The italian quaternary volcanism

The peninsular and insular Italy are punctuated by Quaternary volcanoes and their rocks constitute an important aliquot of the Italian Quaternary sedimentary successions. Also away from volcanoes themselves, volcanic ash layers are a common and frequent feature of the Quaternary records, which provide us with potential relevant stratigraphic and chronological markers at service of a wide array of the Quaternary science issues. In this paper, a broad representation of the Italian volcano logical community has joined to provide an updated comprehensive state of art of the Italian Quaternary volcanism. The eruptive history, style and dynamics and, in some cases, the hazard assessment of about thirty Quaternary volcanoes, from the north ernmost Mt. Amiata, in Tuscany, to the southernmost Pantelleria and Linosa, in Sicily Channel, are here reviewed in the light of the substantial improving of the methodological approaches and the overall knowledge achieved in the last decades in the vol canological field study. We hope that the present review can represent a useful and agile document summarising the knowledege on the Italian volcanism at the service of the Quaternary community operating in central Mediterranean area

A Systems Biology Approach to Characterize the Regulatory Networks Leading to Trabectedin Resistance in an In Vitro Model of Myxoid Liposarcoma

Trabectedin, a new antitumor compound originally derived from a marine tunicate, is clinically effective in soft tissue sarcoma. The drug has shown a high selectivity for myxoid liposarcoma, characterized by the translocation t(12;16)(q13; p11) leading to the expression of FUS-CHOP fusion gene. Trabectedin appears to act interfering with mechanisms of transcription regulation. In particular, the transactivating activity of FUS-CHOP was found to be impaired by trabectedin treatment. Even after prolonged response resistance occurs and thus it is important to elucidate the mechanisms of resistance to trabectedin. To this end we developed and characterized a myxoid liposarcoma cell line resistant to trabectedin (402-91/ET), obtained by exposing the parental 402-91 cell line to stepwise increases in drug concentration. The aim of this study was to compare mRNAs, miRNAs and proteins profiles of 402-91 and 402-91/ET cells through a systems biology approach. We identified 3,083 genes, 47 miRNAs and 336 proteins differentially expressed between 402-91 and 402-91/ET cell lines. Interestingly three miRNAs among those differentially expressed, miR-130a, miR-21 and miR-7, harbored CHOP binding sites in their promoter region. We used computational approaches to integrate the three regulatory layers and to generate a molecular map describing the altered circuits in sensitive and resistant cell lines. By combining transcriptomic and proteomic data, we reconstructed two different networks, i.e. apoptosis and cell cycle regulation, that could play a key role in modulating trabectedin resistance. This approach highlights the central role of genes such as CCDN1, RB1, E2F4, TNF, CDKN1C and ABL1 in both pre- and post-transcriptional regulatory network. The validation of these results in in vivo models might be clinically relevant to stratify myxoid liposarcoma patients with different sensitivity to trabectedin treatment

Il carcinoma epatico fibrolamellare. Considerazioni chirurgiche attuali

Hepatic fibrolamellar carcinoma (FLC) is an uncommon tumour that differs from hepatocellular carcinoma (HCC) in demographics, condition of the affected liver, tumour markers, and prognosis. FLC characteristically manifests as a large hepatic mass in adolescents or young adults with female predominance (mean age 23 years). Cirrhosis, elevated alpha-fetoprotein levels, and risk factors for HCC such as viral hepatitis are typically absent. FLC is usually associated with serum tumour markers such as vitamin B12 binding protein, and neurotensin. FLC is characterized pathologically by cords of tumour cells surrounded by abundant collagenous fibrous tissue arranged in a parallel or lamellar distribution. FLC usually appears on radiologic images as a lobulated heterogeneous mass with a central scar in an otherwise normal liver. The clinical presentation of patients with FLC is variable. These patients commonly have pain, and palpable right upper quadrant abdominal mass. An uncommon presenting sign is gynaecomastia in men. Use of percutaneous biopsy (FNAB) is beneficial if there is diagnostic uncertainty about the radiologic diagnosis (US, CT MRI). Although FLC is frequently recurrent, patients have a better prognosis than those with HCC, and aggressive surgical liver resection with extended lymphadenectomy or liver transplantation may be indicated. The presence of advanced-stage disease, direct invasion of adjacent organs, lymphadenopathy, or limited metastasis does not preclude attempts at curative resection. In inoperable cases, the patient may benefit from chemotherapy, permitting in up to 50% of these cases a curative resection. The case is reported of a 18-year-old man with bilateral gynecomastia secondary to an unknown hepatic fibrolamellar carcinoma producing oestrogens. Serum alpha-fetoprotein was negative; des-gamma-carboxy prothrombin (DCP) level was elevated. CT scan and MRI showed a solid hepatic tumour (theta 10 cm) without evidence of extrahepatic spreading. By a needle biopsy a fibrolamellar carcinoma was diagnosed. On March 1995 a right hemihepatectomy was performed. The postoperative course was uneventful and the patient recovered. Specimen's histologic examination confirmed the preoperative diagnosis. Intracellular (hepatocytes) oestrogens were found, but oestrogen and androgen receptors were negative. After surgery DCP and oestradiol levels rapidly decreased and gynaecomastia disappeared. A follow-up program was established. On April 2000 a probable recurrence within the caudate lobe was discovered by a liver CT scan without evidence of extrahepatic spreading. Tumour markers, FNAB, and bone scintigraphy were negative. On July 2000 the patient underwent second look laparotomy. Only a coeliac lymphadenopathy was found and a lymphadenectomy performed. Specimen's histologic examination showed a metastatic lymph nodal disease (FLC). The postoperative course was uneventful and the patient recovered. He is currently alive without evidence of recurrence 5 years after the second operation