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Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第8期25卷 686-699页

作者： Junfen XU Mengyan TU Department of gynecologic oncology Women’s HospitalZhejiang University School of MedicineHangzhou 310006China Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology Hangzhou 310006China

Objective:The present study used single-cell RNA sequencing(scRNA-seq)to characterize the cellular composition of ovarian carcinosarcoma(OCS)and identify its molecular ***:scRNA-seq was performed in resected primary OCS for an in-depth analysis of tumor cells and the tumor *** staining was used for *** scRNA-seq data of OCS were compared with those of high-grade serous ovarian carcinoma(HGSOC)tumors and other OCS ***:Both malignant epithelial and malignant mesenchymal cells were observed in the OCS patient of this *** identified four epithelial cell subclusters with different biological *** them,epithelial subcluster 4 presented high levels of breast cancer type 1 susceptibility protein homolog(BRCA1)and DNA topoisomerase 2-α(TOP2A)expression and was related to drug resistance and cell *** analyzed the interaction between epithelial and mesenchymal cells and found that fibroblast growth factor(FGF)and pleiotrophin(PTN)signalings were the main pathways contributing to communication between these ***,we compared the malignant epithelial and mesenchymal cells of this OCS tumor with our previous published HGSOC scRNA-seq data and OCS *** the epithelial subclusters in the OCS tumor could be found in the HGSOC ***,the mesenchymal subcluster C14 exhibited specific expression patterns in the OCS tumor,characterized by elevated expression of cytochrome P450 family 24 subfamily A member 1(CYP24A1),collagen type XXIIIα1 chain(COL23A1),cholecystokinin(CCK),bone morphogenetic protein 7(BMP7),PTN,Wnt inhibitory factor 1(WIF1),and insulin-like growth factor 2(IGF2).Moreover,this subcluster showed distinct characteristics when compared with both another previously published OCS tumor and normal ovarian ***:This study provides the single-cell transcriptomics signature of human OCS,which constitutes a new resource for elucidating OCS diversity.

关键词： Ovarian carcinosarcoma Single-cell RNA sequencing(scRNA-seq) Tumor heterogeneity

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Immune rebalancing at the maternal-fetal interface of maternal SARS-CoV-2 infection during early pregnancy

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Protein & Cell 2024年第6期15卷 460-473页

作者： Chenxiang Xi Zihui Yan Dandan Bai Yalin Zhang Beiying Wang Xiaoxiao Han Li Wu Xiaohui Shi Zhiyi Hu Ming Tang Zhongqu Su Yingdong Liu Binya Liu Jiqing Yin Hong Wang Xiaocui Li Yanping Zhang Shaorong Gao Wenqiang Liu Shanghai Key Laboratory of Maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalShanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Jiaxing Maternity and Child Health Care Hospital Jiaxing 314050China

The current coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)remains a threat to pregnant ***,the impact of early pregnancy SARS-CoV-2 infection on the maternal-fetal interface remains poorly ***,we present a comprehensive analysis of single-cell transcriptomics and metabolomics in placental samples infected with SARS-CoV-2 during early *** to control placentas,SARS-CoV-2 infection elicited immune responses at the maternal-fetal interface and induced metabolic alterations in amino acid and phospholipid profiles during the initial weeks ***,subsequent immune cell activation and heightened immune tolerance in trophoblast cells established a novel dynamic equilibrium that mitigated the impact on the maternal-fetal ***,the immune response and metabolic alterations at the maternal-fetal interface exhibited a gradual decline during the second *** study underscores the adaptive immune tolerance mechanisms and establishment of immunological balance during the first two trimesters following maternal SARS-CoV-2 infection.

