Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 7 of 7
Full-Text Articles in Medicine and Health Sciences
C-Jun Inhibits Mammary Apoptosis In Vivo., Sanjay Katiyar, Mathew C Casimiro, Luis Dettin, Xiaoming Ju, Erwin F Wagner, Hirokazu Tanaka, Richard Pestell
C-Jun Inhibits Mammary Apoptosis In Vivo., Sanjay Katiyar, Mathew C Casimiro, Luis Dettin, Xiaoming Ju, Erwin F Wagner, Hirokazu Tanaka, Richard Pestell
Department of Cancer Biology Faculty Papers
c-jun, which is overexpressed in a number of human cancers encodes a critical component of the AP-1 complex. c-jun has been shown to either induce or inhibit cellular apoptosis. Germ line deletion of both c-jun alleles is embryonically lethal. To determine the role of the endogenous c-jun gene in apoptosis, we performed mammary epithelial cell-targeted somatic deletion using floxed c-jun (c-jun(f/f)) conditional knockout mice. Laser capture microdissection demonstrated endogenous c-jun inhibits expression of apoptosis inducing genes and reactive oxygen species (ROS)-reducing genes (MnSOD, catalase). ROS have been implicated in apoptosis and undergo enzymatic elimination via MnSOD and CuZnSOD with further …
Identification Of Methylated Genes Associated With Aggressive Bladder Cancer, Carmen J. Marsit, E. Andres Houseman, Brock C. Christensen, Luc Gagne, Margaret R. Wrensch, Heather H. Nelson, Joseph Weimels, Shichun Zheng, John K. Wiencke, Angeline S. Andrew, Alan R. Schned, Margaret R. Karagas, Karl T. Kelsey
Identification Of Methylated Genes Associated With Aggressive Bladder Cancer, Carmen J. Marsit, E. Andres Houseman, Brock C. Christensen, Luc Gagne, Margaret R. Wrensch, Heather H. Nelson, Joseph Weimels, Shichun Zheng, John K. Wiencke, Angeline S. Andrew, Alan R. Schned, Margaret R. Karagas, Karl T. Kelsey
Dartmouth Scholarship
Approximately 500,000 individuals diagnosed with bladder cancer in the U.S. require routine cystoscopic follow-up to monitor for disease recurrences or progression, resulting in over $ 2 billion in annual expenditures. Identification of new diagnostic and monitoring strategies are clearly needed, and markers related to DNA methylation alterations hold great promise due to their stability, objective measurement, and known associations with the disease and with its clinical features. To identify novel epigenetic markers of aggressive bladder cancer, we utilized a high-throughput DNA methylation bead-array in two distinct population-based series of incident bladder cancer (n = 73 and n = 264, respectively). …
Survival Associated Pathway Identification With Group Lp Penalized Global Auc Maximization., Zhenqiu Liu, Laurence S Magder, Terry Hyslop, Li Mao
Survival Associated Pathway Identification With Group Lp Penalized Global Auc Maximization., Zhenqiu Liu, Laurence S Magder, Terry Hyslop, Li Mao
Department of Pharmacology and Experimental Therapeutics Faculty Papers
It has been demonstrated that genes in a cell do not act independently. They interact with one another to complete certain biological processes or to implement certain molecular functions. How to incorporate biological pathways or functional groups into the model and identify survival associated gene pathways is still a challenging problem. In this paper, we propose a novel iterative gradient based method for survival analysis with group Lp penalized global AUC summary maximization. Unlike LASSO, Lp (p < 1) (with its special implementation entitled adaptive LASSO) is asymptotic unbiased and has oracle properties 1. We first extend Lp for individual gene identification to group Lp penalty for pathway selection, and then develop a novel iterative gradient algorithm for penalized global AUC summary maximization (IGGAUCS). This method incorporates the genetic pathways into global AUC summary maximization and identifies survival associated pathways instead of individual genes. The tuning parameters are determined using 10-fold cross validation with training data only. The prediction performance is evaluated using test data. We apply the proposed method to survival outcome analysis with gene expression profile and identify multiple pathways simultaneously. Experimental results with simulation and gene expression data demonstrate that the proposed procedures can be used for identifying important biological pathways that are related to survival phenotype and for building a parsimonious model for predicting the survival times.
