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Computational Analysis Of Genomic Variants Affecting Predicted Microrna:Target Interactions In Prostate Cancer., Angélica Paola Hernández Pérez 2018 Keck Graduate Institute, KGI

Computational Analysis Of Genomic Variants Affecting Predicted Microrna:Target Interactions In Prostate Cancer., Angélica Paola Hernández Pérez

KGI Theses and Dissertations

Prostate cancer (PCa) is the most common cancer of men in the United States and is third only to lung and colon as a cause of cancer death. Clinical behavior of the disease is variable and the combination of prostate-specific antigen (PSA) screening and Gleason score staging are currently the best available molecular and pathology tools to predict outcomes. Cancer biology research establishes microRNAs (miRNAs) as key molecular components in both normal and pathological states. Thus, elucidating miRNAs perturbed by genomic alterations will expand our understanding of the molecular taxonomy of PCa with the aim to complement current practices in ...


“Do We Know Jack” About Jak? A Closer Look At Jak/Stat Signaling Pathway, Emira Bousoik, Hamidreza Montazeri Aliabadi 2018 Chapman University

“Do We Know Jack” About Jak? A Closer Look At Jak/Stat Signaling Pathway, Emira Bousoik, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Janus tyrosine kinase (JAK) family of proteins have been identified as crucial proteins in signal transduction initiated by a wide range of membrane receptors. Among the proteins in this family JAK2 has been associated with important downstream proteins, including signal transducers and activators of transcription (STATs), which in turn regulate the expression of a variety of proteins involved in induction or prevention of apoptosis. Therefore, the JAK/STAT signaling axis plays a major role in the proliferation and survival of different cancer cells, and may even be involved in resistance mechanisms against molecularly targeted drugs. Despite extensive research focused on ...


Llc Tumor Cells-Derivated Factors Reduces Adipogenesis In Co-Culture System, Magno Alves Lopes, Felipe Oliveira Franco, Felipe Henriques, Sidney Barnabe Peres, Miguel Luiz Batista Jr. 2018 University of Mogi das Cruzes

Llc Tumor Cells-Derivated Factors Reduces Adipogenesis In Co-Culture System, Magno Alves Lopes, Felipe Oliveira Franco, Felipe Henriques, Sidney Barnabe Peres, Miguel Luiz Batista Jr.

Open Access Articles

Cancer cachexia (CC) is a multifactorial syndrome with an unknown etiology. The primary symptom is the progressive reduction of the body weight. Recently, down-regulation of adipogenic and lipogenic genes were demonstrated to be early affected during cachexia progression in adipose tissue (AT), resulting in AT remodeling. Thus, this study aimed to evaluate in a co-culture system the influence of the Lewis Lung Carcinoma (LLC) tumor cells (c/c-LLC) in an established pre-adipocyte cell line 3T3-L1 adipogenic capacity. c/c-LLC in the presence of 3T3-L1 caused a reduction in lipids accumulation, suggesting that secretory tumor cells products may affect adipogenesis. Interestingly ...


Doxorubicin-Induced Elevated Oxidative Stress And Neurochemical Alterations In Brain And Cognitive Decline: Protection By Mesna And Insights Into Mechanisms Of Chemotherapy-Induced Cognitive Impairment ("Chemobrain"), Jeriel T. R. Keeney, Xiaojia Ren, Govind Warrier, Teresa Noel, David K. Powell, Jennifer M. Brelsfoard, Rukhsana Sultana, Kathryn E. Saatman, Daret K. St. Clair, D. Allan Butterfield 2018 University of Kentucky

Doxorubicin-Induced Elevated Oxidative Stress And Neurochemical Alterations In Brain And Cognitive Decline: Protection By Mesna And Insights Into Mechanisms Of Chemotherapy-Induced Cognitive Impairment ("Chemobrain"), Jeriel T. R. Keeney, Xiaojia Ren, Govind Warrier, Teresa Noel, David K. Powell, Jennifer M. Brelsfoard, Rukhsana Sultana, Kathryn E. Saatman, Daret K. St. Clair, D. Allan Butterfield

Chemistry Faculty Publications

Chemotherapy-induced cognitive impairment (CICI) is now widely recognized as a real and too common complication of cancer chemotherapy experienced by an ever-growing number of cancer survivors. Previously, we reported that doxorubicin (Dox), a prototypical reactive oxygen species (ROS)-producing anti-cancer drug, results in oxidation of plasma proteins, including apolipoprotein A-I (ApoA-I) leading to tumor necrosis factor-alpha (TNF-α)-mediated oxidative stress in plasma and brain. We also reported that co-administration of the antioxidant drug, 2-mercaptoethane sulfonate sodium (MESNA), prevents Dox-induced protein oxidation and subsequent TNF-α elevation in plasma. In this study, we measured oxidative stress in both brain and plasma of ...


