Although corticotropin-releasing hormone (CRH) and Fas ligand (FasL) have been documented in ovarian carcinoma, a clear association with tumour progression and immuno-escape has not been established. FasL plays an important role in promoting tumour cells' ability to counterattack immune cells. Here, we examined immunohistochemically the expression of CRH, CRHR1, CRHR2 and FasL in 47 human ovarian cancer cases. The ovarian cancer cell lines OvCa3 and A2780 were further used to test the hypothesis that CRH might contribute to the immune privilege of ovarian tumours, by modulating FasL expression on the cancer cells. We found that CRH, CRHR1, CRHR2 and FasL were expressed in 68.1, 70.2, 63.8 and 63.8% of the cases respectively. Positivity for CRH or FasL expression was associated with higher tumour stage. Finally, CRH increased the expression of FasL in OvCa3 and A2780 cells through CRHR1 thereby potentiated their ability to induce apoptosis of activated peripheral blood lymphocytes. Corticotropinreleasing hormone produced by human ovarian cancer might favour survival and progression of the tumour by promoting its immune privilege. These findings support the hypothesis that CRHR1 antagonists could potentially be used against ovarian cancer.
Dose reductions of Peg-IFNa because of severe neutropenia may affect the virologic response in patients with hepatitis C infection (HCV). Granulocyte colony-stimulating factor (G-CSF) has been used occasionally but studies addressing its safety and efficacy in the current treatment of HCV infection are missing. The database of 232 naïve patients with HCV genotype-1 who received PEG-IFNalpha2b 1.5 mcg/kg/week plus Ribavirin 800-1,400 mg/day and completed the treatment was examined. Nineteen patients who exhibited significant neutropenia and received 150-300 microg G-CSF (Group A) with 19 matched control patients who had dose reductions of Peg-IFNalpha according to the standard recommendations (Group B) were examined. None of the patients had treatment modifications due to thrombocytopenia or anemia. The mean decline of the neutrophils was similar in groups A and B (1,760 +/- 1,030/mm(3) at 11 +/- 8.6 weeks and 1,630 +/- 890 at 12.3 +/- 6.1, respectively). Nadir neutrophil values were also not statistically different. Patients who received G-CSF two before IFNalpha, maintained neutrophils between 1,400/mm(3) and 2,700/mm(3) and remained on G-CSF for 29 weeks (2-40). Virologic response at the end of treatment was observed in 12/19 (63%) patients and at 6 months follow-up in 6/19 (32%) in group A as compared to 9/19 (47%) and 4/19 (21%) in group B, respectively. No side effects related to G-CSF were encountered. Administration of G-CSF 2 days before Peg-IFNalpha is safe, maintains sustained neutrophil count, improves adherence to treatment and seems to increase the virologic response in patients infected with HCV genotype 1 who develop Peg-IFN-alpha2b related severe neutropenia.
Objective: The aim of this study was to investigate the relationship between HLA molecules and the positive or negative response of atopic patients to specific immunotherapy (SIT). Methods: We studied 42 atopic multisensitive patients undergoing grass pollen immunotherapy, 42 parents of patients (30 mothers and 12 fathers) and 173 control individuals. HLA class I and class II antigens were typed by a microlymphocytotoxicity test. The typing of DRB1* alleles for atopic patients and their parents was based on the reverse hybridization principle, while for the control group, DNA-RFLP and PCR-SSP methods were used. Results: The frequency of B14 and DRB1*1101-4 antigens/alleles, as well as the A2B5DR11 haplotype, showed a statistically significant difference in those patients who responded to immunotherapy. On the other hand, HLA-A28, B8 and DRB1*0301 antigens/alleles, as well as the frequency of the A1B8 and A1B8DR3 haplotypes, were found to be significantly higher in patients who responded poorly to SIT. Discussion: Our findings support the hypothesis that treatment responsiveness may show an association to HLA molecules, which could thus play a role in the immunological selection and monitoring of atopic patient candidacy for SIT.
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