Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,Br...Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.展开更多
Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RN...Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.展开更多
Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the m...Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.展开更多
Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug re...Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates.Artemisinin(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine resistance.This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation.Five characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover analysis.Subsequent functional enrichment analyses were conducted.Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized patients.scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC tissues.Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes.These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.展开更多
Tumor deposits(TDs)are defined as discrete,irregular clusters of tumor cells lying in the soft tissue adjacent to but separate from the primary tumor,and are usually found in the lymphatic drainage area of the primary...Tumor deposits(TDs)are defined as discrete,irregular clusters of tumor cells lying in the soft tissue adjacent to but separate from the primary tumor,and are usually found in the lymphatic drainage area of the primary tumor.By definition,no residual lymph node structure should be identified in these tumor masses.At present,TDs are mainly reported in colorectal cancer,with a few reports in gastric cancer.There are very few reports on breast cancer(BC).For TDs,current dominant theories suggest that these are the result of lymph node metastasis of the tumor with complete destruction of the lymph nodes by the tumor tissue.Even some pathologists classify a TD as two lymph node metastases for calculation.Some pathologists also believe that TDs belong to the category of disseminated metastasis.Therefore,regardless of the origin,TDs are an indicator of poor prognosis.Moreover,for BC,sentinel lymph node biopsy is generally used at present.Whether radical axillary lymph node dissection should be adopted for BC with TDs in axillary lymph nodes is still inconclusive.The present commentary of this clinical issue has certain guiding significance.It is aimed to increase the awareness of the scientific community towards this under-recognized problem in BC pathology.展开更多
Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherap...Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.展开更多
In this editorial we comment on the article by Chen et al published in the recent issue of the World Journal of Clinical Oncology.Brain metastasis is one of the most serious complications of breast cancer and causes h...In this editorial we comment on the article by Chen et al published in the recent issue of the World Journal of Clinical Oncology.Brain metastasis is one of the most serious complications of breast cancer and causes high morbidity and mortality.Brain metastases may involve the brain parenchyma and/or leptomeninges.Symptomatic brain metastases develop in 10%-16%of newly recognized cases each year,and this rate increases to 30%in autopsy series.Depending on the size of the metastatic foci,it may be accompanied by extensive vasogenic edema or may occur as small tumor foci.Since brain metastases are a significant cause of morbidity and mortality,early diagnosis can have significant effects on survival and quality of life.The risk of developing brain metastases emerges progressively due to various patient and tumor characteristics.Patient variability may be particularly important in the susceptibility and distribution of brain metastases because malignant blood must cross the brain barrier and move within the brain parenchyma.Some characteristics of the tumor,such as gene expression,may increase the risk of brain metastasis.Clinical growth,tumor stage,tumor grade,growth receptor positivity,HER2 positivity,molecular subtype(such as triple negative status,luminal/nonluminal feature)increase the risk of developing breast cancer metastasis.Factors related to survival due to breast cancer brain metastasis include both tumor/patient characteristics and treatment characteristics,such as patient age,lung metastasis,surgery for brain metastasis,and HER2 positivity.If cases with a high risk of developing brain metastasis can be identified with the help of clinical procedures and artificial intelligence,survival and quality of life can be increased with early diagnosis and treatment.At the same time,it is important to predict the formation of this group in order to develop new treatment methods in cases with low survival expectancy with brain metastases.展开更多
BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In thi...BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.展开更多
BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proli...BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proliferation-related genes with prognosis in HER2+breast cancer(BC)patients is unclear.AIM To identify and evaluate fresh ferroptosis-related biomarkers for HER2+BC.METHODS First,we obtained the mRNA expression profiles and clinical information of HER2+BC patients from the TCGA and METABRIC public databases.A four gene prediction model comprising PROM2,SLC7A11,FANCD2,and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort.Patients were stratified into high-risk and low-risk groups based on their median risk score,an independent predictor of overall survival(OS).Based on these findings,immune infiltration,mutations,and medication sensitivity were analyzed in various risk groupings.Additionally,we assessed patient prognosis by combining the tumor mutation burden(TMB)with risk score.Finally,we evaluated the expression of critical genes by analyzing single-cell RNA sequencing(scRNA-seq)data from malignant vs normal epithelial cells.RESULTS We found that the higher the risk score was,the worse the prognosis was(P<0.05).We also found that the immune cell infiltration,mutation,and drug sensitivity were different between the different risk groups.The highrisk subgroup was associated with lower immune scores and high TMB.Moreover,we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses.HRisk-HTMB patients had the worst prognosis,whereas LRisk-LTMB patients had the best prognosis(P<0.0001).Analysis of the scRNAseq data showed that PROM2,SLC7A11,and FANCD2 were significantly differentially expressed,whereas FH was not,suggesting that these genes are expressed mainly in cancer epithelial cells(P<0.01).CONCLUSION Our model helps guide the prognosis of HER2+breast cancer patients,and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.展开更多
Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, ...Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.展开更多
The Chinese Society of Clinical Oncology Breast Cancer(CSCO BC)guidelines have been widely implemented in China since the first release in 2017.The Guideline Working Committee has also published multiple versions in E...The Chinese Society of Clinical Oncology Breast Cancer(CSCO BC)guidelines have been widely implemented in China since the first release in 2017.The Guideline Working Committee has also published multiple versions in English,Arabic,and other languages to facilitate communications with international experts.展开更多
Adiposity affects lifetime estrogen exposure,which is a key factor in breast carcinogenesis.However,adiposity effects,often assessed as the body mass index(BMI),on pre-and post-menopausal breast cancer risk are parado...Adiposity affects lifetime estrogen exposure,which is a key factor in breast carcinogenesis.However,adiposity effects,often assessed as the body mass index(BMI),on pre-and post-menopausal breast cancer risk are paradoxical.Body weight gain may reflect body fat mass accumulation during adulthood better than the BMI,potentially representing age-related metabolic changes.展开更多
Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)cons...Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and differentiation.Studies have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast cancer.The tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ability.Hence,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer metastasis.In this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory mechanisms.Furthermore,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during metastasis.Overall,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.展开更多
Objectives:This study aimed to reveal the role and possible mechanism of the ubiquitin-conjugating enzyme 2T(UBE2T)in the biological activities of breast cancer stem cells(BCSCs).Methods:The specific protein and gene ...Objectives:This study aimed to reveal the role and possible mechanism of the ubiquitin-conjugating enzyme 2T(UBE2T)in the biological activities of breast cancer stem cells(BCSCs).Methods:The specific protein and gene expression were quantified by Western blotting and quantitative real-time polymerase chain reaction,the proportion of BCSCs was examined by flow cytometry,and the self-renewal and proliferation of BCSCs were verified by serial sphere formation and soft agar.Results:Increasing expression of UBE2T was drastically found in breast cancer than that in adjacent tissues.Furthermore,UBE2T overexpression significantly increased the proportion of BCSCs in breast cancer cells and promoted their self-renewal and proliferation.Silent UBE2T exhibited the opposite functions.UBE2T increased the levels of the mammalian target of rapamycin and the phosphorylated mammalian target of rapamycin.Mammalian target of rapamycin(mTOR)inhibitor rapamycin inhibited the function of UBE2T in BCSCs.Conclusion:UBE2T plays a role in BCSCs through mTOR pathway and may suggest a novel therapeutic strategy for breast cancer.展开更多
Background:Newly diagnosed breast cancer patients experience symptoms that may affect their quality of life,treatment outcomes,and survival.Preventing and managing breast cancer-related symptoms soon after diagnosis i...Background:Newly diagnosed breast cancer patients experience symptoms that may affect their quality of life,treatment outcomes,and survival.Preventing and managing breast cancer-related symptoms soon after diagnosis is essential.The purpose of this study was to investigate the associations between health-related fitness(HRF)and patient-reported symptoms in newly diagnosed breast cancer patients.Methods:This study utilized baseline data from the Alberta Moving Beyond Breast Cancer Cohort Study that were collected within 90 days of diagnosis.HRF measures included peak cardiopulmonary fitness(peak volume of oxygen consumption(VO_(2peak))),maximal muscular strength and endurance,flexibility,and body composition.Symptom measures included depression,sleep quality,and fatigue.Adjusted multivariable logistic regression was performed for analyses.Results:Of 1458 participants,51.5%reported poor sleep quality,26.5%reported significant fatigue,and 10.4%reported moderate depression.In