The University of Texas M. D. Anderson Cancer Center SPORE in Ovarian Cancer

德克萨斯大学安德森癌症中心孢子在卵巢癌中的应用

• 批准号: 9132410
• 负责人: ROBERT C BAST
• 金额: $ 90.17万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9132410
• 关键词: Achievement; Advocate; Algorithms; Antibodies; Autoantibodies; Automobile Driving; Bioinformatics; Biological Markers; Biology; Biometry; CD44 gene; Cancer Center; Cancer Patient; Caring; Clinical; Clinical Research; Clinical Trials; Communities; Detection; Development; Disease; Disease Resistance; Dose; Engraftment; Faculty; Functional disorder; Funding; Goals; Grant; Human; Hypoxia; Interferons; Lead; MAP Kinase Gene; MEK inhibition; MEKs; Malignant Neoplasms; Malignant neoplasm of ovary; Measures; Mesenchymal Stem Cells; Modeling; Molecular; Morbidity - disease rate; Mus; Mutation; Normal tissue morphology; Nuclear; Ovarian Carcinoma; Ovarian Serous Adenocarcinoma; PTEN gene; Pathology; Pathway interactions; Patients; Peer Review; Performance; Pericytes; Perifosine; Phase; Philanthropic Fund; Platinum; Postmenopause; Pre-Clinical Model; Predictive Value; Proteins; Proto-Oncogene Proteins c-akt; Publications; Recruitment Activity; Recurrence; Research Infrastructure; Research Personnel; Research Project Grants; Resistance; Risk; Role; Route; Screening for Ovarian Cancer; Series; Services; Signal Transduction; Small Interfering RNA; Specificity; Staging; Systems Biology; Testing; Time; Translational Research; Translational trial; Ultrasonography; Universities; University of Texas M D Anderson Cancer Center; VEGF Trap; Vascular Endothelial Growth Factors; Visit; WFDC2 gene; Wages; Woman; Work; Xenograft procedure; anticancer research; base; bevacizumab; cancer cell; cancer therapy; career development; docetaxel; human FRAP1 protein; imaging modality; improved; inhibitor/antagonist; innovation; interest; laboratory facility; mTOR Inhibitor; member; mortality; mutant; notch protein; operation; outcome forecast; peritoneal cancer; personalized medicine; population based; pre-clinical; preclinical study; programs; response; screening; targeted treatment; translational clinical trial; trial design; tumor

The overall goal of the University of Texas M. D. Anderson Cancer Center (MDACC) SPORE is to reduce the morbidity and mortality of ovarian cancer through innovative translational research in the detection and treatment of ovarian cancer based upon the molecular, cellular and clinical biology of the disease. IVIDACC contains a unique community of >35 talented investigators who are dedicated to translational, clinical, fundamental and population-based ovarian cancer research, 20 of whom participate directly in the SPORE. Collaborators include 25 investigators from 9 universities and 4 companies. Over the last 4 years IVIDACC has cared for 1,055 new patients with ovarian and peritoneal cancer and have placed 241 on clinical trials. MDACC has given high priority to ovarian cancer research through recruitment, salary support, clinical facilities, laboratory space and philanthropic funds. MDACC with the help of the SPORE has recruited 5 outstanding faculty members with an interest in ovarian cancer research, strengthened the research infrastructure, funded 13 developmental research projects (DRP) and supported 4 career development program (DRP) awardees. Over the last 5 years SPORE investigators have contributed 381 peer-reviewed publications regarding ovarian cancer. Achievements include: 1) development of a two-stage screening strategy for early ovarian cancer that has provided a 30% positive predictive value for detecting early stage disease; 2) identification of a panel of biomarkers that detect 87% of early stage ovarian cancers; 2) discovery of pericytes as targets for anti-angiogenic therapy; 3) observation of a 39% response rate with aflibercept (VEGF-Trap) and docetaxel against platinum-resistant disease; 4) detection of response to the AKT inhibitor perifosine in ovarian cancers with PTEN mutations; 5) discovery that as many as 30% of ovarian cancer patients have BRCA dysfunction; and 6) identification of PVT-1 and PFDN4 as targets for siRNA therapy. Five project proposed for the next grant period will: 1) evaluate a multi-marker algorithm for early detection of ovarian cancer; 2) target Dll4/Notch signaling to reverse resistance and synergize with anti-VEGF therapy; 3) test personalized therapy of low grade cancer with MEK, AKT and IGFR inhibition; 4) personalize treatment for high grade ovarian cancers with activated PI3K signaling or BRCA dysfunction; and 5) develop mesenchymal stem cells as vehicles for tumor tropic delivery of IFN-B in preclinical and clinical studies. This work will be supported by three cores: Administrative; Biostatistics, Bioinformatics and Systems Biology; and Pathology. Support will be provided for DRP and CDP recipients to attain peer-reviewed funding. Valuable advice will continue to be provided by internal, external and advocate advisors.

