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Promotion effect of FOXCUT as a microRNA sponge for miR-24-3p on progression in triple-negative breast cancer through the p38 MAPK signaling pathway

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Chinese Medical Journal 2024年第1期137卷 105-114页

作者： Xiafei Yu Fangze Qian Xiaoqiang Zhang Yanhui Zhu Gao He Junzhe Yang Xian Wu Yi Zhou Li Shen Xiaoyue Shi Hongfei Zhang Xiao’an Liu Department of breast surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China

Background:Triple-negative breast cancer(TNBC)is a type of highly invasive breast cancer with a poor prognosis.According to new research,long noncoding RNAs(lncRNAs)play a significant role in the progression of cancer.Although the role of lncRNAs in breast cancer has been well reported,few studies have focused on TNBC.This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript(FOXCUT)in triple-negative breast cancer.Methods:Based on a bioinformatic analysis of the cancer genome atlas(TCGA)database,we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues,which was further validated in an external cohort of tissues from the General surgery Department of the First Affiliated Hospital of Nanjing Medical University.The functions of FOXCUT in proliferation,migration,and invasion were detected in vitro or in vivo.Luciferase assays and RNA immunoprecipitation(RIP)were performed to reveal that FOXCUT acted as a competitive endogenous RNA(ceRNA)for the microRNA miR-24-3p and consequently inhibited the degradation of p38.Results:lncRNA FOXCUT was markedly highly expressed in breast cancer,which was associated with poor prognosis in some cases.Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo.Mechanistically,FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38,which might act as an oncogene in breast cancer.Conclusion:Collectively,this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.

关键词： Triple negative breast neoplasms RNA,long noncoding FOXCUT miR-24-3p p38 MAPK signaling pathway Disease progression

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Transcriptomic and machine learning analyses identify hub genes of metabolism and host immune response that are associated with the progression of breast capsular contracture

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Genes & Diseases 2024年第3期11卷 427-437页

作者： Yukun Mao Xueying Hou Su Fu Jie Luan breast Plastic and Reconstructive surgery Center Plastic Surgery HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100144China

Capsular contracture is a prevalent and severe complication that affects the post-operative outcomes of patients who receive silicone breast implants.At present,prosthesis replacement is the major treatment for capsular contracture after both breast augmentation procedures and breast reconstruction following breast cancer surgery.However,the mecha-nism(s)underlying breast capsular contracture remains unclear.This study aimed to identify the biological features of breast capsular contracture and reveal the potential underlying mechanism using RNA sequencing.Sample tissues from 12 female patients(15 breast capsules)were divided into low capsular contracture(LCC)and high capsular contracture(HCC)groups based on the Baker grades.Subsequently,41 lipid metabolism-related genes were identified through enrichment analysis,and three of these genes were identified as candidate genes by SVM-RFE and LASSO algorithms.We then compared the proportions of the 22 types of im-mune cells between the LCC and HCC groups using a CIBERSORT analysis and explored the Cor-relation between the candidate hub features and immune cells.Notably,PRKAR2B was positively correlated with the differentially clustered immune cells,which were M1 macro-phages and follicular helper T cells(area under the ROC=0.786).In addition,the expression of PRKAR2B at the mRNA or protein level was lower in the HCC group than in the LCC group.Potential molecular mechanisms were identified based on the expression levels in the high and low PRKAR2B groups.Our findings indicate that PRKAR2B is a novel diagnostic biomarker for breast capsular contracture and might also influence the grade and progression of capsularcontracture.

关键词： Biomarker breastcapsular contracture Immune infiltration Machinelearning algorithms PRKAR2B

Effects of dietary intervention on human diseases:molecular mechanisms and therapeutic potential

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1389-1422页

作者： Yu-Ling Xiao Yue Gong Ying-Jia Qi Zhi-Ming Shao Yi-Zhou Jiang Key Laboratory of breast Cancer in Shanghai Department of Breast SurgeryFudan University Shanghai Cancer CenterShanghaiChina Department of Oncology Shanghai Medical CollegeFudanUniversityShanghai200032China

