Biomedical subjects

Lydia Giannitrapani

Publications and source records attributed to Lydia Giannitrapani.

8 recordsLinked to original sources

PubMed2006

Interleukin-6 and its soluble receptor in patients with liver cirrhosis and hepatocellular carcinoma.

AIM: To evaluate the immunohistochemical localization of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) on tumor tissue specimens from patients with hepatocellular carcinoma (HCC) and the serum levels of IL-6 and sIL-6R in a group of patients with HCC as well as liver cirrhosis (LC) in a group of patients with LC alone and in a control group. METHODS: Three groups of subjects were studied: group I (n = 83) suffering from HCC and LC, group II (n = 72) suffering from LC alone and group III (n = 42) as healthy controls. All patients had hepatitis C virus infection. Serum IL-6 and IL-6R levels were determined using a commercially available ELISA kit. Immunohistochemistry was performed using the streptavidin-biotin complex and rabbit polyclonal antibodies against IL-6 and IL-6R. RESULTS: Immunohistochemistry analysis showed a medium to strong cytoplasmic and membrane reactivity for IL-6 and IL-6R respectively, in at least 40% of cases of HCC, whereas liver cirrhosis patients and controls were negative for IL-6 or showed a very mild and focal dot-like cytoplasmic reaction for IL-6R. Serum IL-6 levels in HCC group were significantly higher than those in LC and control groups (P < 0.0001). There was no significant difference in sIL-6R concentrations among 3 groups. When the patients with HCC were divided into groups according to Okuda's classification, a significant serum increase of IL-6 and sIL-6R level was observed from stage I to stage III (P < 0.02, P < 0.0005). When HCC and LC patients were divided into 3 classes of cirrhosis severity according to Child-Pugh, values in HCC patients were significantly higher than those in LC patients for each corresponding class (P < 0.01). CONCLUSION: IL-6 serum levels in HCC patients are higher than those in LC patients and controls, suggesting an increased production of this cytokine by neoplastic cells. sIL-6R values are similar in all groups, increasing only in stage III HCC patients. These data suggest that they have a closer relationship with the neoplastic mass rather than with the residual functioning hepatic mass.

Adult↗

PubMed2004

Expression of IAPs and alternative splice variants in hepatocellular carcinoma tissues and cells.

IAPs (inhibitors of apoptosis proteins) might have a major role in the apoptotic resistance that marks many cancers. The studies on IAPs in human HCC have focused on survivin or XIAP, indicating that their new or increased expression in this tumor is associated with a more unfavorable prognosis. The present results corroborate these findings, emphasizing the role that the coordinated expression of different IAPs and alternative splice variants might play in the adverse biology of hepatocellular carcinoma.

Alternative Splicing↗

PubMed2004

Expression of WISPs and of their novel alternative variants in human hepatocellular carcinoma cells.

WISPs (Wnt-induced secreted proteins) are members of the CCN (CTGF/Cyr61/Nov) family involved in fibrotic disorders and tumorigenesis. They have a typical structure composed of four conserved cysteine-rich modular domains, but variants of CCN members lacking one or more modules, generated by alternative splicing or gene mutations, have been described in various pathological conditions. WISP genes were first described as downstream targets of the Wnt signaling pathway, which is frequently altered in human hepatocellular carcinoma (HCC). In the present study, WISP mRNA expression was analyzed by RT-PCR in four human HCC cell lines (HepG2, HuH-6, HuH-7, HA22T/VGH). Our results show for the first time that WISP1, WISP1v, and WISP3 are expressed in HCC cell lines. Moreover, we identified two novel variants, generated by alternative splicing of WISP1 and WISP3, respectively, named WISP1 delta ex3-4 and WISP3vL. Overall, our study suggests that WISP transcripts may have a role in the development of HCC, although further studies are necessary to clarify the relative importance of the expression of wild-type WISPs, as well as of their novel variants, in this tumor type.

Alternative Splicing↗

PubMed2004

Induction of apoptosis by the proteasome inhibitor MG132 in human HCC cells: Possible correlation with specific caspase-dependent cleavage of beta-catenin and inhibition of beta-catenin-mediated transactivation.

