SPORE in Pancreatic Cancer

胰腺癌中的孢子

• 批准号: 7287817
• 负责人: DONALD J. BUCHSBAUM
• 金额: $ 85.56万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-16 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7287817
• 关键词: Address; Adenovirus Vector; Animal Model; Antibodies; Area; Award; Biological; Biostatistics Core; Brain; Breast; Cancer Cell Growth; Cancer Model; Cell Line; Cell Proliferation; Cells; Cessation of life; Clinical; Clinical Trials; Combined Modality Therapy; Databases; Death Receptor 5; Development; Diagnosis; Disease; Enhancers; Enzymes; Evaluation; Faculty; Fc Receptor; Fibroblast Growth Factor; Fibroblast Growth Factor Receptor 1; Fibroblast Growth Factor Receptors; Funding; Gene Transduction Agent; Genes; Goals; Grant; Growth Factor; Guidelines; Herpes Simplex Infections; Human; Image; Immunotherapy; In Vitro; Institutes; Institution; Insulin; Lead; Ligands; Malignant Neoplasms; Malignant neoplasm of ovary; Malignant neoplasm of pancreas; Metabolism; Methods; Molecular; Molecular Epidemiology; Multimodal Imaging; Mutation; Neoplasm Metastasis; Numbers; Oncolytic; Pancreas; Pancreatic Adenocarcinoma; Pancreatic carcinoma; Pathology; Pathway interactions; Patients; Phase I Clinical Trials; Phase I/II Trial; Pilot Projects; Population; Prevention; Process; Program Development; Proteins; RGD (sequence); RNA Splicing; Radiation; Radiation Interaction; Rapid Access to Intervention Development; Reproduction spores; Research; Research Project Grants; Resistance; Role; Screening procedure; Signal Transduction; Signal Transduction Pathway; Smad Proteins; Smad protein; TNFRSF10B gene; Time; Toxic effect; Toxin; Translating; Translational Research; Translations; Tumor Suppressor Proteins; United States Food and Drug Administration; University of Alabama at Birmingham Cancer Center; Unresectable; Variant; Viral Vector; Virus; Xenograft procedure; anticancer research; base; cancer cell; capecitabine; career; chemotherapy; cytotoxic; death receptor-4; experience; gene therapy; human TNFRSF10A protein; immunopathology; inhibitor/antagonist; innovation; interest; killings; medical schools; multidisciplinary; novel; novel strategies; pancreatic neoplasm; pancreatic tumorigenesis; pre-clinical; preclinical study; professor; programs; protein degradation; receptor; tissue resource; tumor; tumor growth; vector

DESCRIPTION (provided by applicant): This Pancreatic Adenocarcinoma (Cancer) SPORE will greatly strengthen and expand the pancreatic cancer research of the UAB Comprehensive Cancer Center with an emphasis on translational research. Its themes of Gene Therapy, Death Receptor Targeted Immunotherapy, Growth Factor Mechanisms of chemoresistance, and mechanisms of Tumor Gene Suppression and Protein Degradation are all a critical priority. Four research projects involve interdisciplinary investigative teams including: 1.) "Cytotoxic Resistance: FGFR-1 Signaling and Reversion" which will explore the mechanism of FGFR-1 differential signal transduction and its resistance to cytotoxic insulin (CR) in cytotoxic (chemoradiation) resistance demonstrated in clinical pancreatic cancer. 2.) "Mechanisms of Tumor Suppressor DPC4/Smad4for Protein Instability in Pancreatic Cancer" which will evaluate the role of Jab-1 inhibition and Smad4/DPC4 protein degradation as potential inhibitor of pancreatic tumor growth. 3.) "Multimodality Targeted Therapy of Pancreatic Cancer - Use of Death Receptor (DR) Antibodies Alone and in Combination with Chemotherapy-Radiation Interactions" which will provide early translation for targeted immunotherapy to treat pancreatic cancer via anti DR5 death receptor antibody TR-8 (Anti-DR5). 4.) "Coordinated Virus - Adjunctive therapies (CVAT) for Pancreatic Cancer" which will be a fundamental development and selection of novel gene therapy vectors including early translation trial involving RAID supported conditionally replicative RGD-COX-2 adenoviral vector and a FDA approved HSV 207 oncolytic herpes vector. These projects will be supported by four Cores: 1.) Administrative/Biostatistics Core; 2.) Tissue Resource & Immunopathology Core; 3.) Clinical Core, and 4.) Animal Model and Imaging Core. In addition, the SPORE will have a Career Development Program directed at careers in Pancreatic Cancer Translational Research (5 awards) and a Developmental Research Program (4 pilot projects annually). The SPORE has strong institutional commitments and enthusiastic plans for interaction with other SPOREs including our own Brain, Breast, and Ovarian Cancer SPORE. This SPORE will increase scientific discoveries and rapidly translate findings into innovative clinical trials.

