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Biomedical subjects

A Nicolin

Publications and source records attributed to A Nicolin.

At least 109 records · Page 6Linked to original sources
PubMedDate not supplied

Vaccination of leukemic mice with viable drug-altered leukemic cells.

The treatment in vivo with anti-tumour drugs can induce an antigenic alteration of L1210 leukemia resulting in the rejection of an inoculum of 10 X 10(6) viable cells in syngeneic mice. As drug-induced antigens appeared in excess of any pre-existing tumour-associated transplantation antigens (TATA), viable altered cells have been used to sensitize syngeneic animals. Experiments showed that viable altered cells elicited stronger anti-TATA reaction than X-inactivated parental cells, as measured by host survival to a challenge of L1210 leukemia. TATA immunogenicity of parental cells has been preminent, in the strain of animals used, to determine the sensitizing effectiveness of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) cells. Host protection to an inoculum of parental tumours has been more proficient with the DTIC subline derived from highly immunogenic L1210Ha cells than from poorly immunogenic L1210Cr cells. Immunoprophylactic inocula, proper chemotherapeutic treatments and adoptive transfer of immune lymphocytes used in combination exerted a synergic host protection.

Animals↗
PubMedDate not supplied

Influence of autologous serum on in vitro reactivity of peripheral lymphocytes of patients with breast cancer.

The influence of autologous serum on DNA synthesis and phytohemagglutinin (PHA) or pokeweed mitogen (PWM) stimulation of peripheral blood lymphocytes from mammary tumor-bearing women has been studied. Blood samples were collected from patients at the 4 stages of the TNM classification who had not undergone any therapeutic treatment. Lymphocyte functions were significantly reduced only in patients with the largest tumors and in the latest stage of disease. Autologous cancer sera inhibited spontaneous DNA synthesis of lymphocytes and did not inhibit lymphocyte stimulation by mitogens. It is possible that unrecognized inhibiting and stimulating factors, possibly acting in synergism with mitogens, are present in mammary cancer sera.

Adult↗
PubMedDate not supplied

Inhibition of cellular DNA synthesis and lack of antileukemic activity by non-photoactivated hematoporphyrin derivative.

It has been reported that cytocidal activity of light-activated hematoporphyrin (HPD) within the cells might be exploited in the therapy of experimental and human cancer. As part of a project from this laboratory aimed to study some major biologic features of HPD, it was found that [3H]thymidine incorporation in tumor cells was highly inhibited as a consequence of HPD treatment. HPD-mediated inhibition, obtained by a treatment either in vitro or in vivo, was long lasting and independent of light activation. Cellular DNA synthesis was inhibited by non toxic doses of HPD which were not influential either cell viability or cell oncogenicity. In preliminary studies, HPD-treated cells accumulated in the G1 phase of the cell cycle as detected by cytofluorometric analysis. This finding is in keeping with a likely inhibition exerted in late G1 or at the beginning of the S phase of cell the cycle and might exclude a direct damage of the DNA synthetic machinery. Definitive loss of cell viability and cellular DNA inhibition was obtained immediately after the exposure of HPD-treated cells to He-Ne laser light. HPD-mediated cell lysis was dose dependent and in the other of magnitude of cytocidal doses in different cell systems. HPD antileukemic activity or HPD interactions with chemotherapeutic drugs was ruled out in L1210 leukemic mice.

Animals↗
PubMedDate not supplied

Effect of cyclosporin A on T cell clones from severe aplastic anemia: differential sensitivity of TNF and GM-CSF production.

In this study we have analyzed the activity of Cyclosporin A (CsA) on the "in vitro" production of TNF and IL-3/GM-CSF as a preliminary basis for explaining the successful use of CsA in aplastic patients. Thus, 73 T cell clones, obtained by a limiting dilution technique from the peripheral blood and bone marrow of 3 patients with severe aplastic anemia (SAA), were studied for TNF and IL-3/GM-CSF production as induced by stimulation with 1% PHA plus 1 ng/ml TPA. Lymphokines obtained in this manner were then tested by biological assays. Twelve out of the initial 73 T cell clones were selected for the production of a large quantity of IL-3/GM-CSF and/or TNF. With these clones we studied the ability of CsA to inhibit TNF and IL-3/GM-CSF production, which was stimulated with specific monoclonal antibodies directed against the CD2 and CD3 surface antigens. TNF and IL-3/GM-CSF production displayed a different sensitivity to CsA inhibition. In fact, at 400 ng/ml CsA a residual production of IL-3/GM-CSF was present in all clones tested (CD3: 21.8% and CD2: 14.4% of the maximal IL-3/GM-CSF activity), while secretion of TNF was virtually abrogated at 100 ng/ml. Moreover, the mean ID50 for TNF production was significantly lower than that of IL-3/GM-CSF (CD2: p = 0.028, CD3: p = 0.01). Using specific anti-IL-3 and anti-GM-CSF monoclonal antibodies, we showed that only GM-CSF, and not IL-3, was resistant to CsA inhibition. In conclusion, these results may represent a possible explanation of the successful use of CsA in the treatment of some patients with SAA.

Anemia, Aplastic↗
PubMedDate not supplied

Manipulation of the growth rate of human breast cancer cells by antiandrogen followed by chemotherapy.

