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Biomedical subjects

P Filippini

Publications and source records attributed to P Filippini.

At least 37 records · Page 2Linked to original sources
PubMed2000

Growth inhibitory effects and radiosensitization induced by fatty aromatic acids on human cervical cancer cells.

Evidences have been reported that phenylacetic (PA) and phenylbutyric (PB) fatty aromatic acids can exert tumor growth inhibition in vitro and in vivo. Moreover, clinical trials also showed some activity for these drugs to modulate the expression of genes implicated in tumor growth, metastasis, immunogenicity, and to potentiate the efficacy of cytotoxic agents. The aim of the study was to examine the effects of PA and PB on the growth as well as sensitization to cisplatin and radiation in human cervical cancer cells. The effects of PA and PB on the proliferative activity and apoptosis induction in cervical tumor tissue was investigated. Both PA and PB exhibited a time- and dose-dependent antiproliferative activity in SW756 and ME180 cell lines: after 72-h treatment, the IC50 (concentration able to inhibit 50% of cell growth) of PB was 1.9 +/- 0.2 mM and 1.5 +/- 0.2 mM in SW756 and ME180 cells, respectively, while the IC50 of PA was 13.0 +/- 1.7 mM and 10.0 +/- 1.2 mM in SW756 and ME180 cells, respectively. In tumor tissue biopsies obtained from patients affected by squamous cervical cancer, both drugs resulted in a marked reduction of the percentage of bromodeoxyuridine-labeled cells compared with untreated samples [19.0 +/- 1.63% in untreated tissues with respect to 1.30 +/- 0.54% and 4.20 +/- 2.50% of stained cells after treatment with PA (30 mM) (P < 0.0001) and PB (5 mM) (P < 0.0001), respectively]. Moreover, analysis of the staining with M30 monoclonal antibody revealed that PA (30 mM) and PB (5 mM) were able to produce a marked increase in the number of stained apoptotic nuclei with respect to untreated samples. Finally, PB and PA were shown to enhance the sensitivity of SW756 to radiation and to exert an additive effect when combined with cisplatin. A significant reduction of the processed form of p21ras and rhoB proteins in the membrane fraction of cells exposed to PA and PB was observed. When farnesol, which is able to circumvent the enzymatic step inhibited by PA and PB, was added to the medium only a partial reversal of the growth inhibition and potentiation of sensitivity to radiation induced by PA and PB were found. In conclusion, the growth inhibitory properties of fatty aromatic acids suggest that these molecules could represent the prototype of a new class of compounds with some therapeutic potential in cervical cancer.

Antimetabolites, Antineoplastic↗
PubMed1998

Antiproliferative activity of colchicine analogues on MDR-positive and MDR-negative human cancer cell lines.

In this study the in vitro antitumor activity of a series of 20 colchicine analogues was tested and compared with colchicine and thiocolchicine on three different human cancer cell lines, two of which express the multidrug-resistance (MDR) phenotype. At concentrations from 1 nM to 100 microM, all compounds tested inhibited cancer cell proliferation. The IC50 values indicate that the three fluorinated analogues were the most active compounds, with a similar decreasing order of potency (IDN 5005 > IDN 5079 > IDN 5080) on the two MDR-expressing cell lines, whereas thiocolchicine was the most effective compound on the MDR-negative MDA-MB 231 cells. A strong correlation (r = 0.94; P = 0.004) was found between IC50 values obtained using the two MDR-positive cell lines. Conversely, IC50 values obtained in MDA-MB 231 cells did not show a significant correlation with MDR-positive cell lines, thereby suggesting some difference in the antiproliferative mechanism(s) of colchicine analogues. Cell cycle analysis of the most active analogues in breast cancer cells showed a relationship between cell cycle blocking activity and growth inhibition. The most active agents on the MDR-positive MCF7 ADRr cell line, after 24 h of culture, in terms of cell cycle blocking activity were the three fluorinated analogues. Interestingly, after 72 h, when the cell cycle block subsided, a consistent amount of DNA fragmentation was evident. The extent of cell cycle block, measured as the G2/G1 ratio, was significantly correlated with the apoptosis rate expressed as a percentage of DNA fragmentation on both cell lines, thereby suggesting that a large number of blocked cells underwent the apoptotic pathway.

