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Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report

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World Journal of Clinical Cases 2024年第3期12卷 575-581页

作者： Qing-Qing Dou Ting-Ting Sun Guo-Qiang Wang Wei-bing Tong Graduate Student Institute Inner Mongolia Medical UniversityHohhot 010000Inner Mongolia Autonomous RegionChina central breast area b Beijing University Cancer Hospital Inner Mongolia HospitalHohhot 010000Inner Mongolia Autonomous RegionChina

bACKGROUND breast cancer brain metastasis(bCbM)is an advanced breast disease that is difficult to treat and is associated with a high risk of *** prognosis is usually poor,with reduced quality of *** 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 *** was compliant with regular insulin treatment and had good blood glucose *** 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 *** 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 *** underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 *** metastasis was found 9 mo after *** underwent brain metastasectomy in August *** showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache *** an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and ***-brain radiotherapy was *** patient and her family refused radiotherapy for personal *** September 2021,a routine examination revealed that the brain tumor was considerably *** original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine *** patient’s condition is generally stable,and she has a relatively high qua

关键词： breast cancer brain metastasis Resistance to trastuzumab Macromolecule inetetamab Small molecule tyrosine kinase inhibitor Radiation therapy HER2-positive Case report

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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 *** present,prosthesis replacement is the major treatment for capsular contracture after both breast augmentation procedures and breast reconstruction following breast cancer ***,the mecha-nism(s)underlying breast capsular contracture remains *** study aimed to identify the biological features of breast capsular contracture and reveal the potential underlying mechanism using RNA *** 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 ***,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 *** 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 ***,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 *** molecular mechanisms were identified based on the expression levels in the high and low PRKAR2b *** 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

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Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors

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Chinese Journal of Cancer Research 2024年第2期36卷 124-137页

作者： Jialin Zhang Gengshen Yin Chunmiao Ye Man Feng Changhua Ji Wenzhong Zhou Fei Wang Lixiang Yu Shuya Huang Zhigang Yu Department of breast Surgery the Second Hospital of Shandong UniversityJinan 250033China Institute of Translational Medicine of breast Disease Prevention and Treatment Shandong UniversityJinan 250033China Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of breast Disease Jinan 250033China Department of Pathology the Third Affiliated Hospital of Shandong First Medical University(Affiliated Hospital of Shandong Academy of Medical Sciences)Jinan 250031China Department of Pathology the Second Hospital of Shandong UniversityJinan 250033China

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is ***: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to ***: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase b(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft ***: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance

关键词： breast cancer HER2 pyrotinib trastuzumab primary resistance pertuzumab

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Photo-manipulated polyunsaturated fatty acid-doped liposomal hydrogel for flexible photoimmunotherapy

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Chinese Chemical Letters 2024年第4期35卷 268-274页

作者： Xinyue Lan Junguang Liang Churan Wen Xiaolong Quan Huimin Lin Qinqin Xu Peixian Chen Guangyu Yao Dan Zhou Meng Yu breast Center Department of General SurgeryNanfang HospitalSouthern Medical UniversityGuangzhou 510515China NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of breast Surgery The First People's Hospital of FoshanFoshan 528100China Zhujiang Hospital Southern Medical UniversityGuangzhou 510282China

Despite the synergy of immune checkpoint blockade(ICb) therapy and photodynamic therapy(PDT) holds great promise as countermeasures against breast cancer, exploring long-term or flexible short-time therapeutic strategies in “cold” tumors remains a great challenge. Here, we present a polyunsaturated fatty acid-doped liposomal hydrogel Lp(DHA)@CP Gel loaded with photosensitizer chlorin e6(Ce6) and programmed death-ligand 1 antibody(αPD-L1) for flexible local photoimmunotherapy with merely singledosed administration. The presence of polyunsaturated fatty acid(docosahexaenoic acid, DHA) doped in particle membrane endows liposomes with flexibly reactive oxygen species(ROS)-responsive release capability, which was attributed to the presence of abundant unsaturated groups. The αPD-L1 was repeatedly induced to in situ release in response to the PDT under photo-exposure. The immunogenic cell death(ICD) effect of PDT evoked “cold” breast tumor to “hot” one, and then assisted the cascade releasedαPD-L1 to synergistically boost the immunotherapy. After a single dose of peritumoral administration of Lp(DHA)@CP Gel, the on-demand treatment can maximize patient compliance and safety by adjusting therapeutic behaviors via a photo on-off switch. This work presents a flexible medication platform,showing promise in improving the objective response rate of ICb therapy and minimizing its systemic toxicity.

