Medicine and Health Sciences Commons^™

Microenvironment-Induced Pten Loss By Exosomal Microrna Primes Brain Metastasis Outgrowth, Lin Zhang

Dissertations & Theses (Open Access)

Development of life-threatening cancer metastases at distant organs requires disseminated tumor cells’ adaptation to and co-evolution with the drastically different microenvironments of metastatic sites. Cancer cells of common origin manifest distinct gene expression patterns after metastasizing to different organs. Clearly, the dynamic interplay between metastatic tumor cells and extrinsic signals at individual metastatic organ sites critically impacts the subsequent metastatic outgrowth. Yet, it is unclear when and how disseminated tumor cells acquire the essential traits from the microenvironment of metastatic organs that prime their subsequent outgrowth. Here we show that primary tumor cells with normal expression of PTEN, an important …

Establishing A Clinically Relevant Mouse Model Of Human Aml To Test Novel Transmethylation Inhibitors., Aditya Barve

Electronic Theses and Dissertations

Acute myeloid leukemia (AML) is a highly heterogeneous clonal disorder characterized by an accumulation of malignant immature myeloid progenitors in the bone marrow (BM) that hinder normal hematopoiesis. Patient AML exhibits a dramatic heterogeneity in terms of cytogenetics, disease morphology, and associated prognoses and/or chemotherapeutic sensitivity. Thus it becomes clearly evident that the investigation of novel therapeutics for AML will require model systems that are capable of recapitulating this stark heterogeneity in a patient specific manner. Furthermore, it is now understood that the surrounding bone marrow (BM) microenvironment and supporting cells play a critical role in leukemic progression as well …

Epigenetic Modulation In Braf Mutated Metastatic Colorectal Cancer, Van Morris

Dissertations & Theses (Open Access)

Introduction: BRAF V600E mutations are associated with poor clinical outcomes for patients with metastatic colorectal cancer (mCRC). Unlike other tumors with the same mutation, BRAF inhibitors are ineffective as monotherapy. CRC tumors with BRAF V600E mutations are associated with global hypermethylation, which may turn off tumor suppressor gene expression. We studied demethylation in BRAF V600E mCRC to restore sensitivity to BRAF inhibitors.

Methods: Tumor databanks were investigated for genes differentially expressed according to BRAF mutation status to identify genes which may be particularly susceptible to epigenetic influence. Mouse xenograft models of BRAFV600E mCRC were treated with vemurafenib or azacitidine, alone …