The National Institute of Diabetes & Digestive & Kidney Diseases

The section on Gastrointestinal Cell Biology is involved in research involving the cellular basis of action of gastrointestinal hormones (primarily bombesin related peptides-gastrin-releasing peptide, neuromedin B, CCK related peptides and VIP-secretin related peptides) as well as clinical and laboratory studies on human gastric acid hypersecretory states such as Zollinger-Ellison syndrome.

The studies on GI hormones involve intracellular signaling cascades especially tyrosine phosphorylation (primarily CCK, Bombesin), molecular pharmacology of their receptors (especially Bombesin related peptides), and structure function studies of various receptor ligands to develop selective agonists and antagonists. In addition laboratory studies characterizing the bombesin related receptor, BRS-3 as well as developing ligands to deliver receptor specific chemotherapy to tumors ectopically expressing these receptors is being studied.

Studies of patients with Zollinger-Ellison syndrome involve clinical studies of the diagnosis, localization, and treament of the gastrinoma as well as Multiple endocrine Neoplasia thype 1 which occurs in a propostion of the patients. Laboratory studies involve the characterization of the molecular pathogenesis of gastrinomas and identification of useful prognostic factors.

1. Moody TW Mantey SA Pradhan TK Schumann M Nakagawa T Martinez A Fuselier J Coy DH Jensen RT Development of high affinity camptothecin-bombesin conjugates that have targeted cytotoxicity for bombesin receptor-containing tumor cells. J Biol Chem (279): 23580-9, 2004. [Full Text/Abstract]

2. Norton JA Alexander HR Fraker DL Venzon DJ Gibril F Jensen RT Does the use of routine duodenotomy (DUODX) affect rate of cure, development of liver metastases, or survival in patients with Zollinger-Ellison syndrome? Ann Surg (239): 617-25; discussion 626, 2004. [Full Text/Abstract]

3. Gibril F Schumann M Pace A Jensen RT Multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: a prospective study of 107 cases and comparison with 1009 cases from the literature. Medicine (Baltimore) (83): 43-83, 2004. [Full Text/Abstract]

4. Chen YJ Vortmeyer A Zhuang Z Gibril F Jensen RT X-chromosome loss of heterozygosity frequently occurs in gastrinomas and is correlated with aggressive tumor growth. Cancer (100): 1379-87, 2004. [Full Text/Abstract]

5. Tapia JA Garcia-Marin LJ Jensen RT Cholecystokinin-stimulated protein kinase C-delta kinase activation, tyrosine phosphorylation, and translocation are mediated by Src tyrosine kinases in pancreatic acinar cells. J Biol Chem (278): 35220-30, 2003. [Full Text/Abstract]

6. Schumann M Nakagawa T Mantey SA Tokita K Venzon DJ Hocart SJ Benya RV Jensen RT Importance of amino acids of the central portion of the second intracellular loop of the gastrin-releasing Peptide receptor for phospholipase C activation, internalization, and chronic down-regulation. J Pharmacol Exp Ther (307): 597-607, 2003. [Full Text/Abstract]

7. Chen YJ Vortmeyer A Zhuang Z Huang S Jensen RT Loss of heterozygosity of chromosome 1q in gastrinomas: occurrence and prognostic significance. Cancer Res (63): 817-23, 2003. [Full Text/Abstract]

8. Pace A Garcia-Marin LJ Tapia JA Bragado MJ Jensen RT Phosphospecific site tyrosine phosphorylation of p125FAK and proline-rich kinase 2 is differentially regulated by cholecystokinin receptor type A activation in pancreatic acini. J Biol Chem (278): 19008-16, 2003. [Full Text/Abstract]

9. Abou-Saif A Gibril F Ojeaburu JV Bashir S Entsuah LK Asgharian B Jensen RT Prospective study of the ability of serial measurements of serum chromogranin A and gastrin to detect changes in tumor burden in patients with gastrinomas. Cancer (98): 249-61, 2003. [Full Text/Abstract]

10. Peghini PL Annibale B Azzoni C Milione M Corleto VD Gibril F Venzon DJ Delle Fave G Bordi C Jensen RT Effect of chronic hypergastrinemia on human enterochromaffin-like cells: insights from patients with sporadic gastrinomas. Gastroenterology (123): 68-85, 2002. [Full Text/Abstract]

11. Igarashi H Ito T Pradhan TK Mantey SA Hou W Coy DH Jensen RT Elucidation of the vasoactive intestinal peptide pharmacophore for VPAC(2) receptors in human and rat and comparison to the pharmacophore for VPAC(1) receptors. J Pharmacol Exp Ther (303): 445-60, 2002. [Full Text/Abstract]

12. Tokita K Hocart SJ Coy DH Jensen RT Molecular basis of the selectivity of gastrin-releasing peptide receptor for gastrin-releasing peptide. Mol Pharmacol (61): 1435-43, 2002. [Full Text/Abstract]

13. Tokita K Katsuno T Hocart SJ Coy DH Llinares M Martinez J Jensen RT Molecular basis for selectivity of high affinity peptide antagonists for the gastrin-releasing peptide receptor. J Biol Chem (276): 36652-63, 2001. [Full Text/Abstract]

14. Mantey SA Coy DH Pradhan TK Igarashi H Rizo IM Shen L Hou W Hocart SJ Jensen RT Rational design of a peptide agonist that interacts selectively with the orphan receptor, bombesin receptor subtype 3. J Biol Chem (276): 9219-29, 2001. [Full Text/Abstract]

15. Tokita K Hocart SJ Katsuno T Mantey SA Coy DH Jensen RT Tyrosine 220 in the 5th transmembrane domain of the neuromedin B receptor is critical for the high selectivity of the peptoid antagonist PD168368. J Biol Chem (276): 495-504, 2001. [Full Text/Abstract]

16. Benya RV Kusui T Katsuno T Tsuda T Mantey SA Battey JF Jensen RT Glycosylation of the gastrin-releasing peptide receptor and its effect on expression, G protein coupling, and receptor modulatory processes. Mol Pharmacol (58): 1490-501, 2000. [Full Text/Abstract]

17. Roy PK Venzon DJ Shojamanesh H Abou-Saif A Peghini P Doppman JL Gibril F Jensen RT Zollinger-Ellison syndrome. Clinical presentation in 261 patients. Medicine (Baltimore) (79): 379-411, 2000. [Full Text/Abstract]