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 1,189 records · Page 66Linked to original sources
PubMed1982

51Cr-bleomycin, a new oncophilic radiopharmaceutical. II. Scintigraphic diagnosis of malignant neoplasms.

51Cr-bleomycin was used for the scintigraphic detection of tumours and the assessment of the spread of the disease in 20 patients with various malignancies: 7 with Hodgkin's lymphoma, 5 with other malignant lymphomas, 4 cases of cervix carcinoma and 4 other tumours. The scintigraphy was performed using a Toshiba GC 401 gamma camera coupled to an MDSI computer Trinary. Active foci were scored using a semiquantitative scale of 0 to 5. Results of these studies were compared with those of tests similarly carried out with 57Co-bleomycin (in 9 of the cases) and 67Ga-citrate (11 cases); they demonstrated that the properties of 51Cr-bleomycin for scintigraphic detection of neoplastic foci are similar to those of 57Co-bleomycin.

Bleomycin↗
PubMed1982

[Effect of the antitumor antibiotic bleomycin on DNA polymerase activity].

Treatment with bleomycin activates considerably a repair synthesis of DNA in rat liver chromatin in vitro and can cause loosening of the nucleoprotein complex, which facilitates the accessibility or repair enzymes for lesions in chromatin DNA. The bleomycin action on DNA-template increases severalfold the rate of synthesis catalyzed by DNA polymerase beta inhibits the activity of DNA polymerase I from Escherichia coli and suppresses severalfold the activity of DNA polymerase alpha and DNA polymerase of bacteriophage T4. The effect of bleomycin consists in a prevailing increase of nicks and minimal gaps in DNA as compared to the rise of moderate gaps, thus suggesting that bleomycin is a gamma-mimetic.

Animals↗
PubMed1982

Cellular sensitivity to collagen in bleomycin-treated rats.

Previous reports have suggested that immune mechanisms are involved in the induction of certain types of pulmonary fibrosis. In this study endotracheal bleomycin was used to induce pulmonary fibrosis in rats, and they were then examined for cellular sensitivity to homologous interstitial collagens isolated from lung. Results indicate that rats treated with bleomycin develop transient cellular sensitivity to homologous collagen. Immunity appears to be selective to type I collagen with minimal response to type III collagen. The kinetics of the development of autoimmunity paralleled the transient increase in collagen synthesis in response to bleomycin treatment. This response was abolished upon prior treatment of the challenging antigen with purified bacterial collagenase, but was resistant to trypsin digestion. This finding confirms the true collagenous nature of the stimulating antigen and eliminates the possibility of a noncollagenous contaminant as the effective agent in the antigen preparation. The data suggest that cellular sensitivity to homologous collagen in response to bleomycin treatment may play a role in the overall fibrotic response.

Animals↗
PubMed1983

Unusual sensitivity to bleomycin and joint resistance to 9-beta-D-arabinofuranosyladenine and 1-beta-D-arabinofuranosylcytosine of mouse FM3A cell mutants with altered ribonucleotide reductase and thymidylate synthase.

This paper describes unusual sensitivity to bleomycin; resistance to aphidicolin, 9-beta-D-arabinofuranosyladenine, 1-beta-D-arabinofuranosylcytosine, and hydroxyurea; and a mutator phenotype as common phenotypes of two classes of previously reported mouse FM3A cell mutants with distinct biochemical defects. One class of mutants, selected for aphidicolin resistance, contains altered ribonucleotide reductase desensitized to deoxyadenosine triphosphate, a negative allosteric effector, and the other class contains temperature-sensitive thymidylate synthase. Abnormal levels of deoxyribonucleoside triphosphate pools, especially those of deoxyadenosine triphosphate, were the common biochemical trait for both classes of mutants. The aphidicolin-resistant thymidylate synthase mutants, isolated independently of aphidicolin resistance, showed reduced levels of thymidylate synthase and increased levels of ribonucleotide reductase. Bleomycin was more lethal to both classes of mutants than to wild-type cells, as determined by colony-forming ability. It also caused more marked scissions of DNA in the ribonucleotide reductase mutant cells than in the wildtype cells as analyzed by sedimentation on an alkaline sucrose gradient. Thus, the activity or level of ribonucleotide reductase seems to be one factor determining the bleomycin sensitivity of cells by potentiating the capacity of bleomycin to cleave DNA strands.

