Abstract

The specific objective of this proposed study is to quantify the mechanisms responsible for blood flow modification in normal and tumor tissues due to hyperthermia and hyperglycemia. Mature granulation tissue and VX2 carcinoma grown in a rabbit ear chamber preparation will be used as models for normal and neoplastic tissues, respectively. Using this preparation and the microcirculation experimental setup in our laboratory, modifications in blood flow in individual vessels following hyperthermia and hyperglycemia have been determined. In the proposed study, the role of red and white blood cell rheology in this flow modification will be determined. A micropipette aspiration technique available in our laboratory will be used to study cell deformability during hyperthermia and hyperglycemia. An intravital fluorescent microscopy technique will be used to study cell adhesion to vessels. This study will contribute to basic pathophysiology of tumors and aid in improving present approaches to hyperthermia treatment of tumors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA037239-08
Application #
3175067
Study Section
Radiation Study Section (RAD)
Project Start
1986-07-15
Project End
1994-04-30
Budget Start
1993-05-01
Budget End
1994-04-30
Support Year
8
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Torres Filho, I P; Leunig, M; Yuan, F et al. (1994) Noninvasive measurement of microvascular and interstitial oxygen profiles in a human tumor in SCID mice. Proc Natl Acad Sci U S A 91:2081-5
Zlotecki, R A; Boucher, Y; Lee, I et al. (1993) Effect of angiotensin II induced hypertension on tumor blood flow and interstitial fluid pressure. Cancer Res 53:2466-8
Eskey, C J; Koretsky, A P; Domach, M M et al. (1993) Role of oxygen vs. glucose in energy metabolism in a mammary carcinoma perfused ex vivo: direct measurement by 31P NMR. Proc Natl Acad Sci U S A 90:2646-50
Lee, I; Boucher, Y; Jain, R K (1992) Nicotinamide can lower tumor interstitial fluid pressure: mechanistic and therapeutic implications. Cancer Res 52:3237-40
Boucher, Y; Jain, R K (1992) Microvascular pressure is the principal driving force for interstitial hypertension in solid tumors: implications for vascular collapse. Cancer Res 52:5110-4
Leunig, M; Yuan, F; Menger, M D et al. (1992) Angiogenesis, microvascular architecture, microhemodynamics, and interstitial fluid pressure during early growth of human adenocarcinoma LS174T in SCID mice. Cancer Res 52:6553-60
Eskey, C J; Koretsky, A P; Domach, M M et al. (1992) 2H-nuclear magnetic resonance imaging of tumor blood flow: spatial and temporal heterogeneity in a tissue-isolated mammary adenocarcinoma. Cancer Res 52:6010-9
Less, J R; Skalak, T C; Sevick, E M et al. (1992) Microvascular network architecture in a mammary carcinoma. EXS 61:74-80
Leunig, M; Goetz, A E; Dellian, M et al. (1992) Interstitial fluid pressure in solid tumors following hyperthermia: possible correlation with therapeutic response. Cancer Res 52:487-90
Gutmann, R; Leunig, M; Feyh, J et al. (1992) Interstitial hypertension in head and neck tumors in patients: correlation with tumor size. Cancer Res 52:1993-5

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