Etv4 Transcription Factor And Mmp13 Metalloprotease Are Interplaying Actors Of Breast Tumorigenesis, Mandy Dumortier, Franck Ladam, Isabelle Damour, Sophie Vacher, Ivan Bieche, Nathalie Marchand, Yvan de Launoit, David Tulasne, Anne Chotteau-Lelievre 2018 University of Lille

Etv4 Transcription Factor And Mmp13 Metalloprotease Are Interplaying Actors Of Breast Tumorigenesis, Mandy Dumortier, Franck Ladam, Isabelle Damour, Sophie Vacher, Ivan Bieche, Nathalie Marchand, Yvan De Launoit, David Tulasne, Anne Chotteau-Lelievre

Open Access Articles

BACKGROUND: The ETS transcription factor ETV4 is involved in the main steps of organogenesis and is also a significant mediator of tumorigenesis and metastasis, such as in breast cancer. Indeed, ETV4 is overexpressed in breast tumors and is associated with distant metastasis and poor prognosis. However, the cellular and molecular events regulated by this factor are still misunderstood. In mammary epithelial cells, ETV4 controls the expression of many genes, MMP13 among them. The aim of this study was to understand the function of MMP13 during ETV4-driven tumorigenesis.

METHODS: Different constructs of the MMP13 gene promoter were used to study the ...


Developing Droplet Based 3d Cell Culture Methods To Enable Investigations Of The Chemical Tumor Microenvironment, Jacqueline A. De Lora 2018 University of New Mexico - Main Campus

Developing Droplet Based 3d Cell Culture Methods To Enable Investigations Of The Chemical Tumor Microenvironment, Jacqueline A. De Lora

Biomedical Sciences ETDs

Adaptation of cancer cells to changes in the biochemical microenvironment in an expanding tumor mass is a crucial aspect of malignant progression, tumor metabolism, and drug efficacy. In vitro, it is challenging to mimic the evolution of biochemical gradients and the cellular heterogeneity that characterizes cancer tissues found in vivo. It is well accepted that more realistic and controllable in vitro 3D model systems are required to improve the overall cancer research paradigm and thus improve on the translation of results, but multidisciplinary approaches are needed for these advances. This work develops such approaches and demonstrates that new droplet-based cell-encapsulation ...


Grp78 Is A Targetable Receptor On Cancer And Stromal Cells, Nathalia Araujo, Nikhil Hebbar, Vivek M. Rangnekar 2018 University of Kentucky

Grp78 Is A Targetable Receptor On Cancer And Stromal Cells, Nathalia Araujo, Nikhil Hebbar, Vivek M. Rangnekar

Toxicology and Cancer Biology Faculty Publications

No abstract provided.


Targeting Aberrant Transcription In Invasive Lobular Carcinoma Breast Cancer, Louise Walsh 2018 Royal College of Surgeons in Ireland

Targeting Aberrant Transcription In Invasive Lobular Carcinoma Breast Cancer, Louise Walsh

PhD theses

Invasive lobular carcinoma (ILC) is an understudied breast cancer subtype comprising 8-14% of breast tumours. The majority of ILC (90%) are estrogen receptor (ER)-positive and candidates for endocrine therapy. Unfortunately, de novo resistance to endocrine therapies occurs in 33% of women and a further 40% will relapse on treatment. Therefore, novel therapeutic targets are required for ILC. Deregulated transcription is a recurring theme in cancer, which can be due to epigenetic events. The bromodomain & extra-terminal domain (BET) family of proteins (BRD2, BRD3, BRD4, BRDT) function as chromatin readers that bind acetylated lysine residues on histones and regulate transcription. RNA ...


