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Articles 1 - 14 of 14

Full-Text Articles in Cancer Biology

Retinoblastoma Binding Protein 4 Maintains Cycling Neural Stem Cells And Prevents Dna Damage And Tp53-Dependent Apoptosis In Rb1 Mutant Neural Progenitors, Laura E. Schultz-Rogers, Maira P. Almeida, Wesley A. Wierson, Marcel Kool, Maura Mcgrail Sep 2018

Retinoblastoma Binding Protein 4 Maintains Cycling Neural Stem Cells And Prevents Dna Damage And Tp53-Dependent Apoptosis In Rb1 Mutant Neural Progenitors, Laura E. Schultz-Rogers, Maira P. Almeida, Wesley A. Wierson, Marcel Kool, Maura Mcgrail

Genetics, Development and Cell Biology Publications

Retinoblastoma-binding protein 4 (Rbbp4) is a WDR adaptor protein for multiple chromatin remodelers implicated in human oncogenesis. Here we show Rbbp4 is overexpressed in zebrafish rb1-embryonal brain tumors and is upregulated across the spectrum of human embryonal and glial brain cancers. We demonstrate in vivo Rbbp4 is essential for zebrafish neurogenesis and has distinct roles in neural stem and progenitor cells. rbbp4 mutant neural stem cells show delayed cell cycle progression and become hypertrophic. In contrast, rbbp4 mutant neural precursors accumulate extensive DNA damage and undergo programmed cell death that is dependent on Tp53 signaling. Loss of Rbbp4 and disruption ...


Epigenetic Regulators Rbbp4 And Hdac1 Are Overexpressed In A Zebrafish Model Of Rb1 Embryonal Brain Tumor, And Are Required For Neural Progenitor Survival And Proliferation, Laura E. Schultz, Jeffrey A. Haltom, Maira P. Almeida, Wesley A. Wierson, Staci L. Solin, Trevor J. Weiss, Jordan A. Helmer, Elizabeth J. Sandquist, Heather R. Shive, Maura Mcgrail Jan 2018

Epigenetic Regulators Rbbp4 And Hdac1 Are Overexpressed In A Zebrafish Model Of Rb1 Embryonal Brain Tumor, And Are Required For Neural Progenitor Survival And Proliferation, Laura E. Schultz, Jeffrey A. Haltom, Maira P. Almeida, Wesley A. Wierson, Staci L. Solin, Trevor J. Weiss, Jordan A. Helmer, Elizabeth J. Sandquist, Heather R. Shive, Maura Mcgrail

Genetics, Development and Cell Biology Publications

In this study, we used comparative genomics and developmental genetics to identify epigenetic regulators driving oncogenesis in a zebrafish retinoblastoma 1 (rb1) somatic-targeting model of RB1 mutant embryonal brain tumors. Zebrafish rb1 brain tumors caused by TALEN or CRISPR targeting are histologically similar to human central nervous system primitive neuroectodermal tumors (CNS-PNETs). Like the human oligoneural OLIG2+/SOX10+ CNS-PNET subtype, zebrafish rb1 tumors show elevated expression of neural progenitor transcription factors olig2, sox10, sox8b and the receptor tyrosine kinase erbb3a oncogene. Comparison of rb1 tumor and rb1/rb1 germline mutant larval transcriptomes shows that the altered oligoneural precursor signature is ...


Comprehensive Analysis Of Cancer-Associated Somatic Mutations In Class I Hla Genes, Sachet A. Shukla, Michael S. Rooney, Mohini Rajasagi, Grace Tiao, Philip M. Dixon, Michael S. Lawrence, Jonathan Stevens, William J. Lane, Jamie L. Dellagatta, Scott Steelman, Carrie Sougnez, Kristian Cibulskis, Adam Kiezun, Vladimir Brusic, Catherine J. Wu, Gad Getz Nov 2015

Comprehensive Analysis Of Cancer-Associated Somatic Mutations In Class I Hla Genes, Sachet A. Shukla, Michael S. Rooney, Mohini Rajasagi, Grace Tiao, Philip M. Dixon, Michael S. Lawrence, Jonathan Stevens, William J. Lane, Jamie L. Dellagatta, Scott Steelman, Carrie Sougnez, Kristian Cibulskis, Adam Kiezun, Vladimir Brusic, Catherine J. Wu, Gad Getz

Statistics Publications

Detection of somatic mutations in human leukocyte antigen (HLA) genes using whole-exome sequencing (WES) is hampered by the high polymorphism of the HLA loci, which prevents alignment of sequencing reads to the human reference genome. We describe a computational pipeline that enables accurate inference of germline alleles of class I HLA-A, B and C genes and subsequent detection of mutations in these genes using the inferred alleles as a reference. Analysis of WES data from 7,930 pairs of tumor and healthy tissue from the same patient revealed 298 nonsilent HLA mutations in tumors from 266 patients. These 298 mutations ...


