Pharmacology, Toxicology and Environmental Health Commons^™

Synthesis And In Silico Study Of New Azetidinones Against Non-Small Cell Lung Cancer By Egfr Inhibition, Jainey P. James, T. C. Aiswarya, Swetha P. Shenoy, Vinod Devaraji

The Thai Journal of Pharmaceutical Sciences

Background: Lung cancer is alarmingly increasing and therapies targeting receptors such as human epidermal growth factor have been found to be emerging in treating lung cancer. Many studies report azetidinone bearing compounds to be cytotoxic. This work aims to prove the anti-lung cancer action of synthesized azetidinones that are through epidermal growth factor receptor (EGFR) inhibition. Materials and Methods: Novel azetidinone derivatives were synthesized from Schiff bases; molecular docking analyzed the interactions with EGFR, and pharmacophore modeling revealed the features responsible for the possible interactions. Moreover, the compounds with good docking scores were selected for anti-lung cancer study by MTT …

Formulation, Characterization, And Pharmacokinetic Study Of Methoteraxate-Quercetin Loaded Nanoparticles, Gyanesh Kumar Sahu, Harish Sharma, Swarnali Das Paul, Ajazuddin, Chanchal Deep Kaur

The Thai Journal of Pharmaceutical Sciences

Objectives: Methotrexate (MTX) is a biopharmaceutics classification system Class IV drug having potential cytotoxic action against cancer cells. However, short half-life and poor bioavailability have limited its application. The object of this work was to entrap MTX and an herbal bioenhancer in a nanoparticle system to improve its bioavailability. Methods: We prepared the nanoparticles (NPs) by emulsion solvent evaporation method with Eudragit RLPO (ERLPO) polymer. Results: The result revealed good in vitro properties with 110 to 228 nm particle size range. The percentage of drugs released from all the batches in 72 h was within the range of 82.71 to …

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

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 …

Impact Of Sodium Dichloroacetate Alone And In Combination Therapies On Lung Tumor Growth And Metastasis, Aya Mudhafar A. Al-Azawi

Theses

Lung cancer is the second most common form of cancer with the highest mortality rate worldwide in 2020 despite the advances in targeted- and immuno-therapies. Metabolic reprogramming has been recognized as an essential emerging cancer hallmark in which altered metabolic pathways represent an attractive therapeutic target. Sodium Dichloroacetate (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, effect has been investigated in various tumors. Building on the already published data, this pre-clinical study aims to explore the anticancer potential of DCA in lung cancer alone and in combination with chemo- and targeted therapies using two non-small cell lung cancer (NSCLC) cell lines …

In Silico Discovery Of Potential Diagnostic Biomarkers Of Lung Cancer, Ruzianisra Mohamed, Raja Nur Hidayah Raja Hasnan

The Thai Journal of Pharmaceutical Sciences

Introduction: Understanding hub genes implicated in lung cancer (LC) metastasis will help in finding effective ways to diagnose and cure cancer. Accurate identification of protein biomarkers helps in improving the prognosis of LC. Here, the focus of this.

Investigating The Relationship Of Copd, Lung Cancer, And Polycyclic Aromatic Hydrocarbons From Ambient Air Pollution, Daniel John Kilpatrick

Theses and Dissertations

Polycylic aromatic hydrocarbons (PAHs) are a group of chemically-related compounds with a well-established body of evidence of adverse human health impacts. Additionally, there is a growing area of research on the health outcomes following PAH exposure via air pollution, specifically with chronic obstructive pulmonary disorder (COPD) and lung cancer. The purpose of this dissertation was to investigate the strength of associations among PAHs, COPD, and lung cancer from ambient (outdoor) air pollution. The first objective was to determine if there is a potential environmental link among PAHs, COPD, and lung cancer occurrence among nonsmokers using data from the National Health …

Investigating Sociodemographic Disparities In Cancer Risk Using Web-Based Informatics, Hong-Jun Yoon, Georgia Tourassi

Journal of Human Performance in Extreme Environments

Cancer health disparities due to demographic and socioeconomic factors are an area of great interest in the epidemiological community. Adjusting for such factors is important when developing cancer risk models. However, for digital epidemiology studies relying on online sources such information is not readily available. This paper presents a novel method for extracting demographic and socioeconomic information from openly available online obituaries. The method relies on tailored language processing rules and a probabilistic scheme to map subjects’ occupation history to the occupation classification codes and related earnings provided by the U.S. Census Bureau. Using this information, a case-control study is …

