Pharmacy and Pharmaceutical Sciences Commons^™

Tumor Epithelial Cell Matrix Metalloproteinase 9 (Mmp-9) Is A Prognostic Marker In Colorectal Cancer, Ds Zuzga, Av Gibbons, P Li, Wj Lubbe, I Chervoneva, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Presented at American Association Cancer Research in 2008

Zuzga D.S., Gibbons A.V., Li P., Lubbe W.J., Chervoneva I., Pitari G.M. “Tumor epithelial cell MMP-9 is a prognostic marker in colorectal cancer”. In: American Association for Cancer Research Special Conference, Molecular Diagnostics in Cancer Therapeutic Development: Proceedings; 2008 Sept 22-25; Philadelphia, PA. Abstract A40.

Colorectal cancer is the second leading cause of cancer-related mortality indeveloped nations. Mortality from colon cancer largely reflects metastasis, thespread of the disease to distant sites. Early diagnosis of pre-metastatic diseaseand accurate stratification of patients with metastasis is pivotal to decreasemortality rates from colon cancer by effectively …

The Pharmacokinetics Of Taurolidine Metabolites In Healthy Volunteers., Li Gong, Howard E Greenberg, James L Perhach, Scott A Waldman, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Taurolidine is an experimental antibacterial and antiendotoxic compound whose clinical utility as an antitumor agent is being investigated in human clinical trials. Taurolidine in aqueous solution exists in equilibrium with taurultam. Taurultam is subsequently transformed to taurinamide. The pharmacokinetic profiles of these metabolites are not well established. In this study, 18 healthy volunteers were administered 5.0 g of taurolidine in 250 mL of 5% polyvinylpyrrolidone in water over 2, 1, or 0.5 hours by intravenous infusion in a parallel-group design. All subjects noted discomfort at the infusion site, although there were no serious adverse events. t(max) generally occurred at the …

Transgenic Avian-Derived Recombinant Human Interferon-Alpha2b (Avi-005) In Healthy Subjects: An Open-Label, Single-Dose, Controlled Study., T B Patel, E Pequignot, S H Parker, M C Leavitt, H E Greenberg, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND/AIMS: This study characterized the safety and pharmacological properties of AVI-005, a novel glycosylated recombinant human interferon-alpha2b produced from the egg whites of chickens transfected with human cDNA.

METHODS: 18 healthy volunteers received single subcutaneous rising doses (0.5, 1.66 or 5 million international units, MIU) of AVI-005. A randomized parallel comparator group of 10 subjects received 5 MIU of unglycosylated IFN-alpha2b (Intron A). The pharmacokinetic parameters t1/2, tmax, Cmax, AUC0-24h, Vd, and clearance were compared between AVI-005 and unglycosylated IFN-alpa2b.

RESULTS: At equipotent doses, AVI-005 had a larger AUC0-24h than the control interferon. Pharmacodynamic markers ofneopterin and beta2-microglobulin for the …

Nuovi Approcci Terapeutici Contro Il Cancro Del Colon, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

This presentation was given in Augusta (Siracusa, Italy) for the 2004 Paul Harris Fellow Award, Rotary Foundation of Rotary International. The lecture discusses the clinical significance of the GC-C pathway and its potential as a therapeutic target for colon cancer and metastatic tumors. It underscores the importance of the dysregulation of the GC-C pathway in promoting colorectal tumorigenesis and of dietary calcium in the GC-C-mediated chemoprevention.

Questa e’ la presentazione per il Premio 2004 Paul Harris Fellow del Rotary International (Augusta, Siracusa, Italia). La dissertazione illustra l’importante significato clinico della via moleculare regulata da GC-C e dai suoi ligandi (guanilina, …

Guanylyl Cyclase C Agonists Regulate Progression Through The Cell Cycle Of Human Colon Carcinoma Cells., Giovanni Mario Pitari, M D Di Guglielmo, J Park, S Schulz, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The effects of Escherichia coli heat-stable enterotoxin (ST) and uroguanylin were examined on the proliferation of T84 and Caco2 human colon carcinoma cells that express guanylyl cyclase C (GC-C) and SW480 human colon carcinoma cells that do not express this receptor. ST or uroguanylin inhibited proliferation of T84 and Caco2 cells, but not SW480 cells, in a concentration-dependent fashion, assessed by quantifying cell number, cell protein, and [(3)H]thymidine incorporation into DNA. These agonists did not inhibit proliferation by induction of apoptosis, assessed by TUNEL (terminal deoxynucleotidyl transferase-mediated dNTP-biotin nick end labeling of DNA fragments) assay and DNA laddering, or necrosis, …

Guanylyl Cyclase C (Gc-C) Inhibits Human Colon Carcinoma Cell Growth, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

This is the presentation given for the 2001 Presidential Trainee Young Investigator Award, American Society for Clinical Pharmacology and Therapeutics. An abstract of the presentation has been published in Clin. Pharmacol. Ther., 69(2):P62, 2001. The presentation illustrates the role of the intestinal GC-C receptor as a negative regulator of cell proliferation and cell cycle kinetics in colorectal cancer. It suggests that paracrine GC-C hormones guanylin/uroguanylin are physiological inducers of the proliferation-to-differentiation transition along the intestinal crypt-villus axis. Importantly, the bacterial enterotoxin ST, a potent exogenous GC-C agonist, is offered as a potential cytostatic agent for the prevention and treatment of …