Increased Pulmonary Toxicity with Bleomycin and Cisplatin Chemotherapy Combinations

Rabinowits, Milton; Souhami, Luís; Gil, Roberto Almeida; Andrade, Carlos A. V.; Paiva, H

doi:10.1097/00000421-199004000-00009

Cited by 29 publications

(9 citation statements)

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“…Other occupational exposures such as asbestos, drug exposures such as bleomycin [65, 66], and therapeutic exposures such as radiation [67, 68] have been linked to various forms of pulmonary disease, including fibrosis [69]. Future investigation into the role of gene by environment interactions will be critical to understanding the role that genetic variation plays in disease pathogenesis.…”

Section: Implications Of Recent Findingsmentioning

confidence: 99%

Genetic susceptibility and pulmonary fibrosis

Mathai

Schwartz

Warg

2014

Current Opinion in Pulmonary Medicine

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Purpose of Review Recent genetic findings have identified new targets of investigation in the field of interstitial lung diseases and have the potential to change clinical care. Recent Findings These findings implicate abnormalities in (1) host defense, (2) cell-cell adhesion, and (3) aging and senescence in the pathophysiology of pulmonary fibrosis. At least one common genetic variant strongly associated with pulmonary fibrosis appears to have prognostic implications for patients. Summary The inherited risk for pulmonary fibrosis is substantial, and recent data suggests that genetic risk for familial and sporadic forms of the disease are similar. Further characterization of the genetic risk will influence clinical practice in terms of categorization, diagnosis, and screening of individuals for this disease.

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Section: Implications Of Recent Findingsmentioning

confidence: 99%

Genetic susceptibility and pulmonary fibrosis

Mathai

Schwartz

Warg

2014

Current Opinion in Pulmonary Medicine

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“…Fleischman et al (1971) and McCullough et al (1978) have reported that treatment with BLM resulted in the induction of lung fibrosis in canines and baboons, and BLM induced diffuse alveolar injury and subsequent pulmonary fibrosis (Blum et al, 1973;Rabinowits et al, 1990). Recently, Moeller et al (2008) reported that BLM-induced lung fibrosis model is helpful to illustrate pathobiology in vivo and in vitro and to identify new targets for medication.…”

Section: Introductionmentioning

confidence: 99%

Induction of pulmonary fibrosis by methotrexate treatment in mice lung in vivo and in vitro

et al. 2010

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-Methotrexate (MTX) has been used as the first-line disease-modifying antirheumatic drug (DMARD) in patients with early progressive rheumatoid arthritis (RA). Several severe side effects such as myelosuppression, hepato-, nephro-, and pulmonary toxicities have been reported. However, the pathogenic mechanism of MTX-induced pulmonary fibrosis is still unknown. Here, we evaluated the morphological and biological changes of the pulmonary fibrosis in mice treated with MTX. Three, four and five weeks after consecutive administration of MTX (3 mg/kg/day), hydroxyproline content in the lung tissues increased significantly to about 2 times higher that of the control level. This result closely reflected to the results of hematoxylin and eosin (HE) and Azan stains. Immunohistochemical analysis revealed that MTX treatment resulted in a decrease of alveolar epithelial cells and an increase of fibroblast cells in the mouse lung tissues. When we examined the effects of MTX on primary mouse alveolar epithelial cell (MAEC) and mouse lung fibroblast (MLF) survival in vitro, the efficiency of MTX-induced cytotoxicity and apoptosis in MAEC was more sensitive than MLF cells. Thus, our results indicate that the administration of MTX by an oral route could induce a fibrotic response with cell dysfunction of the alveolar epithelium by which MTX-induced apoptosis. Our results thus suggest that MTX could induce alveolar epithelial cell injury and resulted in the loss of integrity of the alveolar-capillary barrier basement membranes followed by the recruitment and proliferation of myofibroblasts with the deposition of collagens.

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“…Bleomycin (BLM) is an anti-cancer drug that causes diffuse alveolar injury and subsequent pulmonary fibrosis [21,22]. Other investigators have observed that (1) proinflammatory cytokines, such as tumor necrosis factor (TNF)-␣, interleukin (IL)-1␤, and IL-6, (2) C-C chemokines, including monocyte chemoattractant protein (MCP)-1/CCL2, regulated on activation normal T cell expressed and secreted (RANTES)/CCL5 and macrophage inflammatory protein (MIP)-1␣/CCL3, and (3) C-X-C chemokine keratinocyte-derived chemokine (KC)/CXCL1, are involved in BLM-induced lung inflammation and subsequent fibrotic process, including the promotion of fibroblast proliferation and collagen production [23][24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%