The effects induced by the antiandrogen Cyproterone Acetate (CPA) on the proliferation of EVSA-T human breast cancer cells endowed with androgen receptors were studied. Kinetic analyses were carried out by two autoradiographic techniques measuring the percentage of cells in S-phase and the growth fraction (GF). The exposure of the cultures to CPA for 24 h caused a marked inhibition on S-phase cells without significantly affecting the CF. The accumulation of cells in G1-phase, confirmed by cytometric analysis, was rescued to the S compartment by replacing the culture medium 24 h after CPA administration. Exposure of EVSA-T to Doxorubicin or Methotrexate after CPA and medium change at the time of maximal proliferative recruitment, led to an enhancement of cytotoxicity as demonstrated by colony survival assay.

Androgen Antagonists↗
PubMedDate not supplied

Comparison of in vitro drug sensitivity by inhibition of tritium release from [5-3H]-2'-deoxyuridine and a clonogenic assay.

In a search for a rapid and simple method to determine drug-induced cell lethality, the inhibition of tritium release from [5-3H]-2'-deoxyuridine (ITR) was compared with a standard clonogenic assay. Seven drugs were studied. After a 4 hr incubation period, [5-3H]-2'-deoxyuridine was added to cultures of human colon carcinoma cells (HCT-8) in vitro and four dose-response curves were generated for each drug by sampling the culture medium for tritiated H2O formation 4, 24, 48 and 72 hr later. These curves were compared to those obtained by a standard clonogenic assay. The ED50 values for 5 of the 7 drugs tested, methotrexate, 5-fluorouracil, doxorubicin, vincristine and cisplatin, as measured by inhibition of HCT-8 colony growth, were within 3 times the values observed with the metabolic assay. The ITR highly overestimated the cytotoxicity of 5-fluoro-2'-deoxyuridine: the irreversible inhibition of thymidylate synthase by this nucleoside resulted in an ED50 value 100-fold lower than that observed with the clonogenic assay. Opposite results were obtained with 5-fluorouridine. These data indicate that the ITR can be used to determine drug sensitivity of these cells to a host of compounds although it cannot be used indiscriminately for every antineoplastic agent as a cytotoxicity assay.

Adenocarcinoma↗
PubMedDate not supplied

Plasma retinol levels and side effects following high-dose retinyl acetate in breast cancer patients.

Plasma retinol levels and toxicity were evaluated in thirteen metastatic breast cancer patients treated orally with high-dose (300,000 I.U./day) retinyl acetate in combination with oral tamoxifen. Following the first dose of the drug, there was a drop of plasma retinol concentrations followed by a recovery to the pre-treatment levels and by a further increase to reach a plateau six to eight hours after drug administration. During the first two months of treatment cumulative increase of plasma retinol was seen, and long-term systemic concentrations in the +50-60% range level were maintained by the treatment. The toxicity observed was acceptable and included gastrointestinal symptoms, skin toxicity and headache. These toxicities could be related to the long-term increase of retinol systemic concentrations. We concluded that the daily dose of 300,000 I.U. retinyl acetate can be administered to cancer patients over a period of several months, is well tolerated and yields a substantial increase of systemic retinol.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Monoclonal antibodies to alpha DNA polymerase as a marker of cell proliferative activity.

A hybridoma cell line (5F) secreting monoclonal antibodies directed to alpha DNA polymerase has been developed. Kinetic studies on peripheral blood lymphocytes stimulated with mitogen and human colon cancer cell lines established in vitro were made by the two autoradiographic techniques of Thymidine Labelling Index and Primer-dependent alpha DNA polymerase Labelling Index and the immunoperoxidase assay (PAP) with monoclonal antibody to alpha DNA polymerase. We demonstrated the exclusively intranuclear presence of alpha DNA polymerase in lymphocytes induced to proliferate and actively growing colon cancer cells in contrast with the cytoplasmic distribution of the enzyme in resting stage populations. The feasibility of using monoclonal antibodies to alpha DNA polymerase to determine cell growth fraction was evaluated.

Animals↗
PubMedDate not supplied

Doxorubicin cytotoxicity to P388 lymphocytic leukemia as determined by alkaline elution and established assays.

Very large variations exist in the response of individual tumors to antineoplastic agents, even when the tumors are apparently very similar from the point of view of stage and histological classification. It has been recognized for a long time that methods capable of revealing the specific chemosensitivity of individual tumors could be useful for an individual optimization of a chemotherapeutic protocol. The Tumor Colony Forming Assay (TCFA) and the Biochemical Antimetabolic Assay (BAA) have been proposed for this purpose. Their main limitation is a consequence of the fact that the capability of in vitro growth is required from cells of a tumor grown in vivo. This is often lacking or very poor in the first in vitro passages. In this work we have investigated the possibility of using a sensitive method for evaluating DNA damage, the Alkaline Elution technique (AE). Cells treated in vivo can be easily tested directly for DNA damage. No cell proliferation in vitro is required. It is not required that the measured effect is the specific cause of cell death. A P388 Doxorubicin sensitive line and a resistant subline were tested. Correct correlations between DNA damage and chemosensitivity were obtained working both in vivo and in vitro. This test could be useful for assessing the chemosensitivity in vivo of alkylating and intercalating agents.

Animals↗
PubMedDate not supplied

[L-asparaginase].

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Animals↗