Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “bleomycin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,297 records · Page 72Linked to original sources
PubMed1999

Alterations in the immunohistochemical distribution patterns of vascular endothelial growth factor receptors Flk1 and Flt1 in bleomycin-induced rat lung fibrosis.

To investigate the role of vascular endothelial growth factor (VEGF) in fibrogenesis, the distribution patterns of the VEGF receptors Flt1 and Flk1 were studied by immunohistochemistry, double immunofluorescence, and immunoelectron microscopy in normal (n=2) and bleomycin-treated (n=21) adult rats. Lungs were studied at 5, 24, 28, 35, and 42 days after treatment (p.t.). Flt1, Flk1, and VEGF immunoreactivity localised predominantly to the pulmonary epithelium. In control lungs, Flt1 immunoreactivity was present in ciliated bronchial epithelium and type 2 pneumocytes, Flk1 in Clara cells, and VEGF in Clara cells and type 2 pneumocytes. Flk1 localised to mast cells, present in the peribronchovascular and pleural interstitium only. Flt1- and Flk1-mRNAs were observed in Clara cells and type 2 pneumocytes. Bleomycin-induced fibrogenesis was characterised by a decrease in Flk1 immunoreactivity of Clara cells, and an increase in VEGF-immunoreactive myofibroblasts and type 2 pneumocytes by day 5 p.t., followed by a progressive accumulation of Flk1-immunoreactive mast cells by day 24 p.t. in fibrotic lesions containing VEGF-immunoreactive myofibroblasts. After 42 days, fibrotic regions were densely populated by mast cells. Since mast cells are known to be chemotactically attracted by VEGF, we suggest that VEGF/Flk1 represents the molecular link between proliferation of myofibroblasts, accumulation of mast cells, and the burst of fibrosis at sites of initial lesions in bleomycin-induced fibrosis.

Animals↗
PubMed1986

Cyclic chemotherapy with cyclophosphamide, doxorubicin, and cisplatin plus vinblastine and bleomycin in advanced germinal tumors. Results with 100 patients.

One hundred patients with advanced mixed germ-cell tumors were treated with cisplatin, cyclophosphamide, and doxorubicin alternating with vinblastine and bleomycin (cyclic CISCAII/VBIV). The chemotherapy achieved an 89 percent continuous disease-free status (85 percent with chemotherapy, 4 percent with chemotherapy plus surgery). The mean follow-up duration for patients with continuous complete remission was 132 weeks (+/- 6.2), with a median of 126 weeks. Multivariate analysis using a stepwise logistic regression of prognostic variables revealed that a high serum level of the beta subunit of human chorionic gonadotropin (more than 50,000 mIU/ml) was of prognostic significance, followed by the Samuels staging criteria and extragonadal origin of disease. Thirty-two patients underwent exploratory surgery after they had had two courses of chemotherapy beyond the establishment of a stable mass and absent serum biomarkers. No viable cancer was found at exploration, and all patients remain alive and free of disease. The acute toxicity of the cyclic chemotherapy was formidable, but only one patient had a fatal complication. Thirty-six percent of the CISCAII courses and 44 percent of the VBIV courses were associated with leukopenic fever, and 5 percent of the CISCAII courses and 8 percent of the VBIV courses were associated with culture-positive infection. Long-term toxicity was unusual: bleomycin lung toxicity 1 percent, cardiac toxicity 1 percent. CISCAII/VBIV cyclic chemotherapy is superior to cisplatin, vinblastine, and bleomycin (PVB) chemotherapy; it results in a higher complete remission rate, a lower relapse rate, and a lower incidence of long-term complications. Patients with a high risk of failure of PVB chemotherapy (Samuels stage IIIB3 to IIIB5) or with extragonadal tumors should be treated with CISCAII/VBIV.

Adolescent↗
PubMed1975

Cataracts in bleomycin-treated rats.

