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Biomedical subjects

P Lanza

Publications and source records attributed to P Lanza.

At least 19 recordsLinked to original sources
PubMed2001

beta-carotene at high concentrations induces apoptosis by enhancing oxy-radical production in human adenocarcinoma cells.

This is the first report demonstrating a relationship between apoptosis induction and changes of intracellular redox potential in the growth-inhibitory effects of high concentrations of beta-carotene in a tumor cell line. beta-Carotene inhibited the growth of human WiDr colon adenocarcinoma cells in a dose- and time-dependent manner, induced apoptosis, and blocked Bcl-2 expression. These effects were accompanied by an enhanced production of intracellular reactive oxygen species (ROS). The addition of the antioxidant alpha-tocopherol blocked both the pro-oxidant and the growth-inhibitory effects of the carotenoid. These findings suggest that beta-carotene may act as an inductor of apoptosis by its pro-oxidant properties.

Adenocarcinoma↗
PubMed2000

Quercetin inhibits p21-RAS expression in human colon cancer cell lines and in primary colorectal tumors.

Immunocytochemical studies have revealed that 10 microM quercetin reduced the steady state levels of p21-ras proteins in both colon cancer cell lines and primary colorectal tumors. These findings were confirmed by Western blot and flow cytometric analysis showing that the inhibition of p21-ras expression by quercetin was time- and concentration-dependent. Twenty-four-hour treatment with 10 microM quercetin reduced p21-ras levels to about 50% of control values. Quercetin was similarly effective in inhibiting the expression of K-, H-, and N-ras proteins. Moreover, the effect of quercetin on ras oncogene expression was not dependent on the cell cycle position of colon cancer cells and appeared to be specific and not merely a consequence of overall inhibition of protein synthesis. Northern blot analysis revealed that quercetin produced in colon cancer cells an early (30 min) reduction of the steady state levels of K-, H-, and N-ras mRNAs. This reduction was also present after 6 hr of flavonoid treatment. These effects of quercetin suggest a possible chemopreventive role for this compound in colorectal carcinogenesis.

Anticarcinogenic Agents↗
PubMed2000

Beta-carotene antagonizes the effects of eicosapentaenoic acid on cell growth and lipid peroxidation in WiDr adenocarcinoma cells.

The effects of combinations between eicosapentaenoic acid (EPA) and beta-carotene on cell growth and lipid peroxidation were investigated in human WiDr colon adenocarcinoma cells. EPA alone was able to inhibit the growth of WiDr cells in a dose- and time-dependent manner. Such an inhibition involved fatty acid peroxidation, as shown by the remarkable increase in the levels of Malondialdehyde (MDA) in EPA-treated cells. Beta-carotene was capable of reducing the growth inhibitory effects of EPA and the levels of MDA in a dose- and a time-dependent manner. In addition, EPA increased beta-carotene consumption in WiDr cells. This study provides evidence that beta-carotene can antagonize the effects of EPA on colon cancer cell growth and lipid peroxidation.

Adenocarcinoma↗
PubMed1999

Endoprosthesis implantation in the treatment of recurrent urethral stricture: a multicenter study. Sicilian-Calabrian Urology Society.

PURPOSE: This study was conducted by nine urology departments in southern Italy to assess the efficacy of and tolerance to treatment of recurrent urethral stricture using a permanent prosthesis. PATIENTS AND METHODS: Since 1992, 99 prostheses have been implanted to treat inflammatory and iatrogenic (seven departments) or all types (two departments) of urethral strictures. The Urolume Wallstent was used in 94 cases. Three centers implanted more than one prosthesis when this was indicated. Local anesthesia was used by six centers, spinal anesthesia by two, and local or general by one. At three centers, urethrotomy was performed immediately prior to implantation; two centers used dilation to 30F, and two centers performed urethrotomy 24 or 36 hours before implantation. The median follow-up is 29.1 months (range 3-53 months). RESULTS: The results were good in 52%, fair in 34%, and poor in 14% of patients. The maximum flow rate increased >75% in 82% of patients. All departments reported complete reepithelialization of the urethra by 6 months. The short-term complications (7-28 days) were perineal discomfort (86%) and dribbling (14%). The long-term complications were painful erection (44%), mucous hyperplasia (44%), recurring stricture (29%), and incontinence (14%). All departments performed resection for hyperplasia in many cases. CONCLUSION: Permanent urethral endoprostheses can produce excellent results in patients with recurrent urethral strictures.

Adult↗
PubMed1998

Growth-inhibitory effect of tamoxifen and quercetin and presence of type II estrogen binding sites in human laryngeal cancer cell lines and primary laryngeal tumors.