德克萨斯大学 M.D. 安德森癌症中心 (MDACC) SPORE 的总体目标是通过基于疾病的分子、细胞和临床生物学的卵巢癌检测和治疗的创新转化研究来降低卵巢癌的发病率和死亡率。 IVIDACC 拥有一个由超过 35 名才华横溢的研究人员组成的独特社区，他们致力于转化、临床、基础和基于人群的卵巢癌研究，其中 20 人直接参与 SPORE。 合作者包括来自 9 所大学和 4 家公司的 25 名研究人员。在过去 4 年里，IVIDACC 已经治疗了 1,055 名卵巢癌和腹膜癌新患者，并已将 241 名患者纳入临床试验。 MDACC 通过招聘、薪资支持、临床设施、实验室空间和慈善基金高度重视卵巢癌研究。 MDACC 在 SPORE 的帮助下招募了 5 名对卵巢癌研究感兴趣的优秀教员，加强了研究基础设施，资助了 13 个发展研究项目 (DRP) 并支持了 4 名职业发展计划 (DRP) 获奖者。过去 5 年里，SPORE 研究人员发表了 381 篇有关卵巢癌的同行评审出版物。成就包括：1) 开发了早期卵巢癌的两阶段筛查策略，为检测早期疾病提供了 30% 的阳性预测值； 2) 鉴定出一组可检测 87% 早期卵巢癌的生物标志物； 2）发现周细胞作为抗血管生成治疗的靶点； 3) 观察到阿柏西普 (VEGF-Trap) 和多西紫杉醇对抗铂类耐药疾病的缓解率为 39%； 4) 检测 PTEN 突变卵巢癌对 AKT 抑制剂哌立福辛的反应； 5）发现多达30%的卵巢癌患者存在BRCA功能障碍； 6) 鉴定PVT-1和PFDN4作为siRNA治疗的靶点。为下一个资助期提出的五个项目将：1）评估用于早期检测卵巢癌的多标记算法； 2）靶向Dll4/Notch信号传导以逆转耐药性并与抗VEGF疗法协同作用； 3) 通过 MEK、AKT 和 IGFR 抑制测试低度癌症的个性化治疗； 4) 针对PI3K信号激活或BRCA功能障碍的高级别卵巢癌进行个体化治疗； 5) 在临床前和临床研究中开发间充质干细胞作为 IFN-B 向肿瘤递送的载体。这项工作将得到三个核心的支持：行政；生物统计学、生物信息学和系统生物学；和病理学。将为 DRP 和 CDP 接收者提供支持，以获得同行评审的资金。内部、外部和倡导顾问将继续提供宝贵的建议。

项目成果

Calcium-dependent FAK/CREB/TNNC1 signalling mediates the effect of stromal MFAP5 on ovarian cancer metastatic potential.

• DOI: 10.1038/ncomms6092
• 发表时间: 2014-10-03
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Leung, Cecilia S.;Yeung, Tsz-Lun;Yip, Kay-Pong;Pradeep, Sunila;Balasubramanian, Lavanya;Liu, Jinsong;Wong, Kwong-Kwok;Mangala, Lingegowda S.;Armaiz-Pena, Guillermo N.;Lopez-Berestein, Gabriel;Sood, Anil K.;Birrer, Michael J.;Mok, Samuel C.
• 通讯作者: Mok, Samuel C.

A novel hTERT promoter-driven E1A therapeutic for ovarian cancer.

• DOI: 10.1158/1535-7163.mct-09-0056
• 发表时间: 2009-08
• 期刊: Molecular cancer therapeutics
• 影响因子: 5.7
• 作者: Xie X;Hsu JL;Choi MG;Xia W;Yamaguchi H;Chen CT;Trinh BQ;Lu Z;Ueno NT;Wolf JK;Bast RC Jr;Hung MC
• 通讯作者: Hung MC

Up-regulation of stromal versican expression in advanced stage serous ovarian cancer.

• DOI: 10.1016/j.ygyno.2010.05.029
• 发表时间: 2010-10
• 期刊: Gynecologic oncology
• 影响因子: 4.7
• 作者: Ghosh S;Albitar L;LeBaron R;Welch WR;Samimi G;Birrer MJ;Berkowitz RS;Mok SC
• 通讯作者: Mok SC

ELF3 is a negative regulator of epithelial-mesenchymal transition in ovarian cancer cells.

• DOI: 10.18632/oncotarget.15208
• 发表时间: 2017-03-07
• 期刊: Oncotarget
• 作者: Yeung TL;Leung CS;Wong KK;Gutierrez-Hartmann A;Kwong J;Gershenson DM;Mok SC
• 通讯作者: Mok SC

Urinary levels of Bcl-2 are elevated in ovarian cancer patients.

• DOI: 10.1016/j.ygyno.2008.09.037
• 发表时间: 2009-01
• 期刊: GYNECOLOGIC ONCOLOGY
• 影响因子: 4.7
• 作者: Anderson, Nicole S.;Bermudez, Yira;Badgwell, Donna;Chen, Ren;Nicosia, Santo V.;Bast, Robert C., Jr.;Kruk, Patricia A.
• 通讯作者: Kruk, Patricia A.