Antiviral treatment in patients with indolent B-cell lymphomas associated with HCV infection: a study of the Fondazione Italiana Linfomi.

BACKGROUND: Tumor regression after antiviral therapy (AT) is in favor of an etiological role of hepatitis C virus (HCV) in non-Hodgkin's B-cell lymphomas (NHL). PATIENTS AND METHODS: We carried out a cohort study of 704 consecutive HIV-negative, HCV-positive patients with indolent NHL diagnosed and treated from 1993 to 2009 in 39 centers of the Fondazione Italiana Linfomi; 134 patients were managed with AT for lymphoma control. RESULTS: For entire cohort, 5-year overall survival (OS) was 78% [95% confidence interval (CI): 74%-82%] and 5-year progression-free survival (PFS) was 48% (95% CI: 44%-53%). In multivariate analysis, the use of AT during the patients' life had positive impact on OS. Forty-four of the 100 patients treated with first-line AT achieved a complete remission (CR) and 33 a partial response (PR). HCV-RNA clearance was achieved in 80 patients and was related to lymphoma response. At a median follow-up of 3.6 years, 5-year PFS was 63% (95% CI: 50%-73%). CR + PR rate was 85% with AT as second-line treatment. CONCLUSION: AT produces HCV-RNA clearance and consequent tumor regression in most patients with HCV-related indolent NHL. AT used at any time is associated with improved OS. Consequently, AT can be considered an option for patients with indolent lymphomas who do not need immediate cytoreductive treatment.

Long term results of a randomized study performed by Intergruppo Italiano Linfomi comparing Mini-CEOP vs P-VEBEC in elderly patients with diffuse large B-cell lymphoma.

The Intergruppo Italiano Linfomi started, in 1996, a randomized trial for the initial treatment of elderly patients (older than 65 years) with Diffuse Large B-Cell Lymphoma (B-DLCL) comparing 6 courses of Mini-CEOP vs 8 weeks of P-VEBEC chemotherapy. Study objectives were survival, response and Quality of Life (QoL). Two hundred and thirty-two patients were evaluable for final analysis. Complete Response (CR) and Overall Response Rates (ORR) were 54% vs 66% (p = 0.107) and 90% vs 78% (p = 0.021) for P-VEBEC and Mini-CEOP, respectively. With a median follow-up of 72 months, the 5-year Overall Survival (OS), Relapse Free Survival (RFS), and Failure Free Survival (FFS) were 32%, 52%, and 21%, respectively. Subjects achieving a CR showed improvement of QoL regardless of treatment arm. Both Mini-CEOP and P-VEBEC determined a similar outcome for elderly patients with B-DLCL, with a third of patients alive after more than 6 years of follow-up. Both regimens can be considered equally for combination treatment with anti-CD20 monoclonal antibody.

Epstein-Barr virus encoded BALF1 gene is transcribed in Burkitt's lymphoma cell lines and in nasopharyngeal carcinoma's biopsies.

BACKGROUND: The Epstein-Barr virus (EBV) encodes two anti-apoptotic cellular Bcl2 homologs, BALF1 and BHRF1. BHRF1 has an anti-apoptotic activity but is rarely expressed in nasopharyngeal carcinoma (NPC). However, BALF1 is not yet well characterized. OBJECTIVES: The objective of the study was to characterize BALF1 gene. First, the search of its transcriptional expression in EBV-positive B cell lines, EBV-positive Burkitt's lymphoma's cell lines and nasopharyngeal carcinoma's biopsies. Second, the examination of its anti-apoptotic activity in serum dependent assays. STUDY DESIGN: We first analysed the transcriptional expression of BALF1 by reverse transcriptase DNA polymerase chain reaction (RT-PCR) method. For the analysis of its anti-apoptotic activity, we transfected NIH3T3 cells with pBABE-BALF1 expression plasmid and studied serum dependence of these transfectants. RESULTS: BALF1 expression was detected in the latent stage and increased more significantly during the lytic phase in IgG-treated AKATA and TPA-SB-treated P3HR1-TK negative cell lines. As its expression was not affected by the inhibitor of viral DNA synthesis, this gene does not belong to late gene family. When analysed its transcription in Burkitt's lymphoma (BL)-derived cell lines and NPC biopsies, all BL-derived cell lines and more than 80% of NPC biopsies transcribed this gene. The study of serum dependence of BALF1-transfected NIH3T3 cells showed: with 10% of serum, BALF1 transfectants grew significantly more higher cell density than vector alone transfected NIH3T3 cell lines and with 1% of serum, BALF1 transfectants were capable of growing, but with about 40% reduced rate in comparison with those with 10% serum, while vector alone transfected NIH3T3 cells could not almost grow. CONCLUSION: BALF1 gene was transcribed in EBV-associated tumor cells. BALF1 could render cells to serum independent. These results suggest that BALF1 gene could play its role in EBV oncogenesis.

Human auricolar myiasis caused by Wohlfartia magnifica (Schiner) (Diptera: Sarcophagidae): first case found in Sardinia.

The authors report a case of myiasis of the middle ear caused by Wohlfartia magnifica Schiner (Diptera: Sarcophagidae). The entomological aspects, the clinical epidemiological characteristics and the therapeutic solutions of this disease are evaluated. In particular, they underline the rarity of myiasis both because of the aetiologic agent and the anatomical site. The therapeutic aspects are also reported and discussed.

A single amino acid confers barbiturate sensitivity upon the GABA rho 1 receptor.

Many structurally diverse general anaesthetics enhance inhibitory neurotransmission in the central nervous system by interacting with the GABAA receptor. By contrast, GABA receptors composed of the rho 1 subunit are anaesthetic-insensitive. Here, we demonstrate that both delta-hexachlorocyclohexane (delta-HCH; 1-100 microM), a positive allosteric modulator of the GABAA receptor, and the anaesthetic pentobarbitone (10-600 microM) have no effect on GABA-evoked currents mediated by wild-type rho 1 recombinant receptors (expressed in Xenopus laevis oocytes). By contrast, these agents produce up to a 10 fold enhancement of GABA responses transduced by a rho 1 receptor in which a transmembrane located isoleucine residue is replaced by serine. However, not all general anaesthetics were similarly influenced by this mutation, because propofol and 5 beta-pregnan-3 alpha-ol-20-one (5 beta 3 alpha) remained ineffective. These data are discussed in relation to the specificity of general anaesthetic action.