关键词： Photodynamic therapy Immunotherapy Responsive release Immunogenic cell death Liposomal hydrogel

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Roles of THEM4 in the Akt pathway:a double-edged sword

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Journal of Zhejiang University-Science b(biomedicine & biotechnology) 2024年第7期25卷 541-556页

作者： Wen XIE Weidong LIU Lei WANG bin ZHU Cong ZHAO Ziling LIAO Yihan LI Xingjun JIANG Jie LIU Caiping REN NHC Key Laboratory of Carcinogenesis Department of NeurosurgeryXiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China The Key Laboratory of Carcinogenesis and Cancer Invasion of the Ministry of Education Cancer Research InstituteSchool of Basic Medical ScienceCentral South UniversityChangsha 410078China Department of Critical Care Medicine Hainan Hospital of Chinese PLA General HospitalHainan Province Clinical Medical CenterSanya 572013China

The protein kinase b(Akt)pathway can regulate the growth,proliferation,and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes,thus affecting the development and treatment of a range of *** superfamily member 4(THEM4),a member of the thioesterase superfamily,is one of the Akt kinase-binding *** studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its ***,THEM4 was considered an endogenous inhibitor of Akt,which can inhibit the phosphorylation of Akt in diseases such as lung cancer,pancreatic cancer,and liver cancer,but subsequently,THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma,which contradicts previous *** these two distinct views,this review summarizes the important roles of THEM4 in the Akt pathway,focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases,especially *** work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.

关键词： Protein kinase b(Akt) Thioesterase superfamily member 4(THEM4) Tumor proliferation Tumor metastasis

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LncRNA ZFPM2-AS1 promotes phyllodes tumor progression by binding to CDC42 and inhibiting STAT1 activation

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Acta Pharmaceutica Sinica b 2024年第7期14卷 2942-2958页

作者： Shishi He Guowei Huang Rong Lei Rurong Jia Zhanghai He Jiewen Chen Hongyan Huang Zixian Huang Ailifeire Yilihamu Xun Li Zilin Zhuang Mengjia Han Xueman Chen Di Huang Yan Nie Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineMedical Research CenterSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China breast Tumor Center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Pathology Shantou University Medical CollegeShantou 515041China School of basic Medical Science Southern Medical UniversityGuangzhou 510515China Department of Pathology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of breast Medicine Affiliated Foshan Maternity and Child Healthcare HospitalSouthern Medical UniversityFoshan 528000China Department of breast Surgery Zhujiang HospitalSouthern Medical UniversityGuangzhou 510282China Department of Oral and Maxillofacial Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China

breast phyllodes tumor(PT)is a rare fibroepithelial neoplasm with potential malignant *** non-coding RNAs(lncRNAs)play multifaceted roles in various cancers,but their involvement in breast PT remains largely *** this study,microarray was leveraged for the first time to investigate the role of lncRNA in *** identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT,and its overexpression endowed PT with high tumor grade and adverse ***,we elucidated that ZFPM2-AS1 promotes the proliferation,migration,and invasion of malignant PT in *** ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft(PDX)model could effectively inhibit tumor progression in ***,our findings showed that ZFPM2-AS1 is competitively bound to CDC42,inhibiting ACK1 and STAT1 activation,thereby launching the transcription of *** conclusion,our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT,and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.

关键词： LncRNA Phyllodes tumor ZFPM2-AS1 Cell division cycle 42 Activated cdc42 kinase 1 Signal transducer and activator of transcription 1 TNF receptor superfamily member 19 Nano particles

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Microbiota enterotoxigenic bacteroides fragilis-secreted bFT-1 promotes breast cancer cell stemness and chemoresistance through its functional receptor NOD1

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Protein & Cell 2024年第6期15卷 419-440页

作者： Wei Ma Lu Zhang Weilong Chen Zhaoxia Chang Juchuanli Tu Yuanyuan Qin Yuwen Yao Mengxue Dong Jiajun Ding Siqin Li Fengkai Li Qiaodan Deng Yifei Yang Tingting Feng Fanrong Zhang Xiying Shao Xueyan He Lixing Zhang Guohong Hu Quentin Liu Yi-Zhou Jiang Shu Zhu Zhi Xiao Dan Su Tong Liu Suling Liu Fudan University Shanghai Cancer Center & Institutes of biomedical Sciences State Key Laboratory of Genetic EngineeringCancer InstitutesDepartment of OncologyKey Laboratory of Breast Cancer in ShanghaiThe Shanghai Key Laboratory of Medical EpigeneticsShanghai Key Laboratory of Radiation OncologyThe International Co-laboratory of Medical Epigenetics and MetabolismMinistry of Science and TechnologyShanghai Medical CollegeFudan UniversityShanghai 200032China Intelligent Pathology Institute and Department of Pathology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230071China Department of Thyroid Breast and Vascular SurgeryXijing HospitalFourth Military Medical UniversityXi’an 710032China Institute of Immunology CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China Department of Pathology The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China Department of breast Surgery The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China Department of breast Medical Oncology The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China Shanghai Institute of Nutrition and Health University of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China Department of breast Surgery Xiangya HospitalChangsha 410008China Department of breast Surgery Tumor Hospital of Harbin Medic