Rapid Tumor Induction In Zebrafish By Talen-Mediated Somatic Inactivation Of The Retinoblastoma1 Tumor Suppressor Rb1, Staci L. Solin, Heather R. Shive, Kevin D. Woolard, Jeffrey J. Essner, Maura Mcgrail Sep 2015

Rapid Tumor Induction In Zebrafish By Talen-Mediated Somatic Inactivation Of The Retinoblastoma1 Tumor Suppressor Rb1, Staci L. Solin, Heather R. Shive, Kevin D. Woolard, Jeffrey J. Essner, Maura Mcgrail

Genetics, Development and Cell Biology Publications

Investigating the in vivo role of tumor suppressor genes in cancer is technically challenging due to their essential requirement during early animal development. To address this bottleneck, we generated genetic mosaic adult zebrafish using TALEN genome editing and demonstrate somatic inactivation of the tumor suppressor retinoblastoma1 (rb1) induces tumorigenesis at high frequency. 11–33% of 1-cell stage embryos injected with TALEN mRNAs targeting rb1 exon 2 or 3 develop tumors beginning as early as 3.5 months of age. Lesions predominantly arise in the brain and show features of neuroectodermal-like and glial-like tumors. Mutant allele analysis is consistent with tumor ...


Molecular And Cellular Characterization Of A Zebrafish Optic Pathway Tumor Line Implicates Glia-Derived Progenitors In Tumorigenesis, Staci L. Solin, Ying Wang, Joshua Mauldin, Laura E. Schultz, Deborah E. Lincow, Pavel A. Brodskiy, Crystal A. Jones, Judith Syrkin-Nikolau, Jasmine M. Linn, Jeffrey J. Essner, Jesse M. Hostetter, Elizabeth M. Whitley, J. Douglas Cameron, Hui-Hsien Chou, Andrew J. Severin, Donald S. Sakaguchi, Maura Mcgrail Jan 2014

Molecular And Cellular Characterization Of A Zebrafish Optic Pathway Tumor Line Implicates Glia-Derived Progenitors In Tumorigenesis, Staci L. Solin, Ying Wang, Joshua Mauldin, Laura E. Schultz, Deborah E. Lincow, Pavel A. Brodskiy, Crystal A. Jones, Judith Syrkin-Nikolau, Jasmine M. Linn, Jeffrey J. Essner, Jesse M. Hostetter, Elizabeth M. Whitley, J. Douglas Cameron, Hui-Hsien Chou, Andrew J. Severin, Donald S. Sakaguchi, Maura Mcgrail

Genetics, Development and Cell Biology Publications

In this study we describe the molecular and cellular characterization of a zebrafish mutant that develops tumors in the optic pathway. Heterozygous Tg(flk1:RFP)is18 transgenic adults develop tumors of the retina, optic nerve and optic tract. Molecular and genetic mapping demonstrate the tumor phenotype is linked to a high copy number transgene array integrated in the lincRNA gene lincRNAis18/Zv9_00007276 on chromosome 3. TALENs were used to isolate a 147kb deletion allele that removes exons 2–5 of the lincRNAis18 gene. Deletion allele homozygotes are viable and do not develop tumors, indicating loss of function of thelincRNAis18 ...


Directed Cell Migration In Multi-Cue Environments, Laura Lara Rodriguez, Ian C. Schneider Oct 2013

Directed Cell Migration In Multi-Cue Environments, Laura Lara Rodriguez, Ian C. Schneider

Chemical and Biological Engineering Publications

Cell migration plays a critical role in development, angiogenesis, immune response, wound healing and cancer metastasis. During these processes, cells are often directed to migrate towards targets by sensing aligned fibers or gradients in concentration, mechanical properties or electric field. Often times, cells must integrate migrational information from several of these different cues. While the cell migration behavior, signal transduction and cytoskeleton dynamics elicited by individual directional cues has been largely determined, responses to multiple directional cues are much less understood. However, initial work has pointed to several interesting behaviors in multi-cue environments, including competition and cooperation between cues to ...


Plasma-Seq: A Novel Strategy For Metastatic Prostate Cancer Analysis, Caitlin Farris, Jeffrey M. Trimarchi Jan 2013

Plasma-Seq: A Novel Strategy For Metastatic Prostate Cancer Analysis, Caitlin Farris, Jeffrey M. Trimarchi

Genetics, Development and Cell Biology Publications

Personalized genomics will only be useful for monitoring the prognosis of patients with cancer when it becomes much more cost-effective and quicker to apply. A recent study brings this closer to reality with the development of plasma-seq, a rapid, low-cost method that sequences the circulating DNA present in the peripheral blood of patients with cancer. The power of this technique is demonstrated with the examination of tumor genomes from patients with prostate cancer.