关键词： fetal alterations pregnancy

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Long-term survival outcomes and immune checkpoint inhibitor retreatment in patients with advanced cervical cancer treated with camrelizumab plus apatinib in the phase II CLAP study

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Cancer Communications 2024年第6期44卷 654-669页

作者： Chunyan Lan Huaiwu Lu Lin Zhou Kunlun Liao Junxiu Liu Zhiwen Xie Haixi Liang Guorong Zou Ting Yang Qin Xu Xin Huang Department of gynecologic oncology Sun Yat-sen University Cancer CentreGuangzhouGuangdongP.R.China State Key Laboratory of oncology in South China Collaborative Innovation Centre for Cancer MedicineGuangzhouGuangdongP.R.China Department of gynecologic oncology Sun Yat-sen Memorial HospitalGuangzhouGuangdongP.R.China Clinical Research Daytime Treatment Center Sun Yat-sen University Cancer CentreGuangzhouGuangdongP.R.China Department of Obstetrics and Gynecology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Cancer Institute of Panyu Panyu Central HospitalGuangzhouGuangdongP.R.China Medical Affairs Jiangsu Hengrui Pharmaceuticals Co.LtdShanghaiP.R.China Department of Gynecology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhouFujianP.R.China

Background:Camrelizumab plus apatinib have demonstrated robust antitumor activity and safety in patients with advanced cervical cancer(CLAP study;NCT03816553).We herein present the updated long-term results of the CLAP study and explore potential biomarkers for *** outcomes of patients who underwent immune checkpoint inhibitor(ICI)retreatment were also ***:In this phase II trial,eligible patients received camrelizumab 200 mg intravenously every two weeks and apatinib 250 mg orally once daily in 4-week cycles for up to two *** was continued until disease progression,unacceptable toxicity,or withdrawal of ***:Between January 21 and August 1,2019,a total of 45 patients were *** were analyzed as of July 31,2023,representing>48 months since treatment initiation for all ***(20.0%)patients completed the 2-year *** median duration of response(DOR)was 16.6 months,and 45.0%of patients achieved a DOR of≥24 *** 12-month progression-free survival(PFS)rate was 40.7%(95%confidence interval[CI],25.2-55.6),with an 18-month PFS rate of 37.8%(95%CI,22.7-52.8).The median overall survival(OS)was 20.3 months(95%CI,9.3-36.9),and the 24-month OS rate was 47.8%(95%CI,31.7-62.3).Age>50 years,programmed death-ligand 1(PD-L1)combined positive score(CPS)≥1(versus[vs.]<1),CPS≥10(vs.<1),high tumor mutational burden,and PIK3CA mutations were associated with improved PFS(hazard ratio[HR]<1)and longer OS(HR<1).Eight patients who initially responded in the CLAP trial but later experienced disease progression were retreated with *** them,2(25.0%)achieved a partial response,while 5(62.5%)had stable ***,four patients who received retreatment with ICIs survived for more than *** new safety signals were identified in the present ***:Long-term survival follow-up data demonstrated that camrelizumab plus apatinib has robust,sustained,and durable efficacy in patients with advanced cervical ca

关键词： Cemrelizumab apatinib programmed cell death-1(PD-1) programmed death-ligand 1(PD-L1) tumor mutational burden(TMB) PIK3CA advanced cervical cancer

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Diagnostic challenges and individualized treatment of cervical adenocarcinoma metastases to the breast:A case report

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World Journal of Clinical Cases 2024年第2期12卷 412-417页

作者： Allison Akers Susan Read John Feldman Casey Gooden Diana P English Department of Obstetrics and Gynecology University of South FloridaTampaFL 33606United States Department of gynecologic oncology Sky Ridge Medical CenterLone TreeCO 80124United States Department of Radiology University of South FloridaTampaFL 33606United States Department of Pathology University of South FloridaTampaFL 33606United States

BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in *** metastases are associated with poor *** following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized *** SUMMARY A 44-year-old G7P5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina,parametria and lymph node *** biopsies confirmed high grade adenocarcinoma with mucinous features.A positron emission tomography/computed tomography(PET/CT)did not show evidence of metastatic *** received concurrent cisplatin with external beam radiation *** up PET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic *** was lost to follow up for six *** was re-imaged on re-presentation and found to have widely metastatic disease including breast *** biopsy confirmed programmed death-ligand 1 positive metastatic cervical *** patient received six cycles of carboplatin and paclitaxel with *** imaging demonstrated *** continued on pembrolizumab with disease *** Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis *** history and immunohistochemical evaluation of breast lesion,and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the ***,the prognosis is poor,but immunotherapy can be considered in select patients and may result in good disease response.