描述（由申请人提供）：这种胰腺腺癌（癌症）SPORE 将极大地加强和扩大 UAB 综合癌症中心的胰腺癌研究，重点是转化研究。其主题包括基因治疗、死亡受体靶向免疫治疗、生长因子化疗耐药机制、肿瘤基因抑制和蛋白质降解机制等。四个研究项目涉及跨学科研究团队，包括：1.）“细胞毒性抵抗：FGFR-1信号传导和逆转”将探讨FGFR-1差异信号转导机制及其对细胞毒性胰岛素（CR）的细胞毒性（放化疗）抵抗在临床胰腺癌中得到证实。 2.) “胰腺癌中肿瘤抑制因子 DPC4/Smad4 蛋白不稳定性的机制”将评估 Jab-1 抑制和 Smad4/DPC4 蛋白降解作为胰腺肿瘤生长潜在抑制剂的作用。 3.) “胰腺癌的多模式靶向治疗 - 单独使用死亡受体（DR）抗体以及联合化疗-放射相互作用”，这将为通过抗 DR5 死亡受体抗体 TR-8 治疗胰腺癌的靶向免疫疗法提供早期转化（抗 DR5）。 4.) “协调病毒 - 胰腺癌辅助疗法 (CVAT)”，这将是新型基因治疗载体的基础开发和选择，包括涉及 RAID 支持的条件复制 RGD-COX-2 腺病毒载体和 FDA 批准的 HSV 的早期翻译试验207 溶瘤疱疹载体。 这些项目将得到四个核心的支持： 1.) 行政/生物统计核心； 2.) 组织资源和免疫病理学核心； 3.) 临床核心，以及 4.) 动物模型和成像核心。此外，SPORE还将有一个针对胰腺癌转化研究职业的职业发展计划（5个奖项）和一个发展研究计划（每年4个试点项目）。 SPORE 有强有力的机构承诺和热情的计划来与其他 SPORE 互动，包括我们自己的脑、乳腺癌和卵巢癌 SPORE。该 SPORE 将增加科学发现，并迅速将发现转化为创新的临床试验。

项目成果

Therapeutic improvement of a stroma-targeted CRAd by incorporating motives responsive to the melanoma microenvironment.

• DOI: 10.1038/jid.2013.191
• 发表时间: 2013-11
• 期刊: JOURNAL OF INVESTIGATIVE DERMATOLOGY
• 影响因子: 6.5
• 作者: Viale, Diego L.;Cafferata, Eduardo G.;Gould, David;Rotondaro, Cecilia;Chernajovsky, Yuti;Curiel, David T.;Podhajcer, Osvaldo L.;Lopez, M. Veronica
• 通讯作者: Lopez, M. Veronica

Loss of tumor suppressor Merlin results in aberrant activation of Wnt/β-catenin signaling in cancer.

• DOI: 10.18632/oncotarget.7494
• 发表时间: 2016-04-05
• 期刊: Oncotarget
• 作者: Morrow KA;Das S;Meng E;Menezes ME;Bailey SK;Metge BJ;Buchsbaum DJ;Samant RS;Shevde LA
• 通讯作者: Shevde LA

S100A4 promotes pancreatic cancer progression through a dual signaling pathway mediated by Src and focal adhesion kinase.

• DOI: 10.1038/srep08453
• 发表时间: 2015-02-13
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Che P;Yang Y;Han X;Hu M;Sellers JC;Londono-Joshi AI;Cai GQ;Buchsbaum DJ;Christein JD;Tang Q;Chen D;Li Q;Grizzle WE;Lu YY;Ding Q
• 通讯作者: Ding Q

Chapter seven--Cancer treatment with gene therapy and radiation therapy.

• DOI: 10.1016/b978-0-12-398342-8.00007-0
• 发表时间: 2012
• 期刊: ADVANCES IN CANCER RESEARCH
• 作者: Kaliberov, Sergey A.;Buchsbaum, Donald J.
• 通讯作者: Buchsbaum, Donald J.

Intravenous genetic mesothelin vaccine based on human adenovirus 40 inhibits growth and metastasis of pancreatic cancer.

• DOI: 10.1002/ijc.27983
• 发表时间: 2013-07
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Yamasaki, Satoshi;Miura, Yoshiaki;Davydova, Julia;Vickers, Selwyn M.;Yamamoto, Masato
• 通讯作者: Yamamoto, Masato