Medicine and Health Sciences Commons^™

Perceived Stress Levels, Chemotherapy, Radiation Treatment And Tumor Characteristics Are Associated With A Persistent Increased Frequency Of Somatic Chromosomal Instability In Women Diagnosed With Breast Cancer: A One Year Longitudinal Study, Noran Aboalela, Debra E. Lyon, R. K. Elswick Jr., Debra Lynch Kelly, Jenni Brumelle, Harry D. Bear, Colleen Jackson-Cook

Human and Molecular Genetics Publications

While advances in therapeutic approaches have resulted in improved survival rates for women diagnosed with breast cancer, subsets of these survivors develop persistent psychoneurological symptoms (fatigue, depression/anxiety, cognitive dysfunction) that compromise their quality of life. The biological basis for these persistent symptoms is unclear, but could reflect the acquisition of soma-wide chromosomal instability following the multiple biological/psychological exposures associated with the diagnosis/treatment of breast cancer. An essential first step toward testing this hypothesis is to determine if these cancer-related exposures are indeed associated with somatic chromosomal instability frequencies. Towards this end, we longitudinally studied 71 women (ages 23-71) with early-stage …

Differential Expression Analysis Of Rna Sequencing Data By Incorporating Non-Exonic Mapped Reads, Hung-I Harry Chen, Yuanhang Liu, Yi Zou, Zhao Lai, Devanand Sarkar, Yufei Huang, Yidong Chen

Human and Molecular Genetics Publications

Background

RNA sequencing (RNA-seq) is a powerful tool for genome-wide expression profiling of biological samples with the advantage of high-throughput and high resolution. There are many existing algorithms nowadays for quantifying expression levels and detecting differential gene expression, but none of them takes the misaligned reads that are mapped to non-exonic regions into account. We developed a novel algorithm, XBSeq, where a statistical model was established based on the assumption that observed signals are the convolution of true expression signals and sequencing noises. The mapped reads in non-exonic regions are considered as sequencing noises, which follows a Poisson distribution. Given …

Depletion Of The Chromatin Remodeler Chd4 Sensitizes Aml Blasts To Genotoxic Agents And Reduces Tumor Formation, Justin Sperlazza, Mohamed Rahmani, Jason Beckta, Mandy Aust, Elisa Hawkins, Shou Zhen Wang, Sheng Zu Zhu, Shreya Podder, Catherine Dumur, Kellie Archer, Steven Grant, Gordon D. Ginder

Human and Molecular Genetics Publications

Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATPase that alters the phasing of nucleosomes on DNA and has recently been implicated in DNA double-stranded break (DSB) repair. Here, we show that depletion of CHD4 in acute myeloid leukemia (AML) blasts induces a global relaxation of chromatin that renders cells more susceptible to DSB formation, while concurrently impeding their repair. Furthermore, CHD4 depletion renders AML blasts more sensitive both in vitro and in vivo to genotoxic agents used in clinical therapy: daunorubicin (DNR) and cytarabine (ara-C). Sensitization to DNR and ara-C is mediated in part by activation of the ataxia-telangiectasia …

Knockdown Of Cdk2ap1 In Primary Human Fibroblasts Induces P53 Dependent Senescence, Khaled N. Alsayegh, Venkat S. Gadepalli, Shilpa Iyer, Raj R. Rao

Human and Molecular Genetics Publications

Cyclin Dependent Kinase-2 Associated Protein-1 (CDK2AP1) is known to be a tumor suppressor that plays a role in cell cycle regulation by sequestering monomeric CDK2, and targeting it for proteolysis. A reduction of CDK2AP1 expression is considered to be a negative prognostic indicator in patients with oral squamous cell carcinoma and also associated with increased invasion in human gastric cancer tissue. CDK2AP1 overexpression was shown to inhibit growth, reduce invasion and increase apoptosis in prostate cancer cell lines. In this study, we investigated the effect of CDK2AP1 downregulation in primary human dermal fibroblasts. Using a short-hairpin RNA to reduce its …

Evaluation Of Methyl-Binding Domain Based Enrichment Approaches Revisited, Karolina A. Aberg, Linying Xie, Robin F. Chan, Min Zhao, Ashutosh K. Pandey, Gaurav Kumar, Shaunna L. Clark, Edwin J. C. G. Van Den Oord

Human and Molecular Genetics Publications

Methyl-binding domain (MBD) enrichment followed by deep sequencing (MBD-seq), is a robust and cost efficient approach for methylome-wide association studies (MWAS). MBD-seq has been demonstrated to be capable of identifying differentially methylated regions, detecting previously reported robust associations and producing findings that replicate with other technologies such as targeted pyrosequencing of bisulfite converted DNA. There are several kits commercially available that can be used for MBD enrichment. Our previous work has involved MethylMiner (Life Technologies, Foster City, CA, USA) that we chose after careful investigation of its properties. However, in a recent evaluation of five commercially available MBD-enrichment kits the …

Tumor-Specific Expression And Detection Of A Cest Reporter Gene, Il Minn, Amnon Bar-Shir, Keerthi Yarlagadda, Jeff W. M. Bulte, Paul B. Fisher, Hao Wang, Assaf A. Gilad, Martin G. Pomper

Human and Molecular Genetics Publications

Purpose

To develop an imaging tool that enables the detection of malignant tissue with enhanced specificity using the exquisite spatial resolution of MRI.

