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Biomedical subjects

M Federico

Publications and source records attributed to M Federico.

154 records · Page 9Linked to original sources

Effect of mouse interferon alpha/beta on the expression of H-2 (class I) antigens and on the levels of 2'-5' oligoadenylate synthetase activity in interferon-sensitive and interferon-resistant Friend leukemia cell tumors in mice.

DBA/2 mice were injected intraperitoneally (i.p.) with interferon-sensitive 745 or interferon-resistant 3C1-8 Friend erythroleukemia cells (FLC) and then injected i.p. with mouse interferon alpha/beta. Interferon enhanced the expression of histocompatibility (H-2) antigens on individual 745 FLC within the peritoneum, but did not alter the expression of H-2 antigens on individual 3C1-8 FLC. Likewise, interferon treatment resulted in an increase in the level of 2'-5' oligo-adenylate (2-5A) synthetase activity in 745 FLC, but did not affect the level of activity in 3C1-8 FLC. These results provide evidence that the phenotype of interferon sensitivity or resistance of FLC does not change within the peritoneum. An incidental finding was that the basal level of 2-5A synthetase activity of in vivo passaged 745 cells was greater than that of 3C1-8 FLC. The finding that injection of mice bearing 745 FLC with antibody to mouse interferon alpha/beta reduced the level of 2-5A synthetase activity in these cells, but did not alter the level of 2-5A activity in 3C1-8 FLC, suggests that endogenous interferon in the peritoneum may have been the responsible factor.

2',5'-Oligoadenylate Synthetase↗

Transfection of a retroviral construct carrying a non producer HIV-1 variant induces HIV-1 resistance in CD4+ CEMss cells.

The phenotype of Human Immunodeficiency Virus-1 (HIV)-infected HUT-78 cell clone (F12) has been described (Federico et al, AIDS Res Hum Retrov 1989; 5: 365-96). Briefly, F12 cells are: i) CD4 down-regulated, ii) non producer and iii) fully resistant to homologous superinfection. We tested whether this phenotype was dependent upon the expression of the HIV-1 genome integrated therein. The SstI/SstI F12 provirus was cloned and inserted in the pLj retroviral vector bearing the neomycin (neo)-Geneticine resistance gene. CD4+ HIV-susceptible CEMss cells were transfected with this construct in the sense orientation. Neo-resistant clones exhibited an integrated viral DNA, low viral mRNA expression and (as in F12 cells) the presence of uncleaved gp160, no gp41 and a small amount of p55 gag precursor. Superinfection of the F12/HIV-DNA-transfected CEMss clones showed that these CD4+ cells had acquired a significant (0.7-1.5 logs) resistance towards superinfection with HIV-1. This was observed in all four transfected clones where the F12/HIV DNA was expressed, but not in the control clone that was transfected with the pLj vector alone. These results confirm those that were obtained with human CD4+ CEMss cells infected with a recombinant retrovirus bearing the same SstI/SstI F12/HIV genome (Federico et al, J Gen Virol, 1993, in press). Both sets of results indicate that the expression of this genome in bio-engineered CD4+ human cells results in their intracellular immunization against HIV-1.

CD4-Positive T-Lymphocytes↗

Epidoxorubicin vs idarubicin containing regimens in intermediate and high grade non-Hodgkin's lymphoma: preliminary results of a multicentric randomized trial.

BACKGROUND: In recent years many therapeutic regimens have been designed in order to improve response rate and response duration in non-Hodgkin's lymphoma (NHL). In 1991 the Italian Lymphoma Study Group (GISL) started a prospective randomized trial on treatment of aggressive and advanced NHL, focused on the efficacy of two Pro-MACE-CytaBom (P-C) derived protocols. METHODS: From April 1991 to March 1993, 243 cases of intermediate and high grade NHL (Groups D-H according to the Working Formulation) in stage I bulky, II-IV have been registered from 19 institutions and randomized to receive 6 courses of either epidoxorubicin, 30 mg/m2 (P-E) or idarubicin, 6 mg/m2 (P-I) containing P-C. The present study deals with the results of an interim analysis of the first 96 cases enrolled up to December 1991 (median follow up of surviving cases 19 months, range 15-23), in terms of overall response rate, toxicity and dose intensity of the two schedules, and overall survival. RESULTS: The overall response rate was: 55 CR (64.0%), 15 PR (17.4%), 5 NR (5.8%) and 11 PG (12.8%). The actuarial survival rate was 61% at 24 months. Hematological and non-hematological toxicity was comparable in the two arms. Dose intensity was high and similar for the two schedules (90% vs 89%). CONCLUSION: This interim analysis demonstrates that in aggressive NHL both P-C derived schedules with epidoxorubicin or idarubicin are effective, safe and well tolerated, also when used in a large multicentric setting.

Adolescent↗

A randomized, double-blind, cross-over study comparing a levosulpiride-based and a metoclopramide-based combination in the prevention of ProMECE-CytaBOM-induced emesis.