Diet,serving as a vital source of nutrients,exerts a profound influence on human health and disease progression.Recently,dietary interventions have emerged as promising adjunctive treatment strategies not only for cancer but also for neurodegenerative diseases,autoimmune diseases,cardiovascular diseases,and metabolic disorders.These interventions have demonstrated substantial potential in modulating metabolism,disease trajectory,and therapeutic responses.Metabolic reprogramming is a hallmark of malignant progression,and a deeper understanding of this phenomenon in tumors and its effects on immune regulation is a significant challenge that impedes cancer eradication.Dietary intake,as a key environmental factor,can influence tumor metabolism.Emerging evidence indicates that dietary interventions might affect the nutrient availability in tumors,thereby increasing the efficacy of cancer treatments.However,the intricate interplay between dietary interventions and the pathogenesis of cancer and other diseases is complex.Despite encouraging results,the mechanisms underlying diet-based therapeutic strategies remain largely unexplored,often resulting in underutilization in disease management.In this review,we aim to illuminate the potential effects of various dietary interventions,including calorie restriction,fasting-mimicking diet,ketogenic diet,protein restriction diet,high-salt diet,high-fat diet,and high-fiber diet,on cancer and the aforementioned diseases.We explore the multifaceted impacts of these dietary interventions,encompassing their immunomodulatory effects,other biological impacts,and underlying molecular mechanisms.This review offers valuable insights into the potential application of these dietary interventions as adjunctive therapies in disease management.

关键词： diseases metabolism potential

Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase Ⅱ single-arm study

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Chinese Journal of Cancer Research 2024年第1期36卷 55-65页

作者： Yaping Yang Liang Jin Yudong Li Nanyan Rao Chang Gong Shunrong Li Jiannan Wu Jinghua Zhao Linxiaoxiao Ding Fengxia Gan Jun Zhang Ruifa Feng Zhenzhen Liu Qiang Liu breast Tumor Center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene RegulationGuangzhou 510120China Department of Thyroid and breast surgery Shenzhen Qianhai Shekou Free Trade Zone HospitalShenzhen 518000China breast and Thyroid surgery Guilin Medical College Second Affiliated HospitalGuilin 541199China Department of breast Disease Henan Breast Cancer Centerthe Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhou 450008China

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,

关键词： breast cancer HER2-positive breast cancer dual HER2 blockade neoadjuvant therapy sequential therapy

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Multifaceted roles and functions of SOX30 in human cancer

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Cancer Innovation 2024年第2期3卷 11-27页

作者： Na Sun Cheng Wang Pingping Gao Rui Wang Yi Zhang Xiaowei Qi Department of breast and Thyroid surgery The Southwest Hospital of Army Medical UniversityChongqingChina

SRY-box transcription factor 30(SOX30)participates in tumor cell apoptosis in lung cancer.The occurrence of somatic SOX30 mutations,the expression signature of SOX30 in normal and cancer tissues,the correlation of SOX30 with immune cells and immune-related genes,and the clinical significance of SOX30 in various cancers have stimulated interest in SOX30 as a potential cancer biomarker.SOX30 influences drug sensitivity and tumor immunity in specific cancer types.In this review,we have comprehensively summarized the latest research on the role of SOX30 in cancer by combining bioinformatics evidence and a literature review.We summarize recent research on SOX30 in cancer regarding somatic mutations,trials,transcriptome analysis,clinical information,and SOX30-mediated regulation of malignant phenotypes.Additionally,we report on the diagnostic value of SOX30 mRNA expression levels across different cancer types.This review on the role of SOX30 in cancer progression may provide insights into possible research directions for SOX30 in cancer and a theoretical basis for guiding future studies.

关键词： cancer progression prognosis SOX30

Circulating RNA ZFR promotes hepatocellular carcinoma cell proliferation and epithelial-mesenchymal transition process through miR-624-3p/WEE1 axis

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 52-63页

作者： Li Zhang Sai He Hao Guan Yao Zhao Di Zhang Department of General surgery the Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004China Department of breast Cancer Shaanxi Provincial Cancer HospitalXi’an 710000China

Background:Hepatocellular carcinoma(HCC),the most common type of primary liver cancer,is the fourth leading cause of cancer-related deaths worldwide.Previous evidence shows that the expression of circulating RNA ZFR(circZFR)is upregulated in HCC tissues.However,the molecular mechanism of circZFR in HCC is unclear.Methods:Quantitative reverse transcriptase polymerase chain reaction(qRT-PCR)was employed to detect the expression of circZFR,microRNA-624-3p(miR-624-3p)and WEE1 in HCC tissues and cells.RNase R assay and actinomycin D treatment assay were used to analyze the characteristics of circZFR.For functional analysis,the capacities of colony formation,cell proliferation,cell apoptosis,migration and invasion were assessed by colony formation assay,5-ethynyl-2-deoxyuridine(EdU)assay,flow cytometry assay and transwell assay.Western blot was used to examine the protein levels of WEE1 and epithelial-mesenchymal transition(EMT)-related proteins.The interactions between miR-624-3p and circZFR or WEE1 were validated by dual-luciferase reporter assay and RNA immunoprecipitation(RIP)assay.Xenograft models were established to determine the role of circZFR in vivo.Results:circZFR and WEE1 were upregulated,while miR-624-3p expression was reduced in HCC tissues and cells.circZFR could sponge miR-624-3p,and WEE1 was a downstream gene of miR-624-3p.Knockdown of circZFR significantly reduced the malignant behaviors of HCC and that co-transfection with miR624-3p inhibitor restored this change.Overexpression of WEE1 abolished the inhibitory effect of miR624-3p mimic on HCC cells.Mechanistically,circZFR acted as a competitive endogenous RNA(ceRNA)to regulate WEE1 expression by targeting miR-624-3p.Furthermore,in vivo studies have illustrated that circZFR knockdown inhibited tumor growth.Conclusions:circZFR knockdown reduced HCC cell proliferation,migration and invasion and promoted apoptosis by regulating the miR-624-3p/WEE1 axis,suggesting that the circZFR/miR-624-3p/WEE1 axis might be a potential target for HCC treatment.

