Hideo Matsui

Collagen biosynthesis in gastric cancer: immunohistochemical analysis of prolyl 4-hydroxylase.

The mechanism of the desmoplastic response in gastric carcinoma tissues is largely unknown. The objective of this study is to determine the localization of prolyl 4‐hydroxylase (PH), an enzyme that plays a crucial role in collagen biosynthesis.

Gastrointestinal stromal tumor of the stomach successfully treated by laparoscopic proximal gastrectomy with jejunal interposition.

The authors describe a patient with a bleeding gastrointestinal stromal tumor of the stomach who was treated successfully by laparoscopic proximal gastrectomy with jejunal interposition. Immunohistochemically, the tumor was positive for vimentin and CD34 and was diagnosed as a gastrointestinal stromal tumor of low-grade malignancy. Because it is difficult to diagnose this disease preoperatively and a malignant phenotype has been reported, resulting in liver metastasis and peritoneal dissemination, it is desirable to treat this disease with as little manipulation as possible. To achieve this, laparoscopic surgery is a feasible option for the treatment of gastrointestinal stromal tumors.

Experimental and clinical studies on the intraperitoneal administration of cis-diamminedichloroplatinum (II) for peritoneal carcinomatosis caused by gastric cancers.

The effectiveness of the intraperitoneal administration of cis-diamminedichloroplatinum (II) (DDP) on peritoneal carcinomatosis caused by gastric cancers was evaluated. Seventeen patients were treated with one of three protocols, consisting of the intraperitoneal injection (ip) of DDP at doses of 70 and 110 mg/m2, with or without sodium thiosulfate (STS) rescue. The area under the curve (AUC) of DDP for sufficient anticancer activities against cultured human cell lines in vitro was estimated at 240 μg h/ml, which was equivalent to the AUC gained by 110 mg/m2 ip DDP in the clinical studies. The cytotoxic activity of DDP was reduced by approximately 50% with 100-fold STS in the AUC in the experimental studies. However, this was achieved only in urine, and not in either the peritoneal cavity or in plasma in the clinical studies. Three cases of a partial response against peritoneal carcinomatosis were seen from a total of four evaluable cases treated with 110 mg/m2 DDP, and no renal toxicities were observed in those treated with the STS rescue. The results of this study led us to conclude that high-dose ip DDP treatment combined with the STS rescue would be useful chemotherapy against peritoneal carcinomatosis caused by gastric cancers.

Mechanism of metastasis of gastric cancer, from the viewpoint of basement membrane degradative enzyme.

上皮性癌の転移過程では, まず癌原発巣部における癌細胞の基底膜層の通過, 間質内での浸潤, その後に遭遇する脈管基底膜層の通過と脈管内への侵入, さらには転移としての着床部位における脈管外への遊出の際の脈管基底膜層の通過などが考えられ, 転移におけるいわゆるseed and soilの際に癌細胞が基底膜を何回にも渡って通過しなければならない.基底膜は主にIV型コラーゲンから構成されており, IV型コラーゲン分解酵素 (IVase) によって特異的に分解される.そこで癌組織中のIV ase活性はその癌の生物学的悪性度を表す指標となる可能性の追求を, まず組織中IV ase活性測定法を確立し, それを胃癌症例に用いて行い, その可能性を証明した.さらにIV型コラーゲンの分解産物である尿中3-hydroxyprolineが進行胃癌症例で増加していることもわかった.