Bleomycin was administered to 126 normal or human-tumor-bearing baby rats we observed for the development of cataracts. Eighty-four percent of the rats receiving this drug before the age of 10 days developed lens opacities. Bleomycin given to 10-day-old rats or older did not induce cataract formation. The cataracts initially occurred in the nuclear area and later involved most of the lens whether or not bleomycin was later discontinued. The presence of the tunica vasculosa lentis in rats younger than 10 days old may explain why cataracts developed only in these young animals.

Age Factors↗
PubMed1975

Effects of extracts of rat tissues on the action of bleomycin.

The cell sap (105 000 times g supernatant) of various tissues of rats caused DNA degradation in the presence of bleomycin. The activity was fractionated into two peaks by column chromatography on Sephadex G-25. The activity in Peak A (excluded fraction) appeared to be due to some proteinaceous entity, while that recovered in Peak B (retarded fraction), constituting about 90% of the total activity, seemed to be due to ascorbic acid, judging by results of further gel filtration and the effect of treatment with ascorbate oxidase. Incubation of bleomycin with Peak A or B caused loss of the ability of the antibiotic to degrade DNA. It is proposed that the action of bleomycin on DNA, and its inactivation by tissue extracts, depend, at least in part, on the presence of ascorbic acid.

Animals↗
PubMed1978

Specificity of DNA base release by bleomycin.

DNA was treated with bleomycin in the presence of Fe2+ and 2-mercaptoethanol under conditions where only a few percent of the bases were released. Release of all four bases was a linear function of bleomycin concentration, but the amount of thymine released was twice that of cytosine, 7 times that of adenine, and twelve times that of guanine. Unidentified minor products of thymine, of cytosine and of a purine were also released. Bromouracil did not sensitize DNA to bleomycin-induced breakage, and was released at the same rate as thymine.

Bleomycin↗
PubMed1983

Nucleotide sequence cleavage of guanine-modified DNA with aflatoxin B1, dimethyl sulfate, and mitomycin C by bleomycin and deoxyribonuclease I.

In guanine-modified DNA with aflatoxin B1, dimethyl sulfate, and mitomycin C, the nucleotide sequence cleavage of bleomycin or DNase I has been investigated using 32P-labeled DNA fragments. In contrast with cis-dichlorodiammine platinum (II) which induces intrastrand crosslinking of guanine N7 atoms, these mono-covalent modifiers did not give remarkable alteration of the DNA nucleotide cleavage mode by bleomycin and DNase I. From the viewpoint of combination drug, it is of interest that mitomycin C promoted the DNA cleavage activity of bleomycin.

Aflatoxin B1↗
PubMed1983

Photolabelling of dopamine-beta-hydroxylase by bleomycin.

Irradiation of a mixture of dopamine-beta-hydroxylase and bleomycin with light of wavelengths greater than 300 nm. leads to irreversible inhibition which is not prevented in the presence of tyramine. Prephotolysis of bleomycin followed by incubation (in the dark) with dopamine-beta-hydroxylase did not lead to irreversible inhibition. Thus bleomycin is a photolabel of this enzyme.

Bleomycin↗
PubMed1984

Synergistic interactions of ethidium bromide and bleomycin on cellular DNA and growth inhibition.

Bleomycin is an anti-tumor agent whose cytotoxicity is related to the introduction of both single-stranded and double-stranded breaks in cellular DNA. In an assay using isolated nuclei, low levels of ethidium bromide substantially increased bleomycin induced release of nuclear chromatin. Treatment of mouse L1210 leukemia cells in vitro with low levels of ethidium bromide followed 1 hr later by bleomycin produced a synergistic effect that was 8 fold greater than that expected from the additive cytotoxicity of each drug alone. Interestingly, when the order of drug addition was reversed the drug synergism was much reduced (2 fold). The combination of DNA unwinding and strand scission agents may represent a novel and rational approach to the chemotherapy of cancer.

Animals↗
PubMed1992

Enhancement and alteration of bleomycin-catalyzed site-specific DNA cleavage by distamycin A and some minor groove binders.

The effects of compounds which bind in the DNA minor groove of A.T rich sequences, on bleomycin-catalyzed site-specific DNA cleavage were investigated by a DNA sequencing technique. Distamycin A enhanced bleomycin-catalyzed DNA cleavage in G.C rich sequences such as 5'-GGGGC-3' (under scoring; the cleaved nucleotide). The cleavage in such a sequence in the presence of distamycin A was greater than that in the absence of distamycin A by as much as about 100 times. Neither Hoechst 33258, 4',6-diamidino-2-phenylindole (DAPI) nor berenil caused extensive enhancement. The results suggest that the distamycin-induced conformational changes of DNA through interactions other than the DNA minor groove binding in A.T-rich sequences are specifically suitable for the bleomycin action.

Base Sequence↗
PubMed1985

Oxy radical formation during redox cycling of the bleomycin-iron (III) complex by NADPH-cytochrome P-450 reductase.

Bleomycin was aerobically incubated with FeCl3, NADPH, isolated rat-liver microsomal cytochrome P-450 reductase and methional. The conversion of methional to ethene, which indicates oxy radicals, was determined. Ethene formation depended on oxygen, NADPH, FeCl3 and the enzyme. About equimolar concentrations of bleomycin and FeCl3 resulted in optimal ethene formation. Dimethyl sulfoxide, mannitol, glycerol, glutathione and glutathione disulfide inhibited ethene formation. These results indicate that oxy radicals are formed after reduction of the bleomycin-Fe-complex by NADPH-cytochrome P-450 reductase.

Aldehydes↗
PubMed1991

Cytostatic synergism between bromodeoxyuridine, bleomycin, cisplatin and chlorambucil demonstrated by a sensitive cell kinetic assay.

Bromodeoxyuridine/Hoechst flow cytometry was used to analyse the interference of common cytostatic agents with cell activation and cell cycle progression of human B-cell lines. Bleomycin impaired both cell activation and G2 transit, the latter effect being oxygen dependent. The DNA alkylating agents cyclophosphamide, chlorambucil and mitomycin C caused G2 arrest, whereas cisplatin arrested cells in both the S and G2 phase of the cell cycle. Vinblastin interfered with mitosis, but in addition arrested cells in all phases of the cell cycle. The growth inhibitory action of bleomycin, cisplatin and chlorambucil was dependent upon the bromodeoxyuridine (BrdU) concentration in the culture medium. No interaction was found between BrdU and cyclophosphamide, mitomycin C and vinblastin. The cell cycle kinetic mechanism of the interaction between BrdU and bleomycin, cisplatin and chlorambucil was a potentiation of the G2 arrest. In conclusion, BrdU may be useful in clinical chemotherapy as a chemosensitizer for selected cytostatic agents.

Bleomycin↗
PubMed1985

Abnormal cilia in the small airways of mice induced by bleomycin.

The frequency and types of abnormal cilia in the small airways before and after parenteral administration of bleomycin were examined by transmission electron microscopy. Bleomycin was injected subcutaneously at a dose of 40 mg/kg twice weekly for 6 weeks. Bronchioles less than 0.1 mm in diameter from animals sacrificed 1 day after a single dose, 1 day after three doses, 3 days after 8 doses, and 13 days after 12 doses were selected for evaluation. Although ciliated cells proper did not show pronounced alterations, abnormal cilia such as swollen cilia, compound cilia, and cilia with abnormal axonemes frequently occurred. Repeated injections did not necessarily induce much more abnormal cilia than one dose. The results suggested that ciliated cells remain undamaged and that normal cilia can be restored. The specific type of abnormal cilia induced by bleomycin was not identified.

Animals↗
PubMed1986

Bleomycin-detectable iron in plasma from Plasmodium vinckei vinckei-infected mice.