Animals↗
PubMedDate not supplied

Enhanced effect of combined hyperthermia and chemotherapy (bleomycin, BCNU) in a neurogenic rat tumour (BT4A) in vivo.

The neurogenic rat tumour BT4A was serially transplanted to the dorsum of the right hind leg of BD IX rats. The tumours were treated with water bath heating at 44.0 degrees C for one hour alone or combined with bleomycin or BCNU, both given intraperitoneally at a dose of 20 mg/kg. Bleomycin alone had no effect on tumour growth. Hyperthermia or BCNU alone both caused a transient growth delay before regrowth. Combination of hyperthermia and bleomycin caused a significantly enhanced effect with 8 partial regressions in 9 tumours. BCNU and hyperthermia resulted in 9 complete and one partial regressions of 10 treated tumours. Eight of these were cured. We conclude that the antitumour effects as well as the side effects caused by the combination of local hyperthermia and systemic administration of BCNU and bleomycin deserve further investigation.

Animals↗
PubMedDate not supplied

A fatal hyperpyrexial response to bleomycin following prior therapy: a case report and literature review.

Bleomycin is an effective drug used in the therapy of many malignant diseases. Such toxicities as fever, chills, and pulmonary fibrosis are well known to occur following administration of this drug. A rare fatal hyperpyrexial response has also been noted with this agent. We describe a case of fatal hyperthermia after an injection of bleomycin. Unlike earlier reported cases, our patient developed her reaction following prior uneventful therapy with bleomycin rather than as a response to initial treatment. Factors that may be related to the hyperpyrexial response to bleomycin are discussed and the relevant literature reviewed.

Bleomycin↗
PubMed1982

[Oral administration of oil bleomycin combined with sodium polyacrylate for the treatment of esophageal cancer].

With anticipation of potentiation of the regional effect of bleomycin on the lesion of esophageal carcinoma, 12 patients with esophageal carcinoma were medicated orally with 5 ml of a paste-like mixture of 1 g of Sodium polyacrylate (PANA Kayaku) and 30 mg of oil bleomycin every day for 7 to 43 preoperative days. These 12 patients were further medicated with the mixture 1 hour before operation, and in 9 of them, bleomycin levels in the tumor and normal tissue of the resected portion of the esophagus and also in the regional lymph nodes were determined. The level in the normal tissue was on average concentration of 1.2 micrograms/g, while the level in tumor showed a tendency to higher level, being an average concentration of an being 4.4 micrograms/g. Bleomycin was found being efficiently transferred into the regional lymph nodes, where it was detected the average concentration of 1.7 micrograms/g. It may be anticipated that this mixture will be effective against preoperative and inoperable esophageal carcinoma and for ther studies on dosage and administration schedule is desirable.

Acrylic Resins↗
PubMed1983

Morphometric estimates of infiltrative cellular changes during the development of bleomycin-induced pulmonary fibrosis in hamsters.

The sequence of cellular infiltration into interstitial lung tissue subsequent to intratracheal administration of bleomycin was examined in hamsters. Quantitation of lesions following bleomycin treatment showed a transient increase in the percentage of lung involved, which peaked at 21 days and decreased thereafter. Associated with these lesions was a significant increase in interstitial cell profile density at 21 and 28 days. The total number of cell profiles decreased after 28 days. The cellular composition of the lesion was dominated by monocytes, neutrophils, and macrophages in the initial phase of the fibrosis. Subsequently, monocytes were significantly decreased at 21, 28, and 42 days, as compared with the 7-day value. Similarly, neutrophils were significantly decreased at 21 and 28 days, as compared with the 7-day value. In contrast, macrophages were significantly decreased in the initial phase (7 days) of the cellular infiltration and the later phase at 35 and 42 days, as compared with the value at 4 days after treatment. Lesion composition in the later phase exhibited significant increases in fibroblasts and eosinophils, accompanied by a general increase in lymphocytes. It is concluded that bleomycin-induced inflammatory sequela exhibits temporally based changes in cellular composition of the infiltrate and that the temporal changes in cellularity might be one of the determinants in the pathophysiology of pulmonary fibrosis induced by bleomycin.

