Fatal pulmonary fibrosis associated with BCNU: the relative role of platelet-derived growth factor-B, insulin-like growth factor I, transforming growth factor-beta1 and cyclooxygenase-2.
Pulmonary fibrosis is a severe complication associated with bis-chloronitrosourea (BCNU) therapy. However, the pathogenetic mechanism has never been well investigated. We report here a 26-year-old female with diffuse large B-cell lymphoma who died of severe pulmonary fibrosis 81 days after the administration of high-dose BCNU (600 mg/m2). Thoracoscopic wedge resection of left upper lung performed 10 days before patient's death showed severe pulmonary fibrosis with prominent hyperplasia of alveolar macrophages and type II pneumocytes. We further used immunohistochemistry (IHC) to examine the relative role of platelet-derived growth factor-B (PDGF-B), insulin-like growth factor I (IGF-I), transforming growth factor-beta1 (TGF-beta1) and cyclooxygenase-2 (COX-2) in the pathogenesis of BCNU-related pulmonary fibrosis. Strong expressions of PDGF-B and IGF-1 on alveolar macrophages and type II pneumocytes were clearly demonstrated, but in contrast, the expressions of TGF-beta1 and COX-2 were almost undetectable. In conclusion, pulmonary fibrosis can develop early and progress rapidly after the administration of high-dose BCNU. The markedly increased expression of fibrogenic factors PDGF-B and IGF-1 on hyperplastic alveolar macrophages and hyperplastic type II pneumocytes may play an important role in the fibrogenesis of this disease. These novel findings may offer specific therapeutic targets in the treatment of BCNU-associated pulmonary fibrosis.
Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
Y-C
YC
Shen
C-F
CF
Chiu
K-C
KC
Chow
C-L
CL
Chen
Y-C
YC
Liaw
S-P
SP
Yeh
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D002330:Carmustine / Q000009:adverse effects*; D051546:Cyclooxygenase 2; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008168:Lung / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000150:complications / Q000188:drug therapy*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications / Q000188:drug therapy*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D018906:Antineoplastic Agents, Alkylating; D007527:Isoenzymes; D008565:Membrane Proteins; D020574:Proto-Oncogene Proteins c-sis; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007334:Insulin-Like Growth Factor I; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D002330:Carmustine