Plasma from mice heavily parasitized by Plasmodium vinckei vinckei was found to contain micromolar levels of iron as detected by the 'bleomycin assay' (slightly modified) of Gutteridge et al. [(1981) Biochem. J. 199, 263-265]. Uninfected mouse plasma contained little or no bleomycin-detectable iron. Plasma ultrafiltrate from infected mice contained no bleomycin-detectable iron, indicating that such iron was associated with the protein/macromolecule fraction. We speculate that this iron could catalyse reduction of peroxides in vivo and thus play a role in malaria pathology.

Animals↗
PubMed1992

Bleomycin-detectable iron in the plasma of premature and full-term neonates.

The bleomycin assay measures non-transferrin-bound iron, able to catalyze free radical reactions, in human plasma. No bleomycin-detectable iron is present in plasma from healthy adults. However, plasma from 3/15 premature babies was positive in this assay. Plasma from 52 apparently-healthy term babies was analyzed and 11 were positive in the bleomycin assay. Hence not only some premature but also some full-term apparently-healthy babies may be at risk of severe oxidative damage.

Bleomycin↗
PubMed1991

Exchange of copper between serum albumin and bleomycin.

1. The present in vitro study shows that bleomycin is able to take up copper from albumin, which functions as a copper transport protein in plasma. 2. Calculations, based on plasma concentrations of Cu(II)-albumin and bleomycin, suggest that only a small fraction of bleomycin (less than 3%) may directly accept copper from Cu(II)-albumin.

Bleomycin↗
PubMed1991

The reaction of ferric- and ferrous salts with bleomycin.

1. A comparative study shows that ferrous ions give a much better yield of Fe(III)-bleomycin than ferric ions, when iron salt is added to bleomycin in a buffer solution (pH 7.2). 2. The amount of Fe(III)-bleomycin formed after addition of ferric ions was markedly increased in the presence of ferric ion binding compounds (BSA, citrate) or reducing agents (ascorbate, cysteine).

Ascorbic Acid↗
PubMed1986

Combined effects of hyperthermia, bleomycin, and X rays on Ehrlich ascites tumor.

The combined effects of water-bath hyperthermia at 42.5 degrees C for 30 min, 1/10 LD50 Bleomycin iv, and 200 rad x irradiation were studied in DDD strain male mice with Ehrlich ascites tumor. The objective was to acquire data on the optimum regimen for a combined administration of these three modalities. The treatments were given 10 days after the inoculation of 2 X 10(6) of the cells into the right hind limb. Concomitant application of the three modalities led to an 80% regression. A single modality produced no significant effect and a 30-50% regression occurred when only two modalities were combined. To assess the influence of timing and sequence, hyperthermia was applied at 1, 2, 4, and 6 hr before, after, or simultaneously with the combination of Bleomycin and 200 rad X ray. A significant effect was obtained in the case of concomitant application of the three and hyperthermia was effective when applied within 2 hr before or after administration of Bleomycin plus irradiation. This enhancement disappeared at 4-hr intervals.

Animals↗
PubMed1982

The relationship between DNA and chromosome damage after bleomycin treatment: dose-response measurements.

The molecular basis for chromosome aberration formation has been studied using the sensitive techniques of premature chromosome condensation and DNA alkaline elution. The dose response of Chinese hamster ovary cells to bleomycin treatment at the DNA and chromosome levels was compared. Each DNA elution curve showed a 2-component profile, with a more sensitive component apparent at low doses. The chromosome aberration curves also exhibited a 2-component profile when determined in G2-PCC; however, this phenomenon was less apparent when chromosome damage was enumerated in mitotic figures. These results suggest that differential sensitivity to bleomycin exists within the cellular chromatin. The effect of dose rate on aberration formation was examined by administering bleomycin at 2 concentrations that, with different treatment times, yielded equivalent amounts of DNA damage. The chromatid exchange rate was independent of dose rate, suggesting that rapidly repaired DNA lesions are not involved in the formation of exchanges.

Animals↗