Somatic Mutagenesis With A Sleeping Beauty Transposon System Leads To Solid Tumor Formation In Zebrafish, Maura Mcgrail, Julia M. Hatler, Zianyan Kuang, Hsin-Kai Liao, Kishore Nannapaneni, Kristin E. Noack Watt, Juli D. Uhl, David A. Largaespada, Erik Vollbrecht, Todd E. Scheetz, Adam J. Dupuy, Jesse M. Hostetter, Jeffrey J. Essner Apr 2011

Somatic Mutagenesis With A Sleeping Beauty Transposon System Leads To Solid Tumor Formation In Zebrafish, Maura Mcgrail, Julia M. Hatler, Zianyan Kuang, Hsin-Kai Liao, Kishore Nannapaneni, Kristin E. Noack Watt, Juli D. Uhl, David A. Largaespada, Erik Vollbrecht, Todd E. Scheetz, Adam J. Dupuy, Jesse M. Hostetter, Jeffrey J. Essner

Genetics, Development and Cell Biology Publications

Large-scale sequencing of human cancer genomes and mouse transposon-induced tumors has identified a vast number of genes mutated in different cancers. One of the outstanding challenges in this field is to determine which genes, when mutated, contribute to cellular transformation and tumor progression. To identify new and conserved genes that drive tumorigenesis we have developed a novel cancer model in a distantly related vertebrate species, the zebrafish, Danio rerio. The Sleeping Beauty (SB) T2/Onc transposon system was adapted for somatic mutagenesis in zebrafish. The carp ß-actin promoter was cloned into T2/Onc to create T2/OncZ. Two transgenic zebrafish ...


Coexpression Of Normally Incompatible Developmental Pathways In Retinoblastoma Genesis, Justina Mcevoy, Jacqueline Flores-Otero, Jiakun Zhang, Katie Nemeth, Rachel Brennan, Cori Bradley, Fred Krafcik, Carlos Rodriguez-Galindo, Matthew Wilson, Shunbin Xiong, Guillermina Lozano, Julien Sage, Ligia Fu, Lotfi Louhibi, Jeff Trimarchi, Amar Pani, Richard Smeyne, Dianna Johnson, Michael A. Dyer Jan 2011

Coexpression Of Normally Incompatible Developmental Pathways In Retinoblastoma Genesis, Justina Mcevoy, Jacqueline Flores-Otero, Jiakun Zhang, Katie Nemeth, Rachel Brennan, Cori Bradley, Fred Krafcik, Carlos Rodriguez-Galindo, Matthew Wilson, Shunbin Xiong, Guillermina Lozano, Julien Sage, Ligia Fu, Lotfi Louhibi, Jeff Trimarchi, Amar Pani, Richard Smeyne, Dianna Johnson, Michael A. Dyer

Genetics, Development and Cell Biology Publications

It is widely believed that the molecular and cellular features of a tumor reflect its cell of origin and can thus provide clues about treatment targets. The retinoblastoma cell of origin has been debated for over a century. Here, we report that human and mouse retinoblastomas have molecular, cellular, and neurochemical features of multiple cell classes, principally amacrine/horizontal interneurons, retinal progenitor cells, and photoreceptors. Importantly, single-cell gene expression array analysis showed that these multiple cell type-specific developmental programs are coexpressed in individual retinoblastoma cells, which creates a progenitor/neuronal hybrid cell. Furthermore, neurotransmitter receptors, transporters, and biosynthetic enzymes are ...


Rapid Biocompatibility Analysis Of Materials Via In Vivo Fluorescence Imaging Of Mouse Models, Kaitlin M. Bratlie, Tram T. Dang, Stephen Lyle, Matthias Nahrendorf, Ralph Weissleder, Robert Langer, Daniel G. Anderson Apr 2010

Rapid Biocompatibility Analysis Of Materials Via In Vivo Fluorescence Imaging Of Mouse Models, Kaitlin M. Bratlie, Tram T. Dang, Stephen Lyle, Matthias Nahrendorf, Ralph Weissleder, Robert Langer, Daniel G. Anderson

Kaitlin M. Bratlie

Background: Many materials are unsuitable for medical use because of poor biocompatibility. Recently, advances in the high throughput synthesis of biomaterials has significantly increased the number of potential biomaterials, however current biocompatibility analysis methods are slow and require histological analysis. Methodology/Principal Findings: Here we develop rapid, non-invasive methods for in vivo quantification of the inflammatory response to implanted biomaterials. Materials were placed subcutaneously in an array format and monitored for host responses as per ISO 10993-6: 2001. Host cell activity in response to these materials was imaged kinetically, in vivo using fluorescent whole animal imaging. Data captured using whole ...


