Bleomycin lung

Segel MJ, Izbicki G, Cohen PY, et al. Role of interferon-gamma in the evolution of murine bleomycin lung fibrosis. Am J Physiol Lung Cell Mol Physiol... 

Jenkinson S, Duncan C, Lawrence R, Collins J. Lack of enhancement of bleomycin lung injury in vitamin E-deficient rats. J Crit Care 1987 2 264. 

Azambuja, E., Fleck, J. F., Batista, R. G., Menna Barreto, S. S. (2005). Bleomycin lung toxicity Who are the patients with increased risk Pulmonary Pharmacology Therapeutics, 15(5), 363-366. 

In Japan, a movement to clarify the mechanism of action of EM treatment for DPB was formed. A study group on the novel action of macrolides was established in 1994 and many clinical and experimental investigations have been reported on, e.g., the inhibitory effect on experimental bleomycin lung injury, experimental reperfusion lung injury, experimental pulmonary metastasis of... 

Snider GL, Celli BR, Goldstein RH, O Brien JJ, Lucey EC. Chronic interstitial pulmonary fibrosis produced in hamsters by endotracheal bleomycin. Lung volumes, volume-pressure relations, carbon monoxide uptake, and arterial blood gas studied. Am Rev Respir Dis 1978 117 289-297. 

Gilson AJ, Sahn SA. Reactivation of bleomycin lung toxicity followii oxygen administration. A second re nse to corticosteroids. Chest (1985) 88, 304-6. 

Morphometric methods showed that low temperature (4°C for 7 days) inhibited bleomycin lung toxicity in the rat (Berend 1983). 

Newer bleomycins such as peplomycin and especially liblomycin, are more resistant to bleomycin hydrolase. This results in less lung toxicity but more bone marrow toxicity, and allows for a different spectmm of antitumor action. Bleomycin is inactive orally it is given intravenously, intramuscularly, subcutaneously, or directiy into a cavity such as the pleural cavity. The majority of dmg is excreted unchanged in the urine. 

Ortiz LA, Gambelli F, McBride C, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A 2003 100(14) 8407-8411. 

Huaux F, Gharaee-Kermani M, Liu T, et al. Role of eotaxin-1 (CCL11) and CC chemokine receptor 3 (CCR3) in bleomycin-induced lung injury and fibrosis. Am J Pathol 2005 167(6) 1485-1496. 

Huaux F, Liu T, McGarry B, Ullenbruch M, Xing Z, Phan SH. Eosinophils and T lymphocytes possess distinct roles in bleomycin-induced lung injury and fibrosis. J Immunol 2003 171(10) 5470-5481. 

Izbicki G, Or R, Christensen TG, et al. Bleomycin-induced lung fibrosis in IL-4-overexpressing and knockout mice. Am J Physiol Lung Cell Mol Physiol 2002 283(5) L1110-L1116. 

Keane MP, Belperio JA, Burdick MD, Strieter RM. IL-12 attenuates bleomycin-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2001 281(1) ... 

Antioxidant therapy might be promising medication for the treatment of some lung disorders. For example, lecithinized phosphatidylcholine-CuZnSOD suppressed the development of bleomycin-induced pulmonary fibrosis in mice [284] these findings could be of relevance for the treatment of bleomycin-stimulated pulmonary fibrosis in humans. Davis et al. [285] recently demonstrated that the treatment of premature infants with recombinant human CuZnSOD may reduce early pulmonary injury. 

Jones CB, McIntosh J, Huang H, Graytock A, Hoyt DG (2001) Regulation of bleomycin-induced DNA breakage and chromatin structure in lung endothelial cells by integrins and poly(ADP-ribose) polymerase. Mol Pharmacol 59(l) 69-75... 

Short term treatment with TPA sensitized human 2008 ovarian carcinoma cells to cis-platin. This sensitization disappeared completely by seven hours after treatment, indicating that not inhibition, but activation of PKC sensitizes 2008 cells to the antiproliferative activity of cis-platin (Isonishi et al., 1990). Pretreatment of HeLa cells with TPA or PdBu caused a 9-fold increase in cellular sensitivity to cis-platin and 2.5-fold to melphalan, but had now effect on the antiproliferative activity of bleomycin, adriamycin, vincristine, or mitomycin C. The sensitization of HeLa cells by TPA was associated with a 6-fold stimulation of PKC activation and a concentration- and time-dependent increase in cellular platinum content. (Basu et al. 1990). PKC activity was found to be decreased significantly in cis-platin-resistant human small cell lung H69/CP cancer cells compared to the drug-sensitive variant. A similar reduction in PKC activity was noted in ovarian carcinoma 2008 cells that were resistant to cis-platin. A modest decrease in PKC activity was also observed in etoposide-resistant H69 cells but not in taxol-resistant H69 cells or bleomycin-resistant human head and neck carcinoma A-253 cells (Basu et al., 1996), indicating that reduced PKC activity leads to decreased sensitivity in this system. 

Bleomycin hydrolase, which inactivates bleomycin, is an enzyme that is abundant in liver and kidney but virtually absent in lungs and skin the latter two organs are the major targets of bleomycin toxicity. It is thought that bleomycin-induced dermal and pulmonary toxici-ties are related to the persistence of relatively high local concentrations of active drug. 

A potentially fatal lung toxicity occurs in 10 to 20% of patients receiving bleomycin. Patients particularly at risk are those who are over 70 years of age and have had radiation therapy to the chest. Rarely, bleomycin also may cause allergic pneumonitis. Bleomycin skin toxicity is manifested by hyperpigmentation, erythematosus rashes, and thickening of the skin over the dorsum of the hands and at dermal pressure points, such as the elbows. Many patients develop a low-grade transient fever within 24 hours of receiving bleomycin. Less common adverse effects include mucositis, alopecia, headache, nausea, and arteritis of the distal extremities. 

Cisplatin, combined with bleomycin and vinblastine or etoposide, produces cures in most patients with metastatic testicular cancer or germ cell cancer of the ovary. Cisplatin also shows some activity against carcinomas of the head and neck, bladder, cervix, prostate, and lung. 

The anthracycline antibiotics, which include doxorubicin, daunorubicin, bleomycin, and mitomycin C, inhibit DNA and RNA synthesis. Doxorubicin also interfers with topoisomerase II (a DNA gyrase), the activity of which is markedly increased in proliferating cells. Structurally related to doxorubicin are epirubicin and mitozantrone. The cytotoxic antibiotics are used to treat leukaemias and lymphomas and also for solid tumours in the breast, lung, thyroid and ovary. Cardiotoxicity is the major dose-limiting factor, with arrhythmias and myocardial depression (Bacon and Nuzzo 1993). The chronic phase of cardiotoxicity is a dose-dependent cardiomyopathy that leads to congestive heart failure in 2-10% of patients. Myocardial injury is the result of oxygen free radical formation. Children are particularly sensitive to these cardiotoxic reactions and may require a heart transplant in their later years. Epirubicin is less cardiotoxic than doxorubicin. 

Bleomycins are a group of glycopeptide antibiotics that degrade preformed DNA. Bleomycin is used in the treatment of testicular carcinoma, sarcomas, and carcinomas of the oesophagus and lung. In contrast to most anticancer drugs, bleomycin causes little myelotoxicity. It is... 

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