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ACSL3 regulates breast cancer progression via lipid metabolism reprogramming and the YES1/YAP axis

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Cancer Biology & Medicine 2024年第7期21卷 606-635页

作者： Shirong Tan Xiangyu Sun Haoran Dong Mozhi Wang Litong Yao Mengshen Wang Ling Xu Yingying Xu department of breast surgery The First Affiliated Hospital of China Medical University department of Thyroid and breast surgery Affiliated Hospital of Xuzhou Medical University department of Medical Oncology The First Hospital of China Medical University

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 ***: 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 ***: 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 inhibit β-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 ***: 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.

关键词： ACSL3 breast cancer YAP lipid metabolism metastasis

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 *** to new research,long noncoding RNAs(lncRNAs)play a significant role in the progression of *** the role of lncRNAs in breast cancer has been well reported,few studies have focused on *** study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript(FOXCUT)in triple-negative breast ***: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 *** functions of FOXCUT in proliferation,migration,and invasion were detected in vitro or in *** 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 ***:lncRNA FOXCUT was markedly highly expressed in breast cancer,which was associated with poor prognosis in some *** of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in ***,FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38,which might act as an oncogene in breast ***: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

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 ***,dietary interventions have emerged as promising adjunctive treatment strategies not only for cancer but also for neurodegenerative diseases,autoimmune diseases,cardiovascular diseases,and metabolic *** interventions have demonstrated substantial potential in modulating metabolism,disease trajectory,and therapeutic *** 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 *** intake,as a key environmental factor,can influence tumor *** evidence indicates that dietary interventions might affect the nutrient availability in tumors,thereby increasing the efficacy of cancer ***,the intricate interplay between dietary interventions and the pathogenesis of cancer and other diseases is *** encouraging results,the mechanisms underlying diet-based therapeutic strategies remain largely unexplored,often resulting in underutilization in disease *** 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 *** explore the multifaceted impacts of these dietary interventions,encompassing their immunomodulatory effects,other biological impacts,and underlying molecular *** review offers valuable insights into the potential application of these dietary interventions as adjunctive therapies in disease management.

关键词： diseases metabolism potential

Clinical practice guidelines for neoadjuvant therapy in patients with early-stage breast cancer:Chinese Society of breast surgery practice guidelines 2022

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Chinese Medical Journal 2024年第12期137卷 1387-1388页

作者： Juliang Zhang Ting Wang Zhe Wang Jing Fan Xiaolong Xu Jing Kong Xinxin Wen Rui Ling Yinhua Liu department of Thyroid Breast and Vascular SurgeryXijing HospitalThe Fourth Military Medical UniversityXi’anShaanxi 710032China breast Disease Center Peking University First HospitalBeijing 100034China.

Neoadjuvant therapy can yield clinical benefits in earlystage breast cancer with *** indications,treatment regimens,and efficacy of neoadjuvant therapy have been investigated,which have contributed valuable clinical evidence.[1,2]The Chinese Society of breast surgery convened a panel of breast disease experts to review and discuss the literature on neoadjuvant therapy for breast cancer and evaluate relevant evidence by referring to the Grading of Recommendations,Assessment,Development,and Evaluations(GRADE)*** into account China’s specific circumstances,the society and participating experts developed the Clinical Practice Guidelines for Neoadjuvant Therapy for Early-stage breast Cancer(Version 2022)to serve as a reference for breast surgeons in China.

关键词： surgery breast breast

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 *** 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 ***30 influences drug sensitivity and tumor immunity in specific cancer *** this review,we have comprehensively summarized the latest research on the role of SOX30 in cancer by combining bioinformatics evidence and a literature *** summarize recent research on SOX30 in cancer regarding somatic mutations,trials,transcriptome analysis,clinical information,and SOX30-mediated regulation of malignant ***,we report on the diagnostic value of SOX30 mRNA expression levels across different cancer *** 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 *** evidence shows that the expression of circulating RNA ZFR(circZFR)is upregulated in HCC ***,the molecular mechanism of circZFR in HCC is ***: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 *** R assay and actinomycin D treatment assay were used to analyze the characteristics of *** 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 *** blot was used to examine the protein levels of WEE1 and epithelial-mesenchymal transition(EMT)-related *** interactions between miR-624-3p and circZFR or WEE1 were validated by dual-luciferase reporter assay and RNA immunoprecipitation(RIP)*** models were established to determine the role of circZFR in ***:circZFR and WEE1 were upregulated,while miR-624-3p expression was reduced in HCC tissues and *** could sponge miR-624-3p,and WEE1 was a downstream gene of *** of circZFR significantly reduced the malignant behaviors of HCC and that co-transfection with miR624-3p inhibitor restored this *** of WEE1 abolished the inhibitory effect of miR624-3p mimic on HCC ***,circZFR acted as a competitive endogenous RNA(ceRNA)to regulate WEE1 expression by targeting ***,in vivo studies have illustrated that circZFR knockdown inhibited tumor ***: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

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

International standard of Traditional Chinese Medicine techniques: the operating specifications for Chinese medicated bath(2022)

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Journal of Traditional Chinese Medicine 2024年第4期44卷 851-854页

作者： ZHANG Jing WANG Chunhui JIN Xinyan YU Miao FAN Yingyi HAN Xiaoli PEI Xiaohua department of dermatology Beijing University of Chinese Medicine Third Affiliated Hospital department of Chest and breast surgery Beijing University of Chinese Medicine Xiamen Hospital Center for Evidence-Based Medicine Beijing University of Chinese Medicine department of General surgery Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University department of breast surgery Beijing University of Chinese Medicine Third Affiliated Hospital

Chinese medicated bath is one of the external therapies in Traditional Chinese Medicine(TCM), which has been widely used clinically. The “International Standard of Traditional Chinese Medicine Techniques: The Operating Specifications for Chinese Medicated Bath” is drawn up by the Beijing University of Chinese Medicine Third Affiliated Hospital and Beijing University of Chinese Medicine Xiamen Hospital in collaboration with domestic TCM universities and hospitals. The specification includes definition, operating process, points for attention and contraindications. It is targeted to provide reference for TCM providers at home and abroad with TCM background in clinical decision-making.

关键词： Chinese medicated bath international standard operating specifications traditional Chinese medical technology

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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 ***: 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

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

Acyl-CoA thioesterase 7 is oncogenic in breast cancer by promoting oxidative phosphorylation via PGC1a

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Genes & Diseases 2024年第5期11卷 13-16页

作者： Xiangyu Sun Qiang Zhang Mozhi Wang Litong Yao Xiang Li Hongyi Cao Yingying Xu department of breast surgery Liaoning Cancer Hospital&InstituteShenyangLiaoning 110000China department of breast surgery The First Hospital of China Medical UniversityShenyangLiaoning 110000China department of Ultrasound The First Hospital of China Medical UniversityShenyangLiaoning 110000China department of Pathology The First Hospital of China Medical University and College of Basic Medical SciencesShenyangLiaoning 110000China

Metabolic reprogramming is a key feature of tumor cells and plays a key role in the adaptation of tumor cells to increased demands of biosynthesis and rapid proliferation.1 Numerous studies have shown that some key metabolic enzymes are essential for the initiation and progression of breast cancer(BC).These metabolic enzymes are involved in the regulation of many biological processes such as gene transcription,post-translational modification,and antioxidant capacity of cells,which endow tumor cells with the ability to adapt to divergent environmental stimuli.2 Therefore,it is of great significance to identify the role of important metabolic enzymes in the occurrence and development of BC to determine promising therapeutic targets.

关键词： breast cancer oxidative