关键词： Cervical adenocarcinoma Breast metastases Immunotherapy Pembrolizumab Carboplatin Paclitaxel Case report

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High Levels of Vitamin C Intake Modify Effects of Phthalates on Metabolic Dysfunction-associated Steatotic Liver Disease:A Nationally Representative Study

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Journal of Clinical and Translational Hepatology 2024年第10期12卷 892-895页

作者： Ruoqi Zhou Yuwei Wang Xinxin Liu Xia Yu Dajing Xia Yihua Wu Yu Shi State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina Department of Toxicology of School of Public Health and Department of gynecologic oncology of Women’s Hospital Zhejiang University School of MedicineHangzhouZhejiangChina

Metabolic dysfunction-associated steatotic liver disease(MASLD)is a growing cause of chronic liver diseases worldwide,with a global prevalence of 38%.1 Patients with MASLD are at risk of developing liver-related complications,such as cirrhosis,hepatocellular carcinoma,and extra-hepatic adverse events.1 In recent years,endocrine-disrupting chemicals(EDCs)have been linked to the development and progression of MASLD.

关键词： Metabolic liver diseases

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RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 581-593页

作者： Xinyi WEI Conghui WANG Sangsang TANG Qian YANG Zhangjin SHEN Jiawei ZHU Xiaodong CHENG Xinyu WANG Xing XIE Junfen XU Weiguo LU Women's Reproductive Health Laboratory of Zhejiang Province Women�s HospitalZhejiang University School of MedicineHangzhou 310006China Department of gynecologic oncology Women�s HospitalZhejiang University School of MedicineHangzhou 310006China Cancer Center Zhejiang UniversityHangzhou 310058China Department of Obstetrics and Gynecology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology Hangzhou 310006China

Long non-coding RNAs(lncRNAs)play an indispensable role in the occurrence and development of ovarian cancer(OC).However,the potential involvement of lncRNAs in the progression of OC is largely *** investigate the detailed roles and mechanisms of RAD51 homolog B-antisense 1(RAD51B-AS1),a novel lncRNA in OC,reverse transcription-quantitative polymerase chain reaction(RT-qPCR)was performed to verify the expression of *** proliferation,metastasis,and apoptosis were detected using the cell counting kit-8(CCK-8),colony-formation,transwell,and flow cytometry *** xenograft models were established for the detection of *** results revealed that RAD51B-AS1 was significantly upregulated in a highly metastatic human OC cell line and OC ***51B-AS1 significantly increased the proliferation and metastasis of OC cells and enhanced their resistance to *** prediction analysis revealed that the only target gene of RAD51B-AS1 was *** gene function experiments revealed that RAD51B exerts the same biological effects as *** experiments demonstrated that the malignant biological behaviors promoted by RAD51B-AS1 overexpression were partially or completely reversed by RAD51B silencing in vitro and in ***,RAD51B-AS1 promotes the malignant biological behaviors of OC and activates the protein kinase B(Akt)/B cell lymphoma protein-2(Bcl-2)signaling pathway,and these effects may be associated with the positive regulation of RAD51B ***51B-AS1 is expected to serve as a novel molecular biomarker for the diagnosis and prediction of poor prognosis in OC,and as a potential therapeutic target for disease management.