Antineoplastic Agents↗
PubMed1998

Antitumor activity of paclitaxel (taxol) analogues on MDR-positive human cancer cells.

A series of newly developed paclitaxel analogues have been tested for their growth inhibitory activity on two human breast cancer cell lines, one of which expresses the MDR (multidrug resistance) phenotype. Paclitaxel (taxol) was used as a reference compound. Three new classes of taxanes were analyzed: the cephalomannine compounds, the pyrazoline derivatives and the seco-derivatives. Our results demonstrated an increased antiproliferative activity of pyrazoline derivatives on drug-resistant cancer cells with respect to paclitaxel. These compounds were able to block MDR-bearing MCF-7 ADRr cells in the G2/M phase of cell cycle and, consequently, induce programmed cell death. In keeping with the antiproliferative effects, cells treated with paclitaxel derivatives showed a more pronounced cell cycle arrest than the parent compound paclitaxel. Also, apoptotic cell death, calculated as a percent of DNA fragmentation, occurred to a greater extent in cells exposed to pyrazoline derivatives. The development of new paclitaxel analogues with greater antitumour activity on MDR-positive cells may be useful in selecting new taxanes effective on resistant tumors.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Multiple hepatitis virus infections in chronic HBsAg carriers in Naples.

In order to determine the prevalence of multiple infections with hepatitis viruses in chronic HBsAg carriers in Naples, to assess the interaction between HBV, HDV and HCV infections and to evaluate the influence of multiple virus hepatitis infections on the clinical presentation, we studied 198 HBsAg chronic carriers observed consecutively from 1971 to 1988 at our Liver Unit. Of the 198 HBsAg chronic carriers, 171 had undergone percutaneous liver biopsy. The presence of HBcAg or HDAg in the liver biopsy was considered a marker of HBV or HDV replication, respectively; the presence of anti-HCV was considered a marker of HCV infection. Anti-HCV was observed in 13.6% of the 22 subjects with normal liver, in 27.7% of the 47 patients with minimal chronic hepatitis, in 40% of the 50 with mild chronic hepatitis, in 70.6% of the 17 with moderate hepatitis, in 66.7% of the 3 with severe chronic hepatitis and in 65.6% of the 32 with active cirrhosis. Anti-HCV positive cases were antiHD positive more frequently than the anti-HCV negative (59.2% vs. 43%, p = 0.05). HDV infection exerted a clear inhibition on the HBV genome. Among the 171 HBsAg chronic carriers, the finding of an active chronic hepatitis (moderate chronic hepatitis + severe chronic hepatitis + active cirrhosis) is less frequent in subjects with HBV replication alone than in those with HDV replication or HCV infection. Patients with both HBV replication and HCV infection and those with both HDV replication and HCV infection showed a very high prevelance of active chronic hepatitis.

Adolescent↗
PubMed1997

Synergistic antiproliferative activity of tamoxifen and docetaxel on three oestrogen receptor-negative cancer cell lines is mediated by the induction of apoptosis.

The taxanes are a promising family of anti-tumour drugs that block cell cycle replication by interfering with the microtubule network. The clinical use of these drugs involves some problems related to their low solubility and occurrence of resistance, which is mainly dependent on the multidrug-resistant (MDR) phenotype. To investigate the possible interaction between docetaxel and tamoxifen (TAM), three oestrogen receptor-negative cancer cell lines, MDR- MDA-MB 231, MDR + CEM-VBLr and MCF-7 ADRr, were used. In all three cell lines, the combination of docetaxel and TAM was more effective in terms of growth inhibition than single drug exposure. Isobolic analysis confirmed the presence of synergism in all cell lines when docetaxel was used at 0.2 microM and TAM at a dose equal to or higher than 1 microM. Flow cytometric DNA analysis performed on the three cell lines showed that TAM was able to increase the G2/M blocking activity of docetaxel. This blocking activity was followed by an increased flow cytometric DNA fragmentation suggestive of the presence of apoptosis, which was confirmed by DNA gel fragmentation and morphological analysis. While an antagonistic effect on P-glycoprotein (P-gp) activity may contribute to the synergistic effect of tamoxifen and docetaxel on CEM-VBLr and MCF-7 ADRr, other mechanisms must be involved, as the synergistic effect is also apparent with a P-gp-negative cell line.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[Serum anti-HIV IgA in seropositive patients and in subjects at risk of HIV infection].