Quercetin and tamoxifen, in a range of concentrations between 0.01 and 5 microM, exert a dose-dependent inhibition on the anchorage-dependent and anchorage-independent cell growth of Hep2 and CO-K3 laryngeal cancer cell lines. Cell cycle analysis revealed that the growth-inhibitory effect was associated with a block of the cells at the G2/M checkpoint of the cell cycle followed by DNA fragmentation. This suggests that the failure of cells to proceed through the G2/M checkpoint can be a trigger for apoptosis. The induction of apoptosis by quercetin and tamoxifen was confirmed immunocytochemically by the in situ nick end labeling (TUNEL) reaction. These compounds also exerted a dose-dependent growth-inhibitory effect on primary tumor cells, as assessed by colony-forming assay and bromodeoxyuridine labeling. Laryngeal cancer cell lines and primary tumor cells expressed Type II estrogen binding sites (Type II EBS) with binding characteristics similar to those of Type II EBS in other tumor cells. Since the affinities of quercetin and tamoxifen for Type II EBS were correlated with their growth-inhibitory potential while ipriflavone neither interacted with these sites nor inhibited cell growth, the possibility exists that the action of these compounds is mediated, at least in part, by the interaction with Type II EBS. In conclusion, our data indicate that quercetin and tamoxifen could be potentially useful in laryngeal cancer treatment.

Apoptosis↗
PubMed1998

Whole-killed gp120-depleted HIV-1 antigen in a murine model for prophylactic vaccination.

In this study, the effects were examined of dose and adjuvant of whole-killed gp120-depleted HIV-1 antigen on antibody and cytokine responses in a murine model. Immunization with increasing doses of inactivated HIV-1 antigen in Incomplete Freund's Adjuvant (IFA) resulted in increased production of IL-4 and IgG1 antibody with decreased production of interferon gamma. Immunization with inactivated HIV-1 antigen in Detox PC adjuvant produced TH1 type predominant cytokine patterns along with IgG2a subclass antibody. Higher levels of interferon gamma were associated with immunization with inactivated HIV-1 antigen in Detox PC compared with inactivated HIV-1 in IFA or inactivated HIV-1 in saline. Inactivated HIV-1 antigen in Detox PC adjuvant produced a trend of lower levels of the beta-chemokine MIP-1 alpha compared with inactivated HIV-1 in IFA or saline. Dose and adjuvant play an important role in the type of immune response elicited to a whole-killed HIV vaccine. Low doses of inactivated HIV-1 antigen in Detox PC adjuvant are currently being studied in animal models in order to optimize cell-mediated immunity against HIV infection.

AIDS Vaccines↗
PubMed1998

Canthaxanthin induces apoptosis in human cancer cell lines.

To investigate the possibility that canthaxanthin inhibits cancer cell growth by inducing apoptosis, human WiDr colon adenocarcinoma and SK-MEL-2 melanoma cells were treated with two different doses of the carotenoid for 48 h. Canthaxanthin was incorporated and/or associated to cells. The treatment with the carotenoid caused growth inhibition in both cell types. Concomitantly, apoptosis was induced. Increasing time of exposure and carotenoid concentration, this effect was more pronounced. At 48 h, the percentages of apoptotic cells were 13 and 15, using 1 microM canthaxanthin, and 18 and 20, using 10 microM canthaxanthin in WiDr and SK-MEL-2 cells, respectively. This study represents the first demonstration that canthaxanthin is able to induce apoptosis in tumour cells.

Adenocarcinoma↗
PubMed1998

In vitro p24 antigen-stimulated lymphocyte proliferation and beta-chemokine production in human immunodeficiency virus type 1 (HIV-1)-seropositive subjects after immunization with an inactivated gp120-depleted HIV-1 immunogen (Remune).

We examined the effect of immune stimulation by a human immunodeficiency virus type 1 (HIV-1) immunogen (Remune) compared to a non-HIV vaccine (influenza) on HIV-1-specific immune responses in HIV-1-seropositive subjects. HIV-1 p24 antigen-stimulated lymphocyte proliferation was not augmented after immunization with the influenza vaccine. In contrast, subjects increased their lymphocyte proliferative responses to p24 antigen after one immunization with HIV-1 immunogen (Remune) (gp120-depleted inactivated HIV-1 in incomplete Freund's adjuvant). Furthermore, p24 antigen-stimulated beta-chemokine production (RANTES, MIP-1alpha, MIP-1beta) was also augmented after immunization with the HIV-1 immunogen but not influenza vaccine. Taken together, these results suggest that in this cohort, HIV-specific immune responses to p24 antigen can be augmented after immunization with an HIV-1 immunogen. The ability to upregulate immune responses to the more conserved core proteins may have important implications in the development of immunotherapeutic interventions for HIV-1 infection.

AIDS Vaccines↗
PubMed1997

Selective interaction of a conformationally-constrained Arg-Gly-Asp (RGD) motif with the integrin receptor alphavbeta3 expressed on human tumor cells.