Tumor-resident microbiota in breast cancer promotes cancer initiation and malignant ***,targeting microbiota to improve the effects of breast cancer therapy has not been investigated in ***,we evaluated the microbiota composition of breast tumors and found that enterotoxigenic bacteroides fragilis(ETbF)was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant ***,albeit at low biomass,secreted the toxic protein bFT-1 to promote breast cancer cell stemness and *** studies showed that bFT-1 directly bound to NOD1 and stabilized NOD1 ***1 was highly expressed on ALDH+breast cancer stem cells(bCSCs)and cooperated with GAK to phosphorylate NUMb and promote its lysosomal degradation,thereby activating the NOTCH1-HEY1 signaling pathway to increase ***1 inhibition and ETbF clearance increase the chemosensitivity of breast cancer by impairing bCSCs.

关键词： NOD1 breast chemotherapy

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Commentary:Mammokine directs beige adipocytes to reserve energy for milk production in breast

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Acta Pharmaceutica Sinica b 2024年第3期14卷 1472-1476页

作者： Lina Tang Jianping Ye Metabolic Disease Research Center Zhengzhou University Affiliated Zhengzhou Central HospitalZhengzhou 450007China Research Center for basic Medicine Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China

beige/brown adipocytes play a crucial role in regulating the body’s overall energy *** thermogenic function is under the influence of various tissues,including the brain,muscles,and ***,the breast tissue is not in th... 详细信息

关键词： beige breast Epitheliail cells scRNA-seq Thermogenesis

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DNA damage chemotherapeutic drugs suppress basal-like breast cancer growth by down-regulating the transcription of the FOXO1-KLF5 axis

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Genes & Diseases 2024年第1期11卷 91-94页

作者： Qiuxia Cui Jian Sun Jingping Yuan Juanjuan Li Chuanyu Yang Guangshi Du Chengang Zhou Pu Qiu Jidong Gao Yuanqi Zhang Dewei Jiang Ceshi Chen Affiliated Hospital of Guangdong Medical University Science&Technology of China ZhanjiangGuangdong 524000China Department of breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdong 518116China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Department of Pathology Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Department of breast and Thyroid Surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Translational Medicine Research Center of Guizhou Medical University GuiyangGuizhou 550025China Department of breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Yunnan Cancer Hospital and the Third Affiliated Hospital of Kunming Medical University and Yunnan Cancer Center KunmingYunnan 650500China Academy of biomedical Engineering Kunming Medical UniversityKunmingYunnan 650500China

Most basal-like breast cancers(bLbCs)have a poor prognosis and high crossover with triple-negative breast cancers(TNbCs).However,approximately 50%of TNbC patients develop chemoresistance.^(1) Dexamethasone reportedly induces Krüppel-like factor 5(KLF5)and can cause docetaxel and cisplatin resistance in TNbC.A super-enhancer can maintain the transcription of KLF5.

关键词： FOXO1 drugs damage

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Prognostic Factors for Luminal b-like breast Cancer

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Current Medical Science 2019年第3期39卷 396-402页

作者： Nian-hua DING Cong-fan LIU Chun HU Jia-qi YUAN Wei-hua LIAO Zhi XIAO Department of Radiology department of Breast Surgery Xiangya Hospital Central South UniversityChangsha 410008China

This study aimed to examine the prognostic factors of luminal b-like breast *** data of 695 luminal b-like breast cancer patients who had been treated in our hospital during the period of past 4.5 years were collected and analyzed. Estrogen receptor (ER), progesterone receptor (PgR), antigen identified by monoclonal antibody Ki-67 (Ki67) were immunohistochemically detected. Different cutoffs of ER, PgR, and Ki67 were evaluated. Pearson X test was performed to compare categorical parameters. Univariate and multivariate models were used to evaluate predictors of disease free survival (DFS). The results showed that patients who were younger, and had larger tumors, and more positive lymph nodes were more likely to receive neo-adjuvent chemotherapy (NAC). Patients with ER-positive tumors having based chemotherapy and less endocrine therapy than those with ER-positive tumors having >10% positive cells (P=0.004 and P=0.007, respectively);however, patients with ER-positive tumors having 30% received more anthracycline- and taxane-based chemotherapy and had worse DFS than those with tumor tissue Ki67 score 30%, similar to higher clinical T stage, more metastatic lymph nodes, and HER2 positive status, may indicate a worse prognosis for luminal b-like breast cancer patients. Multi-center prospective trials with larger sample sizes are necessary for the continued perfection of our work.

关键词： luminal b-like breast cancer threshold prognostic factor estrogen receptor Ki67

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