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Biomedical subjects

S Pastore

Publications and source records attributed to S Pastore.

14 recordsLinked to original sources

Comparative studies between in vitro and in vivo effects of human beta-interferon on natural killer activity and its relevance to immunochemotherapy.

A good correlation was found between in vivo and in vitro responses of peripheral MNC from breast cancer patients and the NK boosting effect of human beta IFN. In vitro immunochemistry studies showed that marked antitumor effects were obtained against cultured cancer cells when a widely used chemotherapeutic agent such as 5-FU was combined with nonsensitized spontaneously cytolytic MNC, preactivated in vitro with beta IFN. These results suggest that the in vitro susceptibility assay of MNC to IFNs could be used for predicting favorable responses to immunochemotherapy regimens employing IFNs as immunomodulating agents.

Cytotoxicity, Immunologic

Combined effects of host antitumor immune responses and chemotherapy. Studies with hexamethylmelamine.

The antitumor activity of hexamethylmelamine (HMM) was tested in various mouse tumor models in the presence or absence of host-vs-tumor graft responses. The drug was moderately active against Sarcoma-180 growing in different strains of non-sensitized mice. Strong protection was afforded when recipients were preimmunized with irradiated tumor cells 15 days before tumor challenge followed by HMM treatment. The drug did not show antitumor activity against two radiation-induced lymphomas of congenic mice of B10 background, inoculated into H-2 compatible hosts, or into mice incompatible for subregions of H-2. In this model HMM increased mortality of allogeneic mice presumably through impairment of host-vs-lymphoma graft resistance. In conclusion this study shows that synergistic or antagonistic effects can be obtained by combining chemotherapy with antitumor immune responses.

Altretamine

Decline of natural cytotoxicity of human lymphocytes following infection with human T-cell leukemia/lymphoma virus (HTLV).

Cell-mediated natural cytotoxicity (CMNC) of fresh or long-term cultured lymphocytes collected from HTLV-positive patients or infected in vitro with the virus, was tested against K562 target cells. Severe depression of reactivity was found in fresh lymphocytes of three patients with advanced disease, in 12 in vitro established T-cell malignant lines, and two HTLV-infected cord blood (C5/MJ and C91/PL) lines. Moreover, all (eight) HTLV-1 infected cell lines listed showed a significant inhibition of CMNC of peripheral blood lymphocytes of healthy donors. Whether virus infection promotes the outgrowth of pre-existing suppressor cells and/or produce changes of the T-lymphocyte function is unknown.

Adult

Increase of natural killer (NK) activity of mouse lymphocytes following in vitro treatment with cytosine-arabinoside.

The in vitro influence of cytosine-arabinoside (Ara-C) on mouse NK activity was studied treating effector cells, target cells or effector and target mixture with graded concentrations of the drug. Ara-C increased the NK efficiency of mouse splenocytes without enhancing the susceptibility of target cells or the cytolytic events when added to effector-target mixture. This phenomenon was confirmed with splenocytes collected from congenitally athymic (nude) or conventional donors of different ages, untreated or depressed or boosted for NK activity by various agents. In addition Ara-C increased the NK activity of spleen cells of nude mice deprived of nylon-adherent cells, and did not affect suppressor cells capable of inhibiting the lytic phase of NK process. The drug was able to significantly augment the binding ability of spleen cells to the NK-sensitive YAC-1 target. It was concluded that Ara-C would increase the efficiency of natural cytotoxicity presumably through a direct influence on effector lymphocytes.

Animals

Vindesine in the treatment of refractory hematologic malignancies: a phase II study.

A phase II evaluation of vindesine (VDS) was carried out in 46 patients with hematologic malignancies refractory to conventional chemotherapy. Two VDS schedules were employed (at random): (A) a weekly bolus (5 mg/m2 i.v. X 4); (B) fractionated daily injections (0.5 mg/m2 i.v. q.12 h X 10, course to be repeated after 10-15 days). Complete and partial remissions were observed in acute lymphocytic leukemia (3/14 patients), acute non-lymphocytic leukemia (2/12 patients), chronic myelocytic leukemia in blastic crisis (4/12 patients) and non-Hodgkin's lymphoma (4/8 patients). Responses were seen with higher frequency in patients treated with the weekly bolus (42.8 vs 16%). Myelosuppression was the most relevant side effect in both schedules. Neurotoxicity occurred infrequently and was generally mild in degree. Further trials with VDS in combination with other drugs are recommended in hematologic malignancies.

Acute Disease

Amplification of natural killer activity of mouse lymphocytes by vincristine.