multivariable-adjusted models,lower relative VO_(2peak)was independently associated with a greater likelihood of all symptom measures,including moderate depression(p<0.001),poor sleep quality(p=0.009),significant fatigue(p=0.008),any symptom(p<0.001),and multiple symptoms(p<0.001).VO_(2peak)demonstrated threshold associations with all symptom measures such that all 3 lower quartiles exhibited similar elevated risk compared to the highest quartile.The strength of the threshold associations varied by the symptom measure with odds ratios ranging from-1.5 for poor sleep quality to-3.0 for moderate depression and multiple symptoms.Moreover,lower relative upper body muscular endurance was also independently associated with fatigue in a dose-response manner(p=0.001),and higher body weight was independently associated with poor sleep quality in an inverted U pattern(p=0.021).Conclusion:Relative VO_(2peak)appears to be a critical HRF component associated with multiple patient-reported symptoms in newly diagnosed breast cancer patients.Other HRF parameters may also be important for specific symptoms.Exercise interventions targeting different HRF components may help newly diagnosed breast cancer patients manage specific symptoms and improve outcomes.展开更多
Objective Lindqvist-type polyoxometalates(POMs)exhibit potential antitumor activities.This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism.Methods Using dif...Objective Lindqvist-type polyoxometalates(POMs)exhibit potential antitumor activities.This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism.Methods Using different cancer cell lines,the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains.Cell colony formation assay,autophagy detection,mitochondrial observation,qRT-PCR,Western blotting,and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism.Results MO-4,a Lindqvist-type POM linking a proline at its side strain,was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells.It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells.Mechanistically,MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species(ROS)levels and resulting in apoptosis.In vivo,breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment.Conclusion Collectively,the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.展开更多
Objective:To determine the anticancer potential of the methanolic extract from Ephedra alata against breast cancer both in vitro and in vivo.Methods:The effects of the methanolic extract of Ephedra alata on the viabil...Objective:To determine the anticancer potential of the methanolic extract from Ephedra alata against breast cancer both in vitro and in vivo.Methods:The effects of the methanolic extract of Ephedra alata on the viability,migration as well as apoptosis of breast cancer 4T1 cells were measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,Transwell assay,and annexin V-FITC staining assay,respectively.Histological examination was also carried out.Moreover,a murine breast cancer model was established to evaluate the inhibitory effect of the extract.Biochemical parameters including hepatic and non-hepatic enzymes,malondialdehyde,and glutathione were investigated.Results:The methanolic extract of Ephedra alata showed a strong anti-proliferative and anti-migratory activity against 4T1 cells in a dose-dependent manner.It also induced apoptosis in 4T1 cells.In an in vivo mouse model,the extract markedly inhibited tumor growth,reduced malondialdehyde,and hepatic and non-hepatic enzymes as well as increased glutathione level.Conclusions:The methanolic extract of Ephedra alata inhibits breast cancer in vitro and in vivo,which may be a promising anticancer agent.展开更多
Objective:Mitochondrial fatty acid oxidation is a metabolic pathway whose dysregulation is recognized as a critical factor in various cancers,because it sustains cancer cell survival,proliferation,and metastasis.The a...Objective:Mitochondrial fatty acid oxidation is a metabolic pathway whose dysregulation is recognized as a critical factor in various cancers,because it sustains cancer cell survival,proliferation,and metastasis.The acyl-Co A synthetase long-chain(ACSL)family is known to activate long-chain fatty acids,yet the specific role of ACSL3 in breast cancer has not been determined.Methods:We assessed the prognostic value of ACSL3 in breast cancer by using data from tumor samples.Gain-of-function and lossof-function assays were also conducted to determine the roles and downstream regulatory mechanisms of ACSL3 in vitro and in vivo.Results:ACSL3 expression was notably downregulated in breast cancer tissues compared with normal tissues,and this phenotype correlated with improved survival outcomes.Functional experiments revealed that ACSL3 knockdown in breast cancer cells promoted cell proliferation,migration,and epithelial±mesenchymal transition.Mechanistically,ACSL3 was found to inhibitβ-oxidation and the formation of associated byproducts,thereby suppressing malignant behavior in breast cancer.Importantly,ACSL3 was found to interact with YES proto-oncogene 1,a member of the Src family of tyrosine kinases,and to suppress its activation through phosphorylation at Tyr419.The decrease in activated YES1 consequently inhibited YAP1 nuclear colocalization and transcriptional complex formation,and the expression of its downstream genes in breast cancer cell nuclei.Conclusions:ACSL3 suppresses breast cancer progression by impeding lipid metabolism reprogramming,and inhibiting malignant behaviors through phospho-YES1 mediated inhibition of YAP1 and its downstream pathways.These findings suggest that ACSL3 may serve as a potential biomarker and target for comprehensive therapeutic strategies for breast cancer.展开更多
Objectives:This study aimed to explore the effectiveness of the theory-based tailored mHealth physical activity(PA)intervention among patients with breast cancer undergoing chemotherapy.Methods:A quasi-experimental st...Objectives:This study aimed to explore the effectiveness of the theory-based tailored mHealth physical activity(PA)intervention among patients with breast cancer undergoing chemotherapy.Methods:A quasi-experimental study design was adopted.A total of 60 breast cancer patients were selected from two tertiary hospitals in Shanghai and Hangzhou City from September 2019 to August 2021.According to the admission order,30 patients werefirst included in the control group,followed by 30 patients in the intervention group.A smartphone application(app)named“Breast Care”was developed based on social cognitive theory,self-efficacy theory,and the theory of planned behavior.The app integrated various functions,including information browsing,PA monitoring and feedback,symptom reporting,and social interaction.Patients in the intervention group received three months of personalized online PA guidance in addition to routine care.The control group received routine care.Baseline and post-intervention investigations after three months were conducted in two groups using the Short Form of International Physical Activity Questionnaire,the Hospital Anxiety and Depression Scale,and the Functional Assessment of Cancer TherapydBreast cancer.Results:After three months of intervention,compared to the control group,breast cancer patients in the intervention group showed significant improvements in walking,moderate PA,and overall PA(P<0.05).Compared to the baseline data,breast cancer patients in the intervention group had significant improvements in walking and overall PA after three months(P<0.05),whereas the control group experienced significant declines in walking,moderate PA,and overall PA after three months(P<0.05).There were statistically differences between the two groups in scores for anxiety,overall quality of life,and its dimensions,such as physical well-being,emotional well-being,and additional breast cancer well-being(P<0.05).Conclusions:The theory-based tailored mHealth PA intervention has demonstrated a positive impact on promoting PA behavior change and emotional management among breast cancer patients.The‘Breast Care’app integrated various practical behavior change strategies,offering valuable guidance for personalized remote rehabilitation support for cancer patients.展开更多
This study designs a microstrip patch antenna with an inverted T-type notch in the partial ground to detect tumorcells inside the human breast.The size of the current antenna is small enough(18mm×21mm×1.6mm)...This study designs a microstrip patch antenna with an inverted T-type notch in the partial ground to detect tumorcells inside the human breast.The size of the current antenna is small enough(18mm×21mm×1.6mm)todistribute around the breast phantom.The operating frequency has been observed from6–14GHzwith a minimumreturn loss of−61.18 dB and themaximumgain of current proposed antenna is 5.8 dBiwhich is flexiblewith respectto the size of antenna.After the distribution of eight antennas around the breast phantom,the return loss curveswere observed in the presence and absence of tumor cells inside the breast phantom,and these observations showa sharp difference between the presence and absence of tumor cells.The simulated results show that this proposedantenna is suitable for early detection of cancerous cells inside the breast.展开更多
基金supported by the National Natural Science Foundation of China(82203185,82230058,82172875 and 82073094)the National Key Research and Development Program of China(2021YFF1201300 and 2022YFE0103600)+3 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-014,2021-I2M-1-022,and 2022-I2M-2-001)the Open Issue of State Key Laboratory of Molecular Oncology(SKL-KF-2021-16)the Independent Issue of State Key Laboratory of Molecular Oncology(SKL-2021-16)the Beijing Hope Marathon Special Fund of Chinese Cancer Foundation(LC2020B14).
文摘Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.
基金supported by the Basic and Applied Basic Research Foundation of Guangdong Province(2022A1515220184).
文摘Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.
基金funded by the National Natural Science Foundation of China(82003879)Project of Science and Technology Department of Sichuan Province(2023NSFSC1928,2023NSFSC1992)+3 种基金Young Elite Scientists Sponsorship Program China Association for Science and Technology(CACM-2020-QNRC1-01)Project of State Administration of Traditional Chinese Medicine of China(ZYYCXTD-D-202209)Project of Undergraduate Training Programs for Innovation and Entrepreneurship(S202310610637)the Open Research Fund of State Key Laboratory of Southwestern Chinese Medicine Resources(SKLTCM202205).
文摘Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.
基金supported by the National Natural Science Foundation of China(81973839)High Level Chinese Medical Hospital Promotion Project-Special Project on Formulation R&D and New Drug Translation for Medical Institutions(HLCMHPP2023037)Upgrading the Development and Promotion of about 30 Integrated Chinese and Western Medicine Diagnosis and Treatment Programs(Guidelines for the Diagnosis and Treatment of Breast Cancer with the Combination of Traditional Chinese Medicine and Western Medicine)(ZYZB-2022-798).
文摘Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates.Artemisinin(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine resistance.This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation.Five characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover analysis.Subsequent functional enrichment analyses were conducted.Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized patients.scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC tissues.Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes.These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.
文摘Tumor deposits(TDs)are defined as discrete,irregular clusters of tumor cells lying in the soft tissue adjacent to but separate from the primary tumor,and are usually found in the lymphatic drainage area of the primary tumor.By definition,no residual lymph node structure should be identified in these tumor masses.At present,TDs are mainly reported in colorectal cancer,with a few reports in gastric cancer.There are very few reports on breast cancer(BC).For TDs,current dominant theories suggest that these are the result of lymph node metastasis of the tumor with complete destruction of the lymph nodes by the tumor tissue.Even some pathologists classify a TD as two lymph node metastases for calculation.Some pathologists also believe that TDs belong to the category of disseminated metastasis.Therefore,regardless of the origin,TDs are an indicator of poor prognosis.Moreover,for BC,sentinel lymph node biopsy is generally used at present.Whether radical axillary lymph node dissection should be adopted for BC with TDs in axillary lymph nodes is still inconclusive.The present commentary of this clinical issue has certain guiding significance.It is aimed to increase the awareness of the scientific community towards this under-recognized problem in BC pathology.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Ministry of Science and ICT(MSIT)(No.2021R1A2C2012808)Technology Innovation Program(Alchemist Project)(No.20012378)funded by the Ministry of Trade,Industry&Energy(MOTIE),South Korea.
文摘Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.
文摘In this editorial we comment on the article by Chen et al published in the recent issue of the World Journal of Clinical Oncology.Brain metastasis is one of the most serious complications of breast cancer and causes high morbidity and mortality.Brain metastases may involve the brain parenchyma and/or leptomeninges.Symptomatic brain metastases develop in 10%-16%of newly recognized cases each year,and this rate increases to 30%in autopsy series.Depending on the size of the metastatic foci,it may be accompanied by extensive vasogenic edema or may occur as small tumor foci.Since brain metastases are a significant cause of morbidity and mortality,early diagnosis can have significant effects on survival and quality of life.The risk of developing brain metastases emerges progressively due to various patient and tumor characteristics.Patient variability may be particularly important in the susceptibility and distribution of brain metastases because malignant blood must cross the brain barrier and move within the brain parenchyma.Some characteristics of the tumor,such as gene expression,may increase the risk of brain metastasis.Clinical growth,tumor stage,tumor grade,growth receptor positivity,HER2 positivity,molecular subtype(such as triple negative status,luminal/nonluminal feature)increase the risk of developing breast cancer metastasis.Factors related to survival due to breast cancer brain metastasis include both tumor/patient characteristics and treatment characteristics,such as patient age,lung metastasis,surgery for brain metastasis,and HER2 positivity.If cases with a high risk of developing brain metastasis can be identified with the help of clinical procedures and artificial intelligence,survival and quality of life can be increased with early diagnosis and treatment.At the same time,it is important to predict the formation of this group in order to develop new treatment methods in cases with low survival expectancy with brain metastases.
文摘BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.
基金The Science and Technology Commission of Shanxi province,No.201901D111428.
文摘BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proliferation-related genes with prognosis in HER2+breast cancer(BC)patients is unclear.AIM To identify and evaluate fresh ferroptosis-related biomarkers for HER2+BC.METHODS First,we obtained the mRNA expression profiles and clinical information of HER2+BC patients from the TCGA and METABRIC public databases.A four gene prediction model comprising PROM2,SLC7A11,FANCD2,and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort.Patients were stratified into high-risk and low-risk groups based on their median risk score,an independent predictor of overall survival(OS).Based on these findings,immune infiltration,mutations,and medication sensitivity were analyzed in various risk groupings.Additionally,we assessed patient prognosis by combining the tumor mutation burden(TMB)with risk score.Finally,we evaluated the expression of critical genes by analyzing single-cell RNA sequencing(scRNA-seq)data from malignant vs normal epithelial cells.RESULTS We found that the higher the risk score was,the worse the prognosis was(P<0.05).We also found that the immune cell infiltration,mutation,and drug sensitivity were different between the different risk groups.The highrisk subgroup was associated with lower immune scores and high TMB.Moreover,we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses.HRisk-HTMB patients had the worst prognosis,whereas LRisk-LTMB patients had the best prognosis(P<0.0001).Analysis of the scRNAseq data showed that PROM2,SLC7A11,and FANCD2 were significantly differentially expressed,whereas FH was not,suggesting that these genes are expressed mainly in cancer epithelial cells(P<0.01).CONCLUSION Our model helps guide the prognosis of HER2+breast cancer patients,and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.
