Biomedical subjects

B Lathan

Publications and source records attributed to B Lathan.

46 records · Page 3Linked to original sources

PubMed1985

In vitro comparison of vinzolidine and vinblastine: a model for methods of evaluation of analogues in a human tumor cloning system.

Four statistical techniques are described for comparing the in vitro cytotoxic activity of an analogue and its parent compound in the human tumor cloning system. These techniques include: the Spearman rank correlation coefficient; a sequential pairwise analysis; the kappa statistic for measuring agreement; and the McNemar test of symmetry. These statistical procedures were applied to results from 54 human tumor specimens that were simultaneously tested against multiple concentrations of the Vinca alkaloid vinblastine and its semisynthetic analogue, vinzolidine. Based on the percentage of survival of tumor colony-forming units in the human tumor cloning system, vinzolidine was shown to have a 26% in vitro response rate with a spectrum of activity across major tumor types. However, all four statistical procedures indicated that the activity of vinzolidine was not superior to that of its parent compound. Of the four statistical procedures examined, the sequential pairwise design appears to be best suited for comparing in vitro activity of an analogue and its parent compound and could result in a savings of both time and resources required for such comparisons.

Cell Survival↗

PubMed1984

Cytotoxic activity of echinomycin in a human tumor cloning system.

A human tumor cloning system was utilized to screen for in vitro antitumor effects of the investigational anticancer agent Echinomycin. Tumors from 562 patients (24 different histological tumor types) were placed in culture. Two hundred fifty-five specimens were evaluable for drug sensitivity information (i.e., greater than or equal to 20 colonies in control plates). The overall in vitro response rates (defined as less than 50% survival of tumor colony-forming units) at three different doses of Echinomycin (0.001, 0.01, and 0.1 micrograms/ml) were between 16% and 19%. Echinomycin showed minor in vitro cytotoxic activity in breast and colon cancer, and in sarcoma. A comparison of these in vitro results with the results of phase-II clinical trials, as they become available, will help to evaluate the utility of the human tumor cloning system for predicting clinical antitumor activity of new antineoplastics.

Cell Survival↗

PubMed1984

Use of a human tumor cloning system to evaluate analogs of methotrexate and mitoxantrone.

We have utilized a human tumor cloning system to compare the antitumor activity of trimetrexate ( TMQ ), a new dihydrofolate reductase inhibitor, and ametantrone , a new anthracenedione, with that of analogs already in clinical trial (methotrexate and mitoxantrone). Sixty-nine of 136 tumors plated for the TMQ study and 84 of 228 tumors plated for the ametantrone study were evaluable for drug-sensitivity assays. The overall in vitro response rates (defined as a less than or equal to 50% survival of tumor colony-forming units) for TMQ were 20% and 23% at 0.1 and 1 microgram/ml, respectively; for ametantrone they were 13%, 21%, and 26% at 0.1, 1, and 10 micrograms/ml, respectively. The overall in vitro activity for both new compounds was similar to that of their clinically used analogs, but TMQ was active in eight of 47 methotrexate-resistant specimens and ametantrone in nine of 62 mitoxantrone-resistant specimens. A comparison of these in vitro results with the results of phase II clinical trials with both drugs should allow an evaluation of the utility of the human tumor cloning system for predicting clinical antitumor activity of analogs of currently available antineoplastic agents.

Anthraquinones↗

PubMed1980

[Animal experiments for intratumoral chemotherapy with bleomycin (author's transl)].

The intense clinical interest in bleomycin as an anti-tumour agent has led to different methods of administration in an attempt to administer sufficiently high concentrations of the drug to the tumor. Therefore, a study was designed to determine the distribution and the therapeutic effect of a bleomycin emulsion and aqueous bleomycin after different routes of application. The tissue distribution of radioactively labelled bleomycin emulsion and aqueous bleomycin was determined in tumor-free CF 1 and tumor-bearing (EL 4, L 1210) C 57 Bl 6 and DBA 2 mice after local (s.c., i.t.) and systemic (i.v.) injection. The distribution studies for aqueous 57Co-bleomycin showed increased activity in the injection sites and the lymph nodes draining the injection sites after s.c. and i.t. injection compared to i.v. administration of the drug. In comparison to the aqueous local administration, the application of 57Co-bleomycin emulsion resulted in a disproportional increase of the 57Co-bleomycin concentration at the injection sites and in the draining lymph nodes. To prove the therapeutic relevance of the bleomycin tissue distribution tumor-bearing (line 10) strain 2 guinea pigs were treated with different modes of bleomycin. Animals with already lymphogenously metastasized tumors have been cured by means of low i.t. doses of the bleomycin emulsion. Guinea pigs treated with i.t. administration of aqueous bleomycin need, compared to the bleomycin emulsion, five times higher doses for tumor-free survival. Intravenously treated animals died either because of progressive tumor growth or because of toxic bleomycin effects. These findings made by animal experiments favor the i.t. treatment of head and neck carcinomas with a bleomycin emulsion.

Animals↗

PubMed1974

Lead the way.

Explore the source record for details and available documents.

Aged↗

PubMedDate not supplied

Binding of monoclonal anti-interleukin 2 antibody to nucleoli in acute leukemia blast cells.