Epigenetic Alterations Mediate Ipsc Normalization Of Dna-Repair Expression And Tnr Stability In Huntington's Disease, Peter A. Mollica, Martina Zamponi, John Reid, Deepak Sharma, Alyson E. White, Roy C. Ogle, Robert D. Bruno, Patrick C. Sachs 2018 Old Dominion University

Epigenetic Alterations Mediate Ipsc Normalization Of Dna-Repair Expression And Tnr Stability In Huntington's Disease, Peter A. Mollica, Martina Zamponi, John Reid, Deepak Sharma, Alyson E. White, Roy C. Ogle, Robert D. Bruno, Patrick C. Sachs

Medical Diagnostics & Translational Sciences Faculty Publications

Huntington's disease (HD) is a rare autosomal dominant neurodegenerative disorder caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat (TNR) expansion within the HTT gene. The mechanisms underlying HD-associated cellular dysfunction in pluripotency and neurodevelopment are poorly understood. We had previously identified downregulation of selected DNA repair genes in HD fibroblasts relative to wild-type fibroblasts, as a result of promoter hypermethylation. Here, we tested the hypothesis that hypomethylation during cellular reprogramming to the induced pluripotent stem cell (iPSC) state leads to upregulation of DNA repair genes and stabilization of TNRs in HD cells. We sought to determine how the HD TNR ...


Characterizing The Recognition Motif And Novel Substrates Of Carm1, Sitaram gayatri 2018 The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Characterizing The Recognition Motif And Novel Substrates Of Carm1, Sitaram Gayatri

UT GSBS Dissertations and Theses (Open Access)

A limited pool of proteins attains vast functional repertoire due to posttranslational modifications (PTMs). Arginine methylation is a common posttranslational modification, which is catalyzed by a family of nine protein arginine methyltransferases or PRMTs. These enzymes deposit one or two methyl groups to the nitrogen atoms of arginine side-chains. Elucidating the substrate specificity of each PRMT will promote a better understanding of which signaling networks these enzymes contribute to. Although many PRMT substrates have been identified, and their methylation sites mapped, the optimal target motif for each of the nine PRMTs has not been systematically addressed. Here we describe the ...


Design, Synthesis, And Evaluation Of Homochiral Peptides Containing Arginine And Histidine As Molecular Transporters, Naglaa Salem El-Sayed, Taryn Miyake, Amir Nasrolahi Shirazi, Shang Eun Park, Jimmy Clark, Stephani Buchholz, Keykavous Parang, Rakesh Tiwari 2018 Chapman University

Design, Synthesis, And Evaluation Of Homochiral Peptides Containing Arginine And Histidine As Molecular Transporters, Naglaa Salem El-Sayed, Taryn Miyake, Amir Nasrolahi Shirazi, Shang Eun Park, Jimmy Clark, Stephani Buchholz, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Linear (HR)n and cyclic [HR]n peptides (n = 4,5) containing alternate arginine and histidine residues were synthesized. The peptides showed 0–15% cytotoxicity at 5–100 μM in human ovarian adenocarcinoma (SK-OV-3) cells while they exhibited 0–12% toxicity in human leukemia cancer cell line (CCRF-CEM). Among all peptides, cyclic [HR]4 peptide was able to improve the delivery of a cell impermeable fluorescence-labeled phosphopeptide by two-fold. Fatty acids of different alkyl chain length were attached at the N-terminal of the linear peptide (HR)4 to improve the molecular transporter property. Addition of fatty acyl chains was expected ...


Identification Of A Novel Invasion-Promoting Region In Insulin Receptor Substrate 2, Jose Mercado-Matos, Jenny Janusis, Sha Zhu, Samuel S. Chen, Leslie M. Shaw 2018 University of Massachusetts Medical School

Identification Of A Novel Invasion-Promoting Region In Insulin Receptor Substrate 2, Jose Mercado-Matos, Jenny Janusis, Sha Zhu, Samuel S. Chen, Leslie M. Shaw

University of Massachusetts Medical School Faculty Publications

Although the insulin receptor substrate (IRS) proteins IRS1 and IRS2 share considerable homology and activate common signaling pathways, their contributions to breast cancer are distinct. IRS1 has been implicated in the proliferation and survival of breast tumor cells. In contrast, IRS2 facilitates glycolysis, invasion, and metastasis. To determine the mechanistic basis for IRS2-dependent functions, we investigated unique structural features of IRS2 that are required for invasion. Our studies revealed that the ability of IRS2 to promote invasion is dependent upon upstream insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor (IR) activation and the recruitment and activation of phosphatidylinositol 3-kinase (PI3K ...