基金supported by the National Natural Science Foundation of China (No. 82003311, No. 82061148016, No. 82230057 and No. 82272859)National Key R&D Program of China (No. 2022YFC2505101)+2 种基金Sun Yat-Sen Clinical Research Cultivating Program (No. SYS-Q202004)Beijing Medical Award Foundation (No. YXJL2020-0941-0760)Guangzhou Science and Technology Program (No. 202102010272 and No. 202201020486)。
文摘Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.
基金supported by the China Postdoctoral Science Foundation(Grant No.2023T160788)the Beijing Science and Technology Plan(Grant No.Z181100001718215).
文摘The Chinese Society of Clinical Oncology Breast Cancer(CSCO BC)guidelines have been widely implemented in China since the first release in 2017.The Guideline Working Committee has also published multiple versions in English,Arabic,and other languages to facilitate communications with international experts.
基金supported by the Research Program funded by the Korea Centers for Disease Control and Prevention(Grant Nos.2004-E71004-00,2005-E71011-00,2005-E71009-00,2006-E71001-00,2006-E71004-00,2006-E71010-00,2006E71003-00,2007-E71004-00,2007-E71006-00,2008-E7100600,2008-E71008-00,2009-E71009-00,2010-E71006-00,2011E71006-00,2012-E71001-00,2013-E71009-00)。
文摘Adiposity affects lifetime estrogen exposure,which is a key factor in breast carcinogenesis.However,adiposity effects,often assessed as the body mass index(BMI),on pre-and post-menopausal breast cancer risk are paradoxical.Body weight gain may reflect body fat mass accumulation during adulthood better than the BMI,potentially representing age-related metabolic changes.
基金supported by the National Key Research and Development Program of China(2023YFC2506400,2020YFA0112300)National Natural Science Foundation of China(82230103,81930075,82073267,82203399,82372689)+1 种基金Program for Outstanding Leading Talents in ShanghaiInnovative Research Team of High-level Local University in Shanghai。
文摘Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and differentiation.Studies have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast cancer.The tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ability.Hence,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer metastasis.In this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory mechanisms.Furthermore,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during metastasis.Overall,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.
基金This research was partly supported by the Fundamental Research Funds of Shandong University(21510078614097)the Shandong Natural Science Foundation General Project(ZR2022MC093).
文摘Objectives:This study aimed to reveal the role and possible mechanism of the ubiquitin-conjugating enzyme 2T(UBE2T)in the biological activities of breast cancer stem cells(BCSCs).Methods:The specific protein and gene expression were quantified by Western blotting and quantitative real-time polymerase chain reaction,the proportion of BCSCs was examined by flow cytometry,and the self-renewal and proliferation of BCSCs were verified by serial sphere formation and soft agar.Results:Increasing expression of UBE2T was drastically found in breast cancer than that in adjacent tissues.Furthermore,UBE2T overexpression significantly increased the proportion of BCSCs in breast cancer cells and promoted their self-renewal and proliferation.Silent UBE2T exhibited the opposite functions.UBE2T increased the levels of the mammalian target of rapamycin and the phosphorylated mammalian target of rapamycin.Mammalian target of rapamycin(mTOR)inhibitor rapamycin inhibited the function of UBE2T in BCSCs.Conclusion:UBE2T plays a role in BCSCs through mTOR pathway and may suggest a novel therapeutic strategy for breast cancer.
基金funded by a Team Grant(#107534)to KSC,CMF,SNCR,MLM,JKV,GJB,and JRMa Project Grant(#155952)to CMF,KSC,SNCR,MLM,JKV,and JRM+1 种基金a Foundation Grant(#159927)to KSC,CMF,SNCR,MLM,and JKV from the Canadian Institutes of Health Research.KSC and JKV are supported by the Canada Research Chairs ProgramCMF was supported by an Alberta Innovates Health Senior Scholar Award and by the Alberta Cancer Foundation Weekend to End Women’s Cancers Breast Cancer Chair.
