Esophageal cancer is common worldwide and comprises two subtypes: esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC). Unfortunately, most patients present at late stages, thereby making survival rates low at less than 5% at 5 years. This grim prognosis mandates the utilization of innovative and unique genetically engineered mouse models developed by our research team to implement new strategies for functional genomics, prevention, imaging and therapy. The unique consortium involves long-standing collaborations and publications between recognized experts in the field of esophageal cancer from the University of Pennsylvania, Columbia University, and Massachusetts General Hospital. In particular, the Principal Investigators are Dr. Anil Rustgi (University of Pennsylvania), Dr. Timothy Wang (Columbia University) already within the NCI Tumor Microenvironment Network, and Dr. Umar Mahmood (Massachusetts General Hospital). The overarching goals of this U01 grant proposal are the following: (1) To utilize innovative models of esophageal cancer as a platform for elucidating the link between inflammation and cancer in the tumor microenvironment;and (2) To provide new approaches in the imaging of esophageal cancer for advances in translational medicine. These goals will be pursued through five interrelated Specific Aims that are trans-disciplinary and trans-institutional, and provide new We hope that the unique interrelated models developed by Drs. Rustgi and Wang may provide a new, future direction in tissue imaging of precancerous and cancerous lesions facilitated by the development of mouse upper endoscopy, non-invasive imaging technologies and molecular probes (tracking inflammatory/immune cells in the esophageal cancer microenvironment) by Dr. Umar Mahmood, which would have a great impact upon early detection of esophageal cancer in the human. In aggregate, this highly accomplished research team is poised to translate models of esophageal cancer into the eradication of human esophageal cancer, which would alter clinical approaches in the United States and worldwide. The proposed research is in concert with the recommendations by the NCI progress group report on upper Gl cancers, and the NCI Think Tank recommendations on the Tumor Microenvironment as well as Inflammation and Cancer.

Public Health Relevance

Esophageal cancer comprises two main subtypes, esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC), both common in the US and worldwide. In fact, ESCC is the 5th most common cancer amongst males worldwide and afflicts African-Americans with a high predilection in the US. EAC has the fastest rate of increase of any cancer in the US. The proposed research will translate models into improving clinical outcomes of esophageal cancers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA143056-05
Application #
8539290
Study Section
Special Emphasis Panel (ZCA1-SRLB-X (O1))
Program Officer
Mohla, Suresh
Project Start
2009-09-28
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$521,032
Indirect Cost
$102,424
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Habibollahi, Peiman; Waldron, Todd; Heidari, Pedram et al. (2014) Fluorescent nanoparticle imaging allows noninvasive evaluation of immune cell modulation in esophageal dysplasia. Mol Imaging 13:1-11
Turker, N Selcan; Heidari, Pedram; Kucherlapati, Raju et al. (2014) An EGFR targeted PET imaging probe for the detection of colonic adenocarcinomas in the setting of colitis. Theranostics 4:893-903
Heidari, Pedram; Wehrenberg-Klee, Eric; Habibollahi, Peiman et al. (2013) Free somatostatin receptor fraction predicts the antiproliferative effect of octreotide in a neuroendocrine tumor model: implications for dose optimization. Cancer Res 73:6865-73
Wong, Gabrielle S; Habibollahi, Peiman; Heidari, Pedram et al. (2013) Optical imaging of periostin enables early endoscopic detection and characterization of esophageal cancer in mice. Gastroenterology 144:294-7
Quante, Michael; Abrams, Julian A; Wang, Timothy C (2013) The rapid rise in gastroesophageal junction tumors: is inflammation of the gastric cardia the underwater iceberg? Gastroenterology 145:708-11
Liu, Kuancan; Jiang, Ming; Lu, Yun et al. (2013) Sox2 cooperates with inflammation-mediated Stat3 activation in the malignant transformation of foregut basal progenitor cells. Cell Stem Cell 12:304-15
Leece, Alicia K; Heidari, Pedram; Yokell, Daniel L et al. (2013) A container closure system that allows for greater recovery of radiolabeled peptide compared to the standard borosilicate glass system. Appl Radiat Isot 80:99-102
Habibollahi, Peiman; van den Berg, Nynke S; Kuruppu, Darshini et al. (2013) Metformin--an adjunct antineoplastic therapy--divergently modulates tumor metabolism and proliferation, interfering with early response prediction by 18F-FDG PET imaging. J Nucl Med 54:252-8
Quante, Michael; Bhagat, Govind; Abrams, Julian A et al. (2012) Bile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett-like metaplasia. Cancer Cell 21:36-51
Stairs, Douglas B; Bayne, Lauren J; Rhoades, Ben et al. (2011) Deletion of p120-catenin results in a tumor microenvironment with inflammation and cancer that establishes it as a tumor suppressor gene. Cancer Cell 19:470-83

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