Animals↗
PubMed1983

Effect of human fibroblast interferon on the antiviral activity of mammalian cells treated with bleomycin, vincristine, or mitomycin C.

Bleomycin, vincristine, or mitomycin C, when added to HeLa cells simultaneously with human fibroblast interferon (IFN-beta), caused a decrease in cell density and inhibited DNA synthesis compared with HeLa cells treated with IFN-beta alone. However, the IFN-beta-induced antiviral processes were unaffected by the presence of these drugs as determined by in vitro enzyme assays and the development of the antiviral state in the intact HeLa cell. HeLa cells treated with IFN-beta alone or with IFN-beta in combination with bleomycin, vincristine, or mitomycin C were able to induce the double-stranded RNA-dependent adenosine triphosphate:2',5'-oligoadenylic acid adenyltransferase (EC 2.2.2.-) and the double-stranded RNA-dependent protein kinase. Furthermore, the antiviral state as measured by the reduction of plaque-forming units after infection of treated cells (with IFN-beta alone or with IFN-beta plus drugs) with vesicular stomatitis virus was not affected. These results indicate that, under these experimental conditions, the double-stranded RNA-dependent adenosine triphosphate:2',5'-oligoadenylic acid adenyltransferase and protein kinase can be induced by IFN-beta in cells treated with bleomycin, vincristine, or mitomycin C. These cells also develop the antiviral state. These experiments could provide a basis for a careful examination of the effects of interferon on the development of the antiviral state when testing potentially active antineoplastic agents. The possibility that IFN-beta potentiates the cytotoxic effects of bleomycin and mitomycin C on HeLa cells is also discussed.

Antibiotics, Antineoplastic↗
PubMed1983

Photoreactivity of bleomycin and its implications.

The bleomycin family of glycopeptide anti-tumour antibiotics has recently been shown to be markedly photosensitive. This photosensitivity has been observed not only for the free antibiotics but also for complexes with metal ions and with DNA. More importantly, the pattern of DNA cleavage by bleomycin, and some of its metal complexes, is significantly changed by irradiation with light in 300-350 nm or UV regions. Bleomycin is a strong, reversible inhibitor of the enzyme, dopamine beta-hydroxylase (EC 1.14.17.1) in the dark. Photoexposure converts this to a strong irreversible inhibition. In this review the above aspects are discussed along with the chemical nature of the origins of the photoreactivity of bleomycin and analogues. The implications of the photoactivity of this useful drug are pointed out.

Bleomycin↗
PubMed1984

Uptake of main fractions of labelled bleomycin by solid Ehrlich ascites tumours in mice.

Concentrations were studied of 58Co in the solid Ehrlich ascites tumour, blood, muscle and bone of male Swiss mice administered as complexed with total bleomycin commercially available and its isolated fractions A2, B2, demethyl A2, A1, A5, B4 and bleomycinic acid. The tumour/non-tumour ratios were determined 24 hrs after injection of the complexes. The ratios for fraction A2, B2 and total bleomycin were very close to each other. The remaining fractions showed lower values of the ratios. These results suggest that it is unlikely that any of the fractions studied are superior to total labelled bleomycin with respect to tumour scintigraphy.

Animals↗
PubMedDate not supplied

An appraisal of the efficacy of bleomycin in epidermoid carcinoma of the penis.

