Fatal pulmonary fibrosis associated with BCNU

The relative role of platelet-derived growth factor-B, insulin-like growth factor I, transforming growth factor-β1 and cyclooxygenase-2

Y. C. Shen, C. F. Chiu, K. C. Chow, C. L. Chen, Y. C. Liaw, S. P. Yeh

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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-1), transforming growth factor-β1 (TGF-β1) 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-β1 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.

Original languageEnglish
Pages (from-to)609-614
Number of pages6
JournalBone Marrow Transplantation
Volume34
Issue number7
DOIs
Publication statusPublished - Oct 2004
Externally publishedYes

Fingerprint

Proto-Oncogene Proteins c-sis
Pulmonary Fibrosis
Transforming Growth Factors
Cyclooxygenase 2
Insulin-Like Growth Factor I
Alveolar Epithelial Cells
Alveolar Macrophages
Lymphoma, Large B-Cell, Diffuse
Hyperplasia
B-insulin
Therapeutics
Immunohistochemistry
Lung

Keywords

  • BCNU
  • COX-2
  • IGF
  • PDGF
  • Pulmonary fibrosis

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Fatal pulmonary fibrosis associated with BCNU : The relative role of platelet-derived growth factor-B, insulin-like growth factor I, transforming growth factor-β1 and cyclooxygenase-2. / Shen, Y. C.; Chiu, C. F.; Chow, K. C.; Chen, C. L.; Liaw, Y. C.; Yeh, S. P.

In: Bone Marrow Transplantation, Vol. 34, No. 7, 10.2004, p. 609-614.

Research output: Contribution to journalArticle

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abstract = "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-1), transforming growth factor-β1 (TGF-β1) 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-β1 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.",
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AB - 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-1), transforming growth factor-β1 (TGF-β1) 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-β1 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.

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