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Full-Text Articles in Life Sciences

The Roles Of Pon2 In Mitochondrial Physiology, Lung Tumor Cell Proliferation, And Lung Tumorigenesis., Aaron Whitt May 2022

The Roles Of Pon2 In Mitochondrial Physiology, Lung Tumor Cell Proliferation, And Lung Tumorigenesis., Aaron Whitt

Electronic Theses and Dissertations

Paraoxonase 2 (PON2) is an intracellular, multifunctional enzyme with near-ubiquitous tissue distribution. Within cells, PON2 is localized to mitochondria and endoplasmic reticulum (ER), where it mitigates the formation of reactive oxygen species (ROS). PON2’s chief enzymatic function is its lactonase activity, through which it catalyzes the hydrolysis of a bacterial quorum-sensing molecule, N-(3-oxododecanoyl)-l-homoserine lactone (C12), effectively disrupting bacterial intercellular communication and protecting against infection. C12 is produced by the opportunistic pathogen Pseudomonas aeruginosa and has been shown to disrupt various aspects of eukaryotic host cell physiology and evoke apoptotic cell death through the activity of PON2. Additionally, PON2 has garnered …


Translating Particulate Hexavalent Chomium-Induced Chromosome Instability, Loss Of Homologous Recombination Repair And Targeting Of Rad51 From Human Lung Fibroblasts To Human Bronchial Epithelial Cells., Idoia Meaza Isusi Dec 2021

Translating Particulate Hexavalent Chomium-Induced Chromosome Instability, Loss Of Homologous Recombination Repair And Targeting Of Rad51 From Human Lung Fibroblasts To Human Bronchial Epithelial Cells., Idoia Meaza Isusi

Electronic Theses and Dissertations

Particulate hexavalent chromium [Cr(VI)] is a well-established human lung carcinogen. RAD51, a key protein in homologous recombination repair pathway, is inhibited after prolonged exposure to Cr(VI), leading to an increase in chromosome instability after prolonged exposures in human lung fibroblasts. chromosome instability is the proposed driver of Cr(VI) carcinogenesis. Since tumors from chromate workers develop from epithelial cells, we sought to translate these findings from human bronchial fibroblasts to human bronchial epithelial cells. We hypothesized Cr(VI) inhibits RAD51 after prolonged exposure leading to an increase in chromosome instability in human bronchial epithelial cells (BEP2D). We characterized the cytotoxicity and measured …


A Novel Role For Rassf1a In The Regulation Of Ras Activation., Desmond Ramón Harrell Stewart Aug 2020

A Novel Role For Rassf1a In The Regulation Of Ras Activation., Desmond Ramón Harrell Stewart

Electronic Theses and Dissertations

Ras is the most frequently activated oncogene in human cancer. It is not only the most frequently mutated oncogene, but is also rendered hyperactive in the wild-type form by aberrant regulation. Ras drives transformation and contributes to tumor aggressiveness by activating multiple downstream mitogenic effectors. Ras also possesses the paradoxical ability to induce apoptosis and senescence. Ras-induced apoptosis is not well understood, but has been largely attributed to the RASSF tumor suppressors, particularly RASSF1A. RASSF1A mediates Ras-induced apoptosis by activating pro-apoptotic proteins such as the MST kinases and BAX. RASSF1A is among the most frequently inactivated tumor suppressors in human …


Exosomes From Embryonic Stem Cells As A Prophylactic Vaccine Against Lung Cancer., Shuhan Meng May 2020

Exosomes From Embryonic Stem Cells As A Prophylactic Vaccine Against Lung Cancer., Shuhan Meng

Electronic Theses and Dissertations

The antigenic similarity between embryos and tumors has raised the idea of using embryonic materials as a preventative vaccine against neoplastic disease. Indeed, a previous study reported that a vaccine comprised of allogeneic murine embryonic stem cells (ESCs) and murine fibroblasts expressing immune-stimulatory granulocyte macrophage-colony stimulating factor (GM-CSF) successfully blocked the outgrowth of an implantable lung cancer (Lewis lung carcinoma; LLC) and lung tumors caused by a combination of a mutagen followed by chronic pulmonary inflammation. However, such a vaccine is obviously impractical for application to humans. The use of fibroblasts to produce GM-CSF is needlessly complicated, and intact live …


Age-Related Host Factors Regulate Lung Cancer Progression., John Caleb Greenwell Dec 2017

Age-Related Host Factors Regulate Lung Cancer Progression., John Caleb Greenwell

Electronic Theses and Dissertations

Cancer is largely a disease of the elderly. In the United States alone, 87% of all cancers in 2017 will be diagnosed in individuals aged 50 years or older. Among them, lung cancer is the deadliest, accounting for 1 in 4 cancer deaths. The 5-year survival rate is below 20%, a number which has not changed substantially over the past several decades. This underscores a desperate need for new strategies in prevention, early detection and treatment of this deadly disease. While tobacco use is unquestionably the number one risk factor for the development of lung cancer, the majority of diagnoses …