Methods

Two mammalian gene expression vectors were created for the expression of the lysine-rich protein (LRP) under the control of the cytomegalovirus (CMV) promoter and the progression elevated gene-3 promoter (PEG-3 promoter) for constitutive and tumor-specific expression of LRP, respectively. Using those vectors, stable cell lines of rat 9L glioma, 9LCMV-LRP and 9LPEG-LRP, were established and tested for CEST contrast in vitro and in vivo.

Results

9LPEG-LRP cells showed increased CEST contrast compared with 9L cells …

Genetic Risks To Nicotine Dependence Predict Negative Mood And Affect In Current Non-Smokers, Xiangning Chen, Steven H. Aggen, Jingchun Chen, Lingxi Li, Kenneth S. Kendler, Melissa Blank, Thomas Eissenberg

Human and Molecular Genetics Publications

Nicotine is the psychoactive agent involved in nicotine dependence. However, nicotine as a drug, and its effects on human psychology are largely under-investigated in genetic studies. In this study, we recruited 208 current non-smokers to evaluate the effect of nicotine and its relationship to genetic risks to nicotine dependence. Exploratory and confirmatory factor analyses, as well as measurement invariance testing, were conducted to evaluate the latent factor structures of the POMS, PANAS and DEN questionnaires across 3 nicotine doses. Structural models were used to examine the effects of nicotine and their relationship to genetic risks of nicotine dependence. We found …

Tumor-Specific Expression And Detection Of A Cest Reporter Gene, Il Minn, Amnon Bar-Shir, Keerthi Yarlagadda, Jeff W. M. Bulte, Paul B. Fisher, Hao Wang, Assaf A. Gilad, Martin G. Pomper

Human and Molecular Genetics Publications

Purpose

To develop an imaging tool that enables the detection of malignant tissue with enhanced specificity using the exquisite spatial resolution of MRI.

Methods

Two mammalian gene expression vectors were created for the expression of the lysine-rich protein (LRP) under the control of the cytomegalovirus (CMV) promoter and the progression elevated gene-3 promoter (PEG-3 promoter) for constitutive and tumor-specific expression of LRP, respectively. Using those vectors, stable cell lines of rat 9L glioma, 9LCMV-LRP and 9LPEG-LRP, were established and tested for CEST contrast in vitro and in vivo.

Results

9LPEG-LRP cells showed increased CEST contrast compared with 9L cells …

Perceived Stress Levels, Chemotherapy, Radiation Treatment And Tumor Characteristics Are Associated With A Persistent Increased Frequency Of Somatic Chromosomal Instability In Women Diagnosed With Breast Cancer: A One Year Longitudinal Study, Noran Aboalela, Debra E. Lyon, R. K. Elswick Jr., Debra Lynch Kelly, Jenni Brumelle, Harry D. Bear, Colleen Jackson-Cook

Human and Molecular Genetics Publications

While advances in therapeutic approaches have resulted in improved survival rates for women diagnosed with breast cancer, subsets of these survivors develop persistent psychoneurological symptoms (fatigue, depression/anxiety, cognitive dysfunction) that compromise their quality of life. The biological basis for these persistent symptoms is unclear, but could reflect the acquisition of soma-wide chromosomal instability following the multiple biological/psychological exposures associated with the diagnosis/treatment of breast cancer. An essential first step toward testing this hypothesis is to determine if these cancer-related exposures are indeed associated with somatic chromosomal instability frequencies. Towards this end, we longitudinally studied 71 women (ages 23-71) with early-stage …

Knockdown Of Cdk2ap1 In Primary Human Fibroblasts Induces P53 Dependent Senescence, Khaled N. Alsayegh, Venkat S. Gadepalli, Shilpa Iyer, Raj R. Rao

Human and Molecular Genetics Publications

Cyclin Dependent Kinase-2 Associated Protein-1 (CDK2AP1) is known to be a tumor suppressor that plays a role in cell cycle regulation by sequestering monomeric CDK2, and targeting it for proteolysis. A reduction of CDK2AP1 expression is considered to be a negative prognostic indicator in patients with oral squamous cell carcinoma and also associated with increased invasion in human gastric cancer tissue. CDK2AP1 overexpression was shown to inhibit growth, reduce invasion and increase apoptosis in prostate cancer cell lines. In this study, we investigated the effect of CDK2AP1 downregulation in primary human dermal fibroblasts. Using a short-hairpin RNA to reduce its …

Comparison Of Effects Of P53 Null And Gain-Of-Function Mutations On Salivary Tumors In Mmtv-Hras Transgenic Mice, Dadi Jiang, Catherine I. Dumur, H. Davis Massey, Viswanathan Ramakrishnan, Mark A. Subler, Jolene J. Windle

Human and Molecular Genetics Publications

p53 is an important tumor suppressor gene which is mutated in ~50% of all human cancers. Some of these mutants appear to have acquired novel functions beyond merely losing wild-type functions. To investigate these gain-of-function effects in vivo, we generated mice of three different genotypes: MMTV-Hras/p53+/+, MMTV-Hras/p53-/-, and MMTV-Hras/p53R172H/R172H. Salivary tumors from these mice were characterized with regard to age of tumor onset, tumor growth rates, cell cycle distribution, apoptotic levels, tumor histopathology, as well as response to doxorubicin treatment. Microarray analysis was also performed to profile gene expression. The MMTV-Hras/p53-/- and …