To detect the presence of anti-HIV IgA in HIV infected subjects and in seronegative subjects at risk of infection, we assessed a Western Blot using nitrocellulose strips with HIV separated proteins. We tested at least 2 different serum samples from 9 anti-HIV positive subjects (Group A), 9 anti-HIV negative subjects at risk of infection (Group B) and 9 controls (Group C). One subject in Group B became anti-HIV positive during the observation. Anti-HIV IgA were detected in all patients of Group A, in 66.6% of patients of Group B and in no patient of Group C. The subject who seroconverted during the observation showed positivity for IgA anti-HIV in both serum samples, while anti-HIV IgG became detectable only on the second serum sample. A newborn from a seropositive mother showed maternal anti-HIV IgG on the first 2 out of 3 serum samples while showed anti-HIV IgA positivity on the third sample only. This child is still anti-HIV negative.

English Abstract↗
PubMed1997

[Polymerase chain reaction (PCR) for the detection of HIV proviral DNA (pDNA) in subjects at risk of infection].

To detect HlV proviral DNA in lymphocytes from subjects at risk of acquiring HIV infection, we assessed a Polymerase Chain Reaction Assay using the SK38 and SK39 primers for the amplification and the SK19 probe for the hybridization. The detection of amplified HIV-DNA was obtained by a new colorimetric method, the DNA enzyme immunoassay (DEIA). The PCR we performed allowed to detect HIV-pDNA in lymphocytes of 13 out of 64 subjects at risk of acquiring HIV infection. Seven of these 13 became anti-HIV positive during a follow up of 8 months.

English Abstract↗
PubMed1997

[Anti-HAV screening patients with chronic hepatitis].

Following the decrease in HAV endemic levels in the last decades, nowadays in Italy most people aged less than 30 years are susceptible to the infection. We have tested for serum anti HAV IgG 194 chronic hepatitis patients from Naples to evaluate the level of protection against HAV in a category of patients in whom an acute necrosis due to HAV might induce liver failure. The study shows that 90.7% of Neapolitan chronic hepatitis patients has serologic evidence of prior HAV infection. Specifically, 98.1% of the patients over 40 years of age, but only 54.6% of those under 40 tested positive for anti HAV IgG. 102 patients had cirrhosis and only one tested negative. The data suggest that HAV vaccination in susceptible chronic hepatitis patients should be judged by the physicians in care on the basis of the severity of disease, patient's age, real risk of exposure to the infection, and level of education.

English Abstract↗
PubMed1997

[HIV Antigens as complement fixing circulating immune complexes].

To detect HIV antigens in circulating complement fixing immune complexes (ICs) we assessed an ELISA using wells of microtitre plates coated with F(ab)2 anti-C3b and monoclonal antibodies anti-HIV gp120 and anti-HIV p24. We tested 24 anti-HIV positive subjects (Group A), 10 anti-HIV negative subjects at risk of acquiring HIV infection (Group B), 20 normal controls (Group C) and 2 seroconversion panels. We found HIV antigens in ICs in all sera from seroconversion panels, in 25.5% of sera from subjects in Group A, in 28.6% of sera from subjects in Group B and in no serum from subjects in Group C. A subject in Group B acquired HIV infection during the observation. HIV antigens in ICs by our assay were detected 8 months before Anti-HIV and Ag by commercial ELISA.

English Abstract↗
PubMed1996

[Laboratory diagnosis of HIV infection].

