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.

Public Health Relevance

The second leading cause of death in the United States is cancer. Apart from the most commons types of cancer such as breast and prostate, there are a great number of hematopoietic and lymphoid malignancies. Our group has identified greater than fifty related compounds with strong cytotoxic activity against human lymphomas that need to be fully characterized. The identification and characterization of drugs that are cytotoxic to specific types of lymphomas can lead to the implementation of new agents that alone or in combination can cure or increase life expectancy of those affected by specific lymphoid neoplasms.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Continuance Award (SC3)
Project #
1SC3GM103713-01
Application #
8414350
Study Section
Special Emphasis Panel (ZGM1-TWD-Y (SC))
Program Officer
Okita, Richard T
Project Start
2013-07-01
Project End
2017-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$113,125
Indirect Cost
$38,125
Name
University of Texas El Paso
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
132051285
City
El Paso
State
TX
Country
United States
Zip Code
79968
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Seong, Chang-Soo; Varela-Ramirez, Armando; Tang, Xiaolei et al. (2014) Cloning and characterization of a novel Drosophila stress induced DNase. PLoS One 9:e103564
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Santiago-Vazquez, Yahaira; Das, Swagatika; Das, Umashankar et al. (2014) Novel 3,5-bis(arylidene)-4-oxo-1-piperidinyl dimers: structure-activity relationships and potent antileukemic and antilymphoma cytotoxicity. Eur J Med Chem 77:315-22
Pedroza, Diego A; De Leon, Fernando; Varela-Ramirez, Armando et al. (2014) The cytotoxic effect of 2-acylated-1,4-naphthohydroquinones on leukemia/lymphoma cells. Bioorg Med Chem 22:842-7

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