Characterization of novel compounds with anti-lymphoma activity

具有抗淋巴瘤活性的新型化合物的表征

基本信息

批准号：
8414350
负责人：
RENATO J AGUILERA
金额：
$ 11.31万
依托单位：
UNIVERSITY OF TEXAS EL PASO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8414350
关键词：
Adverse effects Affect African American Age Antineoplastic Agents Apoptosis Biological Assay Blood Cells Breast Caucasians Caucasoid Race Cause of Death Cell Death Cell Line Country Cytotoxic agent Data Development Dose Ethnic Origin Future Goals Growth Hematopoietic Neoplasms Hispanics Hodgkin Disease Human Immunodeficient Mouse In Vitro Incidence Lead Libraries Life Expectancy Lymphocyte Lymphoma Malignant Neoplasms Malignant lymphoid neoplasm Mutation New Agents Non-Hodgkin&apos s Lymphoma Pathway interactions Patients Pharmaceutical Preparations Preclinical Drug Evaluation Prostate Research Research Personnel Resistance Staging Survival Rate T-Cell Development T-Cell Lymphoma Testing Therapeutic Therapeutic Agents TimeLine Transplantation United States base cancer type cytotoxic cytotoxicity test health disparity in vivo leukemia/lymphoma lymphoid neoplasm mortality novel novel therapeutics public health relevance screening therapy resistant

项目摘要

DESCRIPTION (provided by applicant): Although the incidence for cancer in the US has declined slightly in the past decade, it still claims the lives of more than half a million individals a year. There are a great number of distinct types of lymphocyte malignancies that represent the various stages of B- and T-cell development and these represent approximately 9% of all cancers in this country. Lymphomas represent ~54% of blood cell cancers and the main forms are Hodgkin and non-Hodgkin lymphomas (NLH). The latter is the most common type of lymphoma and affects Caucasians at a highest rate followed closely by people of Hispanic descent. Patients with NLH have a 5 year survival rate of ~67% while African Americans have a lower survival rate of 56%. Patients with Hodgkin lymphoma have a survival rate of 83% for whites and 77% for African Americans. There are many factors that not only affect cancer incidence but also mortality, and some of these are the likely causes of the observed health disparities. Unfortunately, finding a cure for all types of cancer is highly unlikely as there are many genetic alterations that are involved and many distinct types of cancers. However, there are new drugs being discovered on a fairly frequent basis that affect specific cancer types by targeting specific pathways that interfere with their growth or induce cell death. In recent months, we have developed and validated a screening assay that was used to test a small library of compounds on B- and T-cell lymphomas. These screening efforts have resulted in the identification of several related compounds that are highly cytotoxic to lymphomas. The main goal of this project is to characterize the novel anti-lymphoma compounds that have been identified. The specific aims of the project are to (1) characterize the identified anti-lymphoma compounds (2) determine the mode of action of lead compounds, and (3) examine the effects of the most promising compounds in vivo. The identification and characterization of drugs that are cytotoxic to specific types of lymphomas can lead to novel therapeutic agents.

描述（由申请人提供）：尽管美国的癌症发病率在过去十年中略有下降，但每年仍夺去超过 50 万人的生命。淋巴细胞恶性肿瘤有多种不同类型，代表 B 细胞和 T 细胞发育的不同阶段，约占该国所有癌症的 9%。淋巴瘤约占血细胞癌的 54%，主要形式是霍奇金淋巴瘤和非霍奇金淋巴瘤 (NLH)。后者是最常见的淋巴瘤类型，影响白种人的比例最高，其次是西班牙裔人。 NLH 患者的 5 年生存率约为 67%，而非裔美国人的生存率较低，为 56%。霍奇金淋巴瘤患者的白人存活率为 83%，非洲裔美国人为 77%。有许多因素不仅影响癌症发病率，而且影响死亡率，其中一些因素可能是造成所观察到的健康差异的原因。不幸的是，找到治疗所有类型癌症的方法是不太可能的，因为涉及许多基因改变和许多不同类型的癌症。然而，相当频繁地发现了一些新药，它们通过针对干扰其生长或诱导细胞死亡的特定途径来影响特定的癌症类型。近几个月来，我们开发并验证了一种筛选方法，用于测试 B 细胞和 T 细胞淋巴瘤的小型化合物库。这些筛选工作已鉴定出几种对淋巴瘤具有高度细胞毒性的相关化合物。该项目的主要目标是表征已鉴定的新型抗淋巴瘤化合物。该项目的具体目标是（1）表征已识别的抗淋巴瘤化合物（2）确定先导化合物的作用模式，以及（3）检查最有希望的化合物在体内的作用。对特定类型淋巴瘤具有细胞毒性的药物的鉴定和表征可以产生新的治疗药物。