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Prognostic effect analysis of molecular subtype on young breast cancer patients

Chinese Journal of Cancer Research 2015年第4期27卷 428-436页

作者： Hong-Liang Chen Ang Ding Fu-Wen Wang department of Breast Surgery Obstetrics and Gynecology Hospital of Fudan University

Objective： To make a prognostic effect analysis of molecular subtype on young breast cancer ***： Totally 187 cases of young breast cancer patients less than 40 years old treated in Obstetrics and gynecology Hospital of Fudan University between June 2005 and June 2011 were included in our study. We described their clinical-pathological characteristics, disease-free survival（DFS） rate, and overall survival（OS） rate after a median follow-up period of 61 months. The factors associated with prognosis were also evaluated by univariate and multivariate ***： All patients were premenopausal, with an average age of 35.36±3.88 years old. The mean tumor size was 2.43±1.53 cm. Eighty-one cases had lymph node metastasis（43.3%）, 126 cases had lymphovascular invasion（67.4%）, and 125 cases had histological grade III（66.8%） disease. Twenty-seven cases（14.4%） were Luminal A subtype, 99 cases（52.9%） were Luminal B subtype, 29 cases（15.5%） were human epidermal growth factor receptor 2（HER-2） overexpression subtype, while 32 cases（17.1%） were triple negative breast cancer（TNBC） subtype according to 2013 St Gallen expert consensus. One hundred and thirty-five cases underwent mastectomy whereas 52 cases had breast-conserving surgery. One hundred and seventy-eight cases underwent adjuvant or neoadjuvant chemotherapy. Recurrence or metastasis occurred in 29 cases, 13 of which died. The 5-year DFS and OS rates were 84% and 92%. Multivariate analysis showed that nodal status（P=0.041） and molecular subtype（P=0.037） were both independent prognostic factors of DFS, while nodal status（P=0.037） and TNBC subtype（P=0.048） were both independent prognostic factors of OS. Conclusions： Molecular subtype is an independent prognostic factor of young breast cancer patients. TNBC has a high risk of relapse and death.

关键词： Molecular subtype young breast cancer prognosis

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Sex-determining region Y box-containing genes: regulators and biomarkers in gynecological cancers

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Cancer Biology & Medicine 2019年第3期16卷 462-474页

作者： Jiali Hu Ke Li Zhanghuan Li Chao Gao Fei Guo Yingmei Wang Fengxia Xue department of gynecology and Obstetrics Tianjin Medical University General Hospital

Sex-determining region Y box-containing genes are transcription factors with roles in multiple biological processes, including cell differentiation, proliferation, and ***-determining region Y box-containing genes have also been shown to act as regulators and biomarkers in the progression of many different cancers, including gynecological cancers such as ovarian, cervical,and endometrial *** this review, we summarize the contrasting regulatory roles of Sex-determining region Y box-containing genes in different gynecological cancers, as promotors with high expression levels or as suppressors with low expression *** levels of Sex-determining region Y box-containing genes were also identified as biomarkers of clinical features, including International Federation of gynecology and Obstetrics stage, histopathologic grade together with disease-free survival, and treatment efficacy in patients with gynecological *** understanding of the mechanisms whereby Sex-determining region Y box-containing genes regulate the progression of gynecological cancers will aid in the development of novel diagnostic and therapeutic strategies, while analysis of Sex-determining region Y box-containing expression levels will help to predict the prognosis of patients with gynecological cancers.

关键词： Sex-determining region Y box-containing gene gynecological cancer regulator biomarker clinical feature progression

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MicroRNAs: regulators of cancer metastasis and epithelialmesenchymal transition(EMT)

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Chinese Journal of Cancer 2014年第3期33卷 140-147页

作者： Xiang-Ming Ding department of Obstetrics and gynecology David Geffen School of Medicine at UCLA

Tumor metastasis is the main cause of death in patients with solid tumors. The epithelial-mesenchymal transition(EMT) process, in which epithelial cells are converted into mesenchymal cells, is frequently activated during cancer invasion and metastasis. MicroRNAs(miRNAs) are small, non-coding RNAs that provide widespread expressional control by repressing mRNA translation and inducing mRNA degradation. The fundamental roles of miRNAs in tumor growth and metastasis have been increasingly well recognized. A growing number of miRNAs are reported to regulate tumor invasion/metastasis through EMT-related and/or non-EMT–related mechanisms. In this review, we discuss the functional role and molecular mechanism of miRNAs in regulating cancer metastasis and EMT.

