[Research subject]

Molecular pathology of lung cancer

[Description]
The downstream pathways of receptor tyrosine kinase (RTK) are involved in the regulation of cell proliferation, migration, infiltration, and apoptosis, and play a very important role in carcinogenesis. Mainly three pathways, the Ras/Raf/ERK, PI3K/AKT, and Jak/Stat3 pathways, are considered to be involved. We have thus far reported that the PI3K/AKT pathway becomes more activated than the Ras/Raf/ERK pathway as the disease stage progresses in lung adenocarcinoma and that the phosphorylated protein expression of AKT serves as a prognostic factor. We are investigating the association of adenocarcinoma in situ (AIS) with normal adenocarcinoma in terms of habitual smoking and receptor tyrosine kinase expression. We have accumulated data suggesting that AIS is not the origin of adenocarcinoma.

[Research subject]

Lung transplantation

[Description]
In lung transplantation, the lung obtained from the donor is refluxed in preservation solution and cryopreserved before being transplanted into the recipient, but the allowable ischemic time is limited to approximately 8 hours. In addition, only a small proportion of donated lungs functions well enough to be transplanted because of liver disorders affecting the donors.
If obtained lungs can be refluxed and aerated ex vivo to improve lung function and if storage beyond the allowable ischemic time becomes possible, the supply of lungs that can be transplanted will increase and an improvement in transplantation results can be expected.
Therefore, we have been conducting reflux experiments using porcine and human lungs. Based on our investigations thus far, we have reported that oxygenation is preserved and anaerobic metabolism increases during reflux and that the lactic acid/pyruvic acid ratio is useful as a biomarker.
（http://www.ncbi.nlm.nih.gov/pubmed/21930395）

[Research subject]

Gene transfer in transplantation

[Description]
Aortic dissection is a fatal disease with sudden onset, and there are still a number of cases in which lifesaving is difficult despite the recent progress in diagnostic treatment. Because aortic dissection is believed to develop based on weakening of the vascular wall, stress-responsive signal molecules associated with inflammation and extracellular matrix metabolism are possibly involved. We focused on c-Jun N-terminal kinase (JNK) and investigated how JNK and its isoforms (JNK1 and JNK2) are involved in the pathogenesis of aortic dissection. Based on the results of animal studies and culture experiments using human aortic wall specimens, we elucidated that JNK activation plays an important role in weakening of the aortic wall and the pathological mechanism leading to the onset of dissection.
（http://www.sciencedirect.com/
science/article/pii/S0022480412019567）