Neutralizing anti-IL-2, anti-IL-3, and anti-IL-6 monoclonal antibodies (MAbs) were used for the immunoenzymatic detection of the respective cytokines in blast cells of 38 patients with acute myeloid (AML) and lymphoid (ALL) leukemias by the APAAP-technique. In 20/24 AML-cases (83%) blast cells showed intranuclear staining with MAb anti-IL-2 (DMS-1). In 17 cases reaction was restricted to the nucleoli, in 4 cases additional cytoplasmic staining was observed. Only 2/13 (15%) of the ALL cases showed anti-IL-2 staining. In contrast to IL-2, neither IL-3, IL-6 nor IL-2R alpha-chains were detected in any of the acute leukemias tested. The anti-IL-2 staining of nucleoli in AML cells is distinct from the cytoplasmic staining which is observed in PHA-activated normal lymphocytes and in a minority of AML cells.

Antibodies, Monoclonal↗

PubMedDate not supplied

In vitro drug sensitivity testing with agar-containing glass capillaries.

Capillary cloning has been shown to have advantages over conventional cloning of human tumor cells in Petri dishes. We have recently published in this Journal an optimization of the capillary method towards homogeneous colony distribution and high cloning efficiency. In the present study this modified capillary cloning system was investigated for its feasibility for drug sensitivity testing. For the human breast cancer cell line MDA-231 and the drug sensitive Chinese Hamster Ovary cell line CHO-AB as well as for its multidrug resistant mutant CHO-C5 a similar linear dose response effect was obtained with the capillary cloning system and with the Petri dish system. The capillary cloning system, however, was 2 to 4 fold more sensitive for the detection of cytotoxic drug effects. It was concluded that the optimized capillary cloning system is well suited for drug sensitivity testing.

Agar↗

PubMedDate not supplied

Homogeneous growth of tumor cell colonies in agar containing glass capillaries.

The capillary cloning system has been shown to have advantages over conventional cloning of human tumor cells in Petri dishes. In the present study a further optimization towards homogeneous colony distribution and high cloning efficiency is described. For reasons of reproducibility the study focused on cell lines, i.e. three human linew (MDA-231, HT-29, L363) and one rodent line (CHO-AB). Major variables investigated were the gel length, the capillary tube diameter, the tube sealing and buffer system, and the cell number. Criteria for optimal tumor colony growth included homogeneous colony distribution along the gel, mean colony size and cloning efficiency. It was found that colony distribution as well as overall colony growth depended largely on the gel length, i.e. on the volume of tumor cell containing agar applied per capillary tube. The results showed that optimal tumor cell colony growth was achieved in 100 ul capillary tubes of 1.2 mm internal diameter filled with 30ul, yielding a gel length of 27 mm. Colony formation did not significantly differ between sealed and unsealed tubes, provided that HEPES buffer was added. It was concluded that, for practical reasons, sealing of tube ends and therefore utilization of HEPES buffer is not necessary. In a head to head comparison, cloning efficiency was equal or higher in capillary tubes than in Petri dishes. The capillary cloning system is an alternative for drug development as well as for predictive drug testing. Its major advantage is the utilization of fewer tumor cells.

Agar↗

PubMedDate not supplied

Immunocytochemical detection of a resistance-associated glycoprotein in tissue culture cells, ascites tumors and human tumor xenografts by Mab 265/F4.

The aim of this investigation was to find out whether resistant cells of different tumors can be detected immunocytochemically by the streptavidin-biotin-peroxidase-complex method using the monoclonal antibody 265/F4. This antibody was prepared against the membrane P-glycoprotein of Mr 170 kd from colchicine-resistant CHO cells. For this purpose the acquired resistance of tissue culture cells, ascites tumors and the acquired and inherent resistance of human lung carcinoma xenografts were analyzed. Doxorubicin-resistant S180 cells, daunorubicin-resistant L1210 cells and vincristine-resistant human epidermoid lung carcinoma xenografts showed an intense positive reaction with the monoclonal antibody. In contrast, no specific immunoreactivity was observed with parental (sensitive) tumor cells. These data could eventually provide a prognostic tool for the detection of resistant human tumor cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

In vitro evaluation of the anticancer drug modulatory effect of hyaluronidase in human gastrointestinal cell lines.

In an attempt to establish whether the combination of anticancer drugs with hyaluronidase would result in enhanced cytotoxicity, we have tested a range of 6 continuous cell lines against 4 different chemotherapeutic drugs with or without the addition of various concentrations of the enzyme. Measurement of cytotoxic drug effects has been performed using the Bactec system, a new semiautomated radiometric technique. In only 15 of a total of 144 experiments (11%) was a significant hyaluronidase-mediated potentiation of the single agents' activity seen. In the large majority of experiments, the antiproliferative effect of the combined treatment was classified as additive or subadditive, while in 23% it was antagonistic. Evaluation of the drug modulatory mechanism of hyaluronidase suggested that the combined drug-hyaluronidase effects were independent of the nature of the drug, the exposure mode and the concentration of the enzyme employed. Among the various tumor cell lines tested there was a marked heterogeneity in the sensitivity to the combined effect (P less than 0.0001). In summary, we have not been able to confirm the promising results of early reports of in vitro and in vivo enhancement of the cytotoxicity of antitumor agents by hyaluronidase. Our data emphasize the need for further controlled clinical studies in order to prove or disprove this new therapeutic approach.

Adenocarcinoma↗