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Effect Of Chemotherapeutic Treatment Schedule On A Tissue Transport Model, Dan E. Ganz Nov 2014

Effect Of Chemotherapeutic Treatment Schedule On A Tissue Transport Model, Dan E. Ganz

Masters Theses

Current chemotherapeutic treatment schedule prediction methods rely heavily on PK/PD-based models and overlook the important contribution of tissue-level transport and binding. Tissue-level transport and binding phenomena are essential to understanding drug delivery and efficacy in tumors. Drugs with desirable PK/PD properties often fail in vivo due to poor tissue-level transport. We developed an in silico method to predict the effect of treatment schedule on efficacy that couples PK/PD with tissue-level transport. Treatment schedules were implemented on theoretical drugs with different PK/PD and transport properties. For each drug with a given clearance rate, diffusivity, and binding, treatment schedules consisting of one …


Indoleamine 2,3-Dioxygenase Confers Resistance To Chemotherapy And Γ Radiation To Cancer Cells, Independent Of Direct Immune Involvement, Saman Maleki Vareki Mar 2014

Indoleamine 2,3-Dioxygenase Confers Resistance To Chemotherapy And Γ Radiation To Cancer Cells, Independent Of Direct Immune Involvement, Saman Maleki Vareki

Electronic Thesis and Dissertation Repository

Indoleamine 2,3-dioxygenase-1 (IDO) is an immunosuppressive molecule expressed by most human tumours. IDO levels correlate with poor prognosis in cancer patients and IDO inhibitors are under investigation to enhance endogenous anticancer immunosurveillance. Little is known regarding the immune-independent functions of IDO relevant to cancer therapy. In this thesis I show, for the first time, that IDO mediates human tumour cell resistance, in a cell-autonomous fashion, to single and combination treatment with a diverse group of chemotherapy drugs and g radiation. These drugs include a PARP inhibitor (olaparib), a DNA cross-linking agent (cisplatin), a folate antimetabolite (pemetrexed), a nucleoside analogue (gemcitabine), …


Protective Effects Of Aqueous Extract Of Terminalia Arjuna Bark Against Doxorubicin-Induced Cardiotoxicity, Sarah Elizabeth Bishop Jan 2014

Protective Effects Of Aqueous Extract Of Terminalia Arjuna Bark Against Doxorubicin-Induced Cardiotoxicity, Sarah Elizabeth Bishop

Honors Theses

The bark of Terminalia arjuna (TA), a tropical tree, has been used in Ayurvedic medicine for treatment of cardiovascular disease. TA bark is known to contain various antioxidants, and recently it has been suggested to enhance function of the normal heart as an over-the-counter supplement in the USA. The mechanism underlying cardiac actions of TA bark are unknown. Doxorubicin (DOX), a commonly-used anticancer drug, is known to cause cardiotoxicity, a major concern in chemotherapy. The aim of this study is to investigate whether aqueous extracts of TA bark (TAaq) protect the heart from DOX treatment by …