Proteomic Characterization Of Ovarian And Breast Cancer Microenvironments For Improved Diagnostics And Therapeutic Targeting, Dylan Z. Dieters-Castator 2018 The University of Western Ontario

Proteomic Characterization Of Ovarian And Breast Cancer Microenvironments For Improved Diagnostics And Therapeutic Targeting, Dylan Z. Dieters-Castator

Electronic Thesis and Dissertation Repository

Cancers exist within complex microenvironments formed by heterogeneous cell types. This diversity creates significant challenges for detection, diagnosis and treatment. Mass spectrometry-based proteomics is a powerful approach capable of characterizing complex biological systems which are characteristic of cancer biology. In this thesis, proteomics was utilized to answer several questions related to ovarian cancer diagnosis and detection, and the effects of NODAL, an embryonic morphogen, on the breast cancer secretome and stromal cell recruitment. First, I compared multiple sample preparation techniques and found high-pH/low-pH fractionation to yield the greatest proteome coverage over commonly used approaches. Second, I compared the proteomes ...


Efficient Intracellular Delivery Of Cell-Impermeable Cargo Molecules By Peptides Containing Tryptophan And Histidine, Amir Nasrolahi Shirazi, Saghar Mozaffari, Rinzhin Tshering Sherpa, Rakesh Tiwari, Keykavous Parang 2018 Chapman University

Efficient Intracellular Delivery Of Cell-Impermeable Cargo Molecules By Peptides Containing Tryptophan And Histidine, Amir Nasrolahi Shirazi, Saghar Mozaffari, Rinzhin Tshering Sherpa, Rakesh Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

We have previously evaluated and reported numerous classes of linear and cyclic peptides containing hydrophobic and hydrophilic segments for intracellular delivery of multiple molecular cargos. Herein, a combination of histidine and tryptophan amino acids were designed and evaluated for their efficiency in intracellular delivery of cell-impermeable phosphopeptides and the anti-HIV drug, emtricitabine. Two new decapeptides, with linear and cyclic natures, both containing alternate tryptophan and histidine residues, were synthesized using Fmoc/tBu solid-phase chemistry. The peptides were characterized and purified by using matrix-assisted laser desorption/ionization (MALDI) spectroscopy and high-performance liquid chromatography (HPLC), respectively. These peptides did not show significant ...


Cell Clustering Mediated By The Adhesion Protein Pvrl4 Is Necessary For Alpha6beta4 Integrin-Promoted Ferroptosis Resistance In Matrix-Detached Cells, Caitlin W. Brown, John J. Amante, Arthur M. Mercurio 2018 University of Massachusetts Medical School

Cell Clustering Mediated By The Adhesion Protein Pvrl4 Is Necessary For Alpha6beta4 Integrin-Promoted Ferroptosis Resistance In Matrix-Detached Cells, Caitlin W. Brown, John J. Amante, Arthur M. Mercurio

University of Massachusetts Medical School Faculty Publications

Ferroptosis is an iron-dependent form of programmed cell death characterized by the accumulation of lipid-targeting reactive oxygen species that kill cells by damaging their plasma membrane. The lipid-repair enzyme glutathione peroxidase 4 (GPX4) protects against this oxidative damage and enables cells to resist ferroptosis. Recent work has revealed that matrix-detached carcinoma cells can be susceptible to ferroptosis and that they can evade this fate through the signaling properties of the alpha6beta4 integrin, which sustains GPX4 expression. Although these findings on ferroptosis are provocative, they differ from those in previous studies indicating that matrix-detached cells are prone to apoptosis, via a ...


Dynamics Of Human Protein Kinase Aurora A Linked To Drug Selectivity, Warintra Pitsawong, Vanessa Buosi, Renee Otten, Roman V. Agafonov, Adelajda Zorba, Nadja Kern, Steffen Kutter, Gunther Kern, Ricardo Ap Padua, Xavier Meniche, Dorothee Kern 2018 Brandeis University

Dynamics Of Human Protein Kinase Aurora A Linked To Drug Selectivity, Warintra Pitsawong, Vanessa Buosi, Renee Otten, Roman V. Agafonov, Adelajda Zorba, Nadja Kern, Steffen Kutter, Gunther Kern, Ricardo Ap Padua, Xavier Meniche, Dorothee Kern

Open Access Articles

Protein kinases are major drug targets, but the development of highly-selective inhibitors has been challenging due to the similarity of their active sites. The observation of distinct structural states of the fully-conserved Asp-Phe-Gly (DFG) loop has put the concept of conformational selection for the DFG-state at the center of kinase drug discovery. Recently, it was shown that Gleevec selectivity for the Tyr-kinase Abl was instead rooted in conformational changes after drug binding. Here, we investigate whether protein dynamics after binding is a more general paradigm for drug selectivity by characterizing the binding of several approved drugs to the Ser/Thr-kinase ...