The Lysr-Type Virulence Activator Aphb Regulates The Expression Of Genes In Vibrio Cholerae In Response To Low Ph And Anaerobiosis, Gabriela Kovacikova, Wei Lin, Karen Skorupski
The Lysr-Type Virulence Activator Aphb Regulates The Expression Of Genes In Vibrio Cholerae In Response To Low Ph And Anaerobiosis, Gabriela Kovacikova, Wei Lin, Karen Skorupski
Dartmouth Scholarship
AphB is a LysR-type activator that initiates the expression of the virulence cascade in Vibrio cholerae by cooperating with the quorum-sensing-regulated activator AphA at the tcpPH promoter on the Vibrio pathogenicity island (VPI). To identify the ancestral chromosomal genes in V. cholerae regulated by AphB, we carried out a microarray analysis and show here that AphB influences the expression of a number of genes that are not associated with the VPI. One gene strongly activated by AphB is cadC, which encodes the ToxR-like transcriptional activator responsible for activating the expression of lysine decarboxylase, which plays an important role in …
Notch1 Functions As A Tumor Suppressor In A Model Of K-Ras–Induced Pancreatic Ductal Adenocarcinoma, Linda Hanlon, Jacqueline L Avila, Renée M Demarest, Scott Troutman, Megan Allen, Francesca Ratti, Anil K Rustgi, Ben Z Stanger, Fred Radtke, Volkan Adsay, Fenella Long, Anthony J Capobianco, Joseph L Kissil
Notch1 Functions As A Tumor Suppressor In A Model Of K-Ras–Induced Pancreatic Ductal Adenocarcinoma, Linda Hanlon, Jacqueline L Avila, Renée M Demarest, Scott Troutman, Megan Allen, Francesca Ratti, Anil K Rustgi, Ben Z Stanger, Fred Radtke, Volkan Adsay, Fenella Long, Anthony J Capobianco, Joseph L Kissil
Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship
K-ras is the most commonly mutated oncogene in pancreatic cancer and its activation in murine models is sufficient to recapitulate the spectrum of lesions seen in human pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that Notch receptor signaling becomes reactivated in a subset of PDACs, leading to the hypothesis that Notch1 functions as an oncogene in this setting. To determine whether Notch1 is required for K-ras-induced tumorigenesis, we used a mouse model in which an oncogenic allele of K-ras is activated and Notch1 is deleted simultaneously in the pancreas. Unexpectedly, the loss of Notch1 in this model resulted in increased …
Differential Impact Of Tumor Suppressor Pathways On Dna Damage Response And Therapy-Induced Transformation In A Mouse Primary Cell Model., A Kathleen Mcclendon, Jeffry L Dean, Adam Ertel, Erik S Knudsen
Differential Impact Of Tumor Suppressor Pathways On Dna Damage Response And Therapy-Induced Transformation In A Mouse Primary Cell Model., A Kathleen Mcclendon, Jeffry L Dean, Adam Ertel, Erik S Knudsen
Department of Cancer Biology Faculty Papers
The RB and p53 tumor suppressors are mediators of DNA damage response, and compound inactivation of RB and p53 is a common occurrence in human cancers. Surprisingly, their cooperation in DNA damage signaling in relation to tumorigenesis and therapeutic response remains enigmatic. In the context of individuals with heritable retinoblastoma, there is a predilection for secondary tumor development, which has been associated with the use of radiation-therapy to treat the primary tumor. Furthermore, while germline mutations of the p53 gene are critical drivers for cancer predisposition syndromes, it is postulated that extrinsic stresses play a major role in promoting varying …
Peroxisome Proliferator-Activated Receptor Alpha Target Genes, Maryam Rakhshandehroo, Bianca Knoch, Michael Muller, Sander Kersten
Peroxisome Proliferator-Activated Receptor Alpha Target Genes, Maryam Rakhshandehroo, Bianca Knoch, Michael Muller, Sander Kersten
Illawarra Health and Medical Research Institute
The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrientmetabolism and energy homeostasis. PPARα serves as amolecular target for hypolipidemic fibrates drugs which bind the receptor with high affinity. Furthermore, PPARα binds and is activated by numerous fatty acids and fatty acid-derived compounds. PPARα governs biological processes by altering the expression of a large number of target genes. Accordingly, the specific role of PPARα is directly related to the biological function of its target genes. Here, we present an overview of the involvement …