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RESEARCH PROGRAM
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Research Units
Similar research programs:
- 1 - DISSECTION OF THE MOLECULAR MECHANISMS OF CARCINOGENESIS: IDENTIFICATION OF NOVEL TARGETS FOR DIAGNOSIS AND THERAPY
- 2 - Molecular markers in oral squamous cell carcinoma and their possible use in early diagnosis, prognosis and drug therapy.
- 3 - Assessment of molecular alterations and gene expression profiles in colorectal and pancreatic tumor: identification of possible prognostic indicators and molecular therapeutic targets in eicosanoid and cannabinoid systems
- 4 - THE ROLE OF DENDRITIC CELLS, SEX STEROID HORMONES AND CITOKINES IN THE NATURAL HISTORY OF CHRONIC HEPATIC DISEASES
- 5 - Studies on the molecular mechanisms of abnormal parathyroid proliferation and function, and identification and clinical use of molecular markers of sporadic and familial parathyroid cancer. New insights on the prevalence of skeletal, neuropsychological and metabolic manifestations of primary hyperparathyroidism, their relationship with calcium sensing receptor polymorphisms and course after parathyroidectomy.
- 6 - Control mechanisms of erythropoiesis and congenital and familial polycythemias: role of oxygen-sensing pathways
- 7 - Molecular analysis of erythropoiesis: Post-genomic and functional approach
- 8 - Structural basis of the action mechanism of oncogenic and oncosuppressor factors in nervous system tumors: design of new molecules for therapeutical applications
- 9 - Medilloblastoma: molecular pathways of neoplastic development and progression to identify novel therapeutic approaches
- 10 - Breast and prostate cancer progression: new hormone mechanisms and therapeutical approaches.
Scientific and education field classification
International Patent Classification
- CHEMISTRY; METALLURGY
- BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF (biocides, pest repellants or attractants, or plant growth regulators, containing micro-organisms, viruses, microbial fungi, enzymes, fermentates or substances produced by or extracted from micro-organisms or animal material A01N63/00; food compositions A21, A23; medicinal preparations A61K; chemical aspects of, or use of materials for, bandages, dressings, absorbent pads or surgical articles A61L; fertilisers C05); PROPAGATING, PRESERVING OR MAINTAINING MICRO-ORGANISMS (preservation of living parts of humans or animals A01N1/02); MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (micro-biological testing media C12Q)
- BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- HUMAN NECESSITIES
- MEDICAL OR VETERINARY SCIENCE; HYGIENE
- PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES (bringing into special physical form A61J [N: mechanical aspects]; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; compounds per se C01, C07, C08, C12N; soap compositions C11D; micro-organisms per se C12N) [C0203]
- MEDICAL OR VETERINARY SCIENCE; HYGIENE
Geographical classification
- Region: Sicilia
Keywords
HEPATOCELLULAR CARCINOMA; DRUG RESISTANCE; APOPTOSIS; INHIBITORY OF APOPTOSIS PROTEINS; CYCLOOXYGENASES; AROMATASE; P53, P63, P73; TRANSCRIPTION FACTORS; GROWTH FACTORSDevelopment and progression of hepatocellular carcinoma: molecular mechanisms and therapeutic implications.
Università degli Studi di PalermoAbstract
Hepatocellular carcinoma (HCC) has been previously considered a rare tumor, but its incidence has considerably risen during the last years with alarming data for the mediterranean countries, including Italy. The actual understanding of the etiology and epidemiology of HCC let us forecast a further increase of HCC in Europe.HCC prognosis remains unfavorable for the large portion of patients affected by advanced disease, which is deadly aggressive and does not respond to currently available therapies. This emphasizes the need of developing new strategies for the prevention and treatment of the disease; however, a major obstacle in this sense is represented by the incomplete definition of the molecular characteristics of HCC.
Our aim is to thoroughly examine in clinical HCC and in its laboratory models the expression and regulation of a series of factors and pathways, which emerge for their involvement in tumor cell growth and drug resistance, but whose importance is not well defined for HCC yet. These factors are:
1-The Inhibitory of Apotosis Proteins (IAPs) and their splice variants. The research is aimed to better characterize their expression pattern in HCC and in the predisposing pathologies, with relationship to the clinical, histological and prognostic data and to the etiology. We will examine the importance of different pathways (NF-kB, STATs, AP-1, PI3K/Akt, Cdk and aromatase) in their regulation, by treating with specific inhibitors HCC cells and >>>
Principal Investigator
Natale D'ALESSANDRO Università degli Studi di PALERMOResearch Objectives
Hepatocellular carcinoma (HCC) has been previously considered a rare tumor, but its incidence has considerably risen during the last years with alarming data for the mediterranean countries, including Italy. This likely reflects the stong impact that the ambiental factors have on the pathogenesis of the tumor. There is in fact a clear relationship between persistent infections fron hepatitis viruses (HBV and HCV) or, at least in some areas, chemical carcinogens and tumor formation. At present, HCC is one of the ten more frequent malignant disease in the world. The actual understanding of the natural history of HCV chronic infections (Pagliaro L. et al. Natural history of chronic hepatitis C. Ital G Gastroenterol Hepatol 31, 28-44, 1999) and the biological and epidemiological consequences of, either manifest or occult, co-infections from HBV in HCC chronic hepatitis let us forecast a further increase of HCC in Europe.Nonetheless, in spite of the fact that HCC is a quite frequent disease, only a limited percentage of the patients with chronic viral hepatitis and cirrhosis undergo malignant transformation in a given time lap. This suggest the intervention of-co-oncogenic factors in the multistep process of in vivo transformation: one of the possibilities is that, to manifest the oncogenic potential, the viral proteins may require the activation of pro-proliferative and anti-apoptotic oncogenes or/and the inactivation of genes involved in the in vivo execution of >>>
Timescale
24 monthsNational and international background
IAP (INHIBITORY OF APOPTOSIS PROTEINS)There is a large evidence that an imbalance between unrestrained cell proliferation and low ability to perform apoptosis, either spontaneous or induced from pharmacologic or immunologic agents, is a critical feature of hepatocellular carcinoma (HCC). A major factor which can determine such behavior is the re- or over-expression in HCC of inhibitors of apoptosis like the proteins of the Bcl-2 family and, as also shown by us, the IAPs (1-5).
Human IAPs include NAIP, XIAP, c-IAP-1, c-IAP-2, survivin, livin-alpha and their alternative splice variants (6, 7). They are endowed with a remarkable ability to block apoptosis induced by a wide spectrum of non-related triggers, both through inhibition of caspases and by other mechanisms (8, 9). IAPs exhibit other functions; for example, survivin is required for the execution of cell division and chromosomal segregation. Like the other IAPs, survivin in much more expressed in fetal and tumor tisues than in normal tissues. In tumors like melanoma, the circulating levels of survivin correlate to parameters such as aggressiveness of the disease and survival (10), but nothing is known about the possible correlation between circulating survivin and 1) the expression levels of survivin and the other IAPs in HCC; 2) the clinical-prognostic behavior of HCC; 3) the various stages preceding HCC development (chronic hepatitis, cirrhosis) and 4) the etiology (HCV, HBV, alcohol, others).
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