Research Project 2 - Hypoxia and anaerobic metabolism regulation of cancer cell survival: a novel molecular target for anticancer therapeutics - K.F. Soliman H. Flores-Rozas, S. Darling and E. Mazzio: In the US, African Americans still continue to experience highest death rates from many different types of cancers. Often times, socioeconomic disadvantage places individuals in a compromising position of not being able to afford proper medical care thereby forgoing necessary early detection and treatment. This poses considerable challenge because a cancer can gain strength over time transforming into aggressive malignancy, which is non-responsive to chemotherapy or radiation. This evolutionary process is believed to be the result of events occurring at the core of a primary solid tumor mass. As a tumor grows, its central core becomes exposed to low p02 (hypoxia) resulting In genetic adaptations which foster expression of a diverse array of proteins that promote survival, growth, metastasis and angiogenesis. A lack of O2 prevents HIF-1 a proteosomal degradation, leading to HIF-1 a-HIF-1B dimerization and its translocation to the nucleus where hypoxic response element (HRE) genes initiate transcription of proteins that perpetuate survival. Because late stage cancers are often untreatable, the understanding of molecular, genetic or functional regulation of glucose metabolism in hypoxic tumor cells are critical in order to elucidate targeted therapeutic treatments that will destroy the tumor without harm to the host.. Our preliminary data show that hypoxic tumor cells use glucose to produce ATP in a process that appears to expand beyond the traditional

Agency
National Institute of Health (NIH)
Institute
National Institute on Minority Health and Health Disparities (NIMHD)
Type
Exploratory Grants (P20)
Project #
5P20MD006738-02
Application #
8552024
Study Section
Special Emphasis Panel (ZMD1-RN)
Project Start
2013-02-01
Project End
2017-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
2
Fiscal Year
2013
Total Cost
$73,693
Indirect Cost
$19,513
Name
Florida Agricultural and Mechanical University
Department
Type
DUNS #
623751831
City
Tallahassee
State
FL
Country
United States
Zip Code
32307
Odewumi, Caroline O; Fils-Aime, Shiela; Badisa, Veera L D et al. (2015) Chemoprotective effect of monoisoamyl 2, 3-dimercaptosuccinate (MiADMS) on cytokines expression in cadmium chloride treated human lung cells. Environ Toxicol 30:704-11
Bauer, David; Mazzio, Elizabeth; Soliman, Karam Fa et al. (2014) Diallyl disulfide inhibits TNF?-induced CCL2 release by MDA-MB-231 cells. Anticancer Res 34:2763-70
Green, Jennifer E; Cooperwood, John S; Taka, Equar et al. (2014) Comparative proteomic analysis reveals growth inhibition by 3-N-alkyloxyestradiol derivative (SERM) in prostate cancer cells. Cancer Genomics Proteomics 11:195-200
Patel, Apurva R; Lim, Ed; Francis, Kevin P et al. (2014) Opening up the optical imaging window using nano-luciferin. Pharm Res 31:3073-84
Mazzio, E; Badisa, R; Mack, N et al. (2014) High throughput screening of natural products for anti-mitotic effects in MDA-MB-231 human breast carcinoma cells. Phytother Res 28:856-67
Badisa, Ramesh B; Mina, David A; Latinwo, Lekan M et al. (2014) Selective anticancer activity of neurotoxin 1-methyl-4-phenylpyridinium on non-small cell lung adenocarcinoma A549 cells. Anticancer Res 34:5447-52
Agyare, Edward K; Jaruszewski, Kristen M; Curran, Geoffry L et al. (2014) Engineering theranostic nanovehicles capable of targeting cerebrovascular amyloid deposits. J Control Release 185:121-9
Gangapuram, Madhavi; Mazzio, Elizabeth; Eyunni, Suresh et al. (2014) Synthesis and biological evaluation of substituted N-[3-(1H-pyrrol-1-yl)methyl]-1,2,5,6-tetrahydropyridin-1-yl]benzamide/benzene sulfonamides as anti-inflammatory agents. Arch Pharm (Weinheim) 347:360-9
Mazzio, Elizabeth A; Soliman, Karam F A (2014) Epigenetics and nutritional environmental signals. Integr Comp Biol 54:21-30
Chougule, Mahavir B; Patel, Apurva R; Patlolla, Ram et al. (2014) Epithelial transport of noscapine across cell monolayer and influence of absorption enhancers on in vitro permeation and bioavailability: implications for intestinal absorption. J Drug Target 22:498-508

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