关键词： MicroRNA(miRNA) cancer metastasis EMT

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The Performance of Whole Genome Amplification Methods and Next-Generation Sequencing for Pre-Implantation Genetic Diagnosis of Chromosomal Abnormalities

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Journal of Genetics and Genomics 2015年第4期42卷 151-159页

作者： Na Li Li Wang Hui Wang Minyue Ma Xiaohong Wang Yi Li Wenke Zhang Jianguang Zhang David S.Cram Yuanqing Yao department of gynecology and Obstetrics Reproductive Medicine CenterTangdu HospitalFourth Military Medical University department of Obstetrics and gynecology Affiliated Hospital of Academy of Military Medical Sciences department of Obstetrics and gynecology Chinese PLA General Hospital Berry Genomics C.Limited

Reliable and accurate pre-implantation genetic diagnosis （PGD） of patient＇s embryos by next-generation sequencing （NGS） is dependent on efficient whole genome amplification （WGA） of a representative biopsy sample. However, the performance of the current state of the art WGA methods has not been evaluated for sequencing. Using low template DNA （15 pg） and single cells, we showed that the two PCR-based WGA systems SurePlex and MALBAC are superior to the REPLI-g WGA multiple displacement amplification （MDA） system in terms of consistent and reproducible genome coverage and sequence bias across the 24 chromosomes, allowing better normalization of test to reference sequencing data. When copy number variation sequencing （CNV-Seq） was applied to single cell WGA products derived by either SurePlex or MALBAC amplification, we showed that known disease CNVs in the range of 3-15 Mb could be reliably and accurately detected at the correct genomic positions. These findings indicate that our CNV-Seq pipeline incorporating either SurePlex or MALBAC as the key initial WGA step is a powerful methodology for clinical PGD to identify euploid embryos in a patient＇s cohort for uterine transplantation,

关键词： Single cells Whole genome amplification Next-generation sequencing Copy number variation Pre-implantation genetic diagnosis

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Dys-psychological Stress Effect on Expressions of P53 and NFκBp65 in Human Ovarian Carcinoma In Vivo

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Chinese Journal of Cancer Research 2012年第3期24卷 245-248页

作者： Li-qun Yu Guo-lan Gao Fun-jun Liu Qiong-jing Zeng department of gynecology Aviation General HospitalBeijing 200022Chine department of gynecology and Obstetrics First Affiliated Hospital of Nanchang UniversityNanchang 330006China

Objective： To investigate the dys-psychological stress effect on the growth of subcutaneous xenotransplanted tumor in nude mice bearing human epithelium ovarian carcinoma, and the influence on P53 and NFκBp65 expressions. Methods： The subcutaneous tumor xenografts were established by implanting human epithelium ovarian carcinoma tissues into nude mice and the dys-psychological stress model was established with restraint. The mice were randomized into the following four treatment groups with each group six mice respectively： tumor group （group A）, normal saline intraperitoneal injection; tumor with stress group （group B）, normal saline intraperitoneal injection; tumor therapy group （group C）, cisplatin intraperitoneal injection; and tumor therapy with stress group （group D）, cisplatin intraperitoneal injection. The expressions of P53 and NFκBp65 in tumor tissues were determined by Western blotting. Results： The expressions of P53 and NFκBp65 in each restraint group were enhanced compared with the control groups （P0.05）. Conclusion： The dys-psychological stress may induce the high expressions of P53 and NFκBp65 proteins and further promote tumor growth.

关键词： Constraint stress Oncoprotein Ovarian cancer animal model

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Clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2011年第10期12卷 787-795页

作者： Jun HU Li-rong ZHU Zhi-qing LIANG Yuan-guang MENG Hong-yan GUO Peng-peng QU Cai-ling MA Cong-jian XU Bi-bo YUAN department of gynecology Peking University First Hospital Beijing 100034 China department of gynecology Southwest Hospital of Third Military Medical University Chongqing 400038 China department of gynecology Chinese PLA General Hospital ＆ Chinese PLA Postgraduate Medical School Beijing 100853 China department of gynecology Peking University Third Hospital Beijing 100191 China Tianjin Central Obstetrics and Gynecological Hospital Tianjin 300052 China department of gynecology Xinjiang Medical University First Teaching Hospital Urumqi 830054 China Shanghai Red House Hospital of Obstetrics and gynecology Shanghai 200011 China department of gynecology Tianjin Medical University General Hospital Tianjin 300052 China

Objective:To assess the clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma (EOC).Methods:A retrospective study of young EOC inpatients (≤40 years old) was performed during January 1994 and December 2010 in eight ***:Data were analyzed from 94 patients treated with fertility-sparing surgery with a median follow-up time of 58.7 *** histologic grade increased,overall survival (OS) and disease-free survival (DFS) of patients receiving fertility-sparing surgery *** staging surgery nor laparoscopy of early stage EOC with conservative surgery had a significant effect on OS or *** menstruation recommenced after chemotherapy in 89% of the fertility-sparing *** pregnancies among twelve patients were achieved by the end of the ***:Fertility-sparing treatment for patients with EOC Stage I Grade 1 could be cautiously considered for young *** surgical procedure and surgical route might not significantly influence the *** chemotherapy is not likely to have an evident impact on ovarian function or fertility in young patients.