Soy Isoflavones Have An Antiestrogenic Effect And Alter Mammary Promoter Hypermethylation In Healthy Premenopausal Women1, Wenyi Qin, Weizhu Zhu, Huidong Shi, John E. Hewett, Rachel L. Ruhlen, Ruth S. Macdonald, George E. Rottinghaus, Yin-Chieh Chien, Edward R. Sauter Feb 2009

Soy Isoflavones Have An Antiestrogenic Effect And Alter Mammary Promoter Hypermethylation In Healthy Premenopausal Women1, Wenyi Qin, Weizhu Zhu, Huidong Shi, John E. Hewett, Rachel L. Ruhlen, Ruth S. Macdonald, George E. Rottinghaus, Yin-Chieh Chien, Edward R. Sauter

Food Science and Human Nutrition Publications

We hypothesized that soy isoflavones would have dose related estrogenic and methylation effects. 34 healthy premenopausal women were prospectively enrolled and randomized in double-blind fashion to receive either 40 mg or 140 mg isoflavones daily through one menstrual cycle. Breast specific (NAF) and systemic (serum) estrogenic effects were assessed measuring the estrogenic marker complement (C)3 and changes in cytology, while methylation effects were evaluated in mammary ductoscopy (MD) specimens using methylation specific PCR assessment of five genes (p16, RASSF1A, RARβ2, ER, and CCND2) associated with breast carcinogenesis. Serum genistein significantly increased post treatment in women consuming both isoflavone doses ...


Genistein Affects Her2 Protein Concentration, Activation And Promoter Regulation Via Estrogen Receptor-And Non-Estrogen Receptor-Mediated Mechanisms, Mary S. Sakla, Pete J. Ansell, Nader S. Shenouda, Dennis B. Lubahn, Ruth S. Macdonald Oct 2007

Genistein Affects Her2 Protein Concentration, Activation And Promoter Regulation Via Estrogen Receptor-And Non-Estrogen Receptor-Mediated Mechanisms, Mary S. Sakla, Pete J. Ansell, Nader S. Shenouda, Dennis B. Lubahn, Ruth S. Macdonald

Food Science and Human Nutrition Publications

The HER2 proto-oncogene, a member of the epidermal growth factor receptor family, is overexpressed in 20–30% of breast cancers. Genistein, the main soy isoflavone, interacts with estrogen receptors (ER) and it is also a potent tyrosine kinase inhibitor. Previously, our laboratory found that genistein delayed mammary tumor onset in transgenic mice that overexpress HER2 gene. Our goal was to define the mechanism through which genistein affects mammary tumorigenesis inHER2 overexpressing mice. We hypothesized that genistein inhibits HER2 activation and expression through ER-dependent and ER-independent mechanisms. Genistein inhibited total HER2 protein expression and tyrosine phosphorylation in BT-474, an ERα ...


Phytosterol Pygeum Africanum Regulates Prostate Cancer In Vitro And In Vivo, Nader S. Shenouda, Mary S. Sakla, Leslie G. Newton, Cynthia Besch-Williford, Norman M. Greenberg, Ruth S. Macdonald, Dennis B. Lubahn May 2007

Phytosterol Pygeum Africanum Regulates Prostate Cancer In Vitro And In Vivo, Nader S. Shenouda, Mary S. Sakla, Leslie G. Newton, Cynthia Besch-Williford, Norman M. Greenberg, Ruth S. Macdonald, Dennis B. Lubahn

Food Science and Human Nutrition Publications

Background

Prostate cancer is an important public health problem. It is an excellent candidate disease for chemo-prevention because prostate cancer is typically slow growing and is usually diagnosed in elderly males. Pygeum africanum (Prunus africana or Rosaceae) is an African prune (plum) tree found in tropical Africa. An extract from the bark of Pygeum africanum has been used in Europe as a prevention and treatment of prostate disorders including benign prostatic hypertrophy (BPH). More recently in the USA, the phytotherapeutic preparations of Pygeum africanum and Saw palmetto have been marketed for prostate health including prostate cancer prevention and treatment.

Methods ...


Hras Intracellular Trafficking And Signal Transduction, Jodi Ho-Jung Mckay Jan 2007

Hras Intracellular Trafficking And Signal Transduction, Jodi Ho-Jung Mckay

Retrospective Theses and Dissertations

Cancer, which is characterized by uncontrolled cell division and proliferation, is the second leading cause of death in the United States. Of these deaths, approximately 30% are the result of mutations in Ras protein. When activated, Ras propagates multiple signal transduction cascades and induces cell proliferation, differentiation, and apoptosis. Within the Ras subfamily, there are several isoforms of Ras which differ in their posttranslational modifications. The modifications include proteolytic cleavage of the CAAX box, farnesylation, and palmitoylation which act as plasma membrane anchors where most signal transduction takes place. This dissertation demonstrates that Ras endocytosis takes place through a novel ...