DIRECTION

Daniel E. Gomez, M.D., Ph.D. (Director). Professor and Director of the Doctoral Program in Basic and Applied Sciences, Quilmes National University. Researcher, CONICET. Active Member of the American Association for Cancer Research. Email: degomez@unq.edu.ar

Daniel F. Alonso, M.D., Ph.D. (Codirector). Professor and Director of Biotechnology Career, Quilmes National University. Researcher, CONICET. Active Member of the American Association for Cancer Research. Email: dfalonso@unq.edu.ar

 

TEAM OF RESEARCHERS AND TECHNICIANS

Hernan G. Farina, Biotechnologist, PhD. Adjunct Professor, Quilmes National University. Researcher of Romikin/UNQ R&D contract.

Mariano R. Gabri, Biologist, PhD. Instructor Professor, Quilmes National University. Researcher of ELEA/UNQ R&D contract.

Pablo Lorenzano Menna, Microbiologist/Biotechnologist. Research Fellow of CIC.

Giselle V. Ripoll, Biotechnologist, Research fellow of CONICET.

Santiago Giron, Biotechnologist, Research Fellow of ELEA/UNQ R&D contract.

Romina Parera, undergraduate student of Biotechnology.

Laura Otero, undergraduate student of Biotechnology, Technician.

Valeria Vazquez, undergraduate student of Biotechnology, Technician.

Victoria Romero, Animal Care Technician.

 

TECHNOLOGY TRANSFER ACTIVITIES

Alberto Diaz, Chemist, Professor and Director of Technology Transfer, Quilmes National University. Email: albdiaz@unq.edu.ar

 

FORMER TEAM MEMBERS AND CURRENT AFFILIATIONS

Mariana De Lorenzo. Biologist, PhD. Weill Medical College of Cornell University, Department of Medicine, New York, USA.

Agueda Tejera. Biologist, PhD. Centro Nacional de Investigaciones Oncológicas, Grupo de Telómeros y Telomerasa, Madrid, España.

Debora Bublik. Biologist, Doctoral Fellow SISSA. Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie, Trieste, Italy.

Leticia Peche. Biotechnologist, Doctoral Fellow SISSA. Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie, Trieste, Italy.

Monica Pomies. Biotechnologist. Biocientifica SA, Buenos Aires, Argentina.

 

Research & Development Program

Biology of invasion and metastasis: characterization and development of novel antitumor strategies

 

The aim of the Program is to investigate cellular and molecular mechanisms of invasion and metastasis and translate the results to the management of human cancer. We are analyzing the effect of a protease inhibitor on angiogenesis, the modulation of tumor behavior by intracellular signaling molecules, the development of cancer vaccines and the antitumor properties of drugs of recognized clinical use -such as desmopressin, AZT and lovastatin- and novel synthetic compounds.

 

Ongoing projects for the period 2003-2007:

ü       Mechanisms of angiogenesis and metastasis in syngeneic and transgenic murine models.

ü       Modulation of tumor aggressiveness focusing on molecular targets of intracellular signaling.

ü       Preclinical research and development of synthetic antitumor peptides.

ü       Preclinical research and development of DDAVP and antimetastatic analogs.

ü       Preclinical research and development of cancer vaccines.

ü       Design of molecular diagnostic systems for residual cancer cells.

 

Publications

 

2004:

·         Antitumor effect of a novel proapoptotic peptide that impairs the phospholylation by the protein kinase 2 (casein kinase 2). S.E. Perea, O. Reyes, Y. Puchades, O. Mendoza, N. Santiago, I. Torrens, A. Santos, R. Silva, B. Acevedo, E. Lopez, V. Falcon, D.F. Alonso. Cancer Research 64: 7127-7129, 2004.

·         Potential application of desmopressin as a perioperative adjuvant in cancer surgery. Biological effects, antitumor properties and clinical usefulness.  D.E. Gomez, G.V. Ripoll, S. Giron, D.F. Alonso. Cancer Therapy 2: 279-290, 2004.

·         Long-term exposure to elevated levels of circulating TIMP-1 but not mammary TIMP-1 suppresses growth of mammary carcinomas in transgenic mice. M. Yamazaki, T. Akahane, T. Buck, H. Yoshiji, D.E. Gomez, D.J. Schoeffner, E. Okajima, S.R. Harris, O.R. Bunce, S.S. Thorgeirsson, Thorgeirsson UP. Carcinogenesis 25: 1735-1746, 2004.

