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Yale Medicine Thesis Digital Library

Theses/Dissertations

Cancer

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Full-Text Articles in Medicine and Health Sciences

Changing Selection And Epistasis On Drivers Over Tumorigenesis In Primary And Metastatic Prostate Cancer, Alexander Yang Jan 2022

Changing Selection And Epistasis On Drivers Over Tumorigenesis In Primary And Metastatic Prostate Cancer, Alexander Yang

Yale Medicine Thesis Digital Library

Background: Many attempts have been made to characterize and describe the driver genes and mutations responsible for prostate cancer tumorigenesis. We have quantified the cancer effect size—a direct measurement of the survival advantage a mutation confers—for 2699 primary and metastatic prostate tumor samples. Our measure of cancer effect treats tumorigenesis as an evolutionary process, subject to positive and negative selective pressures. We have applied this metric in a stage-specific manner to elucidate which mutations are selected for as prostate cancer develops.Methods: We analyzed 2699 prostate cancer tumor exomes, genomes, and panel sequences (1648 primary tumors and 1051 metastatic samples). The …


The Role Of Connective Tissue Growth Factor (Ctgf) In Fibrosis Associated With Intestinal Neuroendocrine Tumors, Michael David Shapiro Jan 2005

The Role Of Connective Tissue Growth Factor (Ctgf) In Fibrosis Associated With Intestinal Neuroendocrine Tumors, Michael David Shapiro

Yale Medicine Thesis Digital Library

Carcinoid tumors of the small bowel often present with fibrosis in the peritumoral tissues, distant in the heart or lungs, and locally in the peritoneal cavity. The mechanism of the fibroblastic lesions in patients with small bowel carcinoids is unclear and their timely diagnosis impossible. There exists no test to determine the risk of fibrosis, detect its presence, or monitor its progression once discovered. Furthermore, no current therapy protects against such fibrosis. We have proposed that CTGF, a mediator of the profibrotic activities of TGFâ1 (a known regulator of fibrosis)is directly involved in the genesis of ileal carcinoid-related fibrosis. The …