Circulating transforming growth factor-ß and epidermal growth factor receptor as related to virus infection in liver carcinogenesis.

BACKGROUND: The aim of our study was to improve the detection of HCC by measuring alpha-fetoprotein (AFP) in addition to other molecular markers by estimating the plasma concentration of transforming growth factor beta (TGF-ß) and epidermal growth factor receptor (EGFR). In particular, the role of hepatitis C and B viruses (HCV and HBV) infection was evaluated with relation to TGF-ß and EGFR plasma concentration. MATERIALS AND METHODS: Eighty-five patients with liver disease, 54 with hepatocellular carcinoma (HCC), 16 with liver metastasis (LM), 15 with liver cirrhosis (LC) and 30 healthy volunteers were evaluated. AFP, TGF-ß and EGFR were detected with enzyme-linked immunoassay (ELISA) in plasma of all study participants. RESULTS: The mean values of TGF-ß and EGFR in all patients were much higher than in control group, p<0.0001. In HCC patients the levels of TGF-ß and EGFR were much higher than in LM and LC patients. Moreover, TGF-ß and EGFR were significantly higher in the presence of both viruses or only in the presence of HCV, p=0.002. No decrease or increase of AFP was noted in these patients. CONCLUSION: Our data suggest the reliability of TGF-ß and EGFR in detecting HCC, in particular when the carcinogenesis is affected by virus infection.

Formation of anti-platelet factor 4/heparin antibodies after cardiac surgery: influence of perioperative platelet activation, the inflammatory response, and histocompatibility leukocyte antigen status.

BACKGROUND: Anticoagulation therapy with heparin induces antibodies that recognize multimolecular complexes of platelet factor 4 bound to heparin (anti-platelet factor 4/heparin antibodies). Considering that cardiac surgery induces an intense platelet activation and proinflammatory response, we examined the relationship between formation of anti-platelet factor 4/heparin antibodies and plasma levels of platelet factor 4 and interleukin 6. We also examined the relationship between anti-platelet factor 4/heparin seroconversion and the histocompatibility leukocyte antigen system. METHODS: In 71 patients undergoing cardiac surgery, anti-platelet factor 4/heparin antibody levels were evaluated by means of enzyme-linked immunosorbent assay preoperatively and 14 days postoperatively. Platelet serotonin release assays were performed to assess the platelet-activating potential of the antibodies. Plasma levels of platelet factor 4 and interleukin 6 were assayed at prespecified time points. Histocompatibility leukocyte antigen status was assessed preoperatively in all patients and was compared with that of 6156 healthy subjects. RESULTS: Thirty-seven (52%) patients had anti-platelet factor 4/heparin antibodies with an OD value of 0.45 or greater in 1 or more of the assays. Applying strict seroconversion criteria (>2-fold increase in Optical Density), only 16 (22.5%) patients had evidence of anti-platelet factor 4/heparin antibody seroconversion after the operation. Neither the presence of anti-platelet factor 4/heparin antibodies nor seroconversion influenced postoperative outcomes. The CW4 allele was significantly more frequent among seroconverted patients (46.9% vs 19.1%, P = .002). Platelet factor 4 levels did not influence seroconversion. Patients with anti-platelet factor 4/heparin levels of 0.45 OD units or greater 14 days after the operation had significantly higher interleukin 6 levels measured 1 hour after protamine administration. DISCUSSION: Patients with a greater amount of perioperative inflammation could be more likely to have anti-platelet factor 4/heparin antibodies 1 to 2 weeks later. We provide additional evidence that the histocompatibility leukocyte antigen CW4 confers genetic susceptibility in an acquired inflammatory disorder that includes the anti-platelet factor 4/heparin immune response.

Epidermal growth factor receptor serum levels and prognostic value in malignant gliomas.

AIMS AND BACKGROUND: The epidermal growth factor receptor (EGFR) is a member of a family of cell membrane receptors that use tyrosine kinase activity as the signal transduction mechanism. It is commonly expressed or overexpressed by many solid tumors and correlates with disease progression and a poor clinical prognosis. Increased EGFR expression might therefore be a strong prognostic feature in multiple tumor types, and inhibition of its cellular actions may have substantial therapeutic benefit. The aim of this study was to estimate the EGFR serum concentration for potential use as a biological marker of brain cancer to predict prognosis and follow-up after treatment. METHODS AND STUDY DESIGN: Serum samples obtained from 50 healthy individuals and 65 brain cancer patients (35 glioblastoma multiforme and 30 anaplastic astrocytomas) were collected before and after treatment and assayed for EGFR extracellular domain serum concentrations by a sandwich ELISA. RESULTS: EGFR was elevated in 47 of 65 brain cancer patients, with mean serum values of 84 +/- 18 ng/ml, compared with that of healthy controls (43.6 +/- 11 ng/ml, P = 0.001). There was a significant difference in the mean serum levels of EGFR between glioblastoma multiforme patients (96.2 +/- 12 ng/ml) and anaplastic astrocytoma patients (71.6 +/- 18 ng/ml, P = 0.04). Sixty brain cancer patients underwent surgery; EGFR serum levels did not show significant differences from those observed before surgery. For all patients, median overall survival was 13 months (anaplastic astrocytoma, 18 months; glioblastoma multiforme, 12.5 months). In 47 patients with high EGFR serum levels, overall survival was reduced (P = 0.01), with a median survival time corresponding to 11.5 months (anaplastic astrocytoma, 14.5 months; glioblastoma multiforme, 10.5 months). CONCLUSIONS: Although a prospective study with large sample size is warranted, serum EGFR extracellular domain may be potentially useful as a biological marker of gliomas for prediction of prognosis and follow-up after treatment.

c-erbB-2 protein level in tissue and sera of breast cancer patients: a possibly useful clinical correlation.

AIMS AND BACKGROUND: The aims of this study were to assess the clinical utility of circulating preoperative HER-2 extracellular domain p105 detected by enzyme immunoassay (ELISA), to compare the tissue expression of HER-2/neu determined by immunohistochemistry (IHC), to correlate prognostic factors including tumor size, nodal involvement, and hormone receptor status, and to analyze the prognostic significance of the marker in relation to clinical outcome as measured by disease-free and overall survival. METHODS: In this study, we enrolled 108 consecutive patients with breast carcinoma, and obtained serum samples and frozen tumor tissues. We compared them with 57 women with fibroadenoma and 63 healthy women as controls. RESULTS: Univariate ANOVA analysis showed no relationship between HER-2/neu in tissue and serum. Preoperative serum levels of p105 were significantly higher in breast cancer patients than in women with benign disease or healthy women. Concerning the correlation between p105, HER-2/neu tissue expression, and the other prognostic factors, a statistically significant correlation between high serum p105 levels and ER-negative status in breast cancer patients was found. Kaplan-Meier analysis confirmed that patients with positive HER-2/neu tissue expression had a significantly shorter survival than those with negative expression. Analysis with the Cox model demonstrated that tumor size was the only significant independent prognostic factor. CONCLUSIONS: This research failed to demonstrate a relationship between preoperative tissue overexpression and circulating HER-2/neu, suggesting that p105 does not represent a valid alternative to predict a worsened prognosis in breast cancer, but it could be a diagnostic marker to discriminate healthy subjects from breast cancer patients.

Activation of the coagulation system during coronary artery bypass grafting: comparison between on-pump and off-pump techniques.

OBJECTIVE: The activation of the coagulation and fibrinolytic systems and platelet function in patients undergoing coronary artery bypass surgery on-pump or off-pump techniques was compared. METHODS: Thirty-two patients were randomly assigned to on-pump or off-pump coronary artery bypass grafting. Heparin was given at the same dose. Activation of the coagulation and fibrinolytic systems was evaluated by measurement of several markers. Platelet function was evaluated by in vitro bleeding time test. Blood samples were collected at 7 different times, up to postoperative day 6. RESULTS: Overall tissue factor production was similar in the two groups. Thrombin formation was more elevated in the on-pump group (P < .001), particularly during the operation; prothrombin fragment 1.2 discharge values were higher than the preoperative ones (P = .002). Levels of tissue-plasminogen activator showed no difference between the groups (P = .1). D-dimers release was higher in the on-pump group (P = .0002). In vitro bleeding time was longer in the on-pump group (P < .0001), particularly in the first 24 hours; it was not prolonged in the off-pump group. In both groups, regardless of aspirin treatment, discharge in vitro bleeding times were lower than the preoperative ones (P < .01). CONCLUSION: Although the extrinsic coagulation pathway is similarly activated, thrombin formation is more pronounced in patients having on-pump bypass grafting. Patients subjected to off-pump bypass grafting have normally functioning platelets and a weak activation of the fibrinolytic system. At discharge, both groups have preserved platelet function and increased thrombin formation. Further studies with angiographic evaluation are needed to establish a correlation between coagulation parameters, platelet function, and graft patency.

Blood damage related to cardiopulmonary bypass: in vivo and in vitro comparison of two different centrifugal pumps.

Cardiopulmonary bypass (CPB) induces hemolysis and the activation of the inflammatory and coagulation systems. Several components of the CPB equipment may contribute to such phenomenon. We tested the effects of two differently designed centrifugal pumps (Bio-Pump, Medtronic and Revolution, Cobe) on several markers of hemolysis, coagulation, and inflammation: plasma free hemoglobin,prothrombin fragment 1.2, platelet factor 4, and P-selectin. Twenty patients requiring coronary artery bypass grafting were randomized to undergo CPB with one of the study centrifugal pumps, and 10 experiments (5 for each pump) were performed with a closed loop circuit to assess pumps' performances over 6 circulation hours using human blood. CPB induced a significant elevation of all the tested markers. Neither in the in vivo nor in the in vitro study were significant differences observed between the groups. Because the Revolution centrifugal pump, which was recently designed and distributed, produced results comparable with those obtained with the BioPump, it should be considered as safe as the Bio-Pump to perform clinical CPB.