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At least 1,261 records · Page 70Linked to original sources
PubMed1978

Adriamycin, bleomycin, and CCNU as effective induction chemotherapeutic agents in advanced squamous cell carcinoma (COG Protocol 7333).

Twenty-six member institutions of the Central Oncology Group entered 154 patients in this two-armed, phase III study comparing the effects of adriamycin, bleomycin, and CCNU against a variety of squamous cell carcinomas. The combination of adriamycin and bleomycin produced a 43% overall response rate in primary tumors of the head and neck, which included two complete responses. This compares favorably to the results obtained with methotrexate and other agents previously reported. The combination of adriamycin and bleomycin will probably be the most useful for induction chemotherapy because both drugs have cumulative toxicities and the duration of response to this combination is short.

Aged↗
PubMed1987

Bleomycin-associated pulmonary fibrosis: rapidly fatal progression without chest radiotherapy.

Two patients with carcinoma of the tonsil were treated with bleomycin (396 and 224 units, respectively) but not with radiotherapy. Respiratory insufficiency led to death 45 and 52 days, respectively, after onset of therapy. Chest radiographs before bleomycin therapy revealed no evidence for lung disease. Postmortem examinations showed severe interstitial and intraalveolar pulmonary fibrosis. Comparably rapid progression from radiographically normal pulmonary parenchyma to fatal fibrosis has been documented previously only in patients with thoracic neoplasia as well as, in all but one instance, either prior or concurrent chest radiotherapy. These two cases indicate that chest radiotherapy is not a necessary cofactor for the development of rapidly progressive, fatal, diffuse interstitial pulmonary fibrosis after bleomycin therapy.

Aged↗
PubMed1989

Intracavitary therapy with bleomycin for the treatment of malignant pleural effusions.

This paper briefly reviews the incidence of malignant pleural effusions (MPE) and the measures that have been used to treat this condition. The role of intracavitary bleomycin in controlling MPE, the doses used, and morbidity associated with its use are reviewed in depth with reference to multicenter studies that the author has coordinated as well as the published literature. The short- and long-term results reported when bleomycin was used alone or as compared with other agents are discussed. The author concludes that intracavitary bleomycin is an effective agent comparable to, if not more effective than, most agents used to prevent the recurrence of MPE after simple drainage procedures: it is safe and convenient to use; toxicity is low with minimal side effects and no myelosuppression. It can be safely administered to immunocomprised patients and those undergoing systemic chemotherapy.

Adolescent↗
PubMed1975

CCNU and bleomycin in the treatment of cancer: a Southwest Oncology Group Study.

CCNU and Bleomycin, alone or in combination, were used to treat 397 evaluable cases of advanced cancer. Responses defined as 50% or greater reduction in all tumor masses occurred in 13/35 lymphomas, 8/50 brain cancers, and 28/312 other solid tumors. Hematologic toxicity of a life-threatening degree occurred in 33/298 patients evaluable for CCNU toxicity; in an additional 50 it was considered severe. Pulmonary toxicity was severe in 4 patients. Drug-associated deaths (4) included one each due to leukopenia and thrombocytopenia after CCNU; one due to pulmonary toxicity after Bleomycin; and one due to shock after the 20th dose of Bleomycin. There was no suggestion of synergism or additive activity with the two drugs.

Adenocarcinoma↗
PubMed1978

The effects of prior exposure to bleomycin on the incidence of pulmonary toxicities in a group of patients with disseminated testicular carcinomas.

The incidence of pulmonary toxicities in 12 patients with prior exposure to bleomycin (BLM) was compared to the incidence of pulmonary toxicities in a matched group of 73 patients with state II or IV testicular carcinomas treated with a regimen containing vinblastine, bleomycin, and cis-diamminedichloroplatinum. The comparison demonstrates that prior exposure to bleomycin constitutes a significant risk factor and that the risk is additive; ie, prior doses should be added to current doses to determine the cumulative dose-related probablity of development of pulmonary toxicities.