·         7A7 MAb: A new tool for the preclinical evaluation of EGFr-based therapies. G. Garrido, B. Sanchez, H.M. Rodriguez, P. Lorenzano Menna, D.F. Alonso, L.E. Fernandez. Hybridoma and Hybridomics 23: 168-175, 2004.

·         Role of protein kinase C-dependent signaling pathways in the antiangiogenic properties of nafoxidine. M.S. De Lorenzo, H.G. Farina, D.F. Alonso, D.E. Gomez. Anticancer Research 24: 1737-1743, 2004.

 

2003:

·         Altered tumor angiogenesis and metastasis of B16 melanoma in transgenic mice overexpressing tissue inhibitor of metalloproteinases-1. M.S. De Lorenzo, G.V. Ripoll, H. Yoshiji, M. Yamazaki, U.P. Thorgeirsson, D.F. Alonso, D.E. Gomez. In Vivo, 17: 45-50, 2003.

·         Inhibition of aggressiveness of metastatic mouse mammary carcinoma cells by the b2-chimaerin GAP domain. P. Lorenzano Menna, G. Skilton, F. Coluccio Leskow, D.F. Alonso, D.E. Gomez, M.G. Kazanietz. Cancer Research, 63: 2284-2291, 2003.

·         Ganglioside-based vaccines and anti-idiotype antibodies for active immunotherapy against cancer. L.E. Fernandez, D.F. Alonso, D.E. Gomez, A.M. Vazquez. Expert Review of Vaccines 2: 817-823, 2003.

 

2002:

·         Cancer Vaccines: An update with special focus on ganglioside antigens. R.J. Bitton, M.D. Guthmann, M.R. Gabri, Ariel J.L. Carnero, D.F. Alonso, L. Fainboim, D.E. Gomez. Oncology Reports, 9: 267-276, 2002.

·         Desmopressin inhibits lung and lymph node metastasis in a mouse mammary carcinoma model of surgical manipulation. S Giron, AM Tejera, GV Ripoll, DE Gomez, DF Alonso. Journal of Surgical Oncology, 81: 38-44, 2002.

·         Lovastatin alters cytoskeleton organization and inhibits experimental metastasis of mammary carcinoma cells. HG Farina, DR Bublik, DF Alonso, DE Gomez. Clinical & Experimental Metastasis, 19:551-559, 2002.

·         Rol of cell surface GM3 ganglioside and sialic acid in the antitumor activity of a GM3-based vaccine in the murine B16 melanoma model. M.R. Gabri, G.V. Ripoll, D.F. Alonso, D.E. Gomez. Journal of Cancer Research and Clinical Oncology, 128: 669-677, 2002.

 

2001:

·         Chronic in vitro exposure to 3’-azido-2’,3’-dideoxythymide induces senescence and apoptosis and reduces tumorigenicity of metastatic mouse mammary tumor cells. A.M. Tejera, D.F. Alonso, D.E. Gomez, O.A. Olivero. Breast Cancer Research and Treatment, 65: 93-99, 2001.

·         Genotoxicity of antiretroviral nucleoside analog drug combinations. O.A. Olivero O.A., A.M. Tejera, J.J. Fernandez, B.L. Walker, M.C. Poirier. Mutation Research 483 (S130): 10-15, 2001.

·         Antitumor activity of a Solanum tuberosum extract against mammary carcinoma cells. M.S. De Lorenzo, P. Lorenzano Menna, D.F. Alonso and D.E. Gomez. Planta Medica, 67: 164-166, 2001.

·         A purified GM3 ganglioside conjugated vaccine induces specific, adjuvant-dependent, and non-transient antitumor activity against B16 mouse melanoma in vitro and in vivo. A. Carr, Z. Mazorra, D.F. Alonso, C. Mesa, O. Valiente, D.E. Gomez, R. Perez and L.E. Fernandez. Melanoma Research, 11: 219-227, 2001.

·         The copper-chelating agent, trientine, suppresses tumor development and angiogenesis in the murine hepatocellular carcinoma cells. J. Yoshii, H. Yoshiji, S. Kuriyama, Y. Ikenaka, R. Noguchi, H. Okuda, H. Tsujinoue, T. Nakatani, H. Kishida, D. Nakae, D.E. Gomez, M.S. De Lorenzo, A.T. Tejera and H. Fukui. International Journal of Cancer, 94: 768-773, 2001.

