Medicine and Health Sciences Commons^™

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 Future Of Global Interventional Radiology, Austin-Marley Windham-Herman

Yale Medicine Thesis Digital Library

Interventional Radiology (IR) has become an integral component of modern, developed healthcare systems. The minimally invasive, image-guided procedures that the field offers are highly effective and often lead to significantly less morbidity than alternative surgical options. The growth of IR globally is in an early phase; however, patients and healthcare systems stand to benefit from its rapid expansion and integration around the world.

Globally, billions of people are without access to safe surgery and diagnostic imaging. However, the democratization of radiology resources such as portable ultrasound and low-cost medical devices is making IR more accessible than ever before. Global healthcare …

Immunotherapy For Advanced Cancer Patients With Autoimmune Disease, Huaqi Li

Public Health Theses

Purpose

Immunotherapy (IT) has been shown to improve cancer survival but there is limited evidence regarding use in patients with advanced cancer and pre-existing autoimmune disease (AI). We sought to address these knowledge gaps and determine IT utilization patterns and overall survival (OS) for these patients.

Patients and Methods

This retrospective cohort study used data from Flatiron Health’s nationwide oncology database. Patients diagnosed with advanced cancer where there was ≥ 1 FDA approved IT were included. Baseline demographics were analyzed using χ2 and t-tests. Patterns of IT use were assessed using logistic regression. OS was estimated using Kaplan-Meier and Cox …

Effects Of The New Histone Deacetylase Inhibitor Pxd101 In Bladder Cancer, Hristos Zacharias Kaimakliotis

Yale Medicine Thesis Digital Library

Histone deacetylase inhibitors (HDACIs) mediate gene expression and chromatin assembly, and induce growth arrest and apoptosis of tumor cells, thus representing a new strategy for human cancer therapy. Changes in apoptosis signaling pathways and the effect on cell growth and cell-cycle arrest of a new HDACI, PXD101, on T-24 bladder cancer cells form the basis of this study. T-24 cells were incubated with PXD101 at varying concentrations and times, and viable cell count and proliferation curves were constructed. Cell cycle analysis was conducted with Fluorescent Activated Cell Sorting and changes in apoptosis signaling proteins that were previously found to be …