文摘Background:Newly diagnosed breast cancer patients experience symptoms that may affect their quality of life,treatment outcomes,and survival.Preventing and managing breast cancer-related symptoms soon after diagnosis is essential.The purpose of this study was to investigate the associations between health-related fitness(HRF)and patient-reported symptoms in newly diagnosed breast cancer patients.Methods:This study utilized baseline data from the Alberta Moving Beyond Breast Cancer Cohort Study that were collected within 90 days of diagnosis.HRF measures included peak cardiopulmonary fitness(peak volume of oxygen consumption(VO_(2peak))),maximal muscular strength and endurance,flexibility,and body composition.Symptom measures included depression,sleep quality,and fatigue.Adjusted multivariable logistic regression was performed for analyses.Results:Of 1458 participants,51.5%reported poor sleep quality,26.5%reported significant fatigue,and 10.4%reported moderate depression.In multivariable-adjusted models,lower relative VO_(2peak)was independently associated with a greater likelihood of all symptom measures,including moderate depression(p<0.001),poor sleep quality(p=0.009),significant fatigue(p=0.008),any symptom(p<0.001),and multiple symptoms(p<0.001).VO_(2peak)demonstrated threshold associations with all symptom measures such that all 3 lower quartiles exhibited similar elevated risk compared to the highest quartile.The strength of the threshold associations varied by the symptom measure with odds ratios ranging from-1.5 for poor sleep quality to-3.0 for moderate depression and multiple symptoms.Moreover,lower relative upper body muscular endurance was also independently associated with fatigue in a dose-response manner(p=0.001),and higher body weight was independently associated with poor sleep quality in an inverted U pattern(p=0.021).Conclusion:Relative VO_(2peak)appears to be a critical HRF component associated with multiple patient-reported symptoms in newly diagnosed breast cancer patients.Other HRF parameters may also be important for specific symptoms.Exercise interventions targeting different HRF components may help newly diagnosed breast cancer patients manage specific symptoms and improve outcomes.
基金supported by Open Project Funding of the Key Laboratory of Fermentation Engineering(Ministry of Education)(No.202209EF09)the Natural Science Foundation of Hubei Province(No.2021CFB289)+1 种基金the Key R&D Project of Hubei Province(No.2022BCA018)the initial funding of Hubei University of Technology(No.XJ2022002201).
文摘Objective Lindqvist-type polyoxometalates(POMs)exhibit potential antitumor activities.This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism.Methods Using different cancer cell lines,the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains.Cell colony formation assay,autophagy detection,mitochondrial observation,qRT-PCR,Western blotting,and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism.Results MO-4,a Lindqvist-type POM linking a proline at its side strain,was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells.It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells.Mechanistically,MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species(ROS)levels and resulting in apoptosis.In vivo,breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment.Conclusion Collectively,the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.
文摘Objective:To determine the anticancer potential of the methanolic extract from Ephedra alata against breast cancer both in vitro and in vivo.Methods:The effects of the methanolic extract of Ephedra alata on the viability,migration as well as apoptosis of breast cancer 4T1 cells were measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,Transwell assay,and annexin V-FITC staining assay,respectively.Histological examination was also carried out.Moreover,a murine breast cancer model was established to evaluate the inhibitory effect of the extract.Biochemical parameters including hepatic and non-hepatic enzymes,malondialdehyde,and glutathione were investigated.Results:The methanolic extract of Ephedra alata showed a strong anti-proliferative and anti-migratory activity against 4T1 cells in a dose-dependent manner.It also induced apoptosis in 4T1 cells.In an in vivo mouse model,the extract markedly inhibited tumor growth,reduced malondialdehyde,and hepatic and non-hepatic enzymes as well as increased glutathione level.Conclusions:The methanolic extract of Ephedra alata inhibits breast cancer in vitro and in vivo,which may be a promising anticancer agent.