Proteasome inhibitors, like MG132, can exert cell growth inhibitory and apoptotic effects in different tumor types. The apoptotic mechanism of these compounds involves the activation of the effector caspases. beta-catenin, also an oncogene, represents one of the substrates of these proteases, but the consequences of its cleavage are poorly understood. We investigated its function during apoptosis induced by MG132 in three hepatocellular carcinoma (HCC) cell lines, endowed (HepG2 and HuH-6) or not (HA22T/VGH) with activating mutations of beta-catenin. Induction of apoptosis was associated with cell growth inhibition, accumulation of the cells at the G(2)/M phases of the cell cycle, as well as with fragmentation of beta-catenin (but not of alpha- or gamma-catenin) in all the cell lines. The cleavage of beta-catenin was inhibited by the caspase inhibitors Z-VAD-fmk and Z-DEVD-fmk. Fragmented beta-catenin was found in the nuclei of the treated cells. Analyses through the reporter plasmid pTOPflash showed that MG132 significantly reduces Tcf transcriptional activity in the cells. This was associated with a decrease in the mRNA expression of survivin and c-myc, which are target genes of the APC/beta-catenin/Tcf signaling. Nevertheless, Z-VAD-fmk or Z-DEVD-fmk did not reverse the MG132 effects on Tcf transcriptional activity, suggesting that the compound may affect this activity also by other mechanisms. Overall, the present study supports the therapeutic potential of the proteasome inhibitors in HCC.

Amino Acid Chloromethyl Ketones↗

PubMed2003

Circulating intercellular adhesion molecule-1 in chronic hepatitis C patients with normal or elevated aminotransferase before and after alpha-interferon treatment.

OBJECTIVES: Intercellular adhesion molecule-1 (ICAM-1) plays a fundamental role during liver inflammation. In fact, weak ICAM-1 expression is physiologically restricted to the endothelium of portal vessels and to sinusoidal lining cells, but it becomes markedly evident on sinusoidal lining cells and at the surface of hepatocytes during inflammatory liver diseases. The aim of this study was to evaluate the behaviour of soluble ICAM-1 (sICAM-1) in chronic hepatitis C (CH-C) patients with persistently normal aminotransferase in comparison with patients with CH-C and elevated aminotransferase, and its changes during alpha-interferon (IFN) therapy. Immunohistochemical localization of ICAM-1 was also performed on liver tissue specimens of both groups. METHODS: Sixty subjects were divided into 3 groups: group A included 19 patients with CH-C and persistently normal aminotransferase; group B included 21 patients with CH-C and persistently elevated aminotransferase levels, and group C included 20 healthy subjects representing the control group. The first two groups were treated with recombinant alpha-IFN 2b at a dose of 6 MU 3 times a week for 3 months and followed up with 3 MU 3 times a week for another 3 months. RESULTS: Baseline values of serum ICAM-1 in groups A and B were significantly higher than those in group C (p < 0.0001). The median baseline value of sICAM-1 in group A (525.0 ng/ml) was lower than that of group B (561.0 ng/ml), but the difference was not statistically significant. Furthermore, there was a trend toward higher ICAM-1 values as histological severity increased (Mantel-Haenszel chi(2) 8.8, p < 0.003). Post-treatment sICAM-1 serum values showed a marked decrease in both groups, but only among responder patients, while ICAM-1 levels were unchanged in non-responders. Immunohistochemical localization showed no staining for ICAM-1 in normal liver specimens, while there was a quite similar staining for ICAM-1 in the two groups of patients, consistent with an inflammatory process. CONCLUSIONS: This study shows that circulating ICAM-1 levels in most patients with CH-C and persistently normal aminotransferase are higher than those in a control group and the fact that ICAM-1 molecules are also expressed on the hepatocyte membrane suggests that they could play an important role, in association with other molecules, in the intercellular adhesion processes during the induction and maintenance phases of the immune response. In both groups, only patients responding to alpha-IFN therapy showed a marked decrease in serum ICAM-1 below baseline values.

Adult↗

PubMed2003

Leucocyte interferon-alpha for patients with chronic hepatitis C intolerant to other alpha-interferons.

BACKGROUND: Alpha-interferon (alpha-IFN) is the treatment of choice for chronic hepatitis C but most patients experience adverse effects which sometimes lead to the suspension of therapy. Recently, higher doses of alpha-IFN or prolonged therapy have increased the number of cases of intolerance. STUDY DESIGN: In this open study we evaluated the efficacy and safety of leucocyte interferon-alpha (IFNalpha) [6MU three times a week] in 43 patients with chronic hepatitis C who had been intolerant to previous treatment courses with recombinant or lymphoblastoid IFNalpha. All patients were treated for 6 months and followed-up for an additional 6 months.End of treatment responders were patients in whom hepatitis C virus (HCV)-RNA had been eradicated from the blood by the end of treatment, sustained responders were those patients who maintained negative HCV-RNA at the end of follow-up, and the remaining patients were considered non-responders. Adverse effects were monitored by interviews, laboratory and clinical examinations. RESULTS: Five patients (11.6%) discontinued the treatment, four due to the reappearance of previous adverse effects, and one due to an ex novo adverse effect. In six patients the dose had to be halved. At the end of treatment 11 patients (25.6%) had negative serum HCV-RNA. After discontinuation of therapy, disease flared in four patients, thus seven patients were sustained responders. CONCLUSIONS: This study shows that leucocyte IFNalpha at a dose of 6MU three times a week is well tolerated in patients previously intolerant to recombinant or lymphoblastoid IFNalpha, allowing a high percentage of them to complete a course of treatment in terms of duration and dose.

