8.4.1 ABSTRACT: TUMOR BIOLOGY AND PROGRESSION, The Tumor Biology and Progression program, led by James McCarthy, Ph.D., has 27 members, : representing 16 departments and five schools. As of October 1, 2007, these members have a total of $6.5 million in peer-reviewed, funded research projects for the current budget period. Since June 2003, their research has resulted in 172 publications, of which 14% were intra-programmatic and 15% were interprogrammatic. Research within the Tumor Biology and Progression Program focuses on molecular and cellular mechanisms associated with the progression of malignant tumors. The program has three major scientific focus areas or themes. First, program members are studying the biology of tumor growth/survival and evaluating important contributions of the tumor microenvironment in progression. The role of heat shock protein 70 in the therapeutic resistance of pancreatic cancer cells and identification of specific inhibitors to improve therapy are being pursued. New protocols using neoadjuvant therapies for pancreatic cancer are being developed and tested in orthotopic animal models of the disease. Newly recrujted faculty are studying the importance of macrophage infiltration to early progression associated events in a transgenic animal model of breast cancer. Studies are also in progress to examine mechanisms of action Of defined antiangiogenic agents, including novel engineered nonpeptide mimetic inhibitors of angiogenesis. Second, there is a prostate cancer focus group that consists of clinincal investigators and basic scientists.Projects being pursued include determining how androgen receptors regulate the growth of hormone refractory disease, how intracellular kinases such as CK2 confer survival, and how hyaluronan within the microenvironment facilitates progression. These studies are being extended to evaluate feasibility of delivering RNA interference based therapies using sub 50nm nanocapsules. Synthetic peptides that disrupt hyaluronan/ tumor cell interactions are being evaluated in vitro and in vivo for the ability to limit tumor growth. Development of noninvasive imaging approaches for staging prostate tumors and relating these results to more conventional molecular correlates of progression is also being pursued. Finally, novel immunotoxins are being developed to improve the treatment of various hematopoietic and solid tissue tumors. These studies involve the design of bivalent sFv antibodies coupled with diptheria toxin to target and kill neoplasms: Some of these agents are currently in phase I clinical trials and others are being developed for future clinical studies. The long term goal of the program is to identify and target key pathways used by malignant tumors for dysregulated growth, invasion and resistance to therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
2P30CA077598-11
Application #
7944859
Study Section
Subcommittee G - Education (NCI)
Project Start
2009-04-08
Project End
2014-01-31
Budget Start
2009-04-08
Budget End
2010-01-31
Support Year
11
Fiscal Year
2009
Total Cost
$26,094
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Xu, Bin; Magli, Alessandro; Anugrah, Yoska et al. (2018) Nanotopography-responsive myotube alignment and orientation as a sensitive phenotypic biomarker for Duchenne Muscular Dystrophy. Biomaterials 183:54-66
Nikodemova, Maria; Yee, Jeremiah; Carney, Patrick R et al. (2018) Transcriptional differences between smokers and non-smokers and variance by obesity as a risk factor for human sensitivity to environmental exposures. Environ Int 113:249-258
Rashidi, Armin; Shanley, Ryan; Anasetti, Claudio et al. (2018) Analysis of BMT CTN-0201 and -0901 samples did not reproduce the reported association between recipient REG3A rs7588571 and chronic GVHD. Bone Marrow Transplant :
Lin, Lifeng; Chu, Haitao (2018) Bayesian multivariate meta-analysis of multiple factors. Res Synth Methods 9:261-272
Mondragon-Gonzalez, Ricardo; Perlingeiro, Rita C R (2018) Recapitulating muscle disease phenotypes with myotonic dystrophy 1 induced pluripotent stem cells: a tool for disease modeling and drug discovery. Dis Model Mech 11:
Kim, J-H; Frantz, A M; Sarver, A L et al. (2018) Modulation of fatty acid metabolism and immune suppression are features of in vitro tumour sphere formation in ontogenetically distinct dog cancers. Vet Comp Oncol 16:E176-E184
Jin, Jin; Zhang, Lin; Leng, Ethan et al. (2018) Detection of prostate cancer with multiparametric MRI utilizing the anatomic structure of the prostate. Stat Med 37:3214-3229
Pierpont, Elizabeth I; Hudock, Rebekah L; Foy, Allison M et al. (2018) Social skills in children with RASopathies: a comparison of Noonan syndrome and neurofibromatosis type 1. J Neurodev Disord 10:21
Carlson, Erik S; Upadhyaya, Pramod; Villalta, Peter W et al. (2018) Analysis and Identification of 2'-Deoxyadenosine-Derived Adducts in Lung and Liver DNA of F-344 Rats Treated with the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and Enantiomers of its Metabolite 4-(Methylnitrosamino)-1-(3-p Chem Res Toxicol 31:358-370
Lin, Lifeng; Chu, Haitao; Murad, Mohammad Hassan et al. (2018) Empirical Comparison of Publication Bias Tests in Meta-Analysis. J Gen Intern Med 33:1260-1267

Showing the most recent 10 out of 1013 publications