Phenotype characterization of human melanoma cells resistant to dabrafenib.

In the present study, the phenotype of melanoma cells resistant to dabrafenib (a B-RAF inhibitor) was investigated, to shed more light on melanoma resistance to B-RAF inhibition. Melanoma cells resistant to dabrafenib were generated using 3 different cell lines, A375, 397 and 624.38, all carrying B-RAFV600E, and they were characterized by cytofluorometric analysis, Ion Torrent technology, immunofluorescence and biochemistry.

Lead exposure and plasma mRNA expression in ERBB2 gene.

Epidemiologic data for carcinogenicity in those exposed to lead (Pb) suggests relations with cancers although the totality of the evidence is inconsistent. Alterations in the expression of ERBB receptors have been studied during the development and malignant transformation of different kinds of human tumors where they induce proliferation, angiogenesis and metastasis generation. Relevant clinical data demonstrate the role of ERBB2 receptors in the development and malignancy of human cancers.

MMP-9 overexpression is associated with intragenic hypermethylation of MMP9 gene in melanoma.

Tumor spreading is associated with the degradation of extracellular matrix proteins, mediated by the overexpression of matrix metalloproteinase 9 (MMP-9). Although, such overexpression was linked to epigenetic promoter methylation, the role of intragenic methylation was not clarified yet. Melanoma was used as tumor model to investigate the relationship between the DNA intragenic methylation ofMMP9 gene and MMP-9 overexpression at transcriptional and protein levels.

c-Myc modulation: a key role in melanoma drug response.

Understanding molecular mechanisms involved in melanoma resistance to drugs is a big challenge. Experimental evidences suggested a correlation between mutational status in B-RAF and melanoma cell susceptibility to drugs, such as paclitaxel, doxorubicin and temozolomide, which generate an accumulation of hydrogen peroxide (H2O2) in the cells. We investigated the survival phenotype and the protein level of c-myc, a B-RAF target molecule, in melanoma cells, carrying a different mutational status in B-RAF, upon paclitaxel, doxorubicin and H2O2 treatment.

Ran signaling in melanoma: implications for the development of alternative therapeutic strategies.

We performed a comparative study between two human metastatic melanoma cell lines (A375 and 526), and melanocytes (FOM78) by gene expression profiling and pathway analysis, using Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) software. Genes involved in Ran signaling were significantly over-represented (p ≤ 0.001) and up-regulated in melanoma cells.

Molecular screening in Sicilian families with hereditary non-poliposis colorectal cancer (H.N.P.C.C.) syndrome: identification of a novel mutation in MSH2 gene.

HNPCC is an autosomal inherited cancer syndrome characterized by germinal and somatic mutations of DNA mismatch repair (MMR) genes. The inherited mutation in one allele together with an acquired defect in the other allele of an MMR gene leads to accelerate tumor progression. In this study we analyzed a cohort of 11 subjects belonging to four Sicilian families with HNPCC suspected by molecular analysis of coding regions of hMSH2 (NC_000002) and hMLH1 (NC_000003) genes.

Molecular analysis of the APC gene in Sicilian patients with familial adenomatous polyposis (F.A.P.).

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited syndrome, caused by germline mutations in the adenomatous polyposis coli (APC) suppressor gene. Patients with colorectal polyps are more likely to develop a malignant condition with poor prognosis. Typical FAP is characterized by hundreds to thousands of colorectal adenomatous polyps and by several extra-colonic manifestations; an attenuated form of polyposis (AFAP), presenting less than 100 adenomas and later onset, has been reported.

Emerging targeted therapies for melanoma treatment (review).

Cutaneous melanoma is an aggressive cancer with a poor prognosis for patients with advanced disease. The identification of several key molecular pathways implicated in the pathogenesis of melanoma has led to the development of novel therapies for this devastating disease. In melanoma, both the Ras/Raf/MEK/ERK (MAPK) and the PI3K/AKT (AKT) signalling pathways are constitutively activated through multiple mechanisms.

Immunolocalization of heparin-binding EGF-like growth factor (HB-EGF) as a possible immunotarget in diagnosis of some soft tissue sarcomas.

Heparin-binding EGF-like growth factor (HB-EGF), a member of the family of epidermal growth factors (EGFs), is involved in several biological processes and tumor formation. Several lines of evidence show that HB-EGF plays a key role in the acquisition of malignant phenotype. Studies show that HB-EGF expression is essential in oncogenesis of cancer-derived cell lines.

Therapeutic potential of nitric oxide-modified drugs in colon cancer cells.

We have examined the influence of the nitric oxide (NO)-modified anti-inflammatory drug (S,R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid (VGX-1027) named GIT-27NO or the NO-modified antiviral drug saquinavir (Saq) named Saq-NO on two colon cancer cell lines, mouse CT26CL25 and human HCT116. The effects of the drugs on cell viability, apoptosis, proliferation, and metastatic potential were analyzed. The release of NO and oxygen and nitrogen species was also determined.

The tumor microenvironment in hepatocellular carcinoma (review).

The tumor microenvironment has been largely studied as a dynamic system orchestrated by inflammatory cells, including cancer cells, stroma as well as the extracellular matrix. It is useful to describe and predict the phenotypic characteristics of cancer. Furthermore, a better understanding of its interplay with the various aspects of the tumor cells may be utilized for the discovery of novel molecular targets.

Gene alterations in the PI3K/PTEN/AKT pathway as a mechanism of drug-resistance (review).

The most common therapeutic approach for many cancers is chemotherapy. However, many patients relapse after treatment due to the development of chemoresistance. Recently, targeted therapies represent novel approaches to destroy cancer cells.

Characterization of human melanoma cell lines and melanocytes by proteome analysis.

