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Ryan Ying Cong Tan, Joanne Ngeow
Hereditary diffuse gastric cancer (HDGC) is an inherited autosomal dominant syndrome with a penetrance of up to 80% affecting diverse geographic populations. While it has been shown to be caused mainly by germline alterations in the E-cadherin gene (CDH1), problematically, the genetic diagnosis remains unknown in up to 60% of patients. Given the important knowledge gaps regarding the syndrome, asymptomatic carriers of CDH1 mutations are advised for a prophylactic total gastrectomy. Intensive annual endoscopic surveillance is the alternative for carriers who decline gastrectomy...
September 15, 2015: World Journal of Gastrointestinal Oncology
Shinya Sugimoto, Hirokazu Komatsu, Yuichi Morohoshi, Takanori Kanai
In East Asian countries, gastric cancer incidence is high, but detection rates for germline CDH1 mutations that cause hereditary diffuse gastric cancers (HDGCs) are low. Consequently, screens and genetic testing for HDGC are often considered unimportant. Since the first germline truncating CDH1 mutations in Japanese patients were reported, some HDGC cases have been reported, and some of these involve large germline rearrangements and de novo mutation of CDH1. New methods for mutation detection--such as multiplex ligation-dependent probe amplification, array comparative genomic hybridization, and exome sequencing--have become available, as have new experimental models, including novel gene-knockout mice and gastric organoids...
August 2015: Journal of Gastroenterology
Sujuan Guo, Yanping Liang, Susan F Murphy, Angela Huang, Haihong Shen, Deborah F Kelly, Pablo Sobrado, Zhi Sheng
The lack of a rapid and quantitative autophagy assay has substantially hindered the development and implementation of autophagy-targeting therapies for a variety of human diseases. To address this critical issue, we developed a novel autophagy assay using the newly developed Cyto-ID fluorescence dye. We first verified that the Cyto-ID dye specifically labels autophagic compartments with minimal staining of lysosomes and endosomes. We then developed a new Cyto-ID fluorescence spectrophotometric assay that makes it possible to estimate autophagy flux based on measurements of the Cyto-ID-stained autophagic compartments...
2015: Autophagy
Daniel Gaston, Samantha Hansford, Carla Oliveira, Mathew Nightingale, Hugo Pinheiro, Christine Macgillivray, Pardeep Kaurah, Andrea L Rideout, Patricia Steele, Gabriela Soares, Weei-Yuarn Huang, Scott Whitehouse, Sarah Blowers, Marissa A LeBlanc, Haiyan Jiang, Wenda Greer, Mark E Samuels, Andrew Orr, Conrad V Fernandez, Jacek Majewski, Mark Ludman, Sarah Dyack, Lynette S Penney, Christopher R McMaster, David Huntsman, Karen Bedard
Gastric cancer is among the leading causes of cancer-related deaths worldwide. While heritable forms of gastric cancer are relatively rare, identifying the genes responsible for such cases can inform diagnosis and treatment for both hereditary and sporadic cases of gastric cancer. Mutations in the E-cadherin gene, CDH1, account for 40% of the most common form of familial gastric cancer (FGC), hereditary diffuse gastric cancer (HDGC). The genes responsible for the remaining forms of FGC are currently unknown...
October 2014: PLoS Genetics
Romy Schmidt, Delphine Mieulet, Hans-Michael Hubberten, Toshihiro Obata, Rainer Hoefgen, Alisdair R Fernie, Joachim Fisahn, Blanca San Segundo, Emmanuel Guiderdoni, Jos H M Schippers, Bernd Mueller-Roeber
Early detection of salt stress is vital for plant survival and growth. Still, the molecular processes controlling early salt stress perception and signaling are not fully understood. Here, we identified salt-responsive ERF1 (SERF1), a rice (Oryza sativa) transcription factor (TF) gene that shows a root-specific induction upon salt and hydrogen peroxide (H2O2) treatment. Loss of SERF1 impairs the salt-inducible expression of genes encoding members of a mitogen-activated protein kinase (MAPK) cascade and salt tolerance-mediating TFs...
