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Development Of Rational Combination Therapy With Parp Inhibitors And Kinase Inhibitors In Tnbc, Wen-Hsuan Yu Aug 2016

Development Of Rational Combination Therapy With Parp Inhibitors And Kinase Inhibitors In Tnbc, Wen-Hsuan Yu

Dissertations & Theses (Open Access)

Poly (ADP-ribose) polymerase inhibitors (PARPi) emerge as potential targeting drugs for BRCA-deficient cancers including triple negative breast cancer (TNBC). However, it has been reported that a subgroup of patients even with BRCA mutation fails to respond to PARPi in multiple clinical trials. In this study, we identified c-Met, a tyrosine kinase, phosphorylates PARP1 at Y907 and that the phosphorylation increases PARP1 activity, thereby rendering cancer cells resistant to PARPi. The combination of c-Met inhibitors (METi) and PARPi has a synergistic effect for c-Met overexpressed TNBC in vitro and in vivo. In addition to c-Met, through functional analysis, we found …


Potentially Inappropriate Medication Use In Older Patient With Breast And Colorectal Cancer, Meghan S. Karuturi Aug 2016

Potentially Inappropriate Medication Use In Older Patient With Breast And Colorectal Cancer, Meghan S. Karuturi

Dissertations & Theses (Open Access)

Our objective was to determine predictors of potentially inappropriate medication (PIM) use and its impact on outcomes (including ER visits, hospitalization, all cause death, and composite of three) in breast and colorectal cancer patients receiving chemotherapy. We used data from the SEER database linked to Medicare claims. Our cohort included patients ≥ 66 years diagnosed with of Stage II/III breast or colorectal cancer between 7/1/2007-12/31/2009. Baseline PIM was defined using the Drugs to Avoid in the Elderly list (DAE) or Beers criteria. Univariate and multivariable logistic regression were used to determine the associations of baseline PIMs with different covariates. Event-free …


Non-Invasive Imaging For The Assessment Of Cardiac Dose And Function Following Focused External Beam Irradiation, Omar El-Sherif Jun 2016

Non-Invasive Imaging For The Assessment Of Cardiac Dose And Function Following Focused External Beam Irradiation, Omar El-Sherif

Electronic Thesis and Dissertation Repository

Technological advances in imaging and radiotherapy have led to significant improvement in the survival rate of breast cancer patients. However, a larger proportion of patients are now exhibiting the less understood, latent effects of incidental cardiac irradiation that occurs during left-sided breast radiotherapy. Here, we examine the utility of four-dimensional computed tomography (4D-CT) for the accurate assessment of cardiac dose; and a hybrid positron emission tomography (PET) magnetic resonance imaging (MRI) system to longitudinally study radiation-induced cardiac effects in a canine model.

Using 4D-CT and deformable dose accumulation, we assessed the variation caused by breathing motion in the estimated dose …