关键词： Ovarian cancer(OC) Long non-coding RNA(LncRNA) Metastasis Anoikis

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Shanghai gynecologic oncology Group’s consensus on the academic and industry’s clinical trial types

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中华医学杂志(英文版) 2024年第14期137卷 1744-1746页

作者： Shi Tingyan Liu Jihong Zhu Jianqing Wang Xipeng Jiang Wei Lu Xin Feng Weiwei Zhou Shengtao Shen Yang Chen Gang Wu Zhenyu Zou Dongling Wu Peng Yang Huijuan Wu Sufang Zhu Tao Wang Huaying Zhang Yingli Qiu Lihua Guo Xiaoqing Xiang Libing Zhang Wei Ren Yulan Feng Yanling Liu Yanfei Chen Xiaojun Zang Rongyu Department of gynecologic oncology Fudan University Zhongshan Hospital Institute for Ovarian Cancer Fudan University Shanghai China Department of gynecologic oncology Sun Yat-Sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou Guangdong China Department of gynecologic oncology Zhejiang Cancer Hospital Hangzhou Zhejiang China Department of Obstetrics and Gynecology Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai China Department of Gynecology Obstetrics and Gynecology Hospital Fudan University Shanghai China Department of Obstetrics and Gynecology Ruijin Hospital Shanghai Jiaotong University School of Medicine Shanghai China Department of Obstetrics and Gynecology Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy West China Second Hospital Sichuan University and Collaborative Innovation Center Chengdu Sichuan China Department of Obstetrics and Gynecology Zhongda Hospital School of Medicine Southeast University Nanjing Jiangsu China National Clinical Research Center for Gynecology and Obstetrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China School of Public Health Key Laboratory of Public Health Safety and Collaborative Innovation Center of Social Risks Governance in Health Fudan University Shanghai China gynecologic oncology Center Chongqing University Cancer Hospital Chongqing China Department of Obstetrics and Gynecology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China Department of gynecologic oncology Fudan University Shanghai Cancer Center Shanghai China Department of Obstetrics and Gynecology Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai China Department of Obstetrics and Gynecology Renji Hospital School of Medicine

Shanghai gynecologic oncology Group (SGOG, www. ***), established in 2009, is a non-profit organization of clinical research and the full member of Gynecology Cancer Intergroup (GCIG) since 2012. It was guided by Drs. Jinghe Lang (China), Gavin Stuart (Canada) (2009-2020); Drs. Jinghe Lang (China), Ding Ma (China) (2021-) and was supported by Dr. Zeyi Cao (2009-2012). The mission of SGOG is to actively promote the investigator-initiated trial (IIT) in gynecologic cancers, particularly the innovative phase II clinical trials. Followed by the high quality of management in investigators’ training, trial development, human resources, and research funding, SGOG has initiated phase III clinical trials to improve the future clinical practice. SGOG aims to obtain reliable data by conducting systematic, standardized, and high-quality clinical trials, to guide the clinical practice of ovarian cancer, endometrial cancer, and cervical cancer in China. SGOG holds group meetings twice a year, and actively participates in GCIG international communication and cooperation that expands its international and national influence in the field of clinical research in gynecologic cancers. This coordination is not only particularly relevant between academic groups but also with national and/or international industry partners.

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Recurrent multisystem Langerhans cell histiocytosis involving the female genitalia: A case report

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World Journal of Clinical Cases 2024年第28期12卷 6222-6229页

作者： Chun-Yan Yuan Zhi-Rong Zhang Ming-Fang Guo Na Zhang Department of Gynaecology Fengdu People's HospitalChongqing 408200China Department of gynecologic oncology Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized TreatmentChongqing University Cancer HospitalChongqing Cancer InstituteChongqing Cancer HospitalChongqing 400030China

