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Articles 1 - 6 of 6
Full-Text Articles in Oncology
The Role Of Oxidative Stress In The Establishment Of Resistance To Cisplatin In Epithelial Ovarian Cancer Cells, Jimmy Belotte
The Role Of Oxidative Stress In The Establishment Of Resistance To Cisplatin In Epithelial Ovarian Cancer Cells, Jimmy Belotte
Wayne State University Dissertations
Epithelial ovarian cancer is the deadliest of all gynecologic cancers with an estimated 22,280 new cases and 14,240 deaths expected in 2016 in the US alone. This high mortality rate can be partially attributed to a lack of universal screening and the development of resistance to the recommended chemotherapeutics. Typically, the treatment of ovarian cancer requires both cytoreductive surgery (CRS) and platinum/taxane combination chemotherapy. Initially, 50–80% of patients with advanced disease will achieve complete clinical response. Unfortunately, most will relapse within 18 months with chemoresistant disease. Thus, understanding the mechanisms of platinum resistance is critical in order to improve the …
Structural Characterization And Therapeutic Utility Of The Proton-Coupled Folate Transporter, Michael Roy Wilson
Structural Characterization And Therapeutic Utility Of The Proton-Coupled Folate Transporter, Michael Roy Wilson
Wayne State University Dissertations
Folate is a B9 vitamin essential to DNA synthesis. The proton-coupled folate transporter (PCFT) is a newly discovered proton/folate symporter with an acidic pH optimum and broad expression across a variety of solid tumor types, with limited expression in normal tissues. Several antifolate molecules have been developed as cancer therapeutics, although these classical antifolates display numerous off-target effects due to transport by the ubiquitous reduced folate carrier (RFC). In this dissertation, we determine the roles of multiple PCFT structure/function domains, and develop PCFT-specific antifolates to target solid tumors. We utilize substituted cysteine accessibility methods (SCAM) to identify a novel reentrant …
Identifying Mechanisms Of Resistance And Potential Therapeutic Targets For Pediatric Acute Myeloid Leukemia, John Timothy Caldwell
Identifying Mechanisms Of Resistance And Potential Therapeutic Targets For Pediatric Acute Myeloid Leukemia, John Timothy Caldwell
Wayne State University Dissertations
Acute myeloid leukemia (AML) is a potentially devastating disease that can affect people of all ages. While there are certain patient groups that typically have favorable outcomes, in the pediatric population, overall survival (OS) is approximately 70%, leaving much progress to be made. Children with Down syndrome (DS) have a substantially elevated risk for developing AML, especially of the megakaryocytic phenotype (AMKL).
Patients with DS AMKL almost universally harbor a mutation in the gene encoding the GATA1 transcription factor, resulting in the translation of a short-form protein GATA1s, which has been shown to contribute to chemotherapy sensitivity. In contrast, in …
Principal Component Analysis-Based Anatomical Motion Models For Use In Adaptive Radiation Therapy Of Head And Neck Cancer Patients, Mikhail Aleksandrovich Chetvertkov
Principal Component Analysis-Based Anatomical Motion Models For Use In Adaptive Radiation Therapy Of Head And Neck Cancer Patients, Mikhail Aleksandrovich Chetvertkov
Wayne State University Dissertations
Purpose: To develop standard and regularized principal component analysis (PCA) models of anatomical changes from daily cone beam CTs (CBCTs) of head and neck (H&N) patients, assess their potential use in adaptive radiation therapy (ART), and to extract quantitative information for treatment response assessment.
Methods: Planning CT (pCT) images of H&N patients were artificially deformed to create “digital phantom” images, which modeled systematic anatomical changes during Radiation Therapy (RT). Artificial deformations closely mirrored patients’ actual deformations, and were interpolated to generate 35 synthetic CBCTs, representing evolving anatomy over 35 fractions. Deformation vector fields (DVFs) were acquired between pCT and synthetic …
Toward Magnetic Resonance Only Treatment Planning: Distortion Mitigation And Image-Guided Radiation Therapy Validation, Ryan Glen Price
Toward Magnetic Resonance Only Treatment Planning: Distortion Mitigation And Image-Guided Radiation Therapy Validation, Ryan Glen Price
Wayne State University Dissertations
While MR-only treatment planning has shown promise, there are still several well-known challenges that are currently limiting widespread clinical implementation.
Firstly, MR images are affected by both patient-induced and system-level geometric distortions that can significantly degrade treatment planning accuracy. . In addition, the availability of comprehensive distortion analysis software is currently limited. Also while many groups have been working toward a synthetic CT solution, further study is needed on the implementation of synCTs as the reference datasets for linac-based image-guided radiation therapy (IGRT) to help determine their robustness in an MR-only workflow.
A 36×43×2 cm3 phantom with 255 known landmarks …
Whsc1l1 Regulates Estrogen Receptor Activity In Sum44 Breast Cancer Cells, Jonathan Curtis Irish
Whsc1l1 Regulates Estrogen Receptor Activity In Sum44 Breast Cancer Cells, Jonathan Curtis Irish
Wayne State University Dissertations
Breast cancer is the most common cancer and the second leading
cause of cancer death in women. While ER-positive breast cancer subtypes are initially
well-managed by targeted therapies targeting estrogen signaling, many women are
suffering from recurrence of a more aggressive, hormone insensitive cancer 5 or more years after initial remission. Late recurrence of hormone resistant breast cancer in patients
who were previously successfully treated with anti-estrogen therapies worsens
overall long-term outcomes, and specific oncogenic mutations may be driving late recurring aggressive disease in these patients. More complete characterization of the oncogenome of
a tumor may allow for the possibility …