Immunohistochemical evidence for the association between attenuated mtor signaling and diffuse alveolar damage, a fatal lung complication

Ryoko Saito, Mitsuru Yanai, Yasuhiro Miki, Yuichiro Fukasawa, Junya Tominaga, Masahito Ebina, Hironobu Sasano

研究成果: ジャーナルへの寄稿学術論文査読

3 被引用数 (Scopus)


Targeted anticancer therapies have been developed to interfere with specifc target molecules including those of downstream pathways required for tumor growth and progression. Mammalian target of rapamycin (mTOR) has been considered as one of the target molecules of cancer growth, and its inhibitors have been reported to exert an anticancer effect in various malignant tumors. The pulmonary disorder is one of the major side effects of anticancer drugs including mTOR inhibitor (mTORi), and the diagnosis of lung injury induced by medication is diffcult because of non-specifc nature of the radiological findings. In this study, we present the detailed autopsy findings of a patient who developed diffuse alveolar damage (DAD) following mTORi treatment for metastatic renal cell carcinoma. We also studied 19 cases of DAD derived from other diseases and 9 cases with non-pathological lung. Of interest, pneumocytes of the patients with DAD, who received other anticancer drugs or contacted bacteria, demonstrated significantly lower mTOR activities than pneumocytes of those with non-pathological lung tissue, as judged by the immunohistochemical analysis. In contrast, both pneumocytes and T cells in DAD tissues of the patient treated with mTORi showed higher mTOR activities than those of patients with DAD of other causes, suggesting that the enhanced mTOR signaling may be involved in the development of DAD after mTORi treatment. This unexpected finding needs to be confirmed in other patients treated with mTORi. In conclusion, the attenuated mTOR signaling in pneumocytes may contribute to the pathogenesis of DAD in patients without mTORi treatment.

ジャーナルTohoku Journal of Experimental Medicine
出版ステータス出版済み - 2014 9月 2


「Immunohistochemical evidence for the association between attenuated mtor signaling and diffuse alveolar damage, a fatal lung complication」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。