Isao Sano

Prolonged survival of rat cardiac allograft with proinflammatory cytokine inhibitor.

BACKGROUND Proinflammatory cytokines, such as tumor necrosis factor (TNF-alpha) and interleukin-1 (IL-1), play important roles in acute allograft rejection. FR167653 is an inhibitor of these cytokines that acts through inhibition of the mitogen-activated protein kinase p38 pathway. We examined the effect of FR167653 on allograft rejection. METHODS We used Brown-Norway and Lewis rats as donors and recipients, respectively. We performed heterotopic cardiac transplantation. The control group consisted of untreated rats. In the experimental groups, recipients were intraperitoneally injected with FR167653 just after operation, followed by daily injection of the drug from Day 1 to 10. We divided 20 rats into 5 groups, which received varying doses of FR167653, ranging from 75 to 300 mg/kg/day. RESULTS In the control group, the mean graft survival was 6.8 +/- 0.3 days. FR167653 at 150 mg/kg/day significantly prolonged the survival period (up to 12.1 +/- 1.5 days, p = 0.002). Histologically, FR167653 markedly suppressed cellular infiltration on Day 5 post-transplantation. The serum level of TNF-alpha in the control group was persistently elevated from 9.3 +/- 3.9 pg/ml to 11.3 +/- 3.8 pg/ml, whereas FR167653 significantly suppressed the level to <1.4 +/- 1.4 pg/ml. CONCLUSIONS FR167653 prolonged rat cardiac allograft survival by suppressing the action of proinflammatory cytokines.

Prognostic Impact of the ABCC11/MRP8 Polymorphism in Adjuvant Oral Chemotherapy with S-1 for Non-Small Cell Lung Cancer

Background: Postoperative 1-year administration of S-1, an oral derivative of 5-fluorouracil (5-FU), was shown to be feasible in lung cancer. The 5-year survival rates of postoperative patients treated with S-1 adjuvant chemotherapy and the prognostic impact of clinicopathological factors were examined. Methods: The data of 50 patients with curatively resected pathological stage IB to IIIA non-small cell lung cancer, who were treated with S-1 postoperatively, were analyzed. The prognostic impacts of 22 clinicopathological factors including expressions of the 5-FU pathway enzymes were evaluated. A single-nucleotide polymorphism (SNP), i.e. 538G>A (rs17822931), of ABCC11/MRP8, which encodes a 5-FU excretion enzyme that is known as an earwax type determinant, was also evaluated. Results: The 5-year overall and relapse-free survival rates were 72.5 and 67.5%, respectively. A performance status ≥1, lymphatic vessel invasion, blood vessel invasion, and the A/A type of SNP538, which is responsible for the dry earwax type, were significantly associated with shorter relapse-free survivals. In 34 patients who showed a relative performance of 70% or more for chemotherapy, multivariate survival analysis indicated significant hazard ratios only for the A/A type of SNP538 (p = 0.007). Conclusions: S-1 has sufficient power as adjuvant chemotherapy. However, its effect might be small in the dry earwax type patient group in an adjuvant setting.

A case of primary pulmonary aspergilloma with pneumothorax

30歳男性．胸痛を主訴に近医受診．胸部単純写真にて右気胸，右上肺野結節影を認めた．当院紹介となり胸部CT施行したところ右上葉に嚢胞，および，その内部に径3cm大の球状の充実性成分を認めた．血液検査にてアスペルギルス抗原陽性，β-Dグルカンの上昇を認めた．以上より肺アスペルギローマと診断し胸腔鏡補助下右上葉切除術を施行した．病理では空洞内にアスペルギルス菌糸の増生が認められた．気胸を契機に発見された肺アスペルギローマは稀であるため若干の文献的考察を加え報告する．