Medicine and Health Sciences Commons^™

Limited Sampling Estimates Of Epigallocatechin Gallate Exposures In Cirrhotic And Noncirrhotic Patients With Hepatitis C After Single Oral Doses Of Green Tea Extract., Dina Halegoua-De Marzio, Walter K. Kraft, Constantine Daskalakis, Xie Ying, Roy L Hawke, Victor J. Navarro

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Epigallocatechin-3-gallate (EGCG) has antiangiogenic, antioxidant, and antifibrotic properties that may have therapeutic potential for the treatment of cirrhosis induced by hepatitis C virus (HCV). However, cirrhosis might affect EGCG disposition and augment its reported dose-dependent hepatotoxic potential.

OBJECTIVE: The safety, tolerability, and disposition of a single oral dose of EGCG in cirrhotic patients with HCV were examined in an exploratory fashion.

METHODS: Eleven patients with hepatitis C and detectable viremia were enrolled. Four had Child-Pugh (CP) class A cirrhosis, 4 had Child-Pugh class B cirrhosis, and 3 were noncirrhotic. After a single oral dose of green tea extract 400 …

Dysregulation Of Mir-31 And Mir-21 Induced By Zinc Deficiency Promotes Esophageal Cancer, Hansjuerg Alder, Cristian Taccioli, Hongping Chen, Yubao Jiang, Karl Smalley, Paolo Fadda, Hatice G. Ozer, Kay Huebner, John Farber, Carlo M. Croce, Louise Fong

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Presented at: Hallmarks and Cancer Conference, October 29-31 in San Francisco.

And AICR Annual Meeting, November 1-2, 2012.

Dietary zinc (Zn) deficiency (ZD) in rats induces an inflammatory gene signature that fuels esophageal squamous cell cancer (ESCC). Using nanoStringTM technology, we show that the inflammation is accompanied by altered expression of specific microRNAs in esophagus, as well as skin, lung, pancreas, liver, prostate, and PBMC, predictive of disease development. Particularly, the ZD esophagus has a microRNA signature resembling human ESCC/tongue SCC miRNAomes with overexpression of miR-31 and miR-21 and downregulation of their respective tumor suppressor targets PPP2R2A and …

Phosphorylation Of Vasodilator-Stimulated Phosphoprotein Ser239 Suppresses Filopodia And Invadopodia In Colon Cancer., David S Zuzga, Joshua Pelta-Heller, Peng Li, Alessandro Bombonati, Scott A Waldman, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

In colorectal cancer, the antitumorigenic guanylyl cyclase C (GCC) signalome is defective reflecting ligand deprivation from downregulation of endogenous hormone expression. Although the proximal intracellular mediators of that signal transduction system, including cyclic guanosine monophosphate (cGMP) and cGMP-dependent protein kinase (PKG), are well characterized, the functional significance of its distal effectors remain vague. Dysregulation of ligand-dependent GCC signaling through vasodilator-stimulated phosphoprotein (VASP), an actin-binding protein implicated in membrane protrusion dynamics, drastically reduced cGMP-dependent VASP phosphorylation levels in colorectal tumors from patients. Restoration of cGMP-dependent VASP phosphorylation by GCC agonists suppressed the number and length of locomotory (filopodia) and invasive (invadopodia) …

Molecular Staging Individualizing Cancer Management, Alex Mejia, Stephanie Schulz, Terry Hyslop, David S. Weinberg, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Although the most important prognostic and predictive marker in colorectal cancer is tumor cells in lymph nodes, ∼30% of patients who are node-negative die from occult metastases. Molecular staging employing specific markers and sensitive detection technologies has emerged as a powerful platform to assess prognosis in node-negative colon cancer. Integrating molecular staging into algorithms that individualize patient management will require validation and the definition of relationships between occult tumor cells, prognosis, and responses to chemotherapy. J. Surg. Oncol. 2012; 105:468-474. © 2012 Wiley Periodicals, Inc.

Copyright © 2012 Wiley Periodicals, Inc.

A Glycosylated Recombinant Human Granulocyte Colony Stimulating Factor Produced In A Novel Protein Production System (Avi-014) In Healthy Subjects: A First-In Human, Single Dose, Controlled Study., Roslyn Varki, Ed Pequignot, Mark C Leavitt, Andres Ferber, Walter K Kraft

walter k Kraft

BACKGROUND: AVI-014 is an egg white-derived, recombinant, human granulocyte colony-stimulating factor (G-CSF). This healthy volunteer study is the first human investigation of AVI-014. METHODS: 24 male and female subjects received a single subcutaneous injection of AVI-014 at 4 or 8 mcg/kg. 16 control subjects received 4 or 8 mcg/kg of filgrastim (Neupogen, Amgen) in a partially blinded, parallel fashion. RESULTS: The Geometric Mean Ratio (GMR) (90% CI) of 4 mcg/kg AVI-014/filgrastim AUC(0-72 hr) was 1.00 (0.76, 1.31) and Cmax was 0.86 (0.66, 1.13). At the 8 mcg/kg dose, the AUC(0-72) GMR was 0.89 (0.69, 1.14) and Cmax was 0.76 (0.58, …