The purpose of this study is to quantitate the effects of tumor produced factors on structure and permeability of capillaries that would favor the accumulation of fluid in the interstitial spaces and body cavities. Malignant ascitic fluid produced by the intraabdominal growth of Walker 256 carcinosacroma in rats will be infused into the peritoneal cavity and systemic circulation continuously. Structure and permeability changes of peritoneal and pulmonary capillaries will be quantitated by en-bloc histologic section and Evans blue dye elution techniques. In vivo observation of the effects of malignant ascitic fluid on normal omental microvasculature will be accomplished with intravital microscopy. Microvessel structure and capillary permeability to protein will be quantitated by fluorescence techniques using the intravital microscope. The structure and permeability of capillaries supplying growing solid tumor will also be quantitated using the same intravital microscopic technique. The long-term objective of this project is to define the pathophysiology of tumor microvessel structure and function and to quantitate the effects tumor produced factors induce in normal capillary beds. The genesis of malignant ascites is poorly understood and treatment is at best paliative. Permeability changes in normal and tumor blood vessels would explain the complications seen with peritoneovenous shunting of malignant ascites. Change in capillary permeability to protein may be an essential first step in invasion and metastases and in maintaining nutrition to tumor cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08CA000918-02
Application #
3079393
Study Section
(SRC)
Project Start
1984-04-25
Project End
1986-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Louisville
Department
Type
Schools of Medicine
DUNS #
City
Louisville
State
KY
Country
United States
Zip Code
40292
Heuser, L S; Miller, F N; Gilley-Pietsch, C (1988) Protein leak from normal vasculature due to human malignant ascites. Am J Surg 155:765-9
Heuser, L S; Miller, F N (1986) Differential macromolecular leakage from the vasculature of tumors. Cancer 57:461-4