Adolescent↗
PubMed1979

Cisplatin, bleomycin, and vinblastine combination therapy of testicular tumors: an analysis.

A combination regimen consisting of cisplatin, bleomycin, and vinblastine was evaluated in 86 patients with metastatic testicular tumors. Prior therapy included surgical resection of primary tumor (84 patients), radiotheapy (21 patients), chemotherapy (33 patients). Thirteen patients received prior bleomycin and vincristine or vinblastine. Of 80 evaluable patients 51 achieved complete response (CR) and 26 achieved partial response (PR), for an overall response rate 96.5%. There was no significant difference in response rates or survival with respect to prior therapy, sites of metastatic lesions, and tumor histology. The median survival time was not reached in an observation period of 44+ months. Sixty patients were alive 11+--44+ months, and 57 of these were free of disease. Thirty-two of the 60 patients (53%) had a survival time greater than 20 months. Toxicities included nephrotoxicity (18 patients) leukopenia, (69 patients), thrombocytopenia (nine patients), and anemia (56 patients). Bleomycin-induced pulmonary toxicity was fatal in one patient. Other toxicities included nausea and vomiting, stomatitis, fever, alopecia, and neurological effects.

Adolescent↗
PubMed1982

Low-dose bleomycin lung.

A patient with retroperitoneal diffuse histiocytic lymphoma treated with combination chemotherapy developed breathlessness and fever after receiving 30 units of bleomycin. At this stage pulmonary function tests were impaired and gallium scanning showed diffuse uptake in both lungs although a chest X-ray film was normal. Bleomycin treatment was stopped but interstitial infiltrates appeared on subsequent chest X-ray films. Open lung biopsy showed histologic changes of bleomycin toxicity. After treatment with prednisone, the patient felt well and was shown to have a normal gallium scan ad normal respiratory function studies.

Antineoplastic Agents↗
PubMed1983

Intensive sequential chemotherapy with bleomycin, Oncovin, mitomycin C, and methotrexate followed by adriamycin, cisplatin, and cyclosphosphamide in squamous cell cancer of the head and neck.

Twenty-six patients with advanced squamous cell cancer of the head and neck were treated with bleomycin, Oncovin, mitomycin C, and methotrexate (BOMM) for ten weeks. Partial and nonresponders then received adriamycin, cisplatin, and cyclophosphamide (APC) in a planned sequential program. The response rate to BOMM was 65% (19% complete remission, CR). The overall response rate to APC was 20%. Only three of eight nonresponders to BOMM could receive APC and non responded. Six of seven partial responders received APC and only one responded. One complete responder to BOMM received APC at relapse and attained a partial response. The major side effects of BOMM were mucositis and myelosuppression. Patients receiving methotrexate 60-72 hours following the bleomycin infusion had less myelosuppression than patients who were treated 36-42 hours after bleomycin. The toxicities with APC included nausea, vomiting, and myelosuppression. Including a prior series, a total of 45 patients have been treated with BOMM with a 71% response rate (69% in previously irradiated patients). Twenty-eight percent of previously treated patients achieved complete remission, and two of these patients are disease free at 31 and 37 months. Methotrexate dose-rate alteration to low dose twice weekly followed by a single dose of oral leucovorin did not improve the complete or partial response rate when compared to weekly methotrexate administration. The complete remission rate and response duration were also not improved by the planned sequential use of this cisplatin-containing regimen.

Adult↗
PubMed2004

C-C chemokine receptor 2 (CCR2) deficiency improves bleomycin-induced pulmonary fibrosis by attenuation of both macrophage infiltration and production of macrophage-derived matrix metalloproteinases.