Since 1975 ten patients with advanced bidimensionally measurable epidermoid carcinoma of the penis were treated prospectively with bleomycin as a single agent. In addition, data of four patients with penile cancer treated at Memorial Hospital in 1971-72 as part of a drug-oriented prospective Phase I-II trial of bleomycin are included. Each patient had a complete evaluation including measurement of all measurable lesions by two independent observers. Standard response criteria were used. Bleomycin was given in doses of 3-20 mg/m2/day in a continuous infusion to 8 men and as a daily or weekly bolus in doses of 10-30 mg/m2 to six men. The median age of the patients was 54 years and median KPS 50%. Six patients had previously received two or more chemotherapeutic agents. All patients had Stage III-IV disease. Three (21%) of 14 patients responded including one patient who achieved a complete remission in the primary penile lesion and in malignant inguinal lymphadenopathy. Tumor regression was noted to start rapidly, i.e. within 2 weeks of starting protocol, but the duration of remission was short - median 3 months. The most frequent toxicity was mucositis which occurred in 8 cases. Three patients had a drug-related fever, two a drug rash and 2 had evidence of pulmonary toxicity. There was one instance each of an elevation of tests of liver function, and of alopecia. Within the context of this study, bleomycin has modest activity and moderately severe toxicity in patients with advanced penile carcinoma.

Adult↗
PubMed1976

[Distribution study using 57Co-, 51Cr-, 111In- and 99mTc-bleomycin in mice with a solid Ehrlich carcinoma].

From the comparative studies of 57Co-, 51Cr-, 111In- and 99mTc-Bleomycin using 282 solid Ehrlich-carcinoma-bearing mice, 57Co was found to be the most suitable bleomycin preparation for tumorscintigraphy. The results obtained by 111In-Bleomycin of linear tumor cell absorption indicates a possible use of 111In-Bleomycin as an agent for objective histological differentiation also in cells previously treated with therapeutic agents.

Animals↗
PubMed1976

Response of mammalian cells to bleomycin-induced potentially lethal and sublethal damage.

Both dividing and nondividing cells were able to recover from bleomycin-induced potentially lethal damage, but not from sublethal damage. The recovery from bleomycin-induced potentially lethal damage by nondividing cells was twice as great as that exhibited by dividing cells; and, potentially lethal damage recovery was sufficiently high for cells in both growth states to conceal the true response to sublethal damage. Through the use of integral dose fractions of bleomycin, the recovery from potentially lethal damage can be reduced significantly. These data suggest that closely spaced treatments with fractionated doses of bleomycin may be a more effective means of eradicating tumors containing large nondividing cell populations in vivo.

Animals↗
PubMed1977

Experimentally induced bleomycin sulfate pulmonary toxicity: histopathologic and ultrastructural study in the pheasant.

Morphological alterations in the lungs of pheasants after prolonged high-dosage administration of bleomycin sulfate were studied by light and electron microscopy. Nontreated birds acted as controls, and their lungs showed no abnormalities. Lungs of bleomycin-treated pheasants revealed collapse alternating with overexpansion, marked cuboidalization of atrial epithelium, and incipient interstitial fibrosis. There were neither lymphoplasmacytic or eosinophilic infiltrates, nor evidence of vasculitis. Ultrastructurally, type 1 alveolar epithelial cells were either reactive or conspicuously absent in the air capillaries. Type 2 alveolar epithelial cells appeared hyperplastic with numerous lamellar bodies, many of which extruded into air spaces. Immature fibroblasts were noted in the vicinity of collagen fibrils or amorphous material resembling elastin. No immune deposits were present in basement membranes. These findings are consistent with a direct toxic effect of bleomycin to the pheasant lung rather than a drug hypersensitivity reaction. Reproduction of the bleomycin lesion in a nonmammalian species corroborates even further the high propensity of the drug to affect the lung.

Animals↗
PubMed1977

Effect of bleomycin on the synthesis and function of RNA.