Cip2a Facilitates The G1/S Cell Cycle Transition Via B-Myb In Human Papillomavirus 16 Oncoprotein E6-Expressing Cells, Yonghao Tian, Hanxiang Chen, Lijun Qiao, Wenhao Zhang, Jingyi Zheng, Weiming Zhao, Jason J. Chen, Weifang Zhang 2018 Shandong University

Cip2a Facilitates The G1/S Cell Cycle Transition Via B-Myb In Human Papillomavirus 16 Oncoprotein E6-Expressing Cells, Yonghao Tian, Hanxiang Chen, Lijun Qiao, Wenhao Zhang, Jingyi Zheng, Weiming Zhao, Jason J. Chen, Weifang Zhang

Open Access Articles

Infection with high-risk human papillomaviruses (HR-HPVs, including HPV-16, HPV-18, HPV-31) plays a central aetiologic role in the development of cervical carcinoma. The transforming properties of HR-HPVs mainly reside in viral oncoproteins E6 and E7. E6 protein degrades the tumour suppressor p53 and abrogates cell cycle checkpoints. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that is involved in the carcinogenesis of many human malignancies. Our previous data showed that CIP2A was overexpressed in cervical cancer. However, the regulation of CIP2A by HPV-16E6 remains to be elucidated. In this study, we demonstrated that HPV-16E6 significantly up-regulated CIP2A mRNA and ...


Pd-L1 Is Expressed On Human Platelets And Is Affected By Immune Checkpoint Therapy, Verena Rolfes, Christian Idel, Ralph Pries, Kirstin Plotze-Martin, Jens Habermann, Timo Gemoll, Sabine Bohnet, Eicke Latz, Julika Ribbat-Idel, Bernardo S. Franklin, Barbara Wollenberg 2018 University of Bonn

Pd-L1 Is Expressed On Human Platelets And Is Affected By Immune Checkpoint Therapy, Verena Rolfes, Christian Idel, Ralph Pries, Kirstin Plotze-Martin, Jens Habermann, Timo Gemoll, Sabine Bohnet, Eicke Latz, Julika Ribbat-Idel, Bernardo S. Franklin, Barbara Wollenberg

Open Access Articles

Cancer immunotherapy has been revolutionised by drugs that enhance the ability of the immune system to detect and fight tumors. Immune checkpoint therapies that target the programmed death-1 receptor (PD-1), or its ligand (PD-L1) have shown unprecedented rates of durable clinical responses in patients with various cancer types. However, there is still a large fraction of patients that do not respond to checkpoint inhibitors, and the challenge remains to find cellular and molecular cues that could predict which patients would benefit from these therapies. Using a series of qualitative and quantitative methods we show here that PBMCs and platelets from ...


Alcohol Consumption Promotes Colorectal Carcinoma Metastasis Via A Ccl5-Induced And Ampk-Pathway-Mediated Activation Of Autophagy, Haodong Zhao, Danlei Chen, Rui Cao, Shiqing Wang, Dandan Yu, Yakun Liu, Yu Jiang, Mei Xu, Jia Luo, Siying Wang 2018 Anhui Medical University, China

Alcohol Consumption Promotes Colorectal Carcinoma Metastasis Via A Ccl5-Induced And Ampk-Pathway-Mediated Activation Of Autophagy, Haodong Zhao, Danlei Chen, Rui Cao, Shiqing Wang, Dandan Yu, Yakun Liu, Yu Jiang, Mei Xu, Jia Luo, Siying Wang

Pharmacology and Nutritional Sciences Faculty Publications

There is a definite relationship between alcohol consumption and colorectal cancer (CRC) development. We investigated effect of alcohol consumption on CRC patients’ progression and prognosis by utilizing epidemiological data and found patients with alcohol consumption increased risks of tumor-node-metastasis (TNM), organ metastasis and poorer prognosis. Because their tumor tissues displayed increased expression of C-C chemokine ligand 5 (CCL5), we hypothesized CCL5 might participate in cancer progression in such patients. Ethanol increased the secretion of CCL5 in two CRC cell lines, HT29 and DLD-1. Treatment with CCL5 directly increased migratory ability of these cells, whereas neutralization or knockdown of CCL5 can ...


Two Phase Model To Study The Correlation Between Brain Tumor Growth Rate And The Formation Of Peritumoral Edema, Inmaculada Sorribes, Helen Byrne, Nicholas Moore, Harsh Jain 2018 Florida State University

Two Phase Model To Study The Correlation Between Brain Tumor Growth Rate And The Formation Of Peritumoral Edema, Inmaculada Sorribes, Helen Byrne, Nicholas Moore, Harsh Jain

Biology and Medicine Through Mathematics Conference

No abstract provided.


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