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Full-Text Articles in Pharmacology

Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt May 2019

Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt

Electronic Theses and Dissertations

Non-small cell lung carcinoma (NSCLC) comprises 85% of lung cancer diagnoses and is plagued by drug resistance. Thus, elucidating the underlying mechanisms of NSCLC is paramount to expand future treatment options. Paraoxonase 2 (PON2), an intracellular enzyme with arylesterase and lactonase functions, has well-established anti-atherosclerotic activity. Recent studies show PON2 is overexpressed in a variety of tumors and confers drug resistance, although these interactions have not been thoroughly examined in NSCLC. Thus, we sought to investigate the role of PON2 in cellular proliferation using PON2-knockout mice, primary mouse cells, and NSCLC cell lines. Using these approaches, we demonstrate that PON2 …


Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller Aug 2018

Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller

Electronic Theses and Dissertations

The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug …