Giovanni Gaudino, PhD
Cancer Biology Program
University of Hawaii Cancer Center
- PhD, Biochemistry
University of Torino, Italy
- MS, Biological Sciences
University of Torino, Italy
For the past decade, Dr. Gaudino's research has focused on the molecular carcinogenesis of malignant mesothelioma. Malignant mesothelioma is a very aggressive tumor, resistant to most anticancer therapies and with a median survival rate of about twelve months from diagnosis. Major findings of his research include:i) the identification of autocrine loops for receptor tyrosine kinases and their ligands responsible for mesothelial cell transformation; ii) the demonstration that constitutive Akt activity drives mesothelial cell transformation after exposure to asbestos or asbestos-like (erionite) fibers, iii) the study of the role of constitutively activated Akt and NF-╬║B pathways in mesothelioma cell survival and chemoresistance; and iv) the first microarray cross-evaluation of microRNA (miRNA) and mRNA expression in mesothelioma cells and tissues, with diagnostic and prognostic implications.
These results have led to the following promising therapeutic approaches: 1) combined treatment of the tyrosine kinase inhibitor Imatinib mesylate (Gleevec┬«) with gemcitabine to induce mesothelioma cell death in vitro and tumor remission in vivo (currently tested in phase II clinical trials); 2) local administration of taurolidine on mesothelioma, to induce cancer cell apoptosis, mediated by oxidative stress and Akt inactivation; 3) treatment with the proteasome inhibitor bortezomib (PS-341, Velcade┬«) to block mesothelioma growth, via inhibition of NF-╬║B and/or mitochondrial mediated cell death (currently tested in phase II clinical trials);and 4) design of antagomiRs targeting two specific miRNAs (hsa-miR17-5p and hsa-miR30c) identified as associated with better survival of mesothelioma patients of the more aggressive sarcomatoid subtype.
Most recently, he is studying the tissue tropism of SV40 transformation of human cells related to the role of the viral regulatory region and of c-Met and Notch-1 cellular oncogenes. He is investigating the identification of critical pathways elicited by receptor tyrosine kinases as part of the process of carcinogenesis induced by SV40 infection of mesothelial cells and astrocytes. Based on prior findings, he is testing the hypothesis that, in addition to previously studied SV40 Tag activities, SV40 infection of human cells and their transformation requires the expression of functional p53 in target cells for productive infection. Additionally, he is studying how the expression of p53 and the consequent formation of Tag-p53-pRb multiprotein complexes will possibly activate Receptor Tyrosine Kinases (RTKs) and downstream signaling that stimulates cell proliferation and malignant transformation in tissue culture and in vivo, by using several mice models. He also continues to investigate the mechanisms of mesothelial carcinogenesis by asbestos and asbestos-like fibers and the consequence on the cellular signal transduction leading to expression of genes involved in cell proliferation, motility and invasiveness.
- Busacca S, Germano S, De Cecco L, Rinaldi M, Comoglio F, Favero F, Murer B, Mutti L, Pierotti M, Gaudino G. - MicroRNA Signature of Malignant Mesothelioma with Potential Diagnostic and Prognostic Implications. Am J respir Cell Mol Biol, 2010, 42:312-319.
- Aceto N, Bertino P, Barbone D, Tassi G, Manzo L, Porta C, Mutti L, Gaudino G. - Taurolidine and oxidative stress: a rationale for local treatment of mesothelioma. Eur Respir J., 2009, 34:1399-1407.
- Bertino P, Piccardi F, Porta C, Favoni R, Cilli M, Mutti L, Gaudino G. - Imatinib mesylate enhances therapeutical effects of gemcitabine in human malignant mesothelioma xenografts, Clinical Cancer Research, 2008, 14: 541-548.
- Barbone D, Yang TM, Morgan JR, Gaudino G, Broaddus, VC. - mTOR contributes to the acquired apoptotic resistance of human mesothelioma multicellular spheroids. J Biol Chem, 2008, 283: 13021-13030.
Publication list via PubMed
- G. Gaudino, Principal Investigator
Hawaii Community Foundation
"Role of tumor necrosis factor (TNF) signaling in chrysotile-asbestos induced mesothelioma"
September 01, 2010-September 01, 2012