BACKGROUND: To test two different antiemetic regimens for preventing nausea and vomiting in patient with non-Hodgkin's lymphoma (NHL) undergoing systemic chemotherapy (CT) with ProMECE-CytaBOM (P-C). PATIENTS AND METHODS: Twenty consecutive untreated adult outpatients with histologically confirmed NHL and scheduled to receive P-C chemotherapy were registered in a randomized, double-blind, cross-over study to compare the antiemetic efficacy of a levosulpiride (LS)-based and metoclopramide (MTC)-based regimen. RESULTS: Complete protection from vomiting was recorded in 93% (62/67) of courses with the LS-regimen and in 89% (62/70) with the MTC-regimen (p = 0.428). No nausea was observed in 84% (56/67) of courses with the LS-regimen and in 74% (52/70) with the MTC-regimen (p = 0.183). No differences in prevention of emesis were recorded when patients crossed to the other regimen. Both regimens were well tolerated; however, on day 8 of chemotherapy, when both antiemetic regimens were administered at a higher dose, the LS-based combination showed significantly lower toxicity (p = 0.035). CONCLUSIONS: ProMECE-CytaBOM-induced emesis can be prevented in most cases with appropriate, specifically designed antiemetic therapy. Both the LS- and MTC-based combinations resulted in a high percentage of complete protection from emesis, but the higher incidence of side effects observed with MTC makes the LS-based regimen preferable for patients receiving P-C chemotherapy.

Adult↗

CCNU, vinblastine, procarbazine and prednisone (CVPP) with extended-field radiotherapy in the treatment of early unfavorable Hodgkin's disease. A prospective study on behalf of the Gruppo Italiano per lo Studio dei Linfomi (GISL).

PURPOSE: To test the adequacy of the CVPP four-drug regimen as ancillary chemotherapy associated with extended-field radiotherapy in the treatment of early, unfavorable, clinically staged Hodgkin's disease. PATIENTS AND METHODS: The population of this prospective, multicenter study consisted of 49 patients with stage I-II disease, associated with bulky involvement or unfavorable histology (lymphocyte-depleted nodular sclerosis or lymphocyte depletion), systemic symptoms or extranodal involvement, or presenting with stage III A favorable-histology disease, with or without extranodal involvement. RESULTS: Complete remission was achieved in 39 patients, partial remission in 2, while 8 patients did not respond. Four patients have relapsed so far (median follow-up: 43 months), all of whom were subsequently rescued with different salvage treatments. Dose intensity (mean +/- SD: 0.83 +/- 0.12) and hematological toxicity (including 2 deaths from infection) were higher when RT followed CT than when it was interposed in the middle of the 6 cycles. No growth factors were used. Nonhematological toxicity was very low and fully tolerable. CONCLUSIONS: Results confirmed the mild neurological and gastroenteric side effects of CVPP that make it an interesting MOPP-variant regimen. This combination seems most indicated when a regimen devoid of cardiac and pulmonary toxicity is required for association with full-dosage mediastinal radiotherapy, as is often the case in early, unfavorable Hodgkin's disease. The optimal sequence consists of radiotherapy administered after completion of the chemotherapy program. The use of growth factors for correction (or prevention) of marked leukopenia seems appropriate.

Adult↗

Hodgkin's disease presenting below the diaphragm. The experience of the Gruppo Italiano Studio Linfomi (GISL).

BACKGROUND AND OBJECTIVE: Infradiaphragmatic Hodgkin's disease is rare, making up 5-12% of cases in clinical stages I and II; consequently, several questions concerning prognosis and treatment strategy remain to be answered. The aim of this study was to analyze the clinical and prognostic characteristics and outcome of this condition. METHODS: A series of 282 patients with CS I-II Hodgkin's disease (HD) was investigated. In 31 patients the disease was confined below the diaphragm (BDHD), and in the remaining above the diaphragm (ADHD). The presenting features and outcomes were compared in the two groups. RESULTS: The BDHD group was older (p < 0.0002), had a higher frequency of males (p < 0.08) and a different histological subtype group distribution (p < 0.0001). Stage II BDHD patients had a worse overall survival rate (OS) than stage II ADHD patients (68.8% vs 86.6% at 8 years, p < 0.01) if age is not considered; patients with more than 40 years of age, in fact, had the same survival rates as those with ADHD. BDHD patients with intra-abdominal disease alone had worse prognostic factors and OS (p = 0.12) than patients with inguinal-femoral nodes. INTERPRETATION AND CONCLUSIONS: Although BDHD patients present distinct features, they have the same OS and relapse-free survival rate as age-adjusted ADHD patients. According to our experience patients with stage I peripheral BDHD respond well to radiotherapy-based regimens. Those with stage II and or intra-abdominal disease are more challenging; chemotherapy or a combined therapy seem to be more suitable approaches for these patients.

Abdominal Neoplasms↗