RESUMEN
This paper reports some physico-chemical properties and cytotoxic activity of marycin, a new hematoporphyrin derivative. The data show that marycin is a new compound, different from the other porphyrins tested. This product appears to be pure by adsorption or reversed phase thin-layer chromatography and high performance liquid chromatography and has chromatographic behavior different from those of other porphyrins tested. It does not appear to link to some tested metals and has a UV-visible absorbance spectrum different from that of a hematoporphyrin methylester. Furthermore, marycin has cytotoxic activity against K-562, ZR-75, MCF-7, HT-29, LOVO, human tumor cell lines and the MRC-9 human lung embryonic cell line. The new radiometric assay was used for all cell lines. Marycin decreases the growth index, measured by the radiometric assay as 14CO2 production. The cytotoxic activity is dose-dependent. Marycin is active at low doses but the activity varies with the cell line studied. The compound has low toxicity on the normal cell line MRC-9. Marycin is very liposoluble and would be expected to have high affinity and toxicity for tumors. The compound is active without light activation. How marcyin acts is still a matter for speculation.
Asunto(s)
Antineoplásicos/análisis , Hematoporfirinas/farmacología , Antineoplásicos/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Humanos , Solubilidad , Espectrofotometría Atómica , Espectrofotometría Ultravioleta , Células Tumorales CultivadasRESUMEN
From the 1950s to the 1970s, a number of in vitro systems that measured inhibition of glucose metabolism were used to predict the responsiveness of patients' tumors to chemotherapy. In vitro-in vivo correlations were excellent, with true positive predictions ranging from 68% to 96% and true negative predictions of 95% to 100%. The radiometric system is a new in vitro technique that measures the conversion of 14C-glucose to 14CO2. The system already has been utilized to screen prospective new antineoplastic agents for cytotoxicity. The present study was undertaken to determine if the radiometric system might be used to predict correctly the responsiveness of an individual patient's tumor to single-agent or combination-agent chemotherapy. Fifty-six tumor specimens were divided and tested for drug sensitivity in the radiometric system and a conventional human tumor clonning system. Overall, there was a significant correlation between in vitro and in vivo results for the conventional cloning system (P = 0.03). However, there was no significant relationship between in vitro and in vivo results for the radiometric system. The radiometric system consistently failed to predict the tumor's clinical sensitivity to single agents. A radiometric system is not useful in predicting the responsiveness of a patient's tumor to single agent chemotherapy and is not a replacement for the more biologically attractive human tumor cloning system.
Asunto(s)
Ensayo de Unidades Formadoras de Colonias/métodos , Neoplasias/tratamiento farmacológico , Radiometría/métodos , Ensayo de Tumor de Célula Madre/métodos , Antineoplásicos/farmacología , Células Cultivadas , Estudios de Evaluación como Asunto , Humanos , Estudios RetrospectivosRESUMEN
A rapid, semiautomated radiometric system is described for screening for new antineoplastic agents. This radiometric system utilizes inhibition of conversion of [14C]glucose to 14CO2 as an index of cytotoxicity. In this study the radiometric system (BACTEC 460) was first optimized using a variety of human and animal tumor cell lines. Overall, there was a clear linear relationship between the number of cells seeded and the production of 14CO2 from [14C]glucose. The BACTEC System easily detected antitumor activity of compounds from all four classes of antineoplastic agents (doxorubicin, vinblastine, cis-platinum, and methotrexate.) Human tumor cell lines were used to compare the antitumor activity of the same four agents measured by the BACTEC System versus the antitumor activity of the same agents measured by a conventional cloning system. For all cell lines tested there was good agreement in comparison of percentage of survival measured by the BACTEC System versus the standard cloning system. This agreement was better for a continuous exposure to drug in both systems (r = 87, P = less than 0.001) than for a 1-h exposure to the drug (r = 0.35, P = 0.036). In addition to determining the effect of drugs on tumor cells, the BACTEC System was successfully utilized to determine the cytotoxic effect on normal bone marrow buffy coat cells. By utilizing a comparison of suppression of 14CO2 production by normal versus tumor cells, a measurement of differential cytotoxicity could be made. Based on these findings, the radiometric BACTEC System represents a simple and rapid method to detect cytostatic or cytocidal activity of new compounds. It is ideal for use as a prescreen for testing a large number of new chemical entities against a large number of human tumor cell lines.
Asunto(s)
Antineoplásicos/farmacología , Ensayo de Unidades Formadoras de Colonias , Evaluación Preclínica de Medicamentos/métodos , Ensayo de Tumor de Célula Madre , Dióxido de Carbono/metabolismo , Radioisótopos de Carbono , Línea Celular , Glucosa/metabolismo , Humanos , Neoplasias/metabolismo , Factores de TiempoRESUMEN
Glutamic acid oxidation by Rickettsia prowazeki is not accompanied by hydrogen peroxide generation, nor is added hydrogen peroxide degraded, as measured by a manometric technique.
Asunto(s)
Catalasa/metabolismo , Peróxido de Hidrógeno/metabolismo , Rickettsia prowazekii/metabolismo , Glutamatos/metabolismoRESUMEN
A gonococcal pili antigen preparation was used to detect antibody activity sera obtained from 322 culture-positive asymptomatic females and 150 negative controls. Pili were obtained from a culture of type 2 Neisseria gonorrhoeae (strain 2686) and labeled with 125I for use in a double-antibody radioimmunoassay test system. Of the 322 sera obtained from culture-positive, asymptomatic females, 276 (85.7%) showed antibody activity greater than or equal to 1.8 mug/ml. Negative controls were obtained from three different groups of individuals, and 130 (86.7%) had undetectable antibody activity. Sera from asymptomatic, culture-positive females were absorbed with three different strains of N. gonorrhoeae, one of these strains being the organism used for pili antigen preparations. The absorbed sera were tested for antibody activity, and in each case the activity in the absorbed sera dropped to an undetectable level. When the same sera were absorbed with N. meningitidis, N. catarrhalis, N. perflava, Escherichia coli, Herellea vaginicola, Mima polymorpha, Staphylococcus aureus, and Candida albicans, little, if any, decline in the level of anti-pili antibody activity was observed.