 

2000:

·         Nafoxidine modulates expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in endothelial cells. M.S. De Lorenzo, D.F. Alonso, D.E. Gomez. Anticancer Research, 20: 395-400, 2000.

·         Antitumor properties of an anti-idiotypic monoclonal antibody in relation to N-glycolyl-containing gangliosides. A.M. Vázquez, M.R. Gabri, A.M. Hernández, D.F. Alonso, I. Beausoleil, D.E. Gomez, R.Pérez. Oncology Reports, 7: 751-756, 2000.

·         Tissue inhibitor of metalloproteinases-1 promotes lliver fibrosis development in a transgenic mouse model. H. Yoshiji, S. Kuriyama, Y. Miyamoto, U.P. Thorgeirsson, D.E. Gomez, M. Kawata, J. Yoshii, Y. Ikenaka, R. Noguchi, H. Tsujinoue, T. Nakatani, S.S. Thorgeirsson, H. Fukui. Hepatology, 32: 1248-1254, 2000.

 

1999:

·         A novel hydrophobized GM3 ganglioside/Neisseria meningitidis outer-membrane-protein complex vaccine induces tumor protection in B16 murine melanoma. D.F. Alonso, M.R. Gabri, M.D. Guthmann, L. Fainboim, D.E. Gomez. International Journal of Oncology, 15: 59-66, 1999.

·         Deregulation of the signaling pathways controlling urokinase production. Its relationship with the invasive phenotype. J.A. Aguirre Ghiso, D.F. Alonso, E.F. Farías, D.E. Gomez, E. Bal de Kier Joffé. European Journal of Biochemistry, 263: 295-304, 1999.

·         Expression of collagenases (MMP-1, MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) in schistosomal portal fibrosis. D.E. Gomez, M.S. De Lorenzo, D.F. Alonso, Z.A. Andrade. American Journal of Tropical Medicine and Hygiene, 61: 9-13, 1999.

·         Modulation of urokinase-type plasminogen activator and metalloproteinase activities in cultured mouse mammary carcinoma cells: enhancement by paclitaxel and inhibition by nocodazole. D.F. Alonso, H.G. Farina, C. Arregui, M.A. Aon, D.E. Gomez. International Journal of Cancer, 83: 242-246, 1999.

·         Antimetastatic effect of desmopressin in a mouse mammary tumor model. D.F. Alonso, G. Skilton, E.F. Farías, E. Bal de Kier Joffé, D.E. Gomez. Breast Cancer Research and Treatment, 57: 271-275, 1999.

·         The role of protein kinase C and novel phorbol ester receptors in tumor cell invasion and metastasis. D.E. Gomez, G. Skilton, D.F. Alonso, M.G. Kazanietz. Oncology Reports, 6: 1363-1370, 1999.

·         Role of tumor-derived granulocyte-macrophage colony-stimulating factor in mice bearing a highly invasive and metastatic mammary carcinoma. M.R. Gabri, P. Lorenzano Menna, A.M. Scursoni, D.E. Gomez, D.F. Alonso. Pathobiology, 67: 180-185, 1999.

 

1996-1998:

·         Inhibition of fibrinolysis by a synthetic urokinase inhibitor enhances lung colonization of metastatic murine mammary tumor cells. D.F. Alonso, G.E. Bertolesi, E.F. Farías, D.E. Gomez, E. Bal de Kier Joffé. Oncology Reports, 3: 1055-1058, 1996.

·         Modulation of growth and urokinase secretion by vasopressin and closely related nonapeptides in metastatic mouse mammary tumor cells. D.F. Alonso, G. Skilton, H.G. Farina, M.S. De Lorenzo, D.E. Gomez. International Journal of Oncology, 10: 375-379, 1997.

·         Atypical cilia in testicular cells from normal rats. R. Ponzio, D.F. Alonso, D.E. Gomez. Journal of Submicroscopic Cytology and Pathology, 29: 313-316, 1997.

·         Tissue inhibitors of metalloproteinases; structure, regulation and biological functions. D.E. Gomez, D.F. Alonso, H. Yoshiji, U.P. Thorgeirsson. European Journal of Cell Biology, 74: 111-122, 1997.

·         Antisense oligonucleotides strategies in cancer. D.E. Gomez, D.F. Alonso, A.M. Irribarren. South-American Journal of Cancer, 1: 180-190, 1997.

