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 #
3P30CA077598-14S2
Application #
8533468
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
14
Fiscal Year
2012
Total Cost
$1,776
Indirect Cost
$600
Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Lin, Weiming; Modiano, Jaime F; Ito, Daisuke (2017) Stage-specific embryonic antigen: determining expression in canine glioblastoma, melanoma, and mammary cancer cells. J Vet Sci 18:101-104
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Zhao, Xianda; Li, Lihua; Starr, Timothy K et al. (2017) Tumor location impacts immune response in mouse models of colon cancer. Oncotarget 8:54775-54787
Lynn, Geoffrey E; Oliver, Jonathan D; Cornax, Ingrid et al. (2017) Experimental evaluation of Peromyscus leucopus as a reservoir host of the Ehrlichia muris-like agent. Parasit Vectors 10:48
Luangphakdy, Viviane; Elizabeth Pluhar, G; Piuzzi, Nicolás S et al. (2017) The Effect of Surgical Technique and Spacer Texture on Bone Regeneration: A Caprine Study Using the Masquelet Technique. Clin Orthop Relat Res 475:2575-2585
Boylan, Kristin L M; Buchanan, Petra C; Manion, Rory D et al. (2017) The expression of Nectin-4 on the surface of ovarian cancer cells alters their ability to adhere, migrate, aggregate, and proliferate. Oncotarget 8:9717-9738
Mallhi, K; Orchard, P J; Miller, W P et al. (2017) Non-myeloablative conditioning for second hematopoietic cell transplantation for graft failure in patients with non-malignant disorders: a prospective study and review of the literature. Bone Marrow Transplant 52:726-732
Richardson, Paul G; Smith, Angela R; Triplett, Brandon M et al. (2017) Earlier defibrotide initiation post-diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome improves Day +100 survival following haematopoietic stem cell transplantation. Br J Haematol 178:112-118

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