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Some extensions and applications of multistage carcinogenesis models /Meza, Rafael, January 2006 (has links)
Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (p. 98-109).
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Study of tumorigenesis by means of transgenic mouse models expressing RET/PTC3 rearrangement and E7 under control of bovine thyroglobulin promoter and CD1 mouse strain treated with acrylamide.Jin, Ling 23 June 2009 (has links)
Summary
Thyroid carcinomas are the most common endocrine tumors in humans. There are three major types of carcinomas of thyrocyte origin, including papillary, follicular, and anaplastic carcinomas. Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy accounting 80% of thyroid cancer cases, and present several histologic variants, namely classical (45%), follicular (18%), solid, diffuse-sclerosing, cribriform, … . Specific genetic events represent early initiating and late triggering events. Several genetic lesions have been identified in various thyroid carcinomas and some of them are specifically associated to one type thyroid cancer. For instance, RET/PTC is the most common molecular event in the radiation-associated PTC in childhood.
In the first part of the work, we studied two transgenic mouse models: the Tg-RET/PTC3 (Tg-RP3) mouse and the Tg-E7 mouse. Both strains express the human origin transgene (RET/PTC3 rearrangement or E7) exclusively in the thyroid under the control of the bovine thyroglobulin promoter.
Our study of these two models showed:
In both E7 and RET/PTC3 mouse models, the thyroids exhibited hyperplasia with own 'oncogene-dependent' follicular cell characteristics. Small follicular cells with hyperchromatic nuclei with an increased nucleus/cytoplasm ratio were numerous in the E7 mice, and large cells with convex apical border, a decreased nucleus/cytoplasm ratio, a pale nucleus and dispersed chromatin were found in the RET/PTC3 mice.
At 6, 10 months and later on, E7 mice developed huge heterogeneous, normal functional thyroid goiter, with no tumor formation.
As in previous studies on transgenic RET/PTC3 mouse models, the generally encountered features such as solid tumours were present. We also observed conventional variant of human PTC at late age (since 11 month-old) with quite low incidence (4%). In addition to solid and conventional variant PTCs, 28% of mice developed a peculiar big size thyroid tumor pattern with “proliferative papillary cystic changes with spindle cells and remodelling” and macrophage infiltration in the cysts at as early as 2 month of age; this kind of tumor histologically resembles the rare human young age 'diffused sclerosing' variant PTC (DSVP), but disappeared after 6 month. The other peculiar tumor exhibits morphological similarity with another rare human FAP-associated (Familial Adenomatous colonic polyposis) cribriform PTC, which showed a mixed architecture of several histological patterns (solid, follicular, cribriform). At 6 months, 26% of mice presented the cribriform tumor pattern.
From the analyse of the proliferation index in the two models, we conclude that RET/PTC3 fusion protein over stimulates MAPK and Akt/PKB-signalling pathways, through Ras-Raf-Mek-Erk, Ras-PI3-K/Akt/PKB, particularly in the large cells which were strongly positive for three proliferation markers. E7 bypasses these two pathways, by directly binding to Rb1 protein and releasing the E2F transcription factor which induces cell proliferation.
So RET/PTC3 and E7 mice present several morphologic features which mimic human PTC tumors; RET/PTC3 could therefore be used as a partial model for human PTCs.
Further investigation of gene expression will allow the characterization of the molecular phenotype of the observed variants.
In the second part of the work, we attempted to generate by xenobiotic administration an in vivo model of thyroid carcinoma. Chronic exposure of CD1 mice to acrylamide in the drinking water during 6 and 8 months at doses of 3mg/kg per day similar to those causing thyroid tumorigenesis after 2 years in rats, did not induce any thyroid tumors whatever the level of thyroid stimulation.
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Shape and quantitative analysis of factor #4 (filopodia) and factor #7 (massive protrusions) in tumorigenic cellsMalwade, Santosh. January 2008 (has links)
Thesis (M.S.)--Bowling Green State University, 2008. / Document formatted into pages; contains 40 p. Includes bibliographical references.
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The analysis of neoplastic transformation using somatic cell geneticsThomassen, David George. January 1980 (has links)
Thesis (Ph. D.)--University of Wisconsin--Madison, 1980. / Typescript. Vita. Description based on print version record. Includes bibliographical references (leaves 170-183).
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Phenotypic characterizations of C3H/10T1/2 Cl 8 and its transformed variants isolation of mutants temperature-sensitive for expression of the transformed state from chemically transformed C3H/10T1/2 Cl 8 cells /Boreiko, Craig J. January 1979 (has links)
Thesis--University of Wisconsin--Madison. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.
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The effect of putrescine on the induction of epidermal ornithine decarboxylase activity and epidermal growth by 12-0-tetradecanoylphorbol-13-acetateWeekes, Richard G. January 1978 (has links)
Thesis (M.S.)--Wisconsin. / Includes bibliographical references.
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Studies on the biochemistry of carcinogenesis Sarcoma induction by metal chelates of N-hydroxy-2-acetylaminofluorene, attempts to demonstrate synthesis of urethan in vivo /Mohrhoff, Miriam Christine. January 1964 (has links)
Thesis (M.S.)--University of Wisconsin--Madison, 1964. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.
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Potential role of peroxisome proliferator activated receptors in normal and neoplastic human colonJackson, Lucina January 2001 (has links)
No description available.
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The role of AKT1 and IKK[beta] in ovarian cancer tumorigenesis and chemotherapeutic resistanceNiculaita, Roxana. January 2008 (has links)
Thesis (Ph.D.)--Kent State University, 2008. / Title from PDF t.p. (viewed Dec. 22, 2009). Advisor: Nywana Sizemore. Includes bibliographical references (p. 125-145).
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The effect of cadmium on benzo[a]pyrene-induced DNA damage and repair in Sprague-Dawley rats /Peng, Cheng. January 2001 (has links) (PDF)
Thesis (Ph. D.)--University of Queensland, 2002. / Includes bibliographical references.
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