BACKGROUND Langerhans cell histiocytosis(LCH)is a histiocytic proliferative disease caused by clonal proliferation of Langerhans cells,which is currently defined as an inflam-matory myeloid *** is rare in adults,with an incidence of 1–2 per million,and is highly heterogeneous in clinical presentation,with unpredictable disease progression and *** SUMMARY A 52-year-old postmenopausal female patient presented to the gynecology department in July 2023 with bilateral vulvar *** was diagnosed with recurrent multisystem *** patient had previously been diagnosed with a single-system and single-focal LCH in October 2021 due to a right maxillofacial mass,which resolved after surgical treatment.A chemotherapy regimen was developed after multidisciplinary *** cycles of chemotherapy resulted in partial remission,and maintenance chemotherapy is currently being *** Recurrent LCH involving the bilateral vulva has been poorly ***-hensive imaging and pathological evaluation is important for *** model of joint multidisciplinary specialist diagnosis and treatment is worthy of clinical application.

关键词： Langerhans cell histiocytosis Chemotherapy Vulva Recurrence Case report

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Malignant ovarian tumors during pregnancy:Diagnostic evaluation,optimal treatment,and future perspective

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Chinese Medical Journal 2024年第12期137卷 1474-1476页

作者： Yaru Sheng Jiangjing Yuan Yuhong Li Yudong Wang Department of gynecologic oncology International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200030China Shanghai Municipal Key Clinical Specialty Female Tumor Reproductive SpecialtyShanghai 200030China Shanghai Key Laboratory of Embryo Original Disease Shanghai 200030China

To the Editor:Malignant ovarian tumors during pregnancy(MOTP)rank second after cervical cancer among gynecological malignancies diagnosed during pregnancy,and most women today hope to maintain pregnancy and preserve fertility,which complicates oncologic treatment,as all potential complications and prognoses should be carefully considered for both the mother and fetus.A coordinated approach from a multidisciplinary team involving gynecological oncologists,obstetricians,and pathologists is recommended.

关键词： pregnancy mother treatment

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An emerging antibacterial nanovaccine for enhanced chemotherapy by selectively eliminating tumor-colonizing bacteria

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Science Bulletin 2024年第16期69卷 2565-2579页

作者： Linfu Chen Zheyu Kang Jingjing Shen Rui Zhao Yu Miao Lin Zhang Zixuan Zheng Zhemin Zhang Nanhui Liu Cheng Wang Huapan Fang Jun Zhou Yudong Wang Zhuang Liu Yang Yang Qian Chen Institute of Functional Nano&Soft Materials(FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials&DevicesSoochow UniversitySuzhou 215123China Department of gynecologic oncology The International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200030China Department of Thoracic Surgery Shanghai Pulmonary HospitalTongji University School of MedicineShanghai 200433China

Fusobacterium nucleatum(***),an oral anaerobe,is prevalent in colorectal cancer and is closely related to increased cancer cell growth,metastasis,and poor treatment *** vaccines capable of selectively eliminating bacteria present a promising approach to targeting intratumor ***,thereby enhancing cancer *** adjuvants have been employed to enhance the immune response,the vaccine’s effectiveness is constrained by inadequate T-cell activation necessary for eradicating intracellular *** this study,we developed a minimalistic,biomimetic nanovaccine by integrating highly immunostimulatory adjuvant cholesterol-modified CpG oligonucleotides into the autologously derived *** *** to the traditional vaccines consisting of inactivated bacteria and Alum adjuvant,the nanovaccine coupled with bacterial membranes and adjuvants could remarkably improve multiple antigens and adjuvant co-delivery to dendritic cells,maximizing their ability to achieve effective antigen presentation and strong downstream immune ***,the nanovaccine exhibits outstanding selective prophylactic and therapeutic effects,eliminating *** without affecting intratumoral and gut *** significantly enhances chemotherapy efficacy and reduces cancer metastasis in ***-infected colorectal ***,this work represents the rational application of bacterial nanovaccine and provides a blueprint for future development in enhancing the antitumor effect against bacterial-infected cancer.

关键词： Fusobacterium nucleatum Bacterial vaccine Colorectal cancer Biomimetic nanomedicine Chemotherapy

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