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P Sette

Publications and source records attributed to P Sette.

18 recordsLinked to original sources
PubMed2006

Oncolysis of pancreatic tumour cells by a gamma34.5-deleted HSV-1 does not rely upon Ras-activation, but on the PI 3-kinase pathway.

The ability of viruses to selectively target, replicate within, and destroy tumour cells without deleterious effects in normal cells (oncolysis), makes the use of viruses as an attractive tool for cancer treatment. Pancreatic adenocarcinoma, being insensitive to traditional therapy and having a rather poor prognosis, represents a suitable target to evaluate viral oncolysis as a novel therapeutic approach. Herpes simplex virus (HSV) has been reported to produce an oncolytic effect in cells overexpressing Ras. As Ras signalling is frequently aberrant in pancreatic cancer, we compared four pancreatic cell lines (which differ in the presence of mutated or wild-type ras) for their ability to support growth of gamma34.5-replication attenuated HSV-1 (R3616). Our data show that permissiveness to viral replication is neither associated with enhanced Ras signalling nor with defective PKR activity. By contrast, we provide evidence that disregulation of the PI 3-kinase signalling pathway allows conditionally replication-defective R3616 virus to overcome the cellular antiviral activity.

Adenocarcinoma↗
PubMed1993

Heroin addicts infected by HBV and HIV have a low prevalence of HBV DNA in peripheral blood mononuclear cells.

Several reports show that the prevalence of HBV (hepatitis B virus) carriers in HIV (human immunodeficiency virus) infected populations is significantly higher than in HIV seronegative individuals, independent of the risk group for HIV, that is, homosexuals or drug abusers. In this context, evaluation of the simultaneous presence of HBV and HIV in PBMCs (peripheral blood mononuclear cells) is of particular interest for at least 2 reasons: 1) the possible reciprocal influence of the 2 viruses when they infect the same cell; 2) the possibility that HIV-induced hematological disorders could indirectly influence the settling of HBV in blood cell populations. We report data on the frequency of PCR positivity for HBV DNA in PBMCs from 62 HIV infected patients, rigorously selected by risk group, that is, intravenous use of heroin for at least 3 years and syringe promiscuity. Sixty-seven HIV negative individuals who never used any drug formed the control group. The analysis of the cases positive for HBV DNA in PBMCs showed that: 1) the overall prevalence of PCR positivity found in HIV infected patients was significantly lower than that registered in the control group; 2) PCR positivity among the subjects who were HBsAg negative and anti-HBV positive was extremely low in the HIV infected patients (3.7%) but quite frequent in the HIV negative subjects (37.0%). The results support the hypothesis that, unlike the HIV negative individuals, our HIV infected patients exhibited HBV DNA in PBMCS almost exclusively when they presented with active HBV replication.

Adult↗
PubMed1993

Effects of zidovudine in 30 patients with mild to end-stage AIDS dementia complex.

OBJECTIVE: Zidovudine (ZDV) is an inhibitor of HIV replication that may have a beneficial effect on patients with AIDS dementia complex (ADC). However, little is known about the association between long-term ZDV treatment and severity of ADC, ZDV dose or clinical and laboratory response to therapy. DESIGN: An open study on ZDV administration in 30 consecutive patients with ADC. SETTING: An infectious diseases hospital. PATIENTS: Thirty consecutive patients followed-up for 12 months. INTERVENTIONS: Three oral ZDV doses were used: 1000 mg (nine patients), 750 mg (eight patients) and 500 mg (13 patients) per day, depending on haematological status. MAIN OUTCOME MEASURES: Clinical and neurological examinations, neuropsychological evaluations, high-field brain magnetic resonance imaging (MRI) and 99mTc-HM-PAO single photon emission computerized tomography (SPECT). RESULTS: A favourable clinical response, defined as reversal to a less severe ADC stage (Price and Brew's criteria), was observed after 1, 3, 6, 9 and 12 months in 15, 22, 25, 19 and 14 patients, respectively. Neither severity of ADC at entry nor ZDV dose correlated with response to treatment. Seven patients died during the 12-month follow-up. The only factor associated with longer survival was ADC severity at entry (12-month survival, 0.94 and 0.53, in patients in stages 1 or 2 and in stages 3 or 4, respectively; P < 0.01). After 6-12 months of ZDV treatment six patients who initially responded to therapy showed a relapse in initial ADC stage, and two patients a less severe neurological deterioration. Neuropsychological evaluations showed significant improvement in the Wisconsin Card-Sorting test (P = 0.006 for categories, P = 0.029 for perseverative errors), which is particularly sensitive to cognitive and frontal-lobe type functions. Brain MRI revealed a reduction of the extent of white matter lesions in six out of 13 patients, who also showed clinical improvement. SPECT scanning revealed a reduction in the extent of uptake defects concomitant with clinical response in nine out of 14 patients. CONCLUSIONS: ZDV is effective in most patients with mild to end-stage ADC, although the benefit is sometimes only transient; several relapses and deaths occurred after the sixth month of treatment.

AIDS Dementia Complex↗
PubMed1993

Zidovudine plus interferon alfa-2b treatment in patients with HIV and chronic active viral hepatitis.

Results are reported for a small study of 11 patients positive for HIV and with chronic active viral hepatitis. Low dose zidovudine/interferon alfa-2b combined treatment produced a general reduction in alanine aminotransferase activities and increased the CD4 lymphocyte count, hepatitis B e seroconversion, and the loss of HIV p24 antigen. The treatment was well tolerated and progression of HIV disease was not seen.

Adult↗