of predicting the risk of metastasis to RLNs in patients with BC.
文摘BACKGROUND Breast cancer is one of the most prevalent causes of morbidity and mortality worldwide,presenting an increasing public health challenge,particularly in lowincome and middle-income countries.However,data on the knowledge,attitudes,and preventive practices regarding breast cancer and the associated factors among females in Wollo,Ethiopia,remain limited.AIM To assess the impact of family history(FH)of breast disease on knowledge,attitudes,and breast cancer preventive practices among reproductive-age females.METHODS A community-based cross-sectional study was conducted in May and June 2022 in Northeast Ethiopia and involved 143 reproductive-age females with FH of breast diseases and 209 without such a history.We selected participants using the systematic random sampling technique.We analyzed the data using Statistical Package for Social Science version 25 software,and logistic regression analysis was employed to determine odds ratios for variable associations,with statistical significance set at P<0.05.RESULTS Among participants with FH of breast diseases,the levels of knowledge,attitudes,and preventive practices were found to be 83.9%[95%confidence interval(CI):77.9-89.9],49.0%(95%CI:40.8-57.1),and 74.1%(95%CI:66.9-81.3),respectively.In contrast,among those without FH of breast diseases,these levels were significantly decreased to 10.5%(95%CI:6.4-14.7),32.1%(95%CI:25.7-38.4),and 16.7%(95%CI:11.7-21.8),respectively.This study also indicated that knowledge,attitudes,and preventive practices related to breast cancer are significantly higher among participants with FH of breast diseases compared to those without HF breast diseases.CONCLUSION Educational status,monthly income,and community health insurance were identified as significant factors associated with the levels of knowledge,attitudes,and preventive practices regarding breast cancer among reproductive-age females.
基金supported by the National Natural Science Foundation of China(No.71974162 and No.7231101009).
文摘Objectives This study aimed to develop and preliminarily assess the quality of a Mindfulness Breast Care(MBC)App to reduce body image distress and stigma among breast cancer survivors(BCSs).Methods The development process of the MBC App involved:1)establishing a research group;2)determining of the content of the MBC App based on Mindfulness-Based Cognitive Therapy and 3)technical exploitation and maintenance.A mixed-methods study was conducted.We selected ten BCSs by a convenience sampling method.After using the APP for three months,five assessed the quality using the Mobile App Rating Scale:User Version(uMARS)and another five were interviewed for process evaluation.Results The MBC App was developed with three modules:1)Library to provide health education information on body image,stigma,mindfulness,recovery and etc;2)Mindfulness Yoga to offer 12 Hatha yoga videos for daily practice;and 3)Mindfulness Practices to have 12 sessions of mindfulness videoconferences.Based on the uMARS data,the MBC App received high ratings for functionality(4.10±0.34),aesthetics(3.93±0.55),information quality(4.10±0.72),and perceived impact(4.03±0.96),as well as moderate ratings for engagement(3.72±0.94)and subjective quality(3.87±0.77).Participants indicated that the MBC App provided reliable knowledge,information,and emotional support.Recommendations from participants included categorizing knowledge in the Library Module,recording videoconferences of mindfulness practice,and adding discussion sessions in the videoconference.Afterward,we optimized the MBC App to enhance the user experience accordingly.Conclusions The MBC App offers online mindfulness interventions specifically for BCSs in China.The preliminary quality assessment indicates that the MBC App may be a promising tool for delivering mindfulness interventions to BCSs.
基金supported by National Natural Science Foundation of China(NSFC,Nos.22074022,22374031)the Ministry of Science and Technology of China,National Key R&D Program of China(No.2022YFC2704300).
文摘Lipids serve as fundamental constituents of cell membranes and organelles.Recent studies have highlighted the significance of lipids as biomarkers in the diagnosis of breast cancer.Although liquid chromatography coupled with tandem mass spectrometry(LC-MS/MS)is widely employed for lipid analysis in complex samples,it suffers from limitations such as complexity and time-consuming procedures.In this study,we have developed dopamine-modified TiO_(2)nanoparticles(TiO_(2)-DA)and applied the materials to assist the analysis of lipids by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS).The TiO_(2)-DA can provide large specific surface area and acidic environment,well suited for lipid analysis.The method was initially validated using standard lipid molecules.Good sensitivity,reproducibility and quantification performance was observed.Then,the method was applied to the analysis of 90 serum samples from 30 patients with breast cancer,30 patients with benign breast disease and 30 healthy controls.Five lipid molecules were identified as potential biomarkers for breast cancer.We constructed a classification model based on the MALDI-TOF MS signal of the 5 lipid molecules,and achieved high sensitivity,specificity and accuracy for the differentiation of breast cancer from benign breast disease and healthy control.We further collected another 60 serum samples from 20 healthy controls,20 patients with benign breast disease and 20 patients with breast cancer for MALDITOF MS analysis to verify the accuracy of the classification model.This advancement holds great promise for the development of diagnostic models for other lipid metabolism-related diseases.