关键词： Epithelial ovarian carcinoma Fertility-sparing treatment Overall survival Disease-free survival Pregnancy

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Presence and role of stem cells in ovarian cancer

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World Journal of Stem Cells 2019年第7期11卷 383-397页

作者： Natasa Kenda Suster Irma Virant-Klun department of gynecology Division of Obstetrics and GynecologyUniversity Medical Centre LjubljanaLjubljana 1000Slovenia department of Human Reproduction Division of Obstetrics and GynecologyUniversity Medical Centre LjubljanaLjubljana 1000Slovenia

Ovarian cancer is the deadliest gynecological *** is typically diagnosed at advanced stages of the disease,with metastatic sites disseminated widely within the abdominal *** cancer treatment is challenging due to high disease recurrence and further complicated pursuant to acquired *** stem cell(CSC)theory proposes that both tumor development and progression are driven by undifferentiated stem cells capable of self-renewal and *** most recent evidence revealed that CSCs in terms of ovarian cancer are not only responsible for primary tumor growth,metastasis and relapse of disease,but also for the development of *** the elimination of this cell population is critical for increasing treatment success,a deeper understanding of ovarian CSCs pathobiology,including epithelial-mesenchymal transition,signaling pathways and tumor microenvironment,is ***,before introducing new therapeutic agents for ovarian cancer,targeting CSCs,accurate identification of different ovarian stem cell subpopulations,including the very small embryoniclike stem cells suggested as progenitors,is *** these ends,reliable markers of ovarian CSCs should be *** this review,we present the current knowledge and a critical discussion concerning ovarian CSCs and their clinical role.

关键词： Ovarian cancer Cancer stem cells Very small embryonic-like stem cells Epithelial-mesenchymal transition

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The Expression of Resistin in Adipose Tissues of Patients with Polycystic Ovary Syndrome and Insulin Resistance

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2009年第5期29卷 642-645页

作者：初永丽崔青冯桂姣宋志云姜学强 department of Obstetrics and gynecology Yantai Yuhuangding Hospital

The relationship between the expression of resistin in polycystic ovary syndrome （PCOS） and insulin resistance was investigated. The plasma resistin concentrations in 35 patients with PCOS and 40 controls were measured by ELISA. Luteinizing hormone （LH）, follicle-stimulating hormone （FSH）, and fasting insulin （FIN） were tested by radioimmunoassay. Insulin resistance index （HOMA-IR） was calculated. Fasting plasma glucose （FPG） was determined by oxidase test. Western blot and reverse transcriptase PCR （RT-PCR） methods were used to detect the expression of resistin in adipose tissues. The levels of plasma resistin, LH, LH/FSH and FIN and HOMA-IR in patients with PCOS were significantly higher than those in control group （all P〈0.05）. Plasma resistin was correlated positively with FPG, FIN, HOMA-IR, LH and LH/FSH （r=0.56, 0.60, 0.65, 0.48, and 0.42 respectively）. Resistin protein and mRNA expression levels in patients with PCOS were significantly higher than those in normal tissues （all P〈0.01）. It was concluded that resistin might be involved in the pathogenesis of insulin resistance of PCOS.

关键词： polyeystic ovary syndrome resistin fasting plasma glucose fasting insulin insulin resistance

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Conditioned Medium from Human Umbilical Vein Endothelial Cells Promotes Proliferation,Migration,Invasion and Angiogenesis of Adipose Derived Stem Cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2018年第1期38卷 124-130页

作者： Ming-lian LUO Xiao-ping LIU Fang WANG Xiao-xia LIU Wei-fang LIU Di WU Hui TAO Rong-li WANG Yin ZHAO Jian-wen ZHU Li ZOU department of Obstetrics and gynecology Union HospitalTongji Medical CollegeHuazhong University of Science and Technology department of Obstetrics and gynecology Wuhan First Hospital