Macrophage infiltration is implicated in various types of pulmonary fibrosis. One important pathogenetic process associated with pulmonary fibrosis is injury to basement membranes by matrix metalloproteinases (MMPs) that are produced mainly by macrophages. In this study, C-C chemokine receptor 2-deficient (CCR2-/-) mice were used to explore the relationship between macrophage infiltration and MMP activity in the pathogenesis of pulmonary fibrosis, using the bleomycin-induced model of this disease process. CCR2 is the main (if not only) receptor for monocyte chemoattractant protein-1/C-C chemokine ligand 2 (MCP-1/CCL2), which is a critical mediator of macrophage trafficking, and CCR2 -/- mice demonstrate defective macrophage migration. Pulmonary fibrosis was induced in CCR2-/- and wild-type (CCR2+/+) mice by intratracheal instillation of bleomycin. No significant differences in the total protein concentration in bronchoalveolar lavage (BAL) fluid, or in the degree of histological lung inflammation, were observed in the two groups until day 7. Between days 3 and 21, however, BAL fluid from CCR2-/- mice contained fewer macrophages than BAL fluid from CCR2+/+ mice. Gelatin zymography of BAL fluid and in situ zymography revealed reduced gelatinolytic activity in CCR2-/- mice. Immunocytochemical staining showed weaker expression of MMP-2 and MMP-9 in macrophages in BAL fluid from CCR2-/- mice at day 3. Gelatin zymography of protein extracted from alveolar macrophages showed reduced gelatinolytic activity of MMP-2 and MMP-9 in CCR2-/- mice. At days 14 and 21, lung remodelling and the hydroxyproline content of lung tissues were significantly reduced in CCR2-/- mice. These results suggest that the CCL2/CCR2 functional pathway is involved in the pathogenesis of bleomycin-induced pulmonary fibrosis and that CCR2 deficiency may improve the outcome of this disease by regulating macrophage infiltration and macrophage-derived MMP-2 and MMP-9 production.

Animals↗
PubMed2007

An essential role for CCAAT/enhancer binding protein beta in bleomycin-induced pulmonary fibrosis.

Pulmonary fibrosis is characterized by inflammation, genesis of myofibroblasts, and abnormal tissue repair. Despite extensive research, its pathogenesis remains incompletely understood. Previously, the transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) was found to be a key regulator of myofibroblast differentiation in vitro, and to be involved in the acute phase and inflammatory responses. In an attempt to test the role of C/EBPbeta in the development of pulmonary fibrosis, experiments using C/EBPbeta null mice and their wild-type littermates were conducted. Our findings indicated that, compared to wild-type mice, animals deficient in C/EBPbeta showed significantly reduced fibrotic lesions and collagen deposition in the lung upon endotracheal injection of bleomycin. Further studies on the mechanisms by which C/EBPbeta regulates fibrosis indicated that knockout of C/EBPbeta attenuates inflammatory cytokine expression in bleomycin-treated mice. The reduced alpha-smooth muscle actin gene expression in either isolated lung fibroblasts or lung tissue from bleomycin or saline-treated C/EBPbeta deficient mice suggests that C/EBPbeta regulates myofibroblast differentiation during fibrosis. Consistent with this finding, cells from C/EBPbeta deficient mice exhibited higher proliferative rates than those from wild-type mice. These data suggest that C/EBPbeta plays an essential role in pulmonary fibrosis and that this role appears to be multifactorial with respect to cytokine expression, cell differentiation, and proliferation.

Actins↗
PubMed2001

Molecular monitoring of bleomycin-induced pulmonary fibrosis by cDNA microarray-based gene expression profiling.

Pulmonary fibrosis is a progressive disorder whose molecular pathology is poorly understood. Here we developed an in-house cDNA microarray ("lung chip") originating from a lung-normalized cDNA library. By using this lung chip, we analyzed global gene expression in a murine model of bleomycin-induced fibrosis and selected 82 genes that differed by more than twofold intensity in at least one pairwise comparison with controls. Cluster analysis of these selected genes showed that the expression of genes associated with inflammation reached maximum levels at 5 days after bleomycin administration, while genes involved in the development of fibrosis increased gradually up to 14 days after bleomycin treatment. These changes in gene expression signature were well correlated with observed histopathological changes. The results show that microarray analysis of animal disease models is a powerful approach to understanding the gene expression programs that underlie these disorders.