关键词： Hepatocellular carcinoma circZFR miR-624-3p WEE1 Liver cancer

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Calcification-associated molecular traits and therapeutic strategies in hormone receptor-positive HER2-negative breast cancer

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Cancer Biology & Medicine 2024年第5期21卷 400-415页

作者： Yuwei Li Yuzheng Xu Caijin Lin Xi Jin Ding Ma Zhiming Shao Department of breast surgery Fudan University Shanghai Cancer Center Key Laboratory of breast Cancer in Shanghai Fudan University Shanghai Cancer Center Department of Oncology Shanghai Medical College Fudan University

Objective: Mammographic calcifications are a common feature of breast cancer, but their molecular characteristics and treatment implications in hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-negative(HER2-) breast cancer remain unclear.Methods: We retrospectively collected mammography records of an HR+/HER2-breast cancer cohort(n = 316) with matched clinicopathological, genomic, transcriptomic, and metabolomic data. On the basis of mammographic images, we grouped tumors by calcification status into calcification-negative tumors, tumors with probably benign calcifications, tumors with calcification of lowmoderate suspicion for maligancy and tumors with calcification of high suspicion for maligancy. We then explored the molecular characteristics associated with each calcification status across multiple dimensions.Results: Among the different statuses, tumors with probably benign calcifications exhibited elevated hormone receptor immunohistochemical staining scores, estrogen receptor(ER) pathway activation, lipid metabolism, and sensitivity to endocrine therapy. Tumors with calcifications of high suspicion for malignancy had relatively larger tumor sizes, elevated lymph node metastasis incidence, Ki-67 staining scores, genomic instability, cell cycle pathway activation, and may benefit from cyclin-dependent kinase 4 and 6(CDK4/6) inhibitors.Conclusions: Our research established links between tumor calcifications and molecular features, thus proposing potential precision treatment strategies for HR+/HER2-breast cancer.

关键词： HR+/HER2-breast cancer mammographic calcifications molecular features precision treatment ENDOCRINE THERAPY SENSITIVITY REPAIR

Circular RNAs in breast cancer diagnosis,treatment and prognosis

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Oncology Research 2024年第2期32卷 241-249页

作者： XIAOJIA HUANG CAILU SONG JINHUI ZHANG LEWEI ZHU HAILIN TANG Department of breast Oncology surgery Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhou510095China State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou510060China Department of breast surgery The First People’s Hospital of FoshanFoshan528000China

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.

关键词： CircRNA breast cancer Diagnosis Treatment Biomarker

Basilic vein variation encountered during surgery for arm vein port:A case report

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World Journal of Clinical Cases 2024年第12期12卷 2086-2091页

作者： Cheng-Da Hu Rui Lv Ya-Xin Zhao Ming-Hao Zhang Hong-Dou Zeng Yi-Wen Mao Department of breast surgery The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina

BACKGROUND Venous variations are uncommon and usually hard to identify,and basilic vein variation is particularly rare.Basilic vein variation usually presents without any clinical symptoms and is often regarded as a benign alteration.This case was a patient with congenital basilic vein variation encountered during surgery for an infusion port.CASE SUMMARY We documented and analyzed an uncommon anatomical variation in the basilic vein encountered during arm port insertion.This peculiarity has hitherto remained undescribed in the literature.We offer remedial strategies for addressing this anomaly in the future and precautionary measures to circumvent its occurrence.We conducted a comprehensive review of analogous cases in the literature,offering pertinent therapeutic recommendations and solutions,with the aim of enhancing the efficacy and safety of future arm port implantations.CONCLUSION Venous variation is rare and requires detailed intraoperative and postoperative examination to ensure accuracy,so as not to affect subsequent treatment.

关键词： Totally implantable venous access ports Arm ports Venous variation Postoperative breast cancer Systematic review Case report