ABSTRACT
Naftopidil, an α-1 adrenoceptor antagonist with few adverse effects, is prescribed for prostate hyperplasia. Naftopidil inhibits prostate fibroblast proliferation; however, its effects on lung fibroblasts and fibrosis remain largely unknown. Two normal and one idiopathic pulmonary fibrosis human lung fibroblast lines were cultured with various naftopidil concentrations with or without phenoxybenzamine, an irreversible α-1 adrenoceptor inhibitor. We examined the incorporation of 5-bromo-2'-deoxyuridine into DNA and lactic acid dehydrogenase release by enzyme-linked immunosorbent assay, cell cycle analysis by flow cytometry, scratch wound-healing assay, and mRNA expressions of type IV collagen and α-smooth muscle actin by polymerase chain reaction. Effects of naftopidil on bleomycin-induced lung fibrosis in mice were evaluated using histology, micro-computed tomography, and surfactant protein-D levels in serum. Naftopidil, dose-dependently but independently of phenoxybenzamine, inhibited 5-bromo-2'-deoxyuridine incorporation in lung fibroblasts. Naftopidil induced G1 cell cycle arrest, but lactic acid dehydrogenase release and migration ability of lung fibroblasts were unaffected. Naftopidil decreased mRNA expressions of type IV collagen and α-smooth muscle actin in one normal lung fibroblast line. Histological and micro-computed tomography examination revealed that naftopidil attenuated lung fibrosis and decreased serum surfactant protein-D levels in bleomycin-induced lung fibrosis in mice. In conclusion, naftopidil may have therapeutic effects on lung fibrosis.
Subject(s)
Cell Proliferation/drug effects , Fibroblasts/drug effects , Idiopathic Pulmonary Fibrosis/prevention & control , Lung/drug effects , Naphthalenes/pharmacology , Piperazines/pharmacology , Adrenergic alpha-Antagonists/pharmacology , Animals , Bleomycin , Cell Cycle/drug effects , Cell Line , Cells, Cultured , Fibroblasts/metabolism , Humans , Idiopathic Pulmonary Fibrosis/chemically induced , Idiopathic Pulmonary Fibrosis/metabolism , Lung/metabolism , Lung/pathology , Mice, Inbred C57BL , Pulmonary Surfactant-Associated Protein D/blood , X-Ray MicrotomographyABSTRACT
We report a case of advanced schirrous gastric cancer with carcinomatous peritonitis. Chemotherapy with TS-1 was applied during the first 4 weeks, but the tumor did not respond to this therapy. Next, paclitaxel (TXL) was administered at a weekly dose of 90 mg/body/day for 3 weeks followed by a week interval of rest. Remarkable mass reduction of primary tumor was observed after 3 courses of treatment, and the symptom derived from primary tumor was relieved without significant side effects. The clinical course for schirrous gastric cancer with carcinomatous peritonitis is still miserable for patients, although many attempts have been made to improve its prognosis. A weekly paclitaxel regimen appears to be one of the promising treatment for schirrous gastric cancer.