Animals↗
PubMed2001

Lung interleukin-4 gene expression in a murine model of bleomycin-induced pulmonary fibrosis.

Interleukin-4 (IL-4) is known to activate mononuclear cells as well as fibroblasts, all of which are important in the pathogenesis of pulmonary fibrosis. To investigate the potential role of this cytokine, lung IL-4 expression was examined in a murine model of bleomycin-induced pulmonary fibrosis. Lung fibrosis was induced in CBA/J mice by endotracheal injection of bleomycin on day 0. On selected days after treatment, lungs were harvested for reverse transcriptase polymerase chain reaction (RT-PCR), Northern, in-situ hybridization and immunohistochemical analyses. RT-PCR and Northern analyses revealed significant increases in lung IL-4 mRNA content between days 3 and 14 after induction of lung injury, which decreased toward control level after day 21. Both in-situ hybridization and immunohistochemistry showed low or undetectable IL-4 expression in control lungs and in injured lungs before day 3 after bleomycin injection. There was however elevated expression in mononuclear cells and macrophages between days 3 and 14, localized to areas of active fibrosis. These results demonstrate that IL-4 is upregulated significantly in this model. They suggest a potential role for this cytokine in pulmonary fibrosis, perhaps via its ability to stimulate and amplify the inflammatory response, stimulate collagen synthesis in fibroblasts, and thus promote the progression to fibrosis and end stage lung disease.

Animals↗
PubMed2002

beta-Carotene reduces bleomycin-induced genetic damage in human lymphocytes.

We had previously shown in a human feeding study that ingestion of tomato and carrot juices decreases DNA breaks and oxidized pyrimidine bases in peripheral lymphocytes and enhances expression of glutathione S-transferase (GST) in a subpopulation of the volunteers. The aim of this study was to determine how the major carotenoids of these juices (beta-carotene or lycopene) could contribute to the observed antigenotoxicity. Physiological concentrations (2 microM) of water-soluble beta-carotene and lycopene were incubated for 18-24 h with lymphocytes and then treated with bleomycin or H(2)O(2). Strand breaks, oxidized DNA bases, and persistence of damage (DNA repair) were measured by single-cell microgelelectrophoresis. GST-protein (GSTP1) was determined using an immunoassay and by measuring enzyme activity. HPLC analysis showed that beta-carotene was taken up by the cells after 24 h, and this was associated with a reduction of bleomycin-induced damage (29.11 +/- 1.86% tail intensity without versus 21.54 +/- 2.36% with beta-carotene). Lycopene was ineffective. The carotenoids did not modulate repair of bleomycin- and H(2)O(2)-induced damage and did not alter levels of oxidized pyrimidine bases nor GST expression. The results indicate that beta-carotene can enter the cell and protect against strand breaks but not against oxidized DNA bases. Therefore, beta-carotene accounts for only part of the protection observed in vivo with carotenoid-rich vegetable juices.

Antibiotics, Antineoplastic↗
PubMed1980

The disposition of intraperitoneal bleomycin, melphalan, and vinblastine in cancer patients.

We have studied the disposition of bleomycin, melphalan, or vinblastine after intraperitoneal (IP) instillation in 14 cancer patients. Although IP bleomycin had a somewhat longer terminal-phase plasma half-life than after intravenous (IV) administration (5.5 vs 4.0 h, respectively), its systemic absorption averaged only 44%-52% of the administered dose. IP melphalan's mean terminal-phase half-life of 1.3 h was similar to that seen after IV drug administration. Melphalan's systemic absorption form the IP space averaged only 39% of the administered dose. In contrast, vinblastine plasma levels remained elevated for longer than 24 h after IP instillation. Its use was associated with life-threatening adynamic ileus in two patients. Bleomycin's and melphalan's reduced systemic availability after IP dosing suggests that their dose could be increased safely by a factor of two over their standard IV doses.

