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Biomedical subjects

Francesca Russo

Publications and source records attributed to Francesca Russo.

8 recordsLinked to original sources
PubMed2005

A decade of trials of interferon-alpha for chronic hepatitis C. A meta-regression analysis.

The most relevant randomized controlled trials of interferon-alpha (IFN) for naive patients with chronic hepatitis C (CHC) published in a decade, just before appearance of pegylated IFN trials in 2000, were included in this paper. Its purpose is to review the relationship between sustained biochemical response in active versus control group versus usual clinical variables as IFN regimens, cirrhosis, genotype and versus less frequently addressed variables as funding, methodological quality or location of principal author. Meta-analysis estimates of global treatment effect varied according to trial design: group 1=IFN versus placebo/no treatment, 32 RCTs, 2499 pts, OR 9.5 (6.3-14.2); group 2a=comparison of IFN schedules, 43 RCTs, 7454 pts, OR 1.6 (1.4-1.9); group 2b=IFN+other drugs versus standard IFN, 30 RCTs, 4737 pts, OR 2.0 (1.6-2.6). Fixed effects (arm-level) meta-regression on the complete data set (171 arms, 10,580 pts) revealed that sustained response was most likely in experimental arms of IFN+ribavirin or other drugs (OR 2.4), arms using yearly schedule (OR 2.0), trial principal author from Asia (OR 1.7), trial sample size >200 (OR 1.4) and arms enrolling less than 50% of cirrhotics (OR 1.3). Moreover, focus was on some significant interactions too, as the effect of trial's quality interacting to the recorded funding (more benefit if no-profit, less if for-profit) and the effect of trial funding interacting to the location of first author (more benefit if from Asia). Three main effects (experimental arm, cirrhosis, funding) and one interaction (funding*location of principal author) explained 31% of between study variability in a random-effect meta-regression. In a subgroup analysis on a data set including available information on HCV genotype (93 arms, around 7000 pts), meta-regression revealed that genotype 1 or 4 less than 50% per arm and specialistic journal were significant predictors of either biochemical (transaminases) or virological (HCV-RNA) sustained response, in a model including the same main effects identified in the complete data set analysis. Finally, although mostly captured by different IFN regimens along time, heterogeneity of effect in a large set of (not-pegylated) IFN trials was also explained by HCV genotype and variables of quality and reporting, such as trial's principal author from Asia.

Hepatitis C, Chronic↗
PubMed2005

Antiangiogenesis for rheumatoid arthritis.

Angiogenesis, i.e., the induction of new blood vessels from existing vasculature, is a crucial event in the formation and maintenance of the pannus in rheumatoid arthritis (RA). The arthritis is characterized by destruction of peripheral joints in which the cartilage and bone are destroyed by proliferative synovitis. This is characterized by infiltration of inflammatory cells and formation of new blood vessels. Angiogenesis occurs since the early stage of the disease, and supports progression of the arthritis. It has been demonstrated in animal models of arthritis that inhibition of angiogenesis reduces of the arthritis. This suggests that pharmacological inhibition of angiogenesis may play an important role in the treatment of RA. In particular, disruption of new blood vessels can not only prevent delivery of nutrients to the inflammatory site, but can also lead to vessel regression, hence reversal of disease. To sum up, since angiogenesis is central in maintaining of synovitis in RA, antiangiogenesis probably represents a therapeutic tool. This view is supported by recent studies in animal models of arthritis where antiangiogenic drugs deliver a therapeutic benefit.

Angiogenesis Inhibitors↗
PubMed2004

Serum levels of angiogenic cytokines decrease after antineoplastic radiotherapy.

Serum levels of angiogenic cytokines decrease after radiotherapy in patients with cancer and their may have an impact on response to treatment and progression-free survival. Here, we have evaluated sera of patients before and after radiotherapy for various tumour types for levels of soluble fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) to assess whether these factors decrease after radiotherapy, and whether their diminution is related to the radiation dose, tumour type, age and haemoglobin level. We demonstrate that levels of FGF-2 and VEGF, but not HGF, decrease significantly, and that the extent of their diminution is related to the radiation dose and response.

Adult↗
PubMed2004

CXCR3-binding chemokines in multiple myeloma.

The CXC chemokines I-TAC, Mig and IP10 and their receptor CXCR3 are associated with advanced-stage tumor and contribute to tumor progression, invasion and metastasis. The current study was designed to determine the expression of CXCR3 on four multiple myeloma (MM) cell lines and bone marrow plasma cells from 20 MM patients. Cell functions related to progression, such as tyrosine-kinase phosphorylation, proliferation, chemotaxis and matrix metalloproteinase-2 (MMP-2), and MMP-9 secretion were also investigated following the CXCR3/chemokine interaction. fluorescence activated cell sorting analysis revealed that three cell lines (75%) and 18 patients (90%) express the CXCR3 molecule. We demonstrated both in cell lines and fresh plasma cells that I-TAC, Mig and IP10 are able to induce tyrosine-kinase phosphorylation and chemotaxis, but not proliferation, and to increase the MMP-2 and MMP-9 gelatinolytic activity in the cell conditioned medium. Data suggest that CXCR3/chemokine loop may be important for progression of MM in terms of intramedullary and extramedullary dissemination.

Bone Marrow Cells↗
PubMed2004

A VEGF-dependent autocrine loop mediates proliferation and capillarogenesis in bone marrow endothelial cells of patients with multiple myeloma.

