The Free Radical Cancer Biology Program (FRCBP) is unique to the HCCC and focuses on studying the biology of inherent differences in reductive and oxidative (redox) metabolism between cancer vs. normal cells. Research in the program is determining the role that redox reactions play in cancer phenotypic changes relevant to cell growth, differentiation, signal transduction, metastasis, functional molecular imaging, and therapy. A unifying goal of the program is to utilize a comprehensive basic science understanding of redox biology to develop novel biochemical rationales for improving cancer therapy. Three overlapping themes exist within the program. Theme 1: Understanding the role of redox biochemistry in regulation of genetic and epigenetic gene expression pathways relevant to cancer biology. Within this theme are research areas of focus exploring redox fluctuations and gene expression globally, as well as gene expression changes related of key redox sensitive molecules such as glutathione, thioredoxin, SOD, and AP2. Ttieme 2: Understanding the role of redox regulation in cell biology. Within this theme are research areas exploring the effects of redox on the cell cycle as well as invasion and metastasis. Ttieme 3: Exploring the role of oxidative stress in therapy outcomes. Within this theme are research areas exploring the role of manipulating oxidative stress to improve therapy as well as using imaging of oxidative metabolism as an approach to monitor and guide therapy. Major accomplishments of the FRCBP over the past funding period include findings that (a) cancer cells (relative to normal cells) produce increased steady-state levels of 02*'and H2O2 from mitochondrial metabolism that significantly contribute to differential susceptibility to clonogenic cell killing induced by glucose deprivation;(b) extracellular superoxide dismutase (EcSOD) inhibits invasion and metastasis;(c) expression of MnSOD governs the late production of reactive oxygen species, cell cycle check points, and transformation following radiation exposure;(d) that inhibitors of glucose and hydroperoxide metabolism can be used to enhance responses to radio-chemo-therapy by enhancing metabolic oxidative stress. The FRCBP consists of 18 members from 1 basic science department and 6 clinical departments and 2 colleges. Peer-reviewed, research funding for this program totals $3.9 million with over $2.0 million total costs from NCI. FRCBP members co-authored 237 publications. Of these publications, 20% were intraprogrammatic, 24% were interprogrammatic and 10% were both intra and interprogrammatic, for a total of 54% collaborative publications.
It is becoming clear that metabolic oxidation/reduction reactions are altered in cancer vs. normal cells. The consensus is that cancer cells may exist in a chronic state of metabolic oxidative stress that may represent a significant underlying mechanism contributing to malignancy. A unifying goal of research in the FRCBP is to utilize a comprehensive understanding of cancer vs. normal cell redox biology to develop novel biochemical rationales for improving cancer therapy taking advantage fundamental differences in oxidative metabolism.
|Subramanyam, Shyamal; Kinz-Thompson, Colin D; Gonzalez Jr, Ruben L et al. (2018) Observation and Analysis of RAD51 Nucleation Dynamics at Single-Monomer Resolution. Methods Enzymol 600:201-232|
|Borcherding, Nicholas; Cole, Kimberly; Kluz, Paige et al. (2018) Re-Evaluating E-Cadherin and ?-Catenin: A Pan-Cancer Proteomic Approach with an Emphasis on Breast Cancer. Am J Pathol 188:1910-1920|
|Mansour, John C; Chavin, Kenneth; Morris-Stiff, Gareth et al. (2018) Management of asymptomatic, well-differentiated PNETs: results of the Delphi consensus process of the Americas Hepato-Pancreato-Biliary Association. HPB (Oxford) :|
|Scherer, Laura D; Kullgren, Jeffrey T; Caverly, Tanner et al. (2018) Medical Maximizing-Minimizing Preferences Predict Responses to Information about Prostate-Specific Antigen Screening. Med Decis Making 38:708-718|
|Gupta, Sarika; Karandikar, Nitin J; Ginader, Timothy et al. (2018) Flow cytometric aberrancies in plasma cell myeloma and MGUS - correlation with laboratory parameters. Cytometry B Clin Cytom 94:500-508|
|Zhang, Xuchen; Patil, Deepa; Odze, Robert D et al. (2018) The microscopic anatomy of the esophagus including the individual layers, specialized tissues, and unique components and their responses to injury. Ann N Y Acad Sci :|
|Schaal, Justin B; Maretzky, Thorsten; Tran, Dat Q et al. (2018) Macrocyclic ?-defensins suppress tumor necrosis factor-? (TNF-?) shedding by inhibition of TNF-?-converting enzyme. J Biol Chem 293:2725-2734|
|Tanos, Barbara E; Yeaman, Charles; Rodriguez-Boulan, Enrique (2018) An emerging role for IQGAP1 in tight junction control. Small GTPases 9:375-383|
|Coghill, Anna E; Bellizzi, Andrew M; Lynch, Charles F et al. (2018) Pathology characterization and detection of human papillomavirus type 16 in rectal squamous cell carcinomas. Clin Gastroenterol Hepatol :|
|Robinett, Zachary N; Bathla, Girish; Wu, Angela et al. (2018) Persistent Oxidative Stress in Vestibular Schwannomas After Stereotactic Radiation Therapy. Otol Neurotol 39:1184-1190|
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