·         Insight into the profibrinolytic activity of heparin: effects on the activation of plasminogen mediated by urokinase. G.E. Bertolesi, E.F. Farías, D.F. Alonso, E. Bal de Kier Joffé, L. Lauría de Cidre, A.M. Eiján. Blood Coagulation and Fibrinolysis, 8: 403-410, 1997.

·         Fibrin formation induced by tumor procoagulants enhances urokinase activity produced by mammary carcinoma cells. D.F. Alonso, M.S. De Lorenzo, A.M. Tejera, D.E. Gomez. Oncology Reports, 5: 209-212, 1998.

·         Irreversible telomere shortening by 3’-azido2’,3’-dideoxythymidine (AZT) treatment. D.E. Gomez, A.M. Tejera, O.A. Olivero. Biochemical and Biophysical Research Communications, 246: 107-110, 1998.

·         Reduction of mouse mammary tumor formation and metastasis by lovastatin, an inhibitor of mevalonate pathway of cholesterol synthesis. D.F. Alonso, H.G. Farina, G. Skilton, M.R. Gabri, M.S. De Lorenzo, D.E. Gomez. Breast Cancer Research and Treatment, 50: 83-93, 1998.

·         Histopathological findings in a highly invasive mouse mammary carcinoma transfected with human tisssue inhibitor of metalloproteinases-1. D.F. Alonso, G. Skilton, M.S. De Lorenzo, A.M. Scursoni, H. Yoshiji and D.E. Gomez. Oncology Reports, 5:1083-1087, 1998.

·         Inhibition of mammary tumor cell adhesion, migration, and invasion by the selective synthetic urokinase inhibitor B428. D.F. Alonso, A.M. Tejera, E.F. Farías, E. Bal de Kier Joffé, D.E. Gomez. Anticancer Research, 18: 4499-4504, 1998.

 

Books

·         Introduction to Molecular Oncology. D.E. Gomez and D.F. Alonso. Quilmes National University Editions. Buenos Aires, 1998. (in spanish)

·         The challenge of the crab - Advances in the knowledge, prevention and treatment of cancer. D.F. Alonso. Siglo XXI & Quilmes National University Editions, Buenos Aires, 2002. (in spanish)

·         DNA, 50 years are nothing. A. Diaz and D. Golombek (comps.). Siglo XXI Publishing, Buenos Aires, 2004. (in spanish)

 

Funding Sources

·         Priority R&D Grant Program, Quilmes National University

·         Commission of Scientific Research, Province of Buenos Aires (CIC)

·         National Council for Scientific and Technical Research (CONICET)

·         National Agency of Scientific and Technological Promotion (ANPCYT)

·         National Health Ministry

·         Antorchas Foundation

·         Third World Academy of Sciences (TWAS)

·         International Foundation for Sciences (IFS)

·         National Institutes of Health, Fogarty International Research Collaboration Award (FIRCA)

·         Panamerican Health Organization (PHO)

·         United Nations for Education, Science and Culture Organization (UNESCO)

·         ELEA Laboratories/Recom-Bio

·         Romikin/Biorec

·         Genesica

 

Inventions and Patents

·         Method of inhibiting metastatic dissemination using desmopressin. D.F. Alonso, D.E. Gomez, G. Skilton, E.F. Farías, E. Bal de Kier Joffé. Granted to Quilmes National University in USA (6693082). 02-2004

·         Analogs of 1 deamine-8-D-arginine vasopressin. D.E. Gomez, D.F. Alonso, G.V. Ripoll, S. Girón. Filled by Quilmes National University Transfer Office, New York (PCT/US2003/041166; WO2004/060389). 12-2003

·         Análogos de 1-desamino-8-D-arginina vasopresina. D.E. Gomez, D.F. Alonso, G.V. Ripoll, S. Girón. Filled by Quilmes National University in Argentina (ARP020105123). 12-2002

·         Use of desmopressin in the preparation of a metastatic dissemination-inhibitor medicament during cancer surgery. D.F. Alonso, D.E. Gomez, G. Skilton, E.F. Farías, E. Bal de Kier Joffé. Filled by Quilmes National University in the European Union (EP1031352) and Hong Kong (HKP0120473). 12-2000

Uso de desmopresina para la preparación de un medicamento inhibidor de la diseminación metastásica durante la cirugía del cáncer, composición farmacéutica, procedimiento de preparación de dicha composición y método de tratamiento. D.F. Alonso, D.E. Gomez, G. Skilton, E.F. Farías, E. Bal de Kier Joffé. Filled by Quilmes National University in Argentina (ARP990100736). 12-1999