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 …

M2 Polarization Of Macrophages Facilitates Arsenic-Induced Cell Transformation Of Lung Epithelial Cells, Jiajun Cui, Wenhua Xu, Jian Chen, Hui Li, Lu Dai, Jacqueline A. Frank, Shaojun Peng, Siying Wang, Gang Chen

Pharmacology and Nutritional Sciences Faculty Publications

The alterations in microenvironment upon chronic arsenic exposure may contribute to arsenic-induced lung carcinogenesis. Immune cells, such as macrophages, play an important role in mediating the microenvironment in the lungs. Macrophages carry out their functions after activation. There are two activation status for macrophages: classical (M1) or alternative (M2); the latter is associated with tumorigenesis. Our previous work showed that long-term arsenic exposure induces transformation of lung epithelial cells. However, the crosstalk between epithelial cells and macrophages upon arsenic exposure has not been investigated. In this study, using a co-culture system in which human lung epithelial cells are cultured with …

Exploration Of Cancer Proliferative Signaling In Chemotherapy Drug Resistance And Mdig-Induced Tumorigenesis, Kai Wu

Wayne State University Dissertations

ABSTRACT

EXPLORATION OF CANCER PROLIFERATIVE SIGNALING IN CHEMOTHERAPY DRUG RESISTANCE AND MDIG-INDUCED TUMORIGENESIS

by

KAI WU

August 2016

Advisor: Dr. Fei Chen

Major: Pharmaceutical Sciences

Degree: Doctor of Philosophy

Aberrant intracellular signaling pathway is one of the major driving forces of malignancy through multiple stages of human cancers. Our study demonstrates that in cancer cells, the signaling pathways are profoundly and actively intertwined with each other so they can synergistically affect cell biology, including promoting development of malignancy and compensating the loss of proliferation or survival signals in responses to anti-tumor drug. Moreover, cancer cells can also adopt “non-canonical” mechanisms …

Exploration Of The Srx-Prx Axis As A Small-Molecule Target, Murli Mishra

Theses and Dissertations--Toxicology and Cancer Biology

Lung cancer is a leading cause of cancer-related mortality irrespective of gender. The Sulfiredoxin (Srx) and Peroxiredoxin (Prx) are a group of thiol-based antioxidant proteins that plays an essential role in non-small cell lung cancer. Understanding the molecular characteristics of the Srx-Prx interaction may help design the strategies for future development of therapeutic tools. Based on existing literature and preliminary data from our lab, we hypothesized that the Srx plays a critical role in lung carcinogenesis and targeting the Srx-Prx axis or Srx alone may facilitate future development of targeted therapeutics for prevention and treatment of lung cancer. First, …

Dna Methylation In Lung Tissues Of Mouse Offspring Exposed In Utero To Polycyclic Aromatic Hydrocarbons: Appendix F. Gene Ontology Maps, Trevor Fish, Abby Benninghoff

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This archive includes 10 individual image files, each of which depicts a Gene Ontolgoy map for GO terms representing hypermethylated gene promoters unique for the indicated tissue(s) (listed first in file name) compared to other tissues (listed in parentheses in file name).

Dna Methylation In Lung Tissues Of Mouse Offspring Exposed In Utero To Polycyclic Aromatic Hydrocarbons: Appendix C. Peak Scores Summary Table For All Methylated Genes In Any Data Set, Trevor Fish, Abby Benninghoff

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No abstract provided.

Dna Methylation In Lung Tissues Of Mouse Offspring Exposed In Utero To Polycyclic Aromatic Hydrocarbons: Appendix B. Nimblegen Processed Data Report For Nearest Methylated Peaks, Trevor Fish, Abby Benninghoff

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No abstract provided.

Dna Methylation In Lung Tissues Of Mouse Offspring Exposed In Utero To Polycyclic Aromatic Hydrocarbons: Appendix A. Nimblegen Processed Data Report For All Methylated Peaks, Trevor Fish, Abby Benninghoff

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No abstract provided.

Dna Methylation In Lung Tissues Of Mouse Offspring Exposed In Utero To Polycyclic Aromatic Hydrocarbons: Appendix D. Gene Lists For Ontology Analysis, Trevor Fish, Abby Benninghoff

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No abstract provided.

Gigantol-Induced Apoptosis In Lung Cancer Cell Through Mitochondrial-Dependent Pathway, Sopanya Charoenrungruang, Pithi Chanvorachote, Boonchoo Sritularak, Varisa Pongrakhananon

The Thai Journal of Pharmaceutical Sciences

Lung cancer is identified as a major cause of cancer-related death. Death in this cancer associates with the acquisition of apoptosis avoidance mechanism. Apoptosis, a programmed cell death mechanism, plays an important role on normal cell development an...

Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin

Theses and Dissertations--Pharmacy

Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …