Influence of HLA alleles in response to treatment with pegylated interferon-alpha and ribavirin in patients with chronic hepatitis C.

The objective of this study was to analyse the possible role of HLA polymorphism of chronically infected hepatitis C virus patients in the response outcome to treatment with pegylated interferon-alpha plus ribavirin. To that end, 144 Brazilian patients infected only with genotype 1 of the virus were treated with pegylated interferon-alpha at 1.5 µg kg(-1) in conjunction with ribavirin (1000 mg if patient weight was <75 kg and 1250 mg if >75 kg) for 48 weeks. The patients did not have concomitant HBV or HIV infections or liver disease, did not undergo previous antiviral treatment, and were followed up for 24 weeks after the end of treatment to assure they presented a sustained virological response. Patients were classified according to response to treatment in responsive (SVR), nonresponsive (NRS) and relapsers (REL). HLA class I and class II typing were carried out through PCR-SSO using Luminex technology. A statistically higher frequency of DRB1*11 patients was observed in the SVR group (39.6% vs. 14.3%P = 0.0012; Pc = 0.0156; OR = 3.94; 95% CI = 1.8-8.8). HLA-DQB1*03 patients were also more frequent in the SVR group, but the P value lost significance after Bonferroni correction (62.3% vs. 41.7%P = 0.024; Pc = 0.14, OR = 2.3; 95% CI = 1.14-4.60). HLA class II antigens can positively influence the response to treatment with pegylated interferon-alpha and ribavirin.

Orgotein as a radioprotector in normal tissues. Experiments on mouse skin and a murine adenocarcinoma.

The effects of Orgotein (a superoxide dismutase) on the radiation response of normal and malignant murine tissue in vivo were evaluated. The observations were made on the mouse hind leg bearing, in some cases, an adenocarcinoma. The following irradiation protocols were tested: 1) single dose (e.g., 35 and 53 Gy), 2) conventional fractionation (3 Gy/day, 5 days a week) and 3) multiple fractions per day (2 X 3 Gy/day, 3 h fractionation interval, 5 days a week). Radiation was either delivered alone or preceded by a subcutaneous injection of 20, 100 or 400 mg/kg Orgotein administered 1 or 2 h before the beginning of irradiation. No effects of Orgotein on tumor radiation response were detected. A protective effect on normal tissue was observed when radiation was delivered according to aggressive protocols and a relatively high dosage of Orgotein was administered. Furthermore, an accelerated trend of recovery of normal tissue was observed.

Treatment of tumours with the combination of WR-2721 and cis-dichlorodiammineplatinum (II) or cyclophosphamide.

The ability of WR-2721 [S-2(3-aminopropylamino)ethyl-phosporothioic acid] to selectively protect the host against the toxic effects of multiple doses of cis-dichlorodiammineplatinum [cis-Pt] or cyclophosphamide [CY] has been studied in mice and rats bearing 3 different tumours. Selective protection against cis-Pt induced nephrotoxicity has been demonstrated under all conditions studied, with the extent of protection being inversely related to the size of the cis-Pt dose. For example, pre-treatment with 200 mg/kg of WR-2721 30 min before each weekly dose of 2 mg/kg of cis-Pt allows the administration of this cytotoxic agent for 3 times longer before nephrotoxic injury. In none of these studies was there tumour protection. The same pattern was observed with CY, but quantitation of the extent of marrow protection was not possible for the multiple treatment studies, due to the longer latent period between induced and observed death with this drug. We conclude, therefore, that for both of these drugs, selective protection of the kidney and marrow is not only maintained under conditions of multiple treatment, but actually enhanced due to the need for smaller doses of cytotoxic agents in these protocols.