Adult↗
PubMed1995

Molecular cloning and expression in Escherichia coli of bleomycin-resistance gene from a methicillin-resistant Staphylococcus aureus and its association with IS431 mec.

A gene that confers bleomycin resistance was cloned from the chromosomal DNA of methicillin-resistant Staphylococcus aureus (MRSA) B-26 into the plasmid pUC18. It is of chromosomal origin rather than plasmid and exists in the chromosome making a cluster with the kanamycin-resistance gene. We found that the nucleotide sequence of the bleomycin-resistance gene from the chromosome of MRSA B-26 is identical to that from a staphylococcal plasmid, pUB110. The partial sequence of IS431mec was also found upstream from the DNA fragment containing the bleomycin- and kanamycin-resistance genes.

Base Sequence↗
PubMed1992

The bleomycin resistance gene of transposon Tn5 is an excellent marker for transformation of corynebacteria.

Corynebacteria are highly sensitive to the glycopeptide antibiotic bleomycin. The bleomycin resistance gene of transposon Tn5 is expressed very efficiently in Brevibacterium lactofermentum. This gene constitutes an excellent marker for selection of transformants of corynebacteria. The bleomycin resistance gene is expressed from the same promoter as the neomycin resistance gene, which is already used as marker in many vectors of corynebacteria. The promoter of the neo-ble cluster is expressed in a variety of Gram-negative and Gram-positive microorganisms and eucaryotic organisms.

Biotechnology↗
PubMed1990

Phase I trial of tallysomycin S10b, a bleomycin analogue.

Bleomycin is an agent with significant antitumor efficacy whose major dose limiting toxicity is pulmonary fibrosis. Attempts have thus been made to identify congeners with reduced toxicity and with comparable or greater antitumor activity. Tallysomycin S10b is a bleomycin analogue possessing significantly greater potency, equal or reduced lung toxicity, and slightly greater antineoplastic activity when compared to the parent compound in preclinical studies. This report describes our experience with tallysomycin S10b in 30 patients with a variety of non-hematologic neoplasms. Pulmonary toxicity, occurring in 4 patients, was the major toxicity. The recommended cumulative dose of tallysomycin S10b was difficult to establish from the results of this study, as pulmonary toxicity appeared to be more idiosyncratic than dose- or schedule-dependent. The employment of more sensitive methods for detecting pulmonary toxicity in this study suggest that tallysomycin S10b may have reduced pulmonary toxicity compared to the parent compound. Both bleomycin and tallysomycin S10b have similar t1/2 beta half-lives of 2-4 h. Six patients had prolonged terminal elimination half-lives of tallysomycin S10b, but no clear relationship between this phenomenon and efficacy or toxicity was evident. No complete or partial responses occurred. Disease stabilization occurred in 4 of 15 patients with diagnoses of renal cell carcinoma, rectal cancer and lung cancer. Five of eight patients with non-measurable disease had stable disease, including one with mesothelioma, one with carcinoma of the head and neck, two with renal cell cancer and one with colon carcinoma.

Adult↗
PubMed1981

Bleomycin labelled with 99mTc for differentiation of breast tumors.

Bleomycin labelled with 99mTc was used to differentiate benign and malignant breast tumors. Breast scintigraphy was performed 15 and 60 min following the IV injection of 5 mCi99mTc bleomycin. Thirty-two patients with breast tumor (14 carcinomas and 18 benign nodular lesions) were examined. Cytologic or histologic verification of the tumor was carried out in all cases. All malignant tumors of the breast in the investigated group of patients revealed significantly increased accumulation of 99mTc-bleomycin.

Adult↗