The diagnosis of HIV infection is generally lead using two different ELISAs to detect specific anti-HIV antibodies, the eventual reactivity must then be confirmed by a Western Blot The antibodies can be detected only 1-6 months after the infection; in fact in the earliest phases neither the antibodies, for their low titre, nor the specific antigens, for the antibodies could form immune complexes, can be detected by the achieved methods. Only the viral isolation can reveal the presence of the virus in this early phase, but the isolation must be conducted only in adequately safe laboratories (P3 laboratories). The only test able to replace the viral isolation is the Polymerase Chain Reaction (PCR). The PCR technique can be useful to reveal an HIV infection in its early phase and to monitor the infection progression and the efficacy of an antiretroviral treatment

English Abstract↗
PubMed1993

The role of H2 antagonists in perennial allergic rhinitis.

The biological effects of anti-H2 in allergic reactions are dose dependent: low doses enhance, and high doses significantly decrease the reaction of hypersensitivity. The administration of cimetidine H2 antagonist to 20 perennial allergic rhinitis patients brought about an abatement in the symptoms and a decrease in the total serum immunoglobulin E (IgE) levels in 72% of treated patients, but no variation was perceived in placebo-treated patients. These results strengthen the hypothesis of anti-H2-induced immunoregulatory effects and suggest a possible way of inhibiting IgE synthesis in vivo.

Adolescent↗
PubMed1992

[In vivo and in vitro experimentation with the effects of chlorhexidine in patients who have undergone a periodontal intervention].

The periodontal pack is often used to cover the surgical site after surgery, even when associated with local applications of preparations containing chlorexidine, in order to obtain an antiseptic protection. However many people question whether the drug effectively succeeds in penetrating the pack, or if the presence of the pack itself doesn't obstruct the action of the medication. The aim of this work is to evaluate the efficiency of the clorexidine in the surgical area with and without a periodontal pack. In a first stage, a case was chosen and contemporary operated on in two different but anatomically similar sites at the same time. One of the two sites was covered with a chlorexidine gel for the following week, whilst the other was left without medication. After seven days the stitches removed from the two different sites were placed in culture mediums to number and classify the bacterial strains present. In the second stage of the experiment, another eight patients were operated on in the same way, and the two sites covered with periodontal packs. In one of the two sites a layer of chlorexidine gel was positioned under the pack, and the chlorexidine above and on the sides of the pack was continually renewed throughout the week following the operation. The other site was not treated. The results obtained show that the pack partially reduces the action of the drug medication, probably because an insufficient amount reaches the site. The activity and efficiency of chlorexidine against the strains of bacteria found in vivo were tested in vitro. The chlorexidine destroyed all of them.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗
PubMed1992

Hepatitis B virus DNA in chronic HBsAg carriers: correlation with HBeAg/anti-HBe status, anti-HD and liver histology.

Hepatitis B virus DNA was determined in the sera of 198 chronic hepatitis B surface antigen (HBsAg) carriers by the spot hybridization technique. The results were correlated with hepatitis Be antigen (HBeAg) and antibody (anti-HBe), delta antibody (anti-HD) and liver histology. All subjects had a liver biopsy. The prevalence of HBV DNA was 63% in HBeAg-positive subjects and 8.8% in anti-HBe positives. HBV DNA was not found more frequently in chronic HBsAg carriers who had histological evidence of liver disease than in carriers without such evidence. Anti-HD was detected in 48.5% of subjects, with an increasing trend (p less than 0.001) according to the severity of liver disease. Among patients with more severe liver disease (CAH and cirrhosis), HBV DNA and HBeAg were detected less frequently in anti-HD-positive than in anti-HD-negative subjects (7% vs. 42.3%, p less than 0.001 and 7% vs. 34.4%, p less than 0.005, respectively). These findings indicate that HDV infection jointly affects both HBeAg status and HBV DNA.

Adolescent↗
PubMed1991

Prolonged treatment of children with chronic hepatitis B with recombinant alpha 2a-interferon: a controlled, randomized study.