Bleomycin inhibits cellular RNA synthesis and the inhibition is nonspecific. The ratio of polyadenylate- [poly(A)] containing RNA to non-poly(A)-containing RNA in the drug-treated human lymphocytic cells, line Wil2, was the same as that in untreated cells. Poly(A) RNA isolated from untreated cells was used as a template for reverse transcriptase to synthesize complementary DNA, which was then used as a probe to assay the sequence diversity of poly(A)RNA's from treated and untreated cells. It was found that essentially all of the poly(A) RNA's in the untreated cells were also present in the treated cells. The effect of bleomycin on the biological activity of messenger RNA (mRNA) was tested with globin mRNA in a wheat germ embryo translation system. Although bleomycin inhibited protein synthesis at high concentrations, the inhibition was not due to a modification of mRNA. This was evidenced by the fact that no decrease in the ability of mRNA to function in the test system was found when globin mRNA was pretreated with high concentrations of bleomycin followed by removal of the drug.

Bleomycin↗
PubMed1993

Rat alveolar myofibroblasts acquire alpha-smooth muscle actin expression during bleomycin-induced pulmonary fibrosis.

The majority of fibroblasts in alveolar septa are characterized by the presence of cytoplasmic bundles of microfilaments that contain cytoplasmic actin isoforms; these cells have been named contractile interstitial cells or V-type myofibroblasts. In the rat, they express desmin as intermediate filament protein. In this study, we explored the possibility that modulation and replication of such septal fibroblasts result in the appearance of alpha-smooth muscle (alpha-SM) actin-positive myofibroblasts, typical of lung fibrosis. Experimental pulmonary fibrosis was produced by a unique intratracheal instillation of bleomycin to 28 rats. Eight additional rats used as controls received the equivalent volume of saline. Paraffin and frozen sections of lungs were examined at days 1, 3, 5 and 7 after treatment. Microfilaments and intermediate filaments were stained using antibodies against total actin, alpha-SM actin, desmin, vimentin, keratin, and SM myosin. Electron microscopic labeling of desmin and alpha-SM actin using immunogold technique was done on Lowicryl K4M resin-embedded specimens. alpha-SM actin appeared in desmin-positive alveolar fibroblasts as early as 24 hours after intratracheal bleomycin instillation; the modulation of alpha-SM actin in these cells was preceded by a lymphomonocytic infiltration of alveolar septa. Twenty-four hours to 3 days after bleomycin administration, a proliferation of alveolar myofibroblasts occurred. Fibrosis with laying down of collagen fibers took place after the above mentioned cellular modifications. Our results support the view that septal fibroblastic cells can modulate into typical alpha-SM actin-containing myofibroblasts during experimental bleomycin-induced pulmonary fibrosis. In such a modulation a possible role of cytokines, particularly of transforming growth factor-beta, is considered.

Actin Cytoskeleton↗
PubMed1994

Increased type I procollagen mRNA transcripts in the lungs of mice during the development of bleomycin-induced fibrosis.

In this study, in situ hybridization has been used to investigate the localization of type I procollagen messenger ribonucleic acid (mRNA) in normal lung, and in the lungs of mice during the development of bleomycin-induced pulmonary fibrosis. Lung fibrosis was induced by a single intratracheal instillation of bleomycin sulphate (6 mg.kg-1 body weight), and tissues examined at times up to 35 days thereafter. Tissue transcripts of alpha 2(I) procollagen mRNA were visualized after hybridization with 35S-labelled riboprobes. Hybridization signals were associated with alveolar interstitial cells throughout the normal lung, with additional areas of dense hybridization signals observed subpleurally. Three days following administration of bleomycin, there was no apparent change in the pattern of hybridization. By 10 days, foci of intense hybridization signals indicative of gene activation were observed associated with individual cells in the alveolar interstitium. At 21 days, the increase in hybridization signals appeared to be associated with greater numbers of cells rather than highly activated cells. These results demonstrate that procollagen genes are normally expressed in the mouse lung, and that during bleomycin-induced pulmonary fibrosis hybridization signals increase, suggesting that both enhanced gene expression by individual cells and increased numbers of cells expressing the type I procollagen gene are involved in the pathogenetic mechanism.

Animals↗