The aim of this thesis was to characterize the expression of the peptides ghrelin and obestatin, as well as other neuroendocrine markers in human normal tissues, in invasive breast cancer and a wide panel of neuroendocrine tumors (NETs). In normal tissues the expression of ghrelin and obestatin was mainly localized to the gastric mucosa, and in lesser extent in the remaining gastrointestinal tract, endocrine pancreas and mammary glands. Double immunofluorescence studies demonstrated that ghrelin and obestatin were co-localized in the same cells displaying the same cytoplasmic distribution. In normal breast tissue, ghrelin, obestatin, adrenomedullin, apelin and vesicular monoamine transporter 2 were specifically demonstrated in the luminal epithelial cells. Consecutive sections indicated that mammary epithelial cells could express several of these peptides. Secretogranin II and III were also detected in breast tissue, but their presence was restricted to the outer layer of myoepithelial cells, whereas chromogranin B immunoreactivity was found in both the epithelial and myoepithelial cells. Ghrelin and obestatin immunoreactivity was seen in invasive breast cancer, where the expression could be correlated to factors associated with prognosis. Furthermore, multivariate analysis indicated that ghrelin expression was a possible independent prognostic factor for prolonged recurrence-free and breast cancer-specific survival. In a panel of NETs and endocrine-related disorders it was revealed that ghrelin and obestatin immunoreactivity was primarily found in tumors originating from the respective normal tissues. The two proteins were detected in only a few cases and only occasional tumor cells were immunoreactive. In conclusion, ghrelin and obestatin are localized in the gastrointestinal tract, endocrine pancreas and mammary glands. This thesis has contributed to our understanding of the distribution of ghrelin and obestatin in both normal tissue and tumor cells. A potential role of ghrelin as a prognostic factor in invasive breast cancer has been identified and should be further explored.

The activities of phosphohexose isomerase (EC. 5.3.1.9), isocitrate dehydrogenase (EC. 1.1.1.42) and lactate dehydrogenase (EC. 1.1.1.27) were measured in 14 normal and 21 tumorous mouse mammary tissue samples. Methods of tissue extraction and activity determination in this study employed equipment found in most clinical laboratories.For each of the three enzymes there was a statistically significant (p <.05) elevation of the tumor sample group's activities. The activities of the normal tissues were: PHI x = 9.6 and SD = 4.6, ICD x = 13.2 and SD = 5.3, and IDH x = 10.9 and SD = 5.3. The activities of the tumorous tissues were: PHI x = 55.2 and SD = 29.9, ICD x = 40.5 and SD = 23.8, and IDH x = 55.8 and SD = 31.4.Using values of 20, 27, and 21 for the upper limit of normal activity (x + 2SD) for PHI, ICD, and LDH respectively, the tissue samples can be divided into normal and tumorous groups with l00% sensitivity and 85% specificity.Ball State UniversityMuncie, IN 47306

Thesis (M.S.)--Rutgers University, 2009. / "Graduate Program in Microbiology and Molecular Genetics." Includes bibliographical references (p. 51-61).

Thesis (Ph. D.)--Case Western Reserve University, 2010. / [School of Medicine] Department of Pharmacology. Includes bibliographical references.

Changes in the plasma membrane phospholipid composition may alter the structure and/or fluidity and lead to a variety of changes in membrane functions. Dietary fats are known to influence the composition of lipids in the plasma membrane. The purpose of this investigation was to compare effects of dietary linoleic and stearic acid on the composition of the phospholipids in the plasma membranes of mammary tumors in A/St mice.Plasma membranes were isolated and lipids were extracted. Phospholipids were separated by thin-layer chromatography and identified by detection with molybdenum blue reagent. The Rf values and integration of optical densities were used to compare phospholipid composition in membranes of tumors from mice fed experimental diets. It appears that the amount of dietary fat, but not the type, affects the phospholipid distributions. The phosphatidylinositol was the phospholipid most affected, representing the smallest amount in membranes from tumors in mice fed the low fat diets. / Department of Biology

Prostaglandin E2 (PGE2), a byproduct of arachidonic acid metabolism, has been suspected to be involved in tumor promotion. It has been suggested that diet may modulate PGE2 level in organisms thus affecting the implantation and growth of the tumor tissue. PGE2 content was investigated in mice fed ad libitum four types of fatty acid diets: saturated fatty acid diets: a stearic acid and a palmitic acid, and polyunsaturated fatty acid diets: a low fat (safflower 1%) and a high fat diet (safflower 15%). Tumor cells were implanted subcutaneously in mice and harvested when tumors reached .05- 4g. The extracted PGE2 were derivatized and quantified by High Performance Liquid Chromatography (HPLC). The results showed that there is a negative correlation between the level of PGE2 and the size of the tumors. PGE2 level declined as the tumor grew. This suggests that during the early stage of growth the tumor requires higher level of PGE2 to boost its growth. As the tumor becomes more adapted to its environment, it no longer depends on PGE2 to survive. Diet was also seen to be important in tumor suppression. Saturated fatty acid diet (SA-1) showed a suppressive effect on tumor growth. A visual comparison showed that polyunsaturated high fat diet produced more PGE2 than saturated fatty acid. This high level of PGE2 correlate with the highest tumor weights obtained in the Polyunsaturated high fat diet group. / Department of Biology

Thesis (Ph.D.)--McMaster University, 2003. / Advisor: W. J. Muller. Includes bibliographical references (leaves 259-282). Also available via World Wide Web.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2004. / Härtill 5 uppsatser.