carubicin and Lymphoma

Topics: Aclarubicin; Animals; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Daunorubicin; Doxorubicin; Female; Glycosides; Hodgkin Disease; Humans; Leukemia; Lung Neoplasms; Lymphoma; Naphthacenes; Ovarian Neoplasms; Sarcoma

Topics: Adult; Animals; Antibiotics, Antineoplastic; Carubicin; Chemical Phenomena; Chemistry; Child; Dogs; Humans; Leukemia; Leukemia L1210; Lymphoma; Mice; Rats; Sarcoma

During the 1st stage of the clinical trials of karminomycin 92 patients with leukemia, solid tumors and lymphoma were treated with karminomycin. Two schemes for the antibiotic use were developed. The 1st scheme was a prolonged one with single doses of 10-15 mg (7.5 mg/m2) administered intravenously twice a week for 3 weeks, the course dose being 60-75 mg (34-45 mg/m2) with 4-week intervals between the courses. The course dose for the patients previously subjected to intensive chemotherapy did not exceed 50 mg (30 mg/m2). The 2nd scheme was a short one with single doses of 8-10 mg (5.5 mg/m2) administered intravenously every day for 5 days, the course dose being 40-50 mg (23-30 mg/m2) with 3-week intervals between the courses. Karminomycin induced in a number of patients a direct side effect, such as nausea, vomiting, asthenia, tachycardia, pain in the heart. In some patients leucopenia, thrombocitopenia, rare stomatitis, alopecia, lowered T peak in the chest curves of the cardiograms were observed after using the course dose.

Topics: Adult; Antibiotics, Antineoplastic; Carubicin; Child; Clinical Trials as Topic; Drug Evaluation; Hematopoiesis; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukopenia; Lymphoma; Time Factors

Antitumor activity of doxorubicin made in the USSR was studied on mice in respect to three transplantable tumors (lymphadenosis NK/LI, sarcoma 37 and Ehrlich's carcinoma) and hemocytoblastosis La. Doxorubicin injected intravenously 4 times was shown to be highly active against the above ascites tumors. The highest inhibitory effect of doxorubicin was observed in respect to the development of Ehrlich's carcinoma. By the selectivity of the therapeutic effect on this tumor it was superior to rubomycin and carminomycin. A high antileukemic activity of doxorubicin in respect to hemocytoblastosis La was shown. In experiments with this leukemia, intravenous injection of doxorubicin provided a higher efficacy than intraperitoneal injection. When used intravenously in the doses equivalent by their toxicity doxorubicin was inferior to rubomycin in terms of the therapeutic effect on leukemia La. However, on intraperitoneal injection of the drugs rubomycin showed no such advantage. Doxorubicin made in the USSR did not differ by its antitumor activity from the analogous foreign drug.

Topics: Animals; Carcinoma, Ehrlich Tumor; Carubicin; Daunorubicin; Dose-Response Relationship, Drug; Doxorubicin; Injections, Intraperitoneal; Injections, Intravenous; Leukemia, Experimental; Lymphoma; Male; Mice; Mice, Inbred C57BL; Sarcoma, Experimental

The cytostatic effect of some semi-synthetic derivatives of carminomycin on the tumor cells of mouse lymphadenosis (NK/Ly was studied in primary suspended cultures. A rapid method developed by the authors was used for determination of the drug cytostatic effect. The method is based on measuring the intensity of 3H-thimidine incorporation into the tumor cells. Simultaneously a method based on estimation of the increase of the total amount of the nucleic acids was used. No derivative superior to the initial drug by the level of the cytostatic effect on the tumor cells was found.

Topics: Animals; Carubicin; Daunorubicin; Depression, Chemical; DNA, Neoplasm; Drug Evaluation, Preclinical; In Vitro Techniques; Lymphoma; Mice; Neoplasms, Experimental; RNA, Neoplasm

Bovine serum albumin (BSA) and carminomycin, an anthracycline antibiotic, were subjected to conjugation with glutaraldehyde and their complexes with various contents of the antibiotic were prepared. The molar ratios of carminomycin and BSA were 8:1, 4:1, and 2:1. The antitumor effect of the preparations was studied on the models of mouse transplantable lymphosarcoma LIO equal 1 and ascitic forms of mouse lymphadenosis NK/Ly in vivo and in vitro. Their immunodepressant effect was evaluated from the decrease in the hemagglutinin titers in the mice immunized with sheep red blood cells. It was shown that when the toxicity of the complexes was the same, their antitumor and immunodepressant activities were different. The therapeutic activity of carminomycin in the four- and eight-substituted complexes was much higher than that of carminomycin alone. It is suggested that the differences in the activity of the complexes were connected with differences in their pharmacokinetics. It was found that the chemotherapeutic properties of the complexes may have changed by variation of the number of the cytostatic residues in the albumin molecule. The findings indicate that the whole complex molecule interacts with the malignant cell and not carminomycin preliminarily detached from it.

