This study was designed to determine the distribution of fatty acids and cholesterol in total tumor and mammary tissues. Fatty acid profiles of phospholipid fractions from tumors and mammary glands were also determined. Fatty acids and cholesterols were analyzed by gas liquid chromatography. Methodology was developed for phospholipid separation by high performance liquid chromatography.Tumors derived from mammary glands in Strain A/ST mice were found to contain two to three times the amount of cholesterol compared to normal mammary glands. Mammary glands from safflower fed mice contained significantly higher percentages of linoleic acid. Linoleic acid content in stearicacid (SA-1) fed mice was sharply reduced. linoleic acid in mammary glands of animals fed a high fat Stearic acid (SA-4) , corn oil and stock diet fed animals displayed similar fatty acid profiles. Fatty acid analysis of tumors excised from mice fed the experimental diets showed similar patterns in comparison to normal mammary glands. The similar distributions were in the 18 carbon fatty acids. Distributions of phospholipid fatty acids in tumors and mammary glands were similar. Mammary gland phospholipids displayed increased percentages of short chain (14 carbons and under) fatty acids. Results of these studies demonstrate an increased availability of diet rich in polyunsaturated fatty acids.

The extracellular matrix (ECM) plays an important role in mammary gland development and function. Osteopontin (OPN), a secreted glycophosphoprotein, with several functional and structural properties of ECM proteins, is expressed at elevated levels during normal and pathologic development of the mammary gland and is present in milk. However, whether it plays any developmental role in the mammary gland is unknown. To investigate this possibility, transgenic AS-OPN mice were generated using a transgene expressing OPN antisense RNA under the control of the MMTV-LTR promoter/enhancer. The mammary glands of AS-OPN mice express low levels of OPN, compared to control littermates, show excessive branching of the ductal epithelium at the virgin stage, impaired proliferation of the mammary epithelium, and abnormal alveolar structure formation during pregnancy, and mild to severe lactation deficiency. To further examine the role of OPN at the cellular level, an established murine mammary epithelial cell line (NMuMG), which is capable of differentiation in culture, was transfected with the same DNA construct used to generate AS-OPN mice. Several antisense OPN cDNA transfected clones, which secrete decreased amounts of OPN compared to mock-transfected cells were obtained. These cells were found to have lost their ability to form branched duct-like structures, as judged by branching morphogenesis assays, by growth in collagen gels and stimulation with hepatocyte growth factor. They also failed to spread on type I collagen, although their binding to type IV collagen was unaffected. The antisense transfectants also assumed a mesenchymal phenotype, characterized by fibroblast-like morphology, an apparent loss of cell-cell contacts and spontaneous cell scattering. Transmigration assays and wounding experiments indicated that these cells also have a higher migratory activity than control cells. Northern blot and immunofluorescence analyses showed that migrating cells downregulate OP

Thesis (Ph. D.)--University of Wisconsin--Madison, 1969. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

No description available.

Continuing the study of the relationships between fibrin investment of the tumor, vascularity, and tumor growth, we decided to investigate the relationship of warfarin sodium anticoagulation with tumor growth and vascularization. It was reasoned that if the previously observed altered tumor growth was due the heparin’s anticoagulant effect rather than a direct effect upon the tumor, another anticoagulant with a different mechanism of action would have the same tumor growth reducing capabilities. Warfarin sodium produces reduced fibrin polymer formation by a mechanism entirely different from that of heparin. Heparins’ immediate anticoagulant activity results from a blockade of thrombin’s activity results from a blockade of thrombin’s activity on fibrinogen, prevention of prothrombin conversion to thrombin, and a reduction in platelet adhesiveness. Warfarin’s delayed activity, however, is through an inhibition of vitamin K activity leading to reduced synthesis of several clotting factors. With the decision to use warfarin sodium, experiments were designed to test the hypothesis that a reduction of prevention of fibrin formation and thus tumor encasement with this polymer would alter tumor growth. It was also hypothesized that, accompanying the altered tumor growth, several macroscopic factors including tumor vascularization, extent of tumor attachment, vasodilation of host blood vessels in the locale of the implanted tumor, and local edema fluid would be altered. Experiments were conducted to determine the relationship between the dose of warfarin sodium administered and the degree of alteration of tumor growth and the related factors. An inverse dose-response relationship between dose of warfarin and tumor growth and the related parameters was hypothesized.

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Thesis (Ph. D.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed Feb. 13, 2009). Includes bibliographical references.

No description available.