We have analyzed the proteomes of two human melanoma cell lines (A375 and 526), and of the human melanocytes, (FOM 78), by two-dimensional electrophoresis (2D-PAGE) and liquid chromatography - tandem mass spectrometry (LC-MS/MS). Our comparative proteomic analysis revealed that six proteins were over-expressed in both melanoma cell lines as compared to melanocytes: galectin-1, inosine-5'-monophosphate dehydrogenase 2, serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform, protein DJ-1, cyclophilin A and cofilin-1. We show, for the first time, that only specific isoforms of these molecules are over-expressed in melanoma.

Decreased expression of GRAF1/OPHN-1-L in the X-linked alpha thalassemia mental retardation syndrome.

Background: ATRX is a severe X-linked disorder characterized by mental retardation, facial dysmorphism, urogenital abnormalities and alpha-thalassemia. The disease is caused by mutations in ATRX gene, which encodes a protein belonging to the SWI/SNF DNA helicase family, a group of proteins involved in the regulation of gene transcription at the chromatin level. In order to identify specific genes involved in the pathogenesis of the disease, we compared, by cDNA microarray, the expression levels of approximately 8500 transcripts between ATRX and normal males of comparable age.

Distribution of p53, GST, and MTHFR polymorphisms and risk of cervical intraepithelial lesions in sicily.

Objectives: Host factors, including genetic polymorphisms, may explain some of the individual differences in cervical cancer occurrence, and susceptibility information may be useful to address effective and specific preventive strategies for different countries. The purpose of the present study was to investigate the role of p53 codon 72, glutathione S-transferase class mu (GSTM1), glutathione S-transferase class theta (GSTT1), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms on the risk for infection and/or of cervical intraepithelial lesions in women attending a colposcopy service in Catania, Sicily, with an already reported high prevalence of human papillomavirus.

Methods: To identify the association among individual genetic polymorphisms, human papillomavirus infection, and histological findings, a case-control study was designed.

Human papillomavirus infection: low-risk and high-risk genotypes in women in Catania, Sicily.

Introduction: Human papillomavirus (HPV) infection has been strongly and consistently associated with cervical carcinoma and its cytologic precursors, such as squamous intraepithelial lesions. A cross-sectional survey was conducted with the aim of estimating the prevalence of cervical HPV infection in women attending a service of colposcopy in Catania, Eastern Sicily, Italy.

Methods: The prevalence of type-specific HPV was examined in women with negative colposcopic results and cervical intraepithelial neoplasia grades 1, 2, or 3, with the aim of providing some cross-sectional figures on the local epidemiology of HPV infection.

Ultrasonographic study of gallbladder wall thickness and emptying in cirrhotic patients without gallstones.

Background And Aim: Gallbladder wall thickening and impaired contractility are currently reported in cirrhotic patients and often related to portal hypertension and hepatic failure. The purpose of this work was to evaluate, by ultrasonographic method, gallbladder wall thickness and gallbladder emptying after a standard meal in normal subjects and in patients with compensated liver cirrhosis without gallstones.

Methods: Twenty-three patients with Child-Pugh class A liver cirrhosis and twenty healthy controls were studied.

Activation of the osteopontin/matrix metalloproteinase-9 pathway correlates with prostate cancer progression.

Purpose: Prostate cancer remains the second most frequent cause of tumor-related deaths in the Western world. Additional markers for the identification of prostate cancer development and progression are needed. Osteopontin (OPN), which activates matrix metalloproteinases (MMP), is considered a prognostic biomarker in several cancers.

[Prognostic index of acute hepato-cellular damage].

Introduction: Fulminant hepatic failure is the end result of many different acute damage to the liver. In the present study we compared the clinical to the experimental experience and we postulated the usage of Vascular Endothelial Growth Factor in the clinical arena as a potential treatment in alternative to liver transplantation.

Materials And Methods: Twelve patient diagnosed with fulminat hepatic failure have been enclosed in the present study.

Radioisotopic assessment of gastric emptying of solids in elderly subjects.

Background And Aims: Few studies in literature have investigated the gastric emptying of solids in elderly subjects. We assessed the differences between young and elderly subjects in the gastric emptying rate of solids by a radioisotopic method.

Methods: Two groups of 15 elderly male subjects (mean age 68.

Immune response in addicts with chronic hepatitis C treated with interferon and ribavirin.

Background: The role played by the immune system in the progression of chronic hepatitis C (CHC) is not completely clear. Opioids may facilitate the outbreak of infections through marked immunomodulating effects on the immune response against a virus. To asses if addicts can be treated successfully with interferon (IFN) during detoxification treatment, we evaluated some immune response mediators in addicts affected by CHC.

RT-PCR and in situ hybridization analysis of apolipoprotein H expression in rat normal tissues.

In this study, by using different techniques (i.e. Northern blot hybridization, RT-PCR and Southern blot hybridization) on various normal rat tissues, we were able to identify liver, kidney, heart, small intestine, brain, spleen, stomach and prostate as tissues in which the ApoH gene is transcribed.

Absence of BRAF gene mutation in non-melanoma skin tumors.

Basal cell carcinoma (BCC) is the most common skin cancer, and its incidence is increasing. It was proposed that the RAS oncogene significantly contributes to skin cancer development. Numerous BRAF mutations have been detected in melanoma biopsy specimens and cell lines.

Quantitative evaluation of partial deletions of the DAZ gene cluster.

Partial deletions of the DAZ gene cluster are thought to cause spermatogenesis impairment. The presence of homologous copies of this gene in the Y chromosome does not allow PCR to be used for the identification of this abnormality. Hence, sequence family variants (SFV), following amplification of sY581, sY587 and sY586 and subsequent enzymatic digestion with Sau3A, DraI and TaqI, respectively, and the dual fiber fluorescence in situ hybridization (FISH) have been used to this aim.