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

• 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
• 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' 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

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）：尽管在过去的十年中，美国的癌症发病率略有下降，但它仍然每年拥有超过50万个个人的生活。有许多不同类型的淋巴细胞恶性肿瘤代表了B和T细胞发育的各个阶段，这些阶段约占该国所有癌症的9％。淋巴瘤代表血细胞癌的约54％，主要形式是霍奇金和非霍奇金淋巴瘤（NLH）。后者是最常见的淋巴瘤类型，并以最高的速度影响高加索人，紧密地是西班牙裔下降的人。 NLH患者的生存率为5年约67％，而非裔美国人的存活率较低，为56％。霍奇金淋巴瘤患者的白人生存率为83％，非裔美国人的存活率为77％。有许多因素不仅影响癌症的发病率，而且还影响死亡率，其中一些因素可能是造成观察到的健康差异的原因。不幸的是，找到所有类型癌症的治疗方法极不可能，因为涉及许多遗传变化和许多不同类型的癌症。但是，有一些新药在相当频繁地发现，通过靶向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。最近几个月，我们开发了并验证了一种筛选测定法，该测定法用于测试B和T细胞淋巴瘤上的小型化合物。这些筛查工作导致鉴定了几种相关化合物，这些化合物对淋巴瘤高度细胞毒性。该项目的主要目标是表征已鉴定出的新型抗淋巴瘤化合物。该项目的具体目的是（1）表征已识别的抗淋巴瘤化合物（2）确定铅化合物的作用方式，（3）检查体内最有希望的化合物的效果。对特定类型的淋巴瘤的细胞毒性药物的鉴定和表征会导致新型治疗剂。