Medicine and Health Sciences Commons^™

Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers by organ site with a 5-year survival rate of just 10.8%. This is largely because most patients do not experience symptoms until the disease has already metastasized. The best hope to cure PDAC is surgery, which can only be done with a curative intent at an early stage when the disease is localized. There are no reliable circulating, body-fluid-based biomarkers to detect early stage PDAC or its precursor lesions in a timely manner for effective surgical intervention. When potential PDAC precursor lesions, such as mucinous pancreatic cysts are found, there are …

Advancement Of A 3d Computational Phantom And Its Age Scaling Methodologies For Retrospective Dose Reconstruction Studies, Aashish Gupta

Dissertations & Theses (Open Access)

We have used a 3D age-scalable computational phantom for over two decades for retrospective dose reconstruction studies of childhood cancer survivors (CCS) treated with 2D historic radiotherapy (RT). However, our phantom and its age scaling functions (ASF) must be updated so that it can be used in studies that include survivors treated with contemporary RT. We aimed to implement our phantom and its age scaling functions in DICOM format and determine the feasibility of applying our ASFs to accurately scale the whole-body CT-based anatomies.

In the implementation study, we developed Python scripts that model the phantom and ASFs in a …

The Role Of Ifitm3 In The Immune Response Of Brca-Deficient High Grade Serous Ovarian Carcinoma, Han Cun

Dissertations & Theses (Open Access)

Background: Prior studies showed that BRCA-deficient high grade serous ovarian carcinoma (HGSOC) had increased tumor infiltrating lymphocytes (TILs) compared to BRCA-wildtype (WT). To better understand the underlying immune mechanism in these tumors, a preliminary transcriptome analysis was performed on a set of microdissected HGSOC tumor specimens with BRCA1-mutation, BRCA2-mutation, or WT. This demonstrated an upregulation of IFITM3, an essential gene in modulating immune function. Based on these findings, we hypothesized that BRCA-deficient HGSOC have increased DNA damage leading to upregulation of IFITM3 and subsequent increase in antigen presentation and T-cell activation.

Methods: Following IRB approval, preliminary transcriptome analysis was performed …

Quantitative Magnetic Resonance Imaging For The Early Prediction Of Treatment Response In Triple Negative Breast Cancer, Benjamin C. Musall

Dissertations & Theses (Open Access)

Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer which lacks upregulated hormone receptors. Because of this, it is not vulnerable to clinically available targeted therapies. When treated with standard of care neoadjuvant systemic therapy (NAST), TNBC only shows approximately a 40% rate of pathologic complete response (pCR). A biomarker which could predict TNBC response to NAST early during treatment would be useful, as it would allow for non-responders to be triaged to alternative therapies and potentially allow for the treatment of responders to be de-escalated.

Quantitative Magnetic Resonance Imaging (MRI) may be used to probe and …

Impact Of Intratumor Heterogeneity And The Tumor Microenvironment In Shaping Tumor Evolution And Response To Therapy, Akash Mitra

Dissertations & Theses (Open Access)

Intratumor heterogeneity (ITH) is a crucial challenge in cancer treatment. The genotypic and phenotypic heterogeneity underlying diverse cancer types leads to subclonal variation, which may result in mixed or failed response to therapy. The heterogeneity at the tumor level, along with the tumor microenvironment (TME), often shapes tumor evolution and ultimately clinical outcome. Given that modern treatment paradigms increasingly expose patients with metastatic disease to multiple treatment modalities through the course of their disease, there exists a need to characterize robust and predictive biomarkers of response to therapy. In order to accurately characterize tumor evolution, we need to account for …

Biases And Blind-Spots In Genome-Wide Crispr-Cas9 Knockout Screens, Merve Dede

Dissertations & Theses (Open Access)

Adaptation of the bacterial CRISPR-Cas9 system to mammalian cells revolutionized the field of functional genomics, enabling genome-scale genetic perturbations to study essential genes, whose loss of function results in a severe fitness defect. There are two types of essential genes in a cell. Core essential genes are absolutely required for growth and proliferation in every cell type. On the other hand, context-dependent essential genes become essential in an environmental or genetic context. The concept of context-dependent gene essentiality is particularly important in cancer, since killing cancer cells selectively without harming surrounding healthy tissue remains a major challenge. The toxicity of …

Breast Cancer Risk For Female Relatives Of Male Breast Cancer Patients With Negative Brca1/2 Testing, Emily Martin

Dissertations & Theses (Open Access)

Risk models exist to estimate a female’s lifetime risk of breast cancer in the absence of a hereditary predisposition to cancer, namely Hereditary Breast and Ovarian Cancer syndrome. These risk models consider various factors such as reproductive history and family history, but few models take a family history of male breast cancer into account. This study aims to evaluate if prevalence of breast cancer among female relatives is higher when there is a family history of male breast cancer in the context of uninformative BRCA1 and BRCA2 testing. This information may aid in the process of risk assessments for patients …