Disease relevance of KARMINOMYCIN

• Randomized phase II trial of carminomycin versus 4'-epidoxorubicin in advanced breast cancer [1].
• Acute nonhematologic toxic effects were qualitatively similar but carminomycin produced significantly less gastrointestinal intolerance and alopecia [1].
• Cloning and sequencing of a gene encoding carminomycin 4-O-methyltransferase from Streptomyces peucetius and its expression in Escherichia coli [2].
• Expression of dnrK in Streptomyces lividans and Escherichia coli was done to show that this gene codes for carminomycin 4-O-methyltransferase [2].
• Carminomycin showed the greatest effectivity against the leukemia L1210 [3].

High impact information on KARMINOMYCIN

• Carminomycin (1.75 X 10(-5) M) produced a greater fall in cardiac output than equimolar daunomycin (26 +/- 2 versus 36 +/- 2 ml/min; p less than 0.01) [4].
• Procedures that increased cytosolic calcium relieved heart failure namely, pretreatment with digoxin (62.4 micrograms), isoproterenol (10(-6) M), and increased perfusate Ca2+ (5 mM versus 2.5 mM) all prevented carminomycin-induced fall in cardiac output (41 +/- 1, 47 +/- 5, and 52 +/- 1, respectively, versus 26 +/- 2 ml/min; p less than 0.01) [4].
• The sensitivity of bone marrow granulocyte-macrophage colony-forming cells to 4 anthracyclines, carminomycin, marcellomycin, aclacinomycin A, and N,N-dibenzyldaunorubicin, was studied using the agar diffusion chamber technique which allows exposure of target cells to drug metabolized by the chamber-bearing host after i.v. injection [5].
• A phase I and clinical pharmacology study of intravenously administered carminomycin in cancer patients in the United States [6].
• Within 1 hr after the administration of carminomycin, 20 mg/kg, nucleoli of cardiac and skeletal muscle cells were segregated, while nucleoli of liver parenchyma cells were unaffected [7].

Chemical compound and disease context of KARMINOMYCIN

• Leukemia cells from 4 acute myelocytic leukemia (AML) and 1 acute lymphocytic leukemia (ALL) patients were incubated with a set of 6 anthracycline agents: Adriamycin (Am), 4'-epi-Adriamycin (4'-epi-Am), daunorubicin (Dm), 4-demethoxy-daunorubicin (4-dDm), carminomycin (Cm) and N-trifluoroacetyl-Am-14-valerate (AD32) [8].
• Our data indicate a weak association of net accumulation and the toxicity parameter IC50 for carminomycin and idarubicin [9].
• Twenty-two patients who had metastatic breast cancer previously treated with combination chemotherapy, cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or CMF with vincristine and prednisone, were treated with Carminomycin (carubicin) 20 mg/m2 body surface area by intravenous bolus injection once every 3 weeks [10].
• Thirty-nine adults with clinical stage III or IV diffuse large cell lymphoma were prospectively randomised to receive etoposide with doxorubicin (Group 1: n = 17), the same schedule of etoposide with carminomycin (Group 2: n = 8), or BACOP (Group 3: n = 14) [11].

Biological context of KARMINOMYCIN

• The anthracyclines inhibited cellular RNA synthesis with IC50 values of 1-3 microM (ADM, DNM), 0.3-0.5 microM (CMM, 4D-DNM, PYM), and 0.06 microM (MCM, ACM) [12].
• The number of binding sites per phospholipid molecule (n) and the apparent association constant (Kapp) where K = nKapp, were determined at several temperatures for adriamycin, daunomycin, and carminomycin [13].
• Pharmacokinetics of carminomycin in dogs and humans. Preliminary report [14].
• The influence of pH on the equilibrium, kinetics and dynamics of sorption of anthracycline antibiotics (rubomycin, doxorubicin and carminomycin) on the carboxylic sorbents has been studied [15].
• The reaction product from methylation of carminomycin was confirmed by chromatography and mass spectral analysis to be daunomycin [16].

Anatomical context of KARMINOMYCIN

• These results demonstrate that at sufficiently high doses carminomycin induces ultrastructural lesions in nucleoli of both cardiac and muscle cells [7].
• One-electron reduction of an anthracycline antibiotic carminomycin by a human erythrocyte redox chain [17].
• Effect of carminomycin on the viability of fibroblasts from patients with regular trisomy 21 [18].
• Toxic effects of violamycin Bi, carminomycin and daunorubicin on the myocardium of rabbits [19].
• The cytotoxic effect of daunorubicin, carminomycin, idarubicin and the major metabolite of idarubicin in man, 4-demethoxydaunorubicinol, was investigated in a human normal progenitor myeloid stem cell assay and in a human tumor stem cell assay [20].

Associations of KARMINOMYCIN with other chemical compounds

• Human erythrocyte membranes catalyse the NAD(P)H-dependent generation of the semiquinone of an adriamycin-type antibiotic carminomycin under anaerobic conditions [17].
• Plasma samples were obtained and assayed for carminomycin and carminomycinol by high pressure liquid chromatography with fluorescence detection [14].

Gene context of KARMINOMYCIN

• The difference in the accumulation levels and dynamics and in the intracellular distribution of the free and conjugated DR and CM is likely to underlie the higher cytotoxic activities of the anthracycline conjugates with EGF compared to the free drugs [21].
• These experiments were confirmed using synthetic polynucleotid template poly(rA)n(dT)12-18 for the Rauscher RT enzyme and poly(dA)n . poly(dT)n for E. coli DNA polymerase I. In our work we have shown that Carminomycin, in contrast to Adriamycin and Daunomycin, possesses a highly specific inhibitory effect on the RT enzyme system [22].

Analytical, diagnostic and therapeutic context of KARMINOMYCIN

• Analysis of carminomycin in human serum by fluorometric high-performance liquid chromatography [23].
• Plasma and urine samples were obtained during two subsequent 72-hr periods following drug administration, and assayed for carminomycin (C) and carminomycinol (Col) by HPLC with fluorescence detection [24].
• Eighty-three patients with advanced soft tissue sarcoma who had received no prior chemotherapy entered a randomised phase II study comparing carminomycin (CMM) 20 mg/m2 with adriamycin (ADM) 75 mg/m2, both administered i.v. bolus every 3 weeks [25].

References