基金supported by grants from the Medical Engineering Jiont Fund of the Fudan University(No.IDH2310117)。
文摘Objective:Triple-negative breast cancer(TNBC)is a highly aggressive subtype that lacks targeted therapies,leading to a poorer prognosis.However,some patients achieve long-term recurrence-free survival(RFS),offering valuable insights into tumor biology and potential treatment strategies.Methods:We conducted a comprehensive multi-omics analysis of 132 patients with American Joint Committee on Cancer(AJCC)stage III TNBC,comprising 36 long-term survivors(RFS≥8 years),62 moderate-term survivors(RFS:3-8 years),and 34 short-term survivors(RFS<3 years).Analyses investigated clinicopathological factors,whole-exome sequencing,germline mutations,copy number alterations(CNAs),RNA sequences,and metabolomic profiles.Results:Long-term survivors exhibited fewer metastatic regional lymph nodes,along with tumors showing reduced stromal fibrosis and lower Ki67 index.Molecularly,these tumors exhibited multiple alterations in genes related to homologous recombination repair,with higher frequencies of germline mutations and somatic CNAs.Additionally,tumors from long-term survivors demonstrated significant downregulation of the RTK-RAS signaling pathway.Metabolomic profiling revealed decreased levels of lipids and carbohydrate,particularly those involved in glycerophospholipid,fructose,and mannose metabolism,in long-term survival group.Multivariate Cox analysis identified fibrosis[hazard ratio(HR):12.70,95%confidence interval(95%CI):2.19-73.54,P=0.005]and RAC1copy number loss/deletion(HR:0.22,95%CI:0.06-0.83,P=0.026)as independent predictors of RFS.Higher fructose/mannose metabolism was associated with worse overall survival(HR:1.30,95%CI:1.01-1.68,P=0.045).Our findings emphasize the association between biological determinants and prolonged survival in patients with TNBC.Conclusions:Our study systematically identified the key molecular and metabolic features associated with prolonged survival in AJCC stage III TNBC,suggesting potential therapeutic targets to improve patient outcomes.
基金supported by the National Natural Science Foundation of China(No.82371933)the National Natural Science Foundation of Shandong Province of China(No.ZR2021MH120)+1 种基金the Taishan Scholars Project(No.tsqn202211378)the Shandong Provincial Natural Science Foundation for Excellent Young Scholars(No.ZR2024YQ075).
文摘Objective:Early predicting response before neoadjuvant chemotherapy(NAC)is crucial for personalized treatment plans for locally advanced breast cancer patients.We aim to develop a multi-task model using multiscale whole slide images(WSIs)features to predict the response to breast cancer NAC more finely.Methods:This work collected 1,670 whole slide images for training and validation sets,internal testing sets,external testing sets,and prospective testing sets of the weakly-supervised deep learning-based multi-task model(DLMM)in predicting treatment response and pCR to NAC.Our approach models two-by-two feature interactions across scales by employing concatenate fusion of single-scale feature representations,and controls the expressiveness of each representation via a gating-based attention mechanism.Results:In the retrospective analysis,DLMM exhibited excellent predictive performance for the prediction of treatment response,with area under the receiver operating characteristic curves(AUCs)of 0.869[95%confidence interval(95%CI):0.806−0.933]in the internal testing set and 0.841(95%CI:0.814−0.867)in the external testing sets.For the pCR prediction task,DLMM reached AUCs of 0.865(95%CI:0.763−0.964)in the internal testing and 0.821(95%CI:0.763−0.878)in the pooled external testing set.In the prospective testing study,DLMM also demonstrated favorable predictive performance,with AUCs of 0.829(95%CI:0.754−0.903)and 0.821(95%CI:0.692−0.949)in treatment response and pCR prediction,respectively.DLMM significantly outperformed the baseline models in all testing sets(P<0.05).Heatmaps were employed to interpret the decision-making basis of the model.Furthermore,it was discovered that high DLMM scores were associated with immune-related pathways and cells in the microenvironment during biological basis exploration.Conclusions:The DLMM represents a valuable tool that aids clinicians in selecting personalized treatment strategies for breast cancer patients.