Two antigenized antibodies (AgAbs) were engineered to express peptidic Arg-Gly-Asp (RGD) motifs present in extracellular matrix molecules. The RGD tripeptide sequence was inserted in the third hypervariable loop of an immunoglobulin human/mouse chimeric heavy chain gene as a single or three repeat yielding two antibodies termed gamma1RGD and gamma1(RGD)3, respectively. The antibodies were used to target specific cell-surface receptors of the integrin type expressed by three human tumor cell lines, a melanoma (M21), and osteosarcoma (KRIB) and a fibroblastoma (WI-38). Based on in vitro adhesion assays and flow cytometric analysis, we found that all three cell lines interacted with gamma1(RGD)3 but not with gamma1RGD. Binding of tumor cells to surface-immobilized gamma1(RGD)3 was inhibited in a dose-dependent manner by the RGD-containing synthetic peptides GdRGDSP and RGDS. These synthetic peptides, but no a GDR-containing control peptide, interfered with the binding of tumor cells to surface-immobilized human fibronectin. In their soluble form, neither fibronectin nor gamma1(RGD)3 inhibited tumor cell adhesion to surface-immobilized fibronectin. Gamma1(RGD)3 specifically recognized integrin alphavbeta3 based on two criteria: reactivity with purified integrin receptors and binding to variants of M21 melanoma cells expressing alphavbeta3, alphaIIbbeta3 or no beta3 integrins, respectively. Collectively, our results indicate that the (RGD)3 loop in the antigenized antibody mimics the ligand function of natural extracellular matrix proteins and has a restricted receptor specificity for the alphavbeta3 integrin which is not inherent to short RGD containing peptides.

Amino Acid Sequence↗
PubMed1997

Cross-clade immune responses after immunization with a whole-killed gp120-depleted human immunodeficiency virus type-1 immunogen in incomplete Freund's adjuvant (HIV-1 immunogen, REMUNE) in human immunodeficiency virus type-1 seropositive subjects.

Lymphocyte proliferation responses to gp120-depleted HZ321 virus (clade A) antigen were compared to BAL human immunodeficiency virus (HIV) virus antigen (clade B) responses, clade E HIV virus antigen responses, and purified native p24 antigen responses in 15 human immunodeficiency virus type-1 (HIV-1) seropositive subjects immunized with a whole-killed inactivated gp120-depleted HIV-1 antigen in Incomplete Freund's adjuvant (HIV-1 immunogen, REMUNE). A significant increase in lymphocyte proliferation to HZ321 antigen was observed after immunization with the HIV-1 immunogen (p = 0.02). A strong association was demonstrated between the HIV-1 immunizing antigen, HZ321, and native p24 antigen responses (r = 0.80, p < 0.0001). Furthermore, a strong association in terms of proliferative responses was demonstrated between HZ321 virus (clade A) responses and BAL virus (clade B) (r = 0.95, p < 0.0001) and clade E virus antigen (r = 0.92, p < 0.0001). Proliferative responses to HIV antigens also correlated with baseline CD4 counts. Taken together, these results support the specificity of immune responses induced by REMUNE (HIV-1 immunogen). The development of cross-reactive immune responses between clades and to the more conserved epitopes of the virus have implications in the development of therapeutic and prophylactic HIV vaccines.

AIDS Vaccines↗
PubMed1997

Nocturnal enuresis and daytime wetting: a multicentric trial with oxybutynin and desmopressin.

OBJECTIVE: Different etiopathological mechanisms of enuresis are today under study, and different therapies and drugs have been proposed. The Italian Multicentric Trial was undertaken in twelve pediatric and urological centers in order to assess the efficacy of two of the most popular drugs, desmopressin (DDAVP) and oxybutynin. METHODS: 114 enuretic patients were enrolled in the study. After a 2-week observation period, 66 patients with primary monosymptomatic enuresis were treated with DDAVP, 30 micrograms/day intranasally, for 6 weeks, 48 patients with enuresis and voiding dysfunction were randomly assigned to a protocol with oxybutynin alone or oxybutynin plus DDAVP. The efficacy of the two drugs was measured in terms of reduction of wet nights per week during the 6-week treatment period and a 2-week follow-up period. Children with 0-3 dry nights/week were considered as nonresponders. RESULTS: Patients with monosymptomatic enuresis treated with DDAVP reported a significantly lower number of wet night during treatment than during the baseline period, with 79% showing a 'good' (6-7 dry nights/week) or 'intermediate' response (4-5 dry nights/week). Of the patients with diurnal voiding disturbances and enuresis, those treated with oxybutynin alone had a 54% success rate. The patients treated with both oxybutynin and DDAVP showed a better response, with a 71% rate of success. CONCLUSIONS: The efficacy of the two drugs is confirmed in patients carefully selected on the clinical basis of voiding disturbances. In patients with enuresis and voiding dysfunction, the reduced urinary output and the lower bladder filling rate due to DDAVP can reduce uninhibited bladder contractions, thus enhancing the oxybutynin action.

