COMPOUND HETEROZYGOUS FH AND FDB: IDENTIFICATION OF A SICILIAN FAMILY HARBOURING THE FDB3531 MUTATION AND THE Y398X MUTATION OF THE LDL RECEPTOR GENE.

A NOVEL COMPOUND HETEROZYGOUS MUTATION OF THE LIPOPROTEIN LIPASE GENE IN A NEWBORN WITH CHYLOMICRONEMIA

Mechanisms of Raf-1 Kinase Inhibitor Protein Dysregulation in Triple-Negative Breast Cancers and Identification of Possible Novel Therapeutic Approaches for These Tumors

Triple-negative breast cancers (TNBCs) are a heterogenous group of breast cancers characterized by poor prognosis because they are not amenable to targeted therapies. We have taken into account that altered expression of Raf-1 kinase inhibitor protein (RKIP), a tumor and metastasis suppressor and a promoter of drug-induced apoptosis, is frequent in TNBCs and may be involved in their aggressive biology. Interestingly, the analysis of the possible mechanisms of RKIP downregulation in TNBCs permits the identification and recapitulation of different possible approaches, including epigenetic modulation, e.g., by DNA demethylating agents or histone deacetylase inhibition, and NF-κB inhibition. Th…

Analysis of pharmacologic approaches able to restore RKIP function in hepatocellular carcinoma

Two Italian kindreds carrying the Arg136--Ser mutation of the Apo E gene: development of premature and severe atherosclerosis in the presence of epsilon 2 as second allele.

Abstract Background and Aims: Type III hyperlipoproteinemia, or dysbetalipoproteinemia, is commonly associated with apolipoprotein E2 homozygosity (Cy Background and Aims: 12, Cy Background and Aims: 58). Apo E2-Christchurch (Arg136→Ser), a rare mutation of the Apo E gene, located in the receptor-binding domain of the protein, has been found to be associated in the vast majority of cases of dysbetalipoproteinemia. Methods and Results: This is the first report of two Italian kindreds carrying the Arg136→Ser mutation. One family is a four-generation kindred from Genoa (Liguria, Italy) with a high rate of mortality due to coronary artery disease: the proband was a 51-year-old woman with previo…

Frequent Alteration of the Yin Yang 1/Raf-1 Kinase Inhibitory Protein Ratio in Hepatocellular Carcinoma

The transcription factor Yin Yang 1 (YY1) can favor several aspects of tumorigenesis. In turn, Raf-1 Kinase Inhibitor Protein (RKIP) inhibits the oncogenic activities of MAPK and NF-κB pathways and promotes drug-induced apoptosis. Mutual influences between YY1 and RKIP may exist, and there are already separate evidences that relevant increases in YY1 and reductions in RKIP occur in hepatocellular carcinoma (HCC). However, the levels of the two factors have never been concomitantly examined in HCC. We evaluated by RT-PCR the mRNA levels of YY1, YY1AP, RKIP, and survivin in 35 clinical HCCs (91% HCV-related), in their adjacent cirrhotic tissues and in 6 healthy livers. Immunohistochemical ana…

A novel mutation in the Lipase Maturaction Factor 1 (LMF-1)gene responsible for severe hypertriglyceridemia

Hypertension and diabetes mellitus are associated with cardiovascular events in the elderly without cardiovascular disease. Results of a 15-year follow-up in a Mediterranean population

Abstract Background and aims Epidemiological prospective data on cardiovascular (CV) events in elderly subjects from Mediterranean populations are lacking. We aimed to investigate 15-year incidence of CV events and to evaluate the association with CV risk factors in an elderly Mediterranean population. Methods and results The population of a small Sicilian village were enrolled, visited and a blood sample was drawn at baseline. CV events were recorded in the 15 years of follow-up. From 1351 subjects (75% of the resident population); 315 were in the age range 65–85 years; 266 subjects free from CV disease were analysed. Seventy-seven CV events were recorded in 73 out of 266 subjects, with a …

VARIABLE PHENOTYPIC ESPRESSION IN A LIPID ABSORPTION DISORDER DUE TO A MOLECULAR DEFECT IN THE SARA2 GENE

Alteration of signaling pathways in hepatocellular carcinoma: identification of new pharmacological targets and possible prognosis markers.

