膵胆道系癌への新しい外科的アプロ-チの開発

金沢大学医学部本研究は、これまで外科的に切除された症例の病理組織学的進展式を再度詳細に検討し、併せて膵胆道系における主要血管の合併切除および血行再建が安全かつ確実に行いえるための手術手技の開発を行い、さらに癌腫の進展度に応じた過不足のない適切なリンパ節郭清の範囲を解明し、膵胆道系癌の外科的治療成績のさらなる向上を目指すために計画されたものである。なお、本研究は膵胆道系癌症例を多く持っている施設と血管外科専門領域の施設が合併して総合研究として行った。その結果、前造度の研究ならびに今造度の研究より切除例の進展様式をみると、進行癌に対しては従来の切除方法では膵胆道系癌の治癒切除すらみることができないことが判明し、治癒切除をみるためには、特に胆道癌に対しては肝十二指腸間膜合併切除(肝動脈、門脈、胆管の合併切除)が、膵癌に対しては上腸間膜動静脈の合併切除が問題となった。血管合併切除では。門脈の合併切除ではその手技はほぼ確立して、まず問題なく施行できるとの結論を得た。しかし、動脈合併切除では、その吻合技術はまだ十分とはいえず、各研究者からの報告をみても第1段階に入ったところで、その安全化、適応の広がりについては問題点が残った。しかし、今後の発展によって肝十二指腸膜合併切除と上腸間膜動静脈の合併切除の問題は解決されるであろうとの糸口を見い出した。以上より、さらなる研究の継続と膵胆道系癌の外科治療成績の向上を期待する。This study was designed to reevaluate the pathological spread of resected specimens for pancreato-biliary cancer, develop the operative procedures of resection and reconstruction of the main vessels in the pancreato-biliary system, and elucidate the adequate range of lymphatic dissection according to the extension of the tumor. Some institutes which have ever operated many cases of the same carcinoma, or specialized in the blood vessel surgery joined it. It became clear that the previous procedures might be unable to remove curatively the advanced cancer of the pancreato-biliary system from the pathological investigation of the extension of cancers, and curative removements needed a combined resection of the total hepato-duodenal ligament for biliary cancer and a combined resection of the superior mesenteric vein and artery. In the combined resection of the blood vessels, a combined resection of the portal vein became safer and more certain, but the technique of a combined resection of arteries such as the hepatic artery and the superior mesenteric artery still remained insufficient. However, this study showed that the combined resection of these arteries would be resolved in the near future by the continuous research about these problems.研究課題/領域番号:01304042, 研究期間(年度):1989 – 1990出典：研究課題「膵胆道系癌への新しい外科的アプロ-チの開発」課題番号01304042（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-01304042/013040421990kenkyu_seika_hokoku_gaiyo/）を加工して作

日本およびチリにおける胃癌の組織発生について

金沢大学医学部研究課題/領域番号:63044055, 研究期間(年度):1988出典：研究課題「日本およびチリにおける胃癌の組織発生について」課題番号63044055（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-63044055/）を加工して作

Immunosuppressant FK506 induces interleukin-6 production through the activation of transcription factor nuclear factor (NF)-κB implications for FK506 nephropathy

金沢大学がん研究所がん分子細胞制御FK506 is a powerful immunosuppressive drug currently in use that inhibits the activation of several transcription factors (nuclear factor (NF)-AT and NF-κB) critical for T cell activation. We show here that, contrary to the situation in T cells, FK506 activates transcription factor NF-κB in non-lymphoid cells such as fibroblasts and renal mesangial cells. We further show that FK506 induces NF-κB-regulated IL-6 production in vitro and in vivo, in particular in kidney. IL-6 has been shown previously to produce renal abnormalities in vivo, such as mesangioproliferative glomerulonephritis. Similar renal abnormalities were also observed in FK506-treated animals. These results thus suggest a causal relationship between FK506-induced NF-κB activation/IL-6 production and some of FK506-induced renal abnormalities

Expression of 16 kDa proteolipid of vacuolar-tgpe H+-ATPase in human pancreatic cancer