Administration, Intranasal↗
PubMed1994

Anti-HIV type 1 properties of chemically modified heparins with diminished anticoagulant activity.

Several groups have reported that sulfated polysaccharides are potent and selective in vitro inhibitors of human immunodeficiency virus type 1 (HIV-1); however, their therapeutic application is limited by their anticoagulant activity. In view of possible improvements in therapeutic potential, a number of heparin derivatives with reduced anticoagulant activity were studied for their inhibitory activity of an HIV-dependent syncytium formation assay, in comparison with standard anionic polysaccharides, such as sodium heparin, dextran sulfate, and heparin sulfate. The chemical modifications introduced in the heparin molecule included succinylation of desulfated N groups (Suc-H), exhaustive periodate oxidation and reduction (RO-H), and controlled nitrous acid degradation (LMW-H). The most pronounced anti-HIV activity was observed with RO-H, Suc30-H (standard heparin, 30% succinylated), and Suc100-LMW-H (low molecular weight heparin, 100% succinylated); the latter retained only 5% of the anticoagulant activity of standard heparin, whereas RO-H and Suc30-H retained approximately 35% of the anticoagulant activity of standard heparin. A safety ratio (arbitrary units of anti-HIV activity per anticoagulant international unit) was calculated: by this parameter, RO-H, Suc30-H, and Suc100-LMW-H were, respectively, 48-, 3.6-, and 1644-fold more safe than standard heparin.

Antibodies, Monoclonal↗
PubMed1993

Active immunity against the CD4 receptor by using an antibody antigenized with residues 41-55 of the first extracellular domain.

Using the process of "antibody antigenization," we engineered two antibody molecules carrying in the third complementarity-determining region of the heavy chain variable domain a 7-mer or a 15-mer peptide epitope of the first extracellular domain (D1) of human CD4 receptor--namely, Ser-Phe-Leu-Thr-Lys-Gly-Pro-Ser (SFLTKGPS; positions 42 through 49) and Gly-Ser-Phe-Leu-Thr-Lys-Gly-Pro-Ser-Lys-Leu-Asn-Asp-Arg-Ala (GSFLTKGPSKLNDRA; positions 41 through 55). These amino acid sequences are contained in the consensus binding site for the human immunodeficiency virus (HIV) on CD4 receptor. Both antigenized antibodies (AgAbs) bound recombinant gp120 and were recognized by a prototype monoclonal antibody to CD4 whose binding site is within amino acid residues 41-55. AgAbs were then used as immunogens in rabbits and mice to elicit a humoral response against CD4. Only the AgAb carrying the sequence 41GSFLTKGPSKLN-DRA55 induced a response against CD4. The induced antibodies showed specificity for the amino acid sequence of CD4 engineered in the AgAb molecule, were able to inhibit the formation of syncytia between human CD4+ T cells MOLT-3 and 8E5 (T cells that are constitutively infected with HIV), and stained human CD4+ CEM T cells. Four murine monoclonal antibodies were used to analyze the relationship between syncytia inhibition and CD4 binding at the single antibody level, and indicated that recognition of native CD4 is not an absolute requirement for inhibition of syncytia. This study demonstrates that antigenized antibodies can be used as immunogens to elicit site-specific and biologically active immunity to CD4. The importance of this approach as a general way to induce anti-receptor immunity and as a possible new measure to immunointervention in HIV infection is discussed.

Amino Acid Sequence↗
PubMed1993

Verification of the integral transformation of the projections technique for scatter correction in positron tomographs.

A scatter correction algorithm, based on the integral transformation of the projections, has been implemented when using the C.N.R. positron tomograph in Pisa. The performance of the method has been evaluated by measurements on ad hoc phantoms. The technique allows a significant average reduction of the reconstructed scatter fraction. The limitations of this approach have also been investigated.

Algorithms↗
PubMed1992

A method to analyze the interaction between gp120 of human immunodeficiency virus and CD4.

The study presents a new in vitro method to investigate the interaction between the glycoprotein (gp)120 of human immunodeficiency virus (HIV) and its receptor, CD4. The method is based on the binding of soluble recombinant CD4 to a human T cell line, 8E5, which constitutively expresses gp120 at its surface as a result of infection with HIV (LAV) and lacks reverse transcriptase activity. The binding of CD4 to gp120 on the cell surface is revealed by immunofluorescence using a murine monoclonal antibody to CD4. Binding can be inhibited by different substances like dextran sulfate, heparin, pentosan polysulfate, but not Leu3a. The reasons for this discrepancy are discussed. We propose this assay as a simple, reproducible, and rapid new method to screen new, pharmacological inhibitors of the gp120/CD4 interaction.

CD4 Antigens↗