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 #
1P20MD006738-01
Application #
8355085
Study Section
Special Emphasis Panel (ZMD1-RN (01))
Project Start
2012-06-16
Project End
2017-01-31
Budget Start
2012-06-16
Budget End
2013-01-31
Support Year
1
Fiscal Year
2012
Total Cost
$164,845
Indirect Cost
$42,702
Name
Florida Agricultural and Mechanical University
Department
Type
DUNS #
623751831
City
Tallahassee
State
FL
Country
United States
Zip Code
32307
Badisa, Ramesh B; Batton, Chyree S; Mazzio, Elizabeth et al. (2018) Identification of biochemical and cytotoxic markers in cocaine treated PC12 cells. Sci Rep 8:2710
Cobourne-Duval, Makini K; Taka, Equar; Mendonca, Patricia et al. (2018) Thymoquinone increases the expression of neuroprotective proteins while decreasing the expression of pro-inflammatory cytokines and the gene expression NF?B pathway signaling targets in LPS/IFN? -activated BV-2 microglia cells. J Neuroimmunol 320:87-97
Sojourner, Samantha J; Graham, Willie M; Whitmore, Aurellia M et al. (2018) The Role of HSP40 Conserved Motifs in the Response to Cytotoxic Stress. J Nat Sci 4:
Mazzio, E; Badisa, R; Eyunni, S et al. (2018) Bioactivity-Guided Isolation of Neuritogenic Factor from the Seeds of the Gac Plant (Momordica cochinchinensis). Evid Based Complement Alternat Med 2018:8953958
Mendonca, Patricia; Taka, Equar; Bauer, David et al. (2018) The attenuating effects of 1,2,3,4,6 penta-O-galloyl-?-d-glucose on pro-inflammatory responses of LPS/IFN?-activated BV-2 microglial cells through NF?B and MAPK signaling pathways. J Neuroimmunol 324:43-53
Kutlehria, Shallu; Behl, Gautam; Patel, Ketan et al. (2018) Cholecalciferol-PEG Conjugate Based Nanomicelles of Doxorubicin for Treatment of Triple-Negative Breast Cancer. AAPS PharmSciTech 19:792-802
Badisa, Ramesh B; Wi, Sungsool; Jones, Zachary et al. (2018) Cellular and molecular responses to acute cocaine treatment in neuronal-like N2a cells: potential mechanism for its resistance in cell death. Cell Death Discov 4:13
Miles, Jana S; Sojourner, Samantha J; Whitmore, Aurellia M et al. (2018) Synergistic Effect of Endogenous and Exogenous Aldehydes on Doxorubicin Toxicity in Yeast. Biomed Res Int 2018:4938189
Mazzio, Elizabeth A; Lewis, Charles A; Elhag, Rashid et al. (2018) Effects of Sepantronium Bromide (YM-155) on the Whole Transcriptome of MDA-MB-231 Cells: Highlight on Impaired ATR/ATM Fanconi Anemia DNA Damage Response. Cancer Genomics Proteomics 15:249-264
Miles, Jana S; Sojourner, Samantha J; Jaafar, Lahcen et al. (2018) THE ROLE OF PROTEIN CHAPERONES IN THE SURVIVAL FROM ANTHRACYCLINE-INDUCED OXIDATIVE STRESS IN SACCHAROMYCES CEREVISIAE. Int J Adv Res (Indore) 6:144-152

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