A prospective study was conducted to evaluate the efficacy and tolerance of alpha-interferon in 20 children with biopsy-proven HBsAg/HBeAg/HBV-DNA-positive, anti-delta-negative chronic hepatitis. Patients were randomized to receive alpha 2a-interferon (INF), 3 MU im three times weekly for 12 months, or no treatment (10 patients per group). Five patients receiving IFN showed a marked decrease or negativization of HBV-DNA during treatment. At the end of the study (after 18 month), three patients lost HBV-DNA permanently, and two of them seroconverted to HBeAb 10 and 11 months after disappearance of HBV-DNA with normalization of aminotransferase values. In the control group, one patient had spontaneous clearance of HBV-DNA with conversion to HBeAb and normalization of aminotransferase levels. All treated patients had a febrile reaction in the first month of treatment. The dose of IFN had to be decreased in two patients and was discontinued for persistent intolerance in one of them. Patients who showed a decreased viral replication had higher initial biochemical and histological activity than nonresponders. The data suggest that IFN treatment may favorably influence the progression of chronic B hepatitis in children with a history of acute hepatitis and active chronic disease.

Adolescent↗
PubMed1989

Influence of HDV infection on clinical, biochemical and histological presentation of HBsAg positive chronic hepatitis.

In an attempt to identify some characteristics of HDV infection in the different forms of HBsAg positive chronic hepatitis (CH), we evaluated numerous clinical, biochemical and histological aspects in 203 consecutive HBsAg positive CH patients. The presence of hepatitis delta antigen (HD-Ag) in the liver tissue was the criterion used to identify HDV infection. HD-Ag was observed in none of the 7 patients with non-specific reactive hepatitis, in 14.6% of the 48 with chronic persistent hepatitis (CPH), in 36.4% of the 44 with chronic lobular hepatitis (CLH), in 36% of the 25 with mild chronic active hepatitis (CAH), in 52% of the 36 with severe CAH and in 30.2% of the 43 with inactive or moderately active cirrhosis. Compared with the 139 HD-Ag negative patients in this study, the 64 HD-Ag positive patients more frequently had severe CAH (29.7 vs. 12.2%, p less than 0.01) and less frequently CPH (10.9 vs. 29.5%, p less than 0.01). Of the 139 HD-Ag negative patients, 80 were anti-HD positive and 59 anti-HD negative. The 59 patients with no HD-Ag or anti-HD showed severe CAH less frequently than the 64 HD-Ag positive patients (6.8 vs. 29.7, p less than 0.01) and CPH more frequently (44.1 vs. 10.9, p less than 0.001). Both in CPH and CLH the presence of HD-Ag in the hepatocytes identified subgroups of patients who frequently showed high serum levels of aminotransferases and gammaglobulins and more extended areas of circumscribed lobular necrosis. HD-Ag positive CAH was characterized by a more frequent occurrence of eosinophilic degeneration of hepatocytes without peripolesis (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Hyperendemicity of viral hepatitis in the Neapolitan area: an epidemiological study.

An epidemiological study was performed in order to evaluate the diffusion pattern and risk factors in an area of hyperendemicity of viral hepatitis in the Neapolitan hinterland. Eight hundred-fifty seven asymptomatic subjects, aged 10 to 65 years, who consecutively went to the public health office of the city of Afragola to ask for a health certificate, were studied. They were interviewed with an epidemiological questionnaire and tested for a basic liver profile and serological markers of both hepatitis A and B viruses. Ninety-five percent of the studied population, had anti-HAV with a prevalence of 73% in the class 10-14 years, and of 98% in the class 45-65 years; 78% had either HBsAg or antibodies anti-HBV (60% in the class 10-14 years and 96% in the class 45-65 years). Healthy carriers state was found in 11.4% of the population and acute asymptomatic type B hepatitis in 3%. For HBV infection the interhuman contact in the family setting appeared to play a major role in viral diffusion. Other favouring factors appeared to be the ingestion of raw shellfish and parenteral therapies with glass syringes not properly sterilized. The data suggest that strategies of prevention of hepatitis diffusion in the Neapolitan area should be based on both reinforcing hygienic measures and the educational level of population and active prophylaxis addressed to people in the very young age.

Adolescent↗