The Histopathology Core A provides services and mechanisms for histopathologic characterization and quality assurance of tissues from both human subjects and rodent models of gastric inflammation and neoplasia. Specifically, the Core will provide histology and immunohistochemistry services with interpretation by pathologists experienced in gastric pathology and laser capture microdissection services. Dr. Blanca Piazuelo, GI pathologist, will serve as Director of Core A, and Dr. Pelayo Correa, the former Core Director, will continue as a Co-Investigator. Dr. Barbara Schneider, a molecular biologist with ample expertise in laser capture microdissection, will serve as a Co-Investigator. Mr. Alberto Delgado, an experienced histotechnologist, will perform all histochemistry and immunohistochemistry procedures. Dr. Kay Washington, the Director of Gastrointestinal Pathology at Vanderbilt, will collaborate in the histopathologic interpretation of rodent and human gastric tissues. Drs. Douglas R. Morgan and Luis E. Bravo (Fieldwork Core C) will collaborate on providing human gastric tissues from Central American and Colombian participants for processing and histopathological interpretation by the Core. The Histopathology Core laboratory is fully equipped to perform all techniques planned in this proposal. All three of the component projects of this Program Project Grant rely heavily upon morphologic analysis of gastric tissues from human subjects and/or rodent models of Helicobacter pylori-induced disease. During the past funding period, the Histopathology Core provided services contributing to 31 peer-reviewed publications related to PPG Projects. For the next funding period, the Histopathology Core will receive de-identified paraffin-embedded gastric tissues from human subjects from Colombia and Central America in Project 1 and collected by Core C, and rodent gastric specimens from experiments in Project 3. Rodent gastric tissues will be processed and embedded in paraffin, and all human and animal tissues will be processed for H&E staining; histopathological interpretation will be provided for Projects 1, 2, and 3. Additional staining procedures for human tissues include staining of mucins (AB-PAS and HID-AB) for the classification of intestinal metaplasia, and a modified Steiner silver stain for the identification of H. pylori. In support of Project 3, the Core will perform histopathologic interpretation of tissues from gerbils infected with clinical isolates of H. pylori and also perform immunohistochemistry with scoring for spermine oxidase (SMOX), phosphorylated EGFR and ERBB2, and the pEGFR?ERBB2 dimer that Project 3 has implicated as a molecular signature of gastric carcinogenesis, along with staining for oxidative DNA damage and apoptosis. The Core will also perform laser capture microdissection as needed for methylation studies in Project 1. All data generated by the Histopathology Core A will be deposited in Administrative Core B (Director, Dr. Keith Wilson) for statistical analyses (by Dr. Robertino Mera) and unification of databases.

Public Health Relevance

CORE A HISTOPATHOLOGY ? Narrative: Core A will receive and process stomach tissue samples from human subjects in Colombia and Central America and from animal experiments aimed to detect factors that may influence gastric cancer development. Human and animal gastric tissue sections will be examined under the microscope using a variety of techniques for evaluation of features that may predispose to stomach cancer, for the presence of the bacterium H pylori in the stomach, and for the identification of a variety of molecules that may be involved in progression to cancer. We expect that this work will help to find new ways to predict who will get gastric cancer and thus allow us to prevent this disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA028842-29
Application #
8856049
Study Section
Special Emphasis Panel (ZCA1-RPRB-J (J1))
Project Start
1997-03-01
Project End
2020-06-30
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
29
Fiscal Year
2015
Total Cost
$129,552
Indirect Cost
$36,974
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Bravo, Luis Eduardo; García, Luz Stella; Collazos, Paola et al. (2018) Reliable information for cancer control in Cali, Colombia. Colomb Med (Cali) 49:23-34
Mera, Robertino M; Bravo, Luis E; Camargo, M Constanza et al. (2018) Dynamics of Helicobacter pylori infection as a determinant of progression of gastric precancerous lesions: 16-year follow-up of an eradication trial. Gut 67:1239-1246
García, Luz Stella; Bravo, Luis Eduardo; Collazos, Paola et al. (2018) Cali cancer registry methods. Colomb Med (Cali) 49:109-120
Singh, Kshipra; Coburn, Lori A; Asim, Mohammad et al. (2018) Ornithine Decarboxylase in Macrophages Exacerbates Colitis and Promotes Colitis-Associated Colon Carcinogenesis by Impairing M1 Immune Responses. Cancer Res 78:4303-4315
Ge, Zhongming; Sheh, Alexander; Feng, Yan et al. (2018) Helicobacter pylori-infected C57BL/6 mice with different gastrointestinal microbiota have contrasting gastric pathology, microbial and host immune responses. Sci Rep 8:8014
Gobert, Alain P; Al-Greene, Nicole T; Singh, Kshipra et al. (2018) Distinct Immunomodulatory Effects of Spermine Oxidase in Colitis Induced by Epithelial Injury or Infection. Front Immunol 9:1242
Estevez-Ordonez, Dagoberto; Montalvan-Sanchez, Eleazar E; Wong, Rochelle E et al. (2018) Health Barriers and Patterns of Gastric Cancer Care in Rural Central American Resource-Limited Settings. JAMA Oncol 4:1131-1133
Scoville, Elizabeth A; Allaman, Margaret M; Brown, Caroline T et al. (2018) Alterations in Lipid, Amino Acid, and Energy Metabolism Distinguish Crohn's Disease from Ulcerative Colitis and Control Subjects by Serum Metabolomic Profiling. Metabolomics 14:
Sierra, Johanna C; Asim, Mohammad; Verriere, Thomas G et al. (2018) Epidermal growth factor receptor inhibition downregulates Helicobacter pylori-induced epithelial inflammatory responses, DNA damage and gastric carcinogenesis. Gut 67:1247-1260
Blosse, Alice; Lehours, Philippe; Wilson, Keith T et al. (2018) Helicobacter: Inflammation, immunology, and vaccines. Helicobacter 23 Suppl 1:e12517

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