The expression/function of vascular endothelial growth factor (VEGF) and its receptor 2 (VEGFR-2/KDR) in multiple myeloma (MM)-associated angiogenesis is under scrutiny. We show here that bone marrow endothelial cells (EC) from 16 patients with MM (MMEC) highly expressed VEGF-A (the main VEGF isoform) and VEGFR-2 at both mRNA and protein level, whereas EC from 14 patients with monoclonal gammopathy unassociated/unattributable (MG[u]) (MG[u]EC) and 12 human umbilical veins (HUVEC) expressed very low mRNAs and/or proteins. MMEC showed constitutive autophosphorylation in both VEGFR-2 and the associated extracellular signal-regulated kinase-2 (ERK-2), whereas this was marginal in MG[u]EC and HUVEC. MMEC proliferated rapidly and formed a closely-knit capillary meshwork on Matrigel. These cell functions were reduced in the other EC. Autophosphorylation, proliferation and capillarogenesis were prevented by a neutralizing anti-VEGF-A antibody, and more efficaciously by an anti-VEGFR-2 antibody. Both antibodies had no effect or were poorly effective on the other EC. These findings as a whole suggest the existence of an autocrine loop of VEGF in MMEC. Since this is very likely a mechanism for the amplification of VEGF activity in neovascularization, it would constitute an appropriate target for antiangiogenic management in MM.

Adult↗
PubMed2003

Consensus interferon versus interferon-alpha 2b plus ribavirin in patients with relapsing HCV infection.

Management of HCV infection and related liver disease with treatment currently available lead to a sustained virological response in 20% of patients using interferon (IFN)-alpha mono-therapy and approximately 40-45% in those on combination therapy with ribavirin.The aim of the present investigation was to compare the effect of consensus interferon alphacon-1 (C-IFN), and IFN-alpha 2b plus ribavirin, in patients relapsing after treatment with interferon alone. A total of 112 randomised patients with relapsing HCV infection (M/F=53/59), were treated for 24 weeks with: (A) IFN-alpha 2b starting with 5/6MU/day till negativity of HCV-RNA followed by 3MU every other day, plus ribavirin 15mg/kg/day (n=34); (B) C-IFN 9microg/day (n=40); (C) ursodeoxycholic acid (UDCA; sodium salt) 450mg/day (n=37). At the end of treatment, patients were observed at follow-up for 24 weeks.Clearance of HCV-RNA was achieved by the end of treatment in 23 patients (68%) in Group A and 21 also showed a biochemical response with normal ALT; in Group B, 33 patients (82%) had both a virological and a biochemical response; in Group C, one patient cleared HCV-RNA. At the end of follow-up (sustained-response), 29% of patients in Group A (n=10/34) had negative PCR (seven patients relapsed at the 4th week, six at the 12th); in Group B, a sustained response was achieved in 58% (p<0.03; two patients relapsed at the 4th week, three at the 12th and five at the 24th).MAJOR SIDE EFFECTS COMPRISED: neutropenia (n=17) and decrease in Hb>1.5g/dl (n=33) in Group A, recurrence of psoriasis in two patients in Group B and abdominal discomfort and diarrhoea in 11 patients in Group C.Rapid clearance of circulating HCV-RNA was induced by C-IFN (66% at three weeks, 71% at six weeks): this was a good prognostic index both for end of treatment and sustained response. Treatment with C-IFN lead to a higher response rate compared to that of recombinant IFN-alpha 2b in association with ribavirin. The action of C-IFN is superior in the time taken to reach the maximal response rate during treatment and in the lower prevalence of relapse of the infection.

Journal Article↗
PubMed2002

Amantadine and interferon in the combined treatment of hepatitis C virus in elderly patients.

Background: Treatment of hepatitis C virus (HCV) infection with interferon (IFN) in older patients may not be feasible on account of side effects: we, therefore, attempted combined treatment with amantadine hydrochloride (AH) in order to improve not only the flu-like symptoms associated with IFN but also the anti-viral effect. Methods: Patients over 65 years of age, (n=165), who had failed to eradicate HCV infection after previous treatment with IFN were randomized into three groups and treated for 12 months, group A received AH 100 mg twice per day; group B received IFNalpha-n(3) 6 M units every other day for 3 months followed by 3 MU and group C the same dose of IFNalpha-n(3), as in B, and AH 200 mg per day. Results: Group A, 42 patients agreed to undergo treatment (genotype 1b n=39); at the end of treatment 21 patients (50%) had normal ALT and seven (17%) negative polymerase chain reaction (PCR). HCV-RNA was not detectable in seven patients at the sixth month follow-up and in six (14%) after 23plus minus2 months. Group B, 39 patients accepted the treatment (genotype 1b n=31); at the end of treatment, 17 patients (44%) had normal ALT and 13 negative PCR (13%). HCV-RNA was not detectable in nine patients (23%) at the sixth month of follow-up and in eight (21%) after 22plus minus4 months. Group C, 38 patients accepted the treatment (genotype 1b n=32); at the end of treatment, 20 (53%) patients had normal ALT and 15 negative PCR (39%). HCV-RNA was not detectable in 15 patients at the sixth month follow-up and in 11 after 21plus minus4 months (29%). Forty-six patients did not accept the scheme of treatment and 26 of them had a follow-up of 20plus minus3 months. HCV-RNA copies and prevalence of genotype 1b were comparable to the treated groups: HCV-RNA was fluctuating or unchanged during the entire follow-up. Conclusions: AH associated with IFN was able to improve the negativization of HCV-RNA and sustained response to IFN and decreased the malaise associated with IFN; an increase in viral copies was observed under AH in about 40%.

Journal Article↗