Topics: Animals; Antibiotics, Antineoplastic; Antibody Formation; Carubicin; Daunorubicin; Drug Combinations; Drug Evaluation, Preclinical; In Vitro Techniques; Lethal Dose 50; Lymphoma; Lymphoma, Non-Hodgkin; Male; Mice; Neoplasms, Experimental; Serum Albumin, Bovine; Time Factors

Sensitivity of the mice inoculated with ascitic NK/Ly cells and cured with carminomycin to repeated inoculation with the same tumour was studied. It was found that curing with carminomycin was accompanied by development of resistance to the repeated inoculation. Such resistance might be transferred to intact singeneic mice with a suspension of the cells of the spleen or lymph nodes from unsusceptible donors. The transfer of the thymus cells from the above donors protected the recipients only partially. The spleen cells from intact donors, as well as their lymph node cells did not inhibit the tumour development. The thymus cells of the intact mice induced some suppression, thus probably favouring the active immune response in the recipient. Curing of the NK/Ly-inoculated mice with carminomycin was a more effective method for induction of immunity to the tumour than immunization of mice with NK/Ly cells inactivated by UV irradiation in vitro

Topics: Animals; Carubicin; Daunorubicin; Drug Evaluation, Preclinical; Immunity; Immunization; Immunization, Passive; Lymphoma; Male; Mice; Mice, Inbred CBA; Neoplasm Transplantation; Neoplasms, Experimental; Ultraviolet Rays

Topics: Animals; Carubicin; Daunorubicin; DNA; DNA Repair; Lymphoma; Male; Mice; Micrococcus; Neoplasms, Experimental

Amphotericin B has a significant cytostatic effect on lymphadenosis cells of mice NK/LY. In a concentration of 6 units/ml it inhibits an increase in total nucleic acids by 50 per cent. Such cytostatic effect of amphotericin B combines with the effect of carminomycin and adriamycin. In concentrations having no cytostatic effect amphotericin B does not enhance the action of adriamycin and carminomycin on tumor cells.

Topics: Amphotericin B; Animals; Carubicin; Cells, Cultured; Daunorubicin; Doxorubicin; Drug Evaluation, Preclinical; Drug Synergism; In Vitro Techniques; Lymphoma; Mice; Neoplasms, Experimental

The effect of carminomycin administered intravenously to albino mice on the sedimentation character of the ascitic cell DNA of mouse lymphadenosis NK/Li, as well as the cells of the lungs, kidneys, liver, heart and spleen in alkaline sucrose gradients was studied. It was found that carminomycin in a dose of 3.5 mg/kg (LD50) induced DNA single-strand breaks in the cells of the lungs, kidneys, liver and heart. At the same time the single-strand breaks were not detected in the tumor cells NK/Li and the cells of the spleen. The results are indicative of correlation between sensitivity of the cells to carminomycin and a decreased capacity of the antibiotic for induction of single-strand breaks in DNA. Probably, the cell ability for DNA repair is an important factor defining the antitumor selective effect of carminomycin. Induction of the single-strand breaks reflects the role of the excision repair in healing the damages induced by carminomycin.

Topics: Animals; Carubicin; Daunorubicin; DNA Repair; DNA, Neoplasm; DNA, Single-Stranded; Drug Evaluation, Preclinical; Injections, Intravenous; Lymphoma; Male; Mice; Neoplasm Transplantation; Neoplasms, Experimental

The effect of carminomycin, an antitumor antibiotic of the anthracycline group on DNA of lymphadenosis cells of mice NK/LI was studied. It was found that carminomycin induced single-stranded breaks in DNA. The effect of the antibiotic was proportional to its concentration and depended on the time of the cell exposure to it. When the antibiotic was used in a concentration of 10 gamma/ml, the maximum effect was observed within a minute of incubation. Reparation of DNA must be possible on prolong exposure of the cells to the above dose of the antibiotic. Double-stranded breaks as well as significant degradation of the DNA complex with other nuclear components were not observed.