金沢大学医薬保健研究域医学系Recent studies have shown that bafilomycin A1-sensitive vacuolar-type H+-ATPase (V-ATPase) plays important roles in cell growth and differentiation. However, there is no published study that has focused on the expression of V-ATPase in human tumour tissues. This study was designed to examine the mRNA and protein levels for the 16 kilodalton (kDa) proteolipid of V-ATPase in human pancreatic carcinoma tissues. We first investigated the mRNA level for V-ATPase in six cases of invasive pancreatic cancers and two normal pancreases, using reverse transcription-polymerase chain reaction technique. Then, we examined immunohistochemically the level of V-ATPase protein in 49 pancreatic cancers and ten benign cystic neoplasms of the pancreas, using antisera raised against the 16 kDa proteolipid. There was a notable difference in the level of V-ATPase mRNA between normal and pancreatic carcinoma tissues, with no evident difference in the expression of the β-actin gene. Immunohistochemically, 42 out of 46 invasive ductal cancers (92%) displayed a mild to marked immunoreactivity for V-ATPase in the cytoplasm, whereas neither non-invasive ductal cancers nor benign cystic neoplasms expressed detectable immunoreactive proteins. These findings suggest that the overexpression of V-ATPase protein is characteristic of invasive pancreatic tumours. V-ATPase may play some crucial roles in tumour progression.Embargo Period 12 month

Expression of basic fibroblast growth factor and its receptor in human pancreatic carcinomas

金沢大学医薬保健研究域医学系We examined the expression of basic fibroblast growth factor (FGF) and FGF receptor by immunohistochemistry in 32 human pancreatic ductal adenocarcinomas. Mild to marked basic FGF immunoreactivity was noted in 19 (59.4%) of the 32 tumours examined, and 30 (93.3%) of the tumours exhibited a cytoplasmic staining pattern against FGF receptor. The tumours were divided into two groups according to the proportion of positively stained tumour cells: A low expression group (positive cells ≪ 25%) and a high expression group (positive cells > or = 25%). No statistically significant difference in tumour size, differentiation, metastases or stage was found between the low and high basic FGF expression groups. However, a significant correlation was found between FGF receptor expression level and the presence of retroperitoneal invasion, lymph node metastasis, and tumour stage. In addition, low FGF receptor expression was significantly associated with a longer post-operative survival as compared with high FGF receptor expression, whereas there was no significant difference in post-operative survival between the low and high basic FGF expression groups. Increased expression of FGF receptor is correlated with the extent of malignancy and post-operative survival in human pancreatic ductal adenocarcinomas. Thus, overexpression of FGF receptor may prove to be a more useful prognostic marker than basic FGF expression level in pancreatic cancer patients. © 1995 Stockton Press. All rights reserved.Embargo Period 12 month

Effect of Prostaglandin E1 on Acute Ischemia-Reperfusion of Canine Small Intestine

Ischemia-reperfusion of the small intestine associated with hemorrhage and other shock states is characterized by increased microvascular permeability and mucosal barrier dysfunction. Glycoproteins play an important role as a barrier to diffusion, and some of the functions of prostaglandin E1 (PGE1) are related to mucosal protein synthesis. The present experiment was conducted to clarify the effect of PGE1 on mucosal levels of glycoproteins and ATP following acute ischemia-reperfusion of the small intestine. The canine jejunum was isolated, and the blood flow was blocked for 30min with or without intravenous infusion of PGE1. Mucosal levels of ATP, Na+-K+ ATPase activity, glucosamine, galactosamine, and cAMP decreased, and plasma endotoxin levels in portal blood increased, after reperfusion in the PGE1-non-treated group. These changes were suppressed and mucosal levels of cAMP were increased by the administration of PGE1. These results suggest that mucosal permeability increased and mucin synthesis decreased markedly following acute ischemia-reperfusion and that the administration of PGE1 suppressed these changes by stimulation of ATP and cAMP synthesis. We also conclude that the administration of PGE1 is useful to protect against acute ischemia-reperfusion injury in the small intestine

Serum Granulocytic Elastase and Superoxide Dismutase Activity after Administration of Protease-Inhibitor to Postoperative Patients

Postroperative changes in the plasma levels of granulocytic elastase and superoxide dismutase were examined clinically. Seven patients who had undergone cholecystectomy and eight patients who had undergone subtotal esophageal resection were considered. The protease inhibitor ulinastatin was administered to four of the latter patients. The levels of granulocytic elastase were elevated, and those of superoxide dismutase, decreased, in the non-medicated patients who had undergone esophageal resection (p<0.05). Furthermore, in the patients given the daily medication of 3×105 units of urinastatin for more than 3 days postoperatively, the elevation of granulocytic elastase levels and the decline of the superoxide dismutase levels were markedly suppressed (p<0.05). On the other hand, granulocytic elastase levels of the plasma to which ulinastatin had been added in vitro did not decrease. It is considered that the medicament of ulinastatin may be useful in the prevention of tissue injury caused by granulocytic elastase in cases where a disproportion of proteases and endogenous protease inhibitors exists