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Oral Cancer, Chemoprevention, and Anti-Angiogenesis

口腔癌、化学预防和抗血管生成

基本信息

批准号：
7616443
负责人：
MARK W. LINGEN
金额：
$ 33.78万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-08-01 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7616443
关键词：
ABT-510 Address Angiogenesis Inhibition Angiogenesis Inhibitors Angiogenic Switch Animal Model Animals Blood Vessels Cancer Model Cell Line Cells Chemoprevention Chemopreventive Agent Classification Clinical Development Diagnosis Disease Dysplasia Early Diagnosis Evaluation Genetic Genomics Goals Gold Growth Hamsters Head and Neck Squamous Cell Carcinoma Histologic Human In Vitro Incidence Individual Lesion Life Malignant Neoplasms Modality Modeling Mucous Membrane Mus Neoplasms Oral Outcome Patients Phenotype Prevention Prevention strategy Primary Neoplasm Process Reagent Risk Testing Time Variant Work ZD-6474 angiogenesis antiangiogenesis therapy base cancer chemoprevention cancer prevention effective therapy human tissue in vivo in vivo Model inhibitor/antagonist keratinocyte malignant mouth neoplasm mouse model novel pre-clinical prevent response tumor

项目摘要

DESCRIPTION (provided by applicant): Head and neck squamous cell carcinoma (HNSCC) is an aggressive neoplasm that is the sixth most common malignancy in the world. Despite numerous advances in treatment, the five-year survival has remained unchanged for the last 50 years. This poor outcome is due to a number of variables including delayed diagnosis as well as the development of multiple primary tumors. Therefore, it is essential to supplement early detection with effective strategies for the prevention of this devastating disease. The expression of the angiogenic phenotype is both a very early and an absolutely essential step in the development of HNSCC, making it an attractive target for cancer prevention. However, a number of critical biologic questions remain regarding the timing, mechanisms and dynamics of the angiogenic phenotype during progression. In addition, a detailed and systematic evaluation of the utility of anti-angiogenic therapies targeting the prevention of HNSCC has not been performed. The long-term goal of this proposal is to develop novel, nontoxic chemopreventive strategies for HNSCC that are based upon the inhibition of angiogenesis. The hypothesis of this work is that inhibitors of angiogenesis can effectively prevent HNSCC. The specific aims are: 1.) to characterize the development of the "angiogenic switch" in HNSCC, 2) to investigate the mechanisms and dynamics of the angiogenic phenotype during the development of HNSCC, and 3) to determine if anti-angiogenic agents ZD6474 or ABT-510 are effective as chemopreventive therapies in a pre-clinical animal model of HNSCC. Using preclinical animal models as well as human tissue/cells, the proposed work will determine the timing of the switch of the angiogenic phenotype in HNSCC. It will also investigate the mechanisms and dynamics of this switch. Finally, it will determine if inhibitors of angiogenesis are an effective treatment modality for the prevention of HNSCC, which would be of dramatic clinical benefit to large numbers of patients who are at tremendous risk for developing multiple lesions throughout their upper aerodigestive tract.

描述（由申请人提供）：头颈部鳞状细胞癌（HNSCC）是一种侵袭性肿瘤，是世界上第六大常见恶性肿瘤。尽管在治疗方面取得了许多进步，但在过去的50年里，五年生存率一直没有改变。这种糟糕的结果是由于许多变量，包括延迟诊断以及多发性原发肿瘤的发展。因此，必须在早期发现的基础上补充有效的战略，以预防这一毁灭性疾病。血管生成表型的表达在HNSCC的发展中是一个非常早期和绝对必要的步骤，使其成为癌症预防的一个有吸引力的靶点。然而，一些关键的生物学问题仍然存在，如进展过程中血管生成表型的时间、机制和动力学。此外，还没有对针对HNSCC预防的抗血管生成疗法的效用进行详细和系统的评估。该建议的长期目标是开发基于抑制血管生成的新型、无毒的HNSCC化学预防策略。本研究的假设是血管生成抑制剂可以有效预防HNSCC。

项目成果

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Prediction of in vivo synergistic activity of antiangiogenic compounds by gene expression profiling.

DOI：
发表时间：
2002-12
期刊：
Cancer research
影响因子：
11.2
作者：
E. Cline;S. Bicciato;C. Dibello;M. Lingen
通讯作者：
E. Cline;S. Bicciato;C. Dibello;M. Lingen

Endothelial cell migration assay. A quantitative assay for prediction of in vivo biology.

内皮细胞迁移测定。

DOI：
10.1385/1-59259-332-1:337
发表时间：
2003
期刊：
Methods in molecular medicine
影响因子：
0
作者：
Lingen,MarkW
通讯作者：
Lingen,MarkW

Angiogenesis in oral cancer.

DOI：
10.1002/j.0022-0337.2001.65.11.tb03489.x
发表时间：
2001-11
期刊：
Journal of dental education
影响因子：
2.3
作者：
R. Hasina;M. Lingen
通讯作者：
R. Hasina;M. Lingen

A feed-forward loop involving protein kinase Calpha and microRNAs regulates tumor cell cycle.

DOI：
10.1158/0008-5472.can-08-0377
发表时间：
2009-01-01
期刊：
Cancer research
影响因子：
11.2
作者：
Cohen EE;Zhu H;Lingen MW;Martin LE;Kuo WL;Choi EA;Kocherginsky M;Parker JS;Chung CH;Rosner MR
通讯作者：
Rosner MR

Role of leukocytes and endothelial cells in the development of angiogenesis in inflammation and wound healing.

白细胞和内皮细胞在炎症和伤口愈合中血管生成发展中的作用。