June 2013: Plant Cell
Zhi Jiang Zang, Choon Kiat Ong, Ioana Cutcutache, Willie Yu, Shen Li Zhang, Dachuan Huang, Lian Dee Ler, Karl Dykema, Anna Gan, Jiong Tao, Siyu Lim, Yujing Liu, P Andrew Futreal, Heike Grabsch, Kyle A Furge, Liang Kee Goh, Steve Rozen, Bin Tean Teh, Patrick Tan
Genetic alterations in kinases have been linked to multiple human pathologies. To explore the landscape of kinase genetic variation in gastric cancer (GC), we used targeted, paired-end deep sequencing to analyze 532 protein and phosphoinositide kinases in 14 GC cell lines. We identified 10,604 single-nucleotide variants (SNV) in kinase exons including greater than 300 novel nonsynonymous SNVs. Family-wise analysis of the nonsynonymous SNVs revealed a significant enrichment in mitogen-activated protein kinase (MAPK)-related genes (P < 0...
January 1, 2011: Cancer Research
Yi Shuai, Jun Guo, Yansheng Dong, Weijian Zhong, Ping Xiao, Tong Zhou, Lishi Zhang, Shuangqing Peng
Increasing evidence from in vivo and in vitro studies has indicated that MT exerts protective effects against DOX-induced cardiotoxicity; however the underlying precise mechanisms still remain an enigma. Therefore, the present study was designed using MT knockout mice in concert with genomic approaches to explore the possible molecular and cellular mechanisms in terms of the genetic network changes. MT-I/II null (MT⁻/⁻) mice and corresponding wild-type mice (MT+/+) were administrated with a single dose of DOX (15 mg/kg, i...
January 15, 2011: Toxicology Letters
Errol M Thomson, Andrew Williams, Carole L Yauk, Renaud Vincent
Nose-only exposure is used to study the distribution and toxicity of airborne contaminants. Restraint of animals in nose-only tubes causes stress, but the impact on pulmonary mRNA levels is unknown. Since stress and xenobiotics activate common pathways, we assessed whether nose-only exposure would alter expression of toxicologically relevant genes in the lungs. To identify candidate genes for further analysis, we first interrogated microarray data to examine time-dependent changes in gene expression in air-control animals from a nose-only inhalation study involving male wild-type C57BL/6 mice and transgenic tumor necrosis factor (TNF)-alpha over-expressing littermates...
July 2009: Inhalation Toxicology
Nobuaki Eto, Makoto Miyagishi, Reiko Inagi, Toshiro Fujita, Masaomi Nangaku
Genome-wide screening using a small interfering RNA (siRNA) library has revealed novel molecules that are involved in a wide range of physiological responses. The expression of vascular endothelial growth factor (VEGF) is increased under hypoxic conditions, and plays a crucial role in tumor angiogenesis and tissue responses to ischemia. Here, we used a siRNA expression vector library to elucidate molecules that modify VEGF expression. Screening using an siRNA library revealed that MAPKKK6 (MEKK6/MAP3K6) regulates VEGF expression under both normoxic and hypoxic conditions in vitro, although the biological function of MAP3K6 remains unknown...
April 2009: American Journal of Pathology
J C Ryan, J S Morey, J S Ramsdell, F M Van Dolah
Domoic acid is a rigid analog of the neurotransmitter glutamate and a potent agonist of kainate subtype glutamate receptors. Persistent activation of these receptor subtypes results in rapid excitotoxicity, calcium dependent cell death and neuronal lesions in areas of the brain where kainate pathways are concentrated. To better understand responses to domoic acid induced excitotoxicity, microarrays were used to profile gene expression in mouse brain following domoic acid exposure. Adult female mice were subjected intraperitoneally to domoic acid at the lethal dose 50, killed and dissected at 30, 60 and 240 min post-injection...
2005: Neuroscience
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