CLINICAL AND MOLECULAR CHARACTERIZATION OF HYPERCHOLESTEROLEMIC SICILIAN FAMILIES AND DESCRIPTION OF 3 NOVEL MUTATIONS IN THE LDLR GENE

INTERACTION OF THE INTRACELLULAR DOMAIN OF THE LOW DENSITY LIPOPROTEIN (LDL) RECPTOR WITH METALLOTHIONEIN2 (MT2).

SEVERE MALABSORPTION AND DECREASED TRIGLYCERIDE RICH LIPOPROTEINS PRODUCTION IN A PROBAND CARRYING A MUTATION ENCODING FOR A TRUNCATED APOLIPOPROTEIN B100 VARIANT (APO B 34.8).

Analysis of UGT1A1*28 and DPYD*2A polymorphisms in Sicilians patients with metastatic colorectal cancer treated with Irinotecan and 5-fluorouracil.

Analysis of Possible Mechanisms Accounting for Raf-1 Kinase Inhibitor Protein Downregulation in Hepatocellular Carcinoma

Abstract Raf-1 kinase inhibitor protein (RKIP) is a tumor and metastasis suppressor that promotes drug-induced apoptosis in cancer cells. It is frequently downregulated, both at the mRNA and protein level, in hepatocellular carcinoma (HCC), but the mechanisms leading to this reduction are obscure. We sequenced the whole RKIP gene in three human HCC cell lines (HA22T/VGH, HepG2, and Hep3B), and in five clinical HCC samples, but could not find any gene variant that might account for their low RKIP levels. We also examined whether gene methylation may be responsible for the altered RKIP expression. No methylation of the RKIP gene was found in the tumor samples, while among the cell lines only …

Raf-1 Kinase Inhibitor Protein down-regulation in hepatocellular carcinoma: investigation of possible mechanisms

Possible mechanisms of Raf-1 Kinase Inhibitor Protein down-regulation in hepatocellular carcinoma

FAMILIAL LIGAND-DEFECTIVE APOLIPOPROTEIN B: IDENTIFICATION OF A FAMILY HARBOURING THE ARG3531CYS (FDB3531) OF THE APOB GENE

CEREBROTENDINOUS XANTHOMATOSIS: A SICILIAN FAMILY HARBOURING THE R362C MUTATION IN THE STEROL 27-HYDROXYLASE GENE

ΒETA ARRESTIN-2: A NEW “ACTOR” IN THE LDL-R ENDOCYTOSIS?

Epigenetic changes and nuclear factor-κB activation, but not microRNA-224, downregulate Raf-1 kinase inhibitor protein in triple-negative breast cancer SUM 159 cells

Raf-1 kinase inhibitor protein (RKIP) is a tumor suppressor and metastasis inhibitor, which enhances drug-induced apoptosis of cancer cells. Downregulation of RKIP may be significant in the biology of highly aggressive and drug-resistant tumors, for example triple-negative breast cancers (TNBCs). Potential causes for the low levels of RKIP expressed by SUM 159 TNBC cells were investigated in the present study. Bisulphite modification, methylation specific-polymerase chain reaction (PCR) and a TransAM NF-κB assay were performed and the results suggested that various mechanisms, including methylation of the gene promoter, histone deacetylation and nuclear factor-κB (NF-κB) activation, but not…

PREVALENCE OF METABOLIC SYNDROME IN A RURAL SICILIAN POPULATION AND RELATIONS WITH CLINICAL EVENTS: THE VENTIMIGLIA HEART PROJECT.

C-reactive protein but not soluble CD40 ligand and homocysteine is associated to common atherosclerotic risk factors in a cohort of coronary artery disease patients.

Abstract Objectives One third to one half of the variation in vascular disease occurrence remains unexplained by traditional risk factors. Since atherosclerosis may, in part, be an inflammatory disease, circulating factors related to inflammation may be predictors of cardiovascular disease. The aim of this study was to evaluate the association between common atherosclerotic risk factors and markers of inflammation. Design and methods Serum levels of soluble CD40 (sCD40L), high-sensitive C-reactive protein (hs-CRP) and homocysteine (Hcy) were measured in 251 patients selected from a series of 438 subjects affected by previous myocardial infarction, angina or other cardiovascular diseases. Re…

Restoration of Raf-1 Kinase Inhibitor Protein levels as a possible therapeutic approach in hepatocellular carcinoma.

PREVALENCE OF APOB VARIANTS IN A SAMPLE OF SUBJECTS WITH HYPOCHOLESTEROLEMIA