基金supported by the Research Project of Maternal and Child Health Hospital of Hubei Province(No.2023SFYM008)Key Project of Hubei Provincial Natural Science Foundation(No.JCZRLH202500304).
文摘Objective ZW10 interacting kinetochore protein(ZWINT)has been demonstrated to play a pivotal role in the growth,invasion,and migration of cancers.Nevertheless,whether the expression levels of ZWINT are significantly correlated with clinicopathological characteristics and prognostic outcomes of patients with breast cancer remains elusive.This study systematically investigated the clinical significance of ZWINT expression in breast cancer through integrated molecular subtyping and survival analysis.Methods We systematically characterized the spatial expression pattern of ZWINT across various breast cancer subtypes and assessed its prognostic significance using an integrated bioinformatics approach that involved multi-omics analysis.The approach included the Breast Cancer Gene-Expression Miner v5.1(bc-GenExMiner v5.1),TNMplot,MuTarget,PrognoScan database,and Database for Annotation,Visualization,and Integrated Discovery(DAVID).Results Our analysis revealed consistent upregulation of ZWINT mRNA and protein expression across distinct clinicopathological subtypes of breast cancer.ZWINT overexpression demonstrated significant co-occurrence with truncating mutations in cadherin 1(CDH1)and tumor protein p53(TP53),suggesting potential functional crosstalk in tumor progression pathways.The overexpression of ZWINT correlated with adverse clinical outcomes,showing 48%increased mortality risk(overall survival:HR 1.48,95%CI 1.23–1.79),66%higher recurrence probability(relapse-free survival:1.66,95%CI 1.50–1.84),and 63%elevated metastasis risk(distant metastasis-free survival:HR 1.63,95%CI 1.39–1.90).Multivariate Cox regression incorporating TNM staging and molecular subtypes confirmed ZWINT as an independent prognostic determinant(P<0.001,Harrell’s C-index=0.7827),which was validated through bootstrap resampling(1000 iterations).Conclusion ZWINT may serve as a potential biomarker for prognosis and a possible therapeutic target alongside TP53/CDH1 in breast cancer.
基金the Xuzhou Science and Technology Bureau,No.KC23186,Jiangsu Provincial Key Laboratory of New Drug Research and Clinical Pharmacy Project(No.XZSYSKF2023013)Key Medical Disciplines of Jiangsu Province’s 14th Five-Year Plan(ZDXK202237).
文摘Background:Cisplatin(DDP)has been used in the treatment of various human cancers.However,DDP alone lacks efficacy in treating triple-negative breast cancer(TNBC),and its clinical application is often hampered by side effects.Astragalus polysaccharide(APS)is one of the active components extracted from Astragalus membranaceus and has gained attention for its various biological properties.This research is aimed to evaluate the effectiveness of a combination of APS and DDP on TNBC and explore the potential mechanisms.Methods:The efficacy and mechanisms of single or combined treatment were evaluated using Cell Counting Kit-8(CCK8)assay,Annexin V-fluorescein isothiocyanate(FITC)/propidium iodide(PI)staining,wound healing assay,trans-well invasion/migration assay,hematoxylin-eosin(HE)staining,immunohistochemical(IHC)staining,Western Blot(WB)analysis,and fluorescence-activated cell sorting(FACS).An orthotopic model of TNBC was used to assess the in vivo treatment efficacy of single or combination treatment.Results:APS significantly enhanced the anti-proliferative,anti-migratory,and anti-invasive effects of DDP on TNBC cells.The combination of APS and DDP downregulated anti-apoptotic genes(Bcl2 and Bcl-xL)while upregulating pro-apoptotic genes(Puma,Cle-Caspase3,Cle-PARP),leading to enhanced apoptosis.This combination treatment increased E-cadherin levels,decreased Vimentin,Snail,Slug,and Twist levels,and effectively suppressed epithelial-mesenchymal transition(EMT)-associated cell invasion.In the orthotopic model of TNBC,a synergistic reduction in tumor growth was observed in mice treated with APS and DDP.Additionally,the combination of APS and DDP induced the infiltration of CD8+T lymphocytes into the tumor immune microenvironment.Conclusion:The combination of APS and DDP exhibits more potent tumor inhibition and anti-tumor immunity than either agent alone,representing a novel approach to enhance therapeutic efficacy without increasing the side effects of DDP.
