The fundamental hypothesis driving this program is that the development and clinical implementation of non-invasive imaging of tumor hypoxia will lead to improved management of patients with solid tumors. However, the hypoxic phenotype is complex and in order to assess the clinical value of noninvasive images of tumor hypoxia, we must first understand the mechanisms operating at a microscopic level that are responsible for the generation of the macroscopic images. For an imaging procedure to successfully discriminate between hypoxic and non-hypoxic tumors at the global level it must also, when examined with sufficient spatial resolution, reflect the differences in hypoxia that exist within tumors at a microscopic level. There is no single """"""""gold standard"""""""" technique for determining tumor hypoxia that can be used to verify all the others - each technique has its own particular strengths and weaknesses. This means we must use multiple techniques with the goal of achieving a consensus and require a systematic approach to registration, correlation and validation. The role of the tumor and radiation biology core is to provide a set of model systems and assays that enable tumor hypoxia to be studied and the components of the multi-modality imaging approach to be compared with relevant biological indices. The specific tasks of this core are to: 1. characterize tumor cell lines in terms of their oxygen-dependent behavior in-vitro and tumor morphology in-vivo and identify suitable model systems for study by the research projects; 2. generate and characterize appropriate tumor cell lines stably transfected with the TKeGFP fusion gene expressed either constitutively or under the control of a hypoxia response element; 3. implement and validate immunohistochemical methods of detecting endogenous markers related to tumor hypoxia and exogenous tracers of tumor hypoxia; 4. implement and validate assays of radiobiological damage in tumor samples and sections; 5. optimize the use of invasive oxygen probes to measure intratumoral oxygen tension.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA115675-05
Application #
8109177
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
5
Fiscal Year
2010
Total Cost
$274,628
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Leftin, Avigdor; Koutcher, Jason A (2018) Quantification of Nanoparticle Enhancement in Polarized Breast Tumor Macrophage Deposits by Spatial Analysis of MRI and Histological Iron Contrast Using Computer Vision. Contrast Media Mol Imaging 2018:3526438
Dong, Jun; Ren, Yufeng; Zhang, Tian et al. (2018) Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end-joining of radiation-induced double strand break repair. Oncol Rep 39:912-920
Dong, Jun; Zhang, Tian; Ren, Yufeng et al. (2017) Inhibiting DNA-PKcs in a non-homologous end-joining pathway in response to DNA double-strand breaks. Oncotarget 8:22662-22673
Leftin, Avigdor; Zhao, Huiyong; Turkekul, Mesru et al. (2017) Iron deposition is associated with differential macrophage infiltration and therapeutic response to iron chelation in prostate cancer. Sci Rep 7:11632
Zanzonico, Pat B (2016) The Neglected Side of the Coin: Quantitative Benefit-risk Analyses in Medical Imaging. Health Phys 110:301-4
Shaffer, Travis M; Harmsen, Stefan; Khwaja, Emaad et al. (2016) Stable Radiolabeling of Sulfur-Functionalized Silica Nanoparticles with Copper-64. Nano Lett 16:5601-4
Simões, Rui V; Serganova, Inna S; Kruchevsky, Natalia et al. (2015) Metabolic plasticity of metastatic breast cancer cells: adaptation to changes in the microenvironment. Neoplasia 17:671-84
Sun, Xiaorong; Ackerstaff, Ellen; He, Fuqiu et al. (2015) Visualizing the antivascular effect of bortezomib on the hypoxic tumor microenvironment. Oncotarget 6:34732-44
Shaffer, Travis M; Wall, Matthew A; Harmsen, Stefan et al. (2015) Silica nanoparticles as substrates for chelator-free labeling of oxophilic radioisotopes. Nano Lett 15:864-8
Hsiao, Hung Tsung; Xing, Ligang; Deng, Xuelong et al. (2014) Hypoxia-targeted triple suicide gene therapy radiosensitizes human colorectal cancer cells. Oncol Rep 32:723-9

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