Antiviral Agents↗

PubMed2002

Extreme thrombocytosis as a sign of coeliac disease in the elderly: case report.

Increase in the number of blood platelets to over 1,000,000/mm3 in elderly patients is generally considered secondary to a myeloproliferative or neoplastic disease. To report the case of an elderly woman hospitalized for extreme thrombocytosis associated with severe anaemia, who was found to be suffering from coeliac disease. The patient, aged 83 years, was hospitalized presenting with fatigue. Laboratory tests showed microcytic hypochromic anaemia (haemoglobin 4 g/dl) and extreme thrombocytosis (platelet count 1,400,000/mm3). Physical examination was normal, with the exception of marked thinness. There was no evidence of macroscopic bleeding from the gastrointestinal or genitourinary tracts. She had never suffered from gastrointestinal problems and had no family history of gastroenterological diseases. Oesophagogastroduodenoscopy and histology of the gastric and duodenal mucosa evidenced atrophic gastritis and an adenomatous polyp. The duodenal mucosa showed total villous atrophy, suggesting the diagnosis of coeliac disease. Antiendomysial IgA and anti-transglutaminase IgA antibodies were also positive. Colonoscopy was negative. An ultrasound examination of the abdomen was normal, and the spleen was within the normal range. A peripheral blood smear showed no alterations in erythrocyte morphology typical of hyposplenism due to coeliac disease. The platelet count decreased rapidly after blood transfusions, when both serum iron and ferritin levels were still below normal limits. Furthermore, we observed a significant inverse correlation between the platelet count and haemoglobin concentration (r = -0.94, P < 0.003). Platelet count and red blood cell count normalized after 2 months of a gluten-free diet; the haemoglobin concentration was also normal at this time. After 1 year of following a gluten-free diet, the patient remained well and had no complaints. There were no gastrointestinal disturbances. All haematological parameters were within normal limits. Intestinal biopsies showed normal villi and crypts without inflammatory infiltration of the lamina propria. This case shows that the association of haematological signs--extreme thrombocytosis and severe anaemia--considered in an elderly patient to be typical of myeloproliferative disorders or neoplastic conditions can be due to coeliac disease; thus, coeliac disease must also be considered among the possible diagnoses.

Aged↗

PubMed2002

Epidemiology, risk factors, and natural history of hepatocellular carcinoma.

The incidence of hepatocellular carcinoma is increasing in many countries. The estimated number of new cases annually is over 500,000, and the yearly incidence comprises between 2.5 and 7% of patients with liver cirrhosis. The incidence varies between different geographic areas, being higher in developing areas; males are predominantly affected, with a 2:3 male/female ratio. The heterogeneous geographic distribution reflects the epidemiologic impact of the main etiologic factors and environmental risk, which are the hepatitis B (HBV) and hepatitis C (HCV) viruses. The percentage of cases of hepatocellular carcinoma attributable to HBV worldwide is 52.3% and is higher in Asia where the seroprevalence of HBsAg in the population is high. However, the vaccination campaign against this virus in some eastern countries has tended to lower the incidence of new cases of hepatocellular carcinoma. The percentage of cases of hepatocellular carcinoma attributable to HCV is 25%, and it is more prevalent in Japan, Spain, and Italy where the association between hepatocellular carcinoma and antibodies to HCV ranges between 50 and 70%. In most cases hepatocellular carcinoma develops in cirrhotic livers, where the persistent proliferation of liver cells represents the key factor of progression to hepatocellular carcinoma independent of the etiology. Another minor risk factor is aflatoxin B1 consumption, which is responsible for most cases of hepatocellular carcinoma in Africa, where the consumption of contaminated foods is common. Other known risk factors are some hereditary diseases, such as hemochromatosis, porphyria cutanea tarda, hereditary tyrosinemia, and alpha1 anti-trypsin deficiency. The natural history of hepatocellular carcinoma is heterogeneous and is influenced by nodule dimension, the mono- or plurifocality of lesions at diagnosis, the growth rate of the tumor, and the stage of the underlying cirrhosis. Available data to date suggest that tumor growth in a cirrhotic liver is variable and that the time in which a lesion in undetectable until it becomes 2 cm is between 4 and 12 months. Therefore, the suggested interval for surveillance screening with ultrasound in patients with liver cirrhosis has been set at 6 months. Patients who should benefit from screening programs are those who would be treated with curative therapy if diagnosed with hepatocellular carcinoma. Thus, the ideal target population should be limited to Child-Pugh's class A cirrhotic patients without significant comorbidity.

Aflatoxin B1↗