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At least 19 recordsLinked to original sources
PubMed1975

Binding of bleomycin to DNA in bleomycin-sensitive and -resistant rat ascites hepatoma cells.

The 14C activity of [14C]bleomycin bound to DNA in bleomycin-sensitive rat ascites hepatoma cells (AH-66) was 8.7 times higher than in resistant cells (AH-66F) when the cells were incubated with [14C]bleomycin. The difference in permeability to bleomycin was not significant; uptake of [14C]bleomycin by the sensitive cells was only 1.2 times larger than that by the resistant cells, and the radioactivity incorporated into the nuclei of sensitive cells was only 1.3-fold greater. The bleomycin-inactivating enzyme level in the resistant cells was 3.5 times higher than in the sensitive cells, indicating that the antibiotic incorporated into the resistent cells was reduced in DNA-binding activity to a large extent. The level of protein-free thiol compound in the sensitive cells was 1.8-fold higher than in the resistant cells, suggesting a possible enhancement of bleomycin action by intracellular thiol compound as is found in vitro. These factors probably affect the DNA strand scission and the sensitivity of cells to this antibiotic. Binding of [14C]bleomycin to DNA in vitro was studied in the presence and the absence of dithiothreitol. A large portion of the radioactivity bound in the presence of dithiothreitol was unstable to acid, but the acid-resistant binding was also enhanced by this thiol compound.

Animals↗
PubMed1977

Comparison of oncophilic radiopharmaceuticals, *I-fibrinogen, 67Ga-citrate, 111In-bleomycin, and *I-bleomycin in tumor-bearing mice.

The pharmacokinetics of 67Ga-citrate, 111In-bleomycin, *I-bleomycin, and *I-fibrinogen were compared in a murine KHJJ tumor model in order to assess their relative potential as agents for in vivo detection of cancer. Although all four agents have been reported to be clinically efficacious, in this tumor model, *I-fibrinogen and 67Ga-citrate had the greatest tumor accumulation with maximum concentrations of 11.7% and 10.5% respectively. However, both these radiopharmaceuticals cleared slowly from the blood and animal. The maximum tumor concentrations of 111In-bleomycin and *I-bleomycin were 2.9% and 2.6% respectively, but *I-bleomycin had the advantage of rapid clearance from the blood and animal. 67Ga-citrate did not achieve its maximum tumor concentration until 24 hours after administration, whereas the other radiopharmaceuticals achieved maximum tumor concentration within several hours of administration. From these observations 123I-bleomycin seems to deserve clinical trials in patients. 123I-fibrinogen appears to have significant oncophilic potential if its clearance from the animal can be accelerated without altering its accumulation in the tumor.

Animals↗
PubMed1979

Structural studies of of "active complex" of bleomycin: assignment of ligands to the ferrous ion in a ferrous-bleomycin-carbon monoxide complex.

Proton NMR studies at 360 MHz establish the binary Fe(II)-bleomycin complex to be paramagnetic with a spectrum covering 70 ppm. Addition of carbon monoxide generates a stable, diamagnetic Fe(II)-bleomycin-CO complex that is a putative structural analog of the "active" Fe(II)-bleomycin-O2 complex. The following six groups have been determined to be coordinated to the Fe(II) ion from analysis of the highly resolved 1H NMR spectra of this complex: CO, the primary and secondary amine nitrogens of the beta-aminoalanine moiety, the carbamoyl moiety on the 3-position of mannose, the pyrimidine N-1, and the imidazole N-1. The Fe(II)-bleomycin-CO complex binds to DNA, as shown by fluorescence quenching experiments, but Fe(II)-bleomycin-CO does not mediate thymine release. These results necessitate a major revision in the current model for metal coordination to bleomycin.

Bleomycin↗
PubMed1979

Oxygenated iron bleomycin. A short-lived intermediate in the reaction of ferrous bleomycin with O2.

The reaction of Fe(II) . bleomycin with O2 to yield Fe(III) . bleomycin has been resolved into two kinetic events by stopped-flow spectrophotometry. The first event is first order with respect to both bleomycin and O2 and may be regarded as a second order reaction (k = 6.1 x 10(3) M-1s-1 at 2 degrees C). The first product has no EPR spectrum. The optical spectrum resembles those of Fe(II) . bleomycin complexes with CO, NO, and ethyl isocyanide. We propose that the first product is an Fe(II) . bleomycin . O2 complex. The second kinetic event is first order with respect to the first accumulated product (k = 0.11 s-1 at 2 degrees C) and independent of oxygen concentration. The product of this reaction is indistinguishable from Fe(III) . bleomycin by optical and EPR spectroscopy.

Bleomycin↗
PubMedDate not supplied

Therapy of advanced esophageal cancer with bleomycin, irradiation and combination of bleomycin with irradiation.

Results from treating 51 patients with advanced esophageal cancer are presented. Fifteen patients were treated with Bleomycin, 12 with radiotherapy, and 24 with a combination of bleomycin and radiotherapy. The best results were achieved in the group of patients treated with combined therapy showing 62% objective remissions (15/24) which was statistically significant (P less than 0.001) in comparison to the other groups. In the Bleomycin therapy group, there were 26% objective remissions (4/15), and in the group treated only with radiotherapy 33% (4/12)- The median duration of remission was 9 months in the combined therapy group, 6.3 months in the group treated with radiotherapy, and 2.6 months in the Bleomycin treated group. The authors concluded that the combination of Bleomycin and radiotherapy seems to be a further step in palliative treatment of advanced esophageal cancer.

Adult↗
PubMed1976

[Effect of continuous bleomycin treatment and of oil-suspended bleomycin on experimental tumor growth (author's transl)].

Effects of continuous administration of bleomycin solution and of intralesional injection of sesame oil-suspended bleomycin on tumor growth were studied. Experimental animal tumors were 3 rd generation isotransplants of a spontaneous C3H mouse mammary carcinoma. Bleomycin treatments were started when transplanted tumors reached 8 mm in diameter and the measurement of tumor volume was followed. Dose administered was fixed as 100 mg/kg in all the groups. Bleomycin solution was given intralesionally in a single or 4 daily doses, or intraperitoneally by continuous infusion. The latter method inhibited tumor growth most effectively, while the single injection was the last effective. Intralesional injection of oil-suspended exhibited similar effectiveness as the continuous infusion, and it was independent of the number of fractions. These results were interpreted by the several features in the response of mammalian cells to the antibiotic.

Animals↗
PubMed1976

Bleomycin in advanced squamous cell carcinoma: a random controlled trial. Report of Medical Research Council Working Party on Bleomycin.

Bleomycin was compared with conventional cytotoxic drugs in the treatment of 70 patients with advanced squamous cell carcinoma; the primary deposit was in the head and neck in 50 patients and in the perineum or skin in 20. Thirty-four patients received bleomycin while 36 received other cytotoxic drugs. No significant difference was detected between the two groups either in the proportion showing tumour regression or in the survival rates. If bleomycin is to advance the treatment of squamous cell carcinoma it can be only in combination with other drugs or with radiotherapy.

Adult↗
PubMed1992

[Bleomycin emulsion for intralesional instillation in advanced oropharyngeal carcinomas. A case report on local bleomycin application].

Local therapy of head and neck cancer using a special bleomycin emulsion as an intratumoral applicarted cytotoxic agent is not established in regular antitumor therapy. It's use only is supposed to be regarded as an "ultima ratio" possibility when other usual methods like surgery, radiotherapy or systemic cytostatic therapy have failed. The procedure of intralesional bleomycin emulsion application will be described and the advantages and disadvantages will be discussed by means of a long-term case report.

Adult↗