基金supported by the National Natural Science Foundation of China(Grant No.82203786)the Natural Science Foundation of Liaoning Province of China(Grant No.2022-YGJC-68 and Grant No.2023-BS-105)the Chinese Young Breast Experts Research Project(Grant No.CYBER-2021-A02 and Grant No.CYBER-2022-001)。
文摘Objective:Mitochondrial fatty acid oxidation is a metabolic pathway whose dysregulation is recognized as a critical factor in various cancers,because it sustains cancer cell survival,proliferation,and metastasis.The acyl-Co A synthetase long-chain(ACSL)family is known to activate long-chain fatty acids,yet the specific role of ACSL3 in breast cancer has not been determined.Methods:We assessed the prognostic value of ACSL3 in breast cancer by using data from tumor samples.Gain-of-function and lossof-function assays were also conducted to determine the roles and downstream regulatory mechanisms of ACSL3 in vitro and in vivo.Results:ACSL3 expression was notably downregulated in breast cancer tissues compared with normal tissues,and this phenotype correlated with improved survival outcomes.Functional experiments revealed that ACSL3 knockdown in breast cancer cells promoted cell proliferation,migration,and epithelial±mesenchymal transition.Mechanistically,ACSL3 was found to inhibitβ-oxidation and the formation of associated byproducts,thereby suppressing malignant behavior in breast cancer.Importantly,ACSL3 was found to interact with YES proto-oncogene 1,a member of the Src family of tyrosine kinases,and to suppress its activation through phosphorylation at Tyr419.The decrease in activated YES1 consequently inhibited YAP1 nuclear colocalization and transcriptional complex formation,and the expression of its downstream genes in breast cancer cell nuclei.Conclusions:ACSL3 suppresses breast cancer progression by impeding lipid metabolism reprogramming,and inhibiting malignant behaviors through phospho-YES1 mediated inhibition of YAP1 and its downstream pathways.These findings suggest that ACSL3 may serve as a potential biomarker and target for comprehensive therapeutic strategies for breast cancer.
基金the National Natural Science Foundation of China(72104145)the Humanities and Social Science Research Project of the Ministry of Education(21YJCZH032)+1 种基金the Shanghai Science and Technology Innovation Action Plan Sail-ing Project(21YF1447700)The funders had no role in the study design,collection,analysis and interpretation of data,writing of the report,or the decision to submit the article for publication.
文摘Objectives:This study aimed to explore the effectiveness of the theory-based tailored mHealth physical activity(PA)intervention among patients with breast cancer undergoing chemotherapy.Methods:A quasi-experimental study design was adopted.A total of 60 breast cancer patients were selected from two tertiary hospitals in Shanghai and Hangzhou City from September 2019 to August 2021.According to the admission order,30 patients werefirst included in the control group,followed by 30 patients in the intervention group.A smartphone application(app)named“Breast Care”was developed based on social cognitive theory,self-efficacy theory,and the theory of planned behavior.The app integrated various functions,including information browsing,PA monitoring and feedback,symptom reporting,and social interaction.Patients in the intervention group received three months of personalized online PA guidance in addition to routine care.The control group received routine care.Baseline and post-intervention investigations after three months were conducted in two groups using the Short Form of International Physical Activity Questionnaire,the Hospital Anxiety and Depression Scale,and the Functional Assessment of Cancer TherapydBreast cancer.Results:After three months of intervention,compared to the control group,breast cancer patients in the intervention group showed significant improvements in walking,moderate PA,and overall PA(P<0.05).Compared to the baseline data,breast cancer patients in the intervention group had significant improvements in walking and overall PA after three months(P<0.05),whereas the control group experienced significant declines in walking,moderate PA,and overall PA after three months(P<0.05).There were statistically differences between the two groups in scores for anxiety,overall quality of life,and its dimensions,such as physical well-being,emotional well-being,and additional breast cancer well-being(P<0.05).Conclusions:The theory-based tailored mHealth PA intervention has demonstrated a positive impact on promoting PA behavior change and emotional management among breast cancer patients.The‘Breast Care’app integrated various practical behavior change strategies,offering valuable guidance for personalized remote rehabilitation support for cancer patients.
基金the International Science and Technology Cooperation Project of the Shenzhen Science and Technology Commission(GJHZ20200731095804014).
文摘This study designs a microstrip patch antenna with an inverted T-type notch in the partial ground to detect tumorcells inside the human breast.The size of the current antenna is small enough(18mm×21mm×1.6mm)todistribute around the breast phantom.The operating frequency has been observed from6–14GHzwith a minimumreturn loss of−61.18 dB and themaximumgain of current proposed antenna is 5.8 dBiwhich is flexiblewith respectto the size of antenna.After the distribution of eight antennas around the breast phantom,the return loss curveswere observed in the presence and absence of tumor cells inside the breast phantom,and these observations showa sharp difference between the presence and absence of tumor cells.The simulated results show that this proposedantenna is suitable for early detection of cancerous cells inside the breast.