芳香族炭化水素受容体(AhR)の腎細胞癌の浸潤や進展との関連を解析した。AhRの発現は予後不良因子であり, 活性化によって上皮間葉転換が促進され, 腫瘍の浸潤を促進することを示した。スニチニブ治療後のがん組織を解析した結果, 腫瘍血管はほとんど死滅しているものの, 細かな腫瘍血管が残存し, その腫瘍血管にはVasohibin-1が発現していることを発見した。またスニチニブの効果に血中のMDSC(myeloid derived suppressor cell)の数が予後不良因子であることを示した。
Aryl hydrocarbon receptor (AhR) was investigated in 120 patients with RCC using immunohistochemistry. AhR was predominantly expressed in the nuclei of high-grade clear cell RCC (ccRCC) and tumor-infiltrating lymphocytes (TILs), and its expression levels in cancer cells and TILs correlated with the pathological tumor stage and histological grade. Expression of VASH1 were immunohistochemically examined. Multivariate Cox analysis indicated that an elevated VASH1 density, but not microvascular density, was a significant and independent predictor of overall survival (odds ratio, 7.71 ; P=0.003). Blood samples were collected at baseline in 90 patients to analyze serum angiogenic and inflammatory markers together with peripheral blood immunological marker. Immunologic (myeloid-derived suppressor cells, percentage of T helper type 1 cells) markers at baseline predicted the response to sunitinib therapy and/or disease progression in patients with metastatic renal cell carcinoma.

研究種目 : 基盤研究(B)(一般)
研究期間 : 2015～2017
課題番号 : 15H04977
研究分野 : 泌尿器科学, 腫瘍学