The possible influence of Vincristine (VCR) on NK-mediated cytolysis has been studied pretreating effector (E) or target (T) cells with the drug or adding the agent to E + T mixture during the 18-hour assay. Substantial increase of cytotoxicity was found when VCR was added to E + T cells, but not when effector or target cells were pretreated with the drug. This phenomenon was confirmed with effector splenocytes of various strains of mice, including athymic nude donors deprived of plastic-adherent or nylon-wool adherent accessory cells. Moreover, the agent did not produce irreversible inactivation of the suppression activity of splenocytes collected from DBA/2 donors infected with Friend leukaemia virus.

Animals

Selective growth of natural cytotoxic but not natural killer effector cells in interleukin-3.

Interleukin-3 (IL-3) can promote the proliferation of certain classes of lymphocytes distinct from those that are dependent on interleukin-2 (IL-2) for growth. Culture conditions for its production are identical to those required for IL-2 and in both cases the producer cell appears to be Thy 1.2+, Lyt1+, Lyt2- However, unlike the IL-2 responder cells, the cells that proliferate in IL-3 are generally Lyt2-. Here we have measured the natural cytotoxic (NC) activity as well as natural killer (NK) cell activity of the IL-3-dependent cells. Both of these activities are part of a repertoire of spontaneous cytotoxic functions found in mice that might serve in early defence against infectious agents or immunosurveillance against tumours in vivo. We report a new finding that IL-3 selectively maintains NC cells but not NK cells in culture. This is in contrast to the known requirement for IL-2 in NK cell growth. This provides a means of isolating NC cells from NK cells in the mouse as an initial step in the study of the relative contribution of these two cell types in tumour immunity.

Animals

Influence of vindesine on the lytic phase of mouse natural cytotoxicity against human leukemic cells.

Vindesine (VDS), a structural analogue of Vinca Alkaloids, was found to increase the NK-mediated cytolytic effects of mouse lymphocytes against human K562 target cells in a 18-hr assay. Pretreatment of effector or target cells with the drug did not affect substantially the NK reaction. The phenomenon has been detected using splenocytes of either congenitally athymic or conventional euthymic mice of different strains. Effector lymphocytes deprived of cells adherent to plastic surface or to nylon-wool column were still competent for drug-mediated increase of NK function. It is suggested that modification of the membrane make-up of effector or target cells reversibly induced by VDS, would promote higher NK-mediated cytolytic effects.

Animals

Mitoxantrone in combination with etoposide and cytarabine for treatment of poor prognosis acute non lymphoid leukemia patients.

BACKGROUND: The proved effectiveness and relatively low extrahematological toxicity of Mitoxantrone, Ara-C and Etoposide as single agents and in combination in the treatment of acute non lymphoid leukemia (ANLL) are well established. In a phase II study the efficacy and toxicity of an induction combination regimen with Mitoxantrone, Ara-C and Etoposide were evaluated for treatment of poor risk ANLL patients. METHODS: Twenty-seven poor prognosis ANLL patients were treated with Mitoxantrone, 7 mg/sm days 1-3; VP16, 150 mg/sm days 1-3; Ara-C, 200 mg/sm continuous infusion days 1-5. Median age of treated patients was 63 (17-78): 10 de novo leukemias (4 greater than 65 yrs 3 with cardiomyopathy); 12 secondary leukemias (5 secondary to a myelodysplastic syndrome, 5 to myeloproliferative syndrome, 2 to other neoplasias); 3 relapses; 2 refractory. RESULTS: Fifteen patients (55.5%) achieved CR (8 de novo leukemias, 3 relapses, 4 secondary leukemias); 7 died in induction, 5 progressed. Median remission duration was 27 weeks (range 5-70 wks) and overall median survival 13 weeks (range 4-80). Extraematological toxicity was low, but five patients died from infections and two from hemorrhages. CONCLUSIONS: The combination tested in this trial proved effective in the treatment of "poor risk" ANLL, but the results need to be confirmed on greater numbers of patients, mainly in the group of de novo leukemias that can't be treated with more aggressive regimens.

Antineoplastic Combined Chemotherapy Protocols

Rapid pentachlorophenol evaluation in solid matrixes by second derivative UV spectroscopy for application to wood and leather samples.

A method for the quail-quantitative evaluation of pentachlorophenol (PCP) in solid matrixes has been developed. The procedure is based on solid-liquid extraction of solid samples (leather or wood), followed by purification on a cyanopropyl column and determination of the preservative by second derivative UV spectroscopy considering the PCP A peak-through value (304-297 nm). The method allows rapid PCP determination in the concentration range 1-40 micrograms/mL; any matrix interference is avoided by the purification step and recoveries of the preservative were 99.12% (RSD% 0.13) for the leather matrix and 98.03 (RSD% 0.17) for the wood matrix.

Microchemistry