Topics: Animals; Antibiotics, Antineoplastic; Carubicin; Centrifugation, Density Gradient; DNA, Neoplasm; DNA, Single-Stranded; Dose-Response Relationship, Drug; In Vitro Techniques; Lymphoma; Mice; Neoplasms, Experimental; Time Factors

Anthracycline antibiotics rubomycin (daunomycin) and carminomycin rapidly accumulated in the bacterial and ascitic tumor cells and their intracellular concentrations significantly exceeded the concentrations in the medium. The strains of Staph. aureus and Fisher mouse ascitic lymphadenosis L-5178/P resistant to rubomycin preserved sensitivity to carminomycin. The resistance of the bacterial and tumor strains to rubomycin was accompanied by a significant decrease in the accumulation of rubomycin in the cells. At the same time carminomycin also effectively accumulated in the cells of Staph. aureus and Fisher ascitic lymphadenosis adapted to rubomycin, the same as in the cells of the parent strains.

Topics: Adaptation, Physiological; Animals; Antibiotics, Antineoplastic; Carubicin; Cell Line; Daunorubicin; Drug Resistance; Drug Resistance, Microbial; In Vitro Techniques; Kinetics; Lymphoma; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Staphylococcus aureus

The antiblastomic activity of the carminomycin complex components was studied with respect to 8 strains of transplantable tumors of mice: lymphosarcoma L10-1, prestomach cancer OZh-5, sarcoma 180, lymphoid leucosis L 1210, lung bronchogenic cancer RL, lymphodenosis NK/LI, Ehrlich carcinoma and Garding-Passy melanoma. It was shown that components I, II and III possessed almost the same high antiblastomic activity and the same optimal administration schemes should be used for them. The scheme consisted of two-fold administration of the drug at intervals of 96-120 hours. Component I had broader therapeutic ranges and was more active against the lung bronchogenic cancer as compared to component II. All 3 components had no selective antiblastomic effect on the ascitic form of Ehrlich carcinoma. A comparative study of the component toxicity and pharmacology is required for final conclusion as to the recommendation of one of the components for clinical trials.

Topics: Animals; Antibiotics, Antineoplastic; Carcinoma, Bronchogenic; Carcinoma, Ehrlich Tumor; Carubicin; Drug Evaluation, Preclinical; Lethal Dose 50; Leukemia L1210; Lung Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin; Melanoma; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred DBA; Neoplasms, Experimental; Sarcoma 180; Time Factors

The variants of the tumor cells of Fisher lymphadenosis, strain L-5178 and Staph. aureus resistant to rubomycin simultaneously became partially less sensitive to adriamycin. Sensitivity to karminomycin in the rubomycin resistant strains did not practically change as compared to the sensitivity of the initial strains. Sensitivity to adriamycin and rubomycin in Staph. aureus decreased 67 and 4 times respectively after 7 passages on media with increasing concentrations of adriamycin, while sensitivity to karminomycin decreased only 1.5 times, i.e. remained practically unchanged. After 22 passages of Staph. aureus to karminomycinrubomycin and adriamycin decreased 16, 67 and 33 times respectively. The results of the study may be explained by differences in the changes of the cell membrane permeability due to the drug effect.

Topics: Animals; Antibiotics, Antineoplastic; Carubicin; Cell Line; Cells, Cultured; Daunorubicin; Dose-Response Relationship, Drug; Doxorubicin; Drug Resistance; Drug Resistance, Microbial; Lymphoma; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Staphylococcus aureus

Antitumor activity of karminomycin used perorally was studied with respect to 3 strains of mouse transplantable tumors, i. e. one ascitic strain of lymphadenosis NK/LI and two solid strains of lymphosarcoma L10-1 and sarcoma 180. Karminomycin was shown to have a high antitumor activity against the above tumors on its oral administration. In the experiments with lymphadenosis NK/LI the efficiency of karminomycin was higher when it was used perorally as compared to its intravenous administration. It was found that karminomycin had practically the same inhibitory effect on growth of lymphosarcoma L10-1 and sarcoma 180 on its peroral and intravenous administration in doses equivalent by their toxicity.

Topics: Administration, Oral; Animals; Antibiotics, Antineoplastic; Carubicin; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Injections, Intravenous; Lymphoma; Lymphoma, Non-Hodgkin; Male; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Sarcoma 180; Time Factors