Preeclampsia（PE） is a pregnancy-specific hypertensive complication,closely related to endothelial *** derived stem cells（ADSCs） have the capacity to differentiate into endothelial cells for vascular ***,we hypothesized that induced endothelial differentiation of ADSCs might hold great potential for the treatment of *** this study,the primary ADSCs and human umbilical vein endothelial cells（HUVECs） were isolated by the collagenase digestion *** supernatant of HUVECs was collected from the first generation of ***,ADSCs were divided into two groups：ADSCs alone group and induced ADSCs（i ADSCs） *** i ADSCs group,ADSCs were induced by HUVECs conditioned medium and ADSCs special culture medium at a ratio of 1：1 over a two-week *** order to identify the endothelial characteristics of i ADSCs,CD31 and CD34 were examined by flow *** proliferation,migration,invasion and angiogenesis assays were employed to compare the bioactivity of i ADSCs and ***,The levels of angiogenic related factors including vascular endothelial growth factor（VEGF） and placenta growth factor（Pl GF） were detected by RT-PCR and Western *** showed conditioned medium from HUVECs promoted ADSCs proliferation,migration,invasion and *** addition,the levels of VEGF and Pl GF were significantly enhanced in i ADSCs *** study uncovered the i ADSCs application potential in the therapy and intervention of PE.

关键词： adipose derived stem cells endothelial differentiation angiogenesis preeclampsia

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Oridonin induces apoptosis via PI3K/Akt pathway in cervical carcinoma HeLa cell line

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Acta Pharmacologica Sinica 2007年第11期28卷 1819-1826页

作者： Hong-zhen HU~2,Yue-bo YANG~3,Xiang-dong XU~4,Hong-wei SHEN~5,Yi-min SHU~6,Zi REN~7,Xiao-mao LI~3,Hui-ming SHEN~3,Hai-tao ZENG~(3,8)~2 department of gynecology and Obstetrics,Yijishan Hospital,Wannan Medical College,Wuhu 241001,China ~3 department of gynecologyand Obstetrics,the Third Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China ~4 department of Surgery,the First AffiliatedHospital,Sun Yat-sen University,Guangzhou 510080,China ~2 department of gynecology and Obstetrics,the First Affiliated Hospital,SunYat-sen University,Guangzhou 510080.China ~6 department of Obstetrics and gynecology,IVF Program,Stanford University MedicalCenter,Palo Alto,CA 94304,USA ~7 department of gynecology and Obstetrics,Guangdong Provincial People's Hospital,Guangzhou510080.China department of gynecology and Obstetrics Yijishan Hospital Wannan Medical College Wuhu China department of gynecology and Obstetrics the Third Affiliated Hospital Sun Yat-sen University Guangzhou China department of Surgery the First Affiliated Hospital Sun Yat-sen University Guangzhou China department of gynecology and Obstetrics the First Affiliated Hospital Sun Yat-sen University Guangzhou China department of Obstetrics and gynecology IVF Program Stanford University Medical Center Palo Alto USA department of gynecology and Obstetrics Guangdong Provincial People's Hospital Guangzhou China

Aim:To investigate the apoptosis-inducing effect of oridonin,a diterpenoid iso-lated from Rabdosia rubescens,in the human cervical carcinoma HeLa cell ***:A morphological analysis,nuclear condensation,and fragmentation ofchromatin were monitored using Hoechst 33342 *** viability was as-sessed using the 3-(4,5-dimethylthiazol-(2)-yl)-2,5-diphenyl tetrazolium bromide(MTT) *** apoptosis and the apoptosis-related activation in the HeLa cellline were evaluated by flow cytometry and Western ***:Oridoninsuppressed the proliferation of the HeLa cell line in a dose-and *** treatment downregulated the activation of protein kinase B(Akt),the expression of forkhead box class O (FOXO) transcription factor,andglycogen synthase kinase 3 (GSK3).Oridonin also induced the release of cyto-chrome c accompanied by the activation of caspase-3 and poly-adenosine diphos-phate-ribose polymerase *** addition,Z-D(OMe)-E(OMe)-V-D(OMe)-FMK (z-DEVD-fmk),an inhibitor of caspases,prevented caspase-3 activation andabrogated oridonin-induced cell ***,oridonin treatment of the HeLa cellline downregulated the expression of the inhibitor of the apoptosis ***:Our results showed that oridonin-induced apoptosis involved sev-eral molecular *** may suppress constitutively activated targetsof phosphatidylinositol 3-kinase (Akt,FOXO,and GSK3) in the HeLa cell line,inhibiting the proliferation and induction of caspase-dependent apoptosis.

关键词： cervical carcinoma oridonin apoptosis Akt

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