Ca2+拮抗剤併用癌化学療法の基礎的検討 : In vitro, In vivoにおける効果と解析

Ca2+拮抗剤Verapamilを制癌剤,主として5-FU(その他ADM,VCR,BLM)と併用し,その抗腫瘍効果に及ぼす影響を,まず培養細胞を用いin vitroで検索,ついでこの成績にもとづきin vivoの実験として,担癌マウスに5-FUとVerapamilを連日併用投与し,survivalに及ぼす影響をも検討した.I.In vitro(1)Verapamilは単独でも高濃度では増殖抑制がみられたが,5μM以下の低濃度ではほとんど影響しなかった.(2)増殖に影響のない濃度のVerapamilを5-FUと併用すると,制癌剤が低濃度であるほどより大きい効果増強が認められた.(3)14C-5-FUを用いた細胞内取り込み実験では,14C-5-FUは細胞内へ経時的に移行するが,これにVerapamil 5μMを併用すると,無添加の14C-5-FU単独群に比べて,5-FUの移行は有意に高値となった.II.In vivo(1)Verapamil単独では,大量を負荷しても抗腫瘍効果はみられなかった.(2)5-FU 5mg/kgとVerapamil 20mg/kgを併用すると,投与期間に関係なく併用効果を認め,5-FU単独群に比べ有意の生存期間の延長を得,低濃度で併用効果のあることが判った.(3)5-FUとVerapamil 40mg/kgとの併用は,併用にもとづく副作用が出現し,5-FU単独投与群に比べ生存期間はかえって短縮した.以上より,5-FUにおいてもVerapamilとの併用効果が示されたが,その機序についてはいまだ不明な点が多い.5-FUとVerapamilの併用は,投与方法や投与量の決定にはなお慎重を要すとしても,癌化学療法における効果増強の新しい可能性として期待される.The influence of the Ca2+ antagonist on anticancer agents has not as yet well been clarified. Many reports have implied that the Ca2+ antagonist enhances the effect of anticancer drugs (Vinca-alkaloid, anthracycline agents) on drug resistant cells. However, there have been a few reports on the effect of the Ca2+ antagonist on sensitive tumor cells. This report deals with the effect of Verapamil as at of the Ca2+ antagonist on chiefly 5-FU on Ehrlich ascites tumor cells (EA cells), both in vitro and in vivo. I. In vitro (1) Verapamil inhibited the growth of EA cells by itself at a high concentration. (2) Verapamil enhanced greatly the cytotoxicity of 5-FU at a noncytotoxic dose, and even at a low concentration. (3) A kinetic experiment showed that the uptake of 14C-5-FU into EA cells increased with time. It was observed that the amount of cellular 14C-5-FU is greatly increased in the presence of 5μM Verapamil. II. In vivo (1) Verapamil alone showed no therapeutic effect even at a high dose. (2) When 5-FU (5mg/kg) was administered with Verapamil (20mg/kg), the life span of EA cell-bearing mice was significantly prolongated, irrespective of administration. (3) When 5-FU was administered with Verapamil (40mg/kg), an inverse effect appeared, and the life span was shortened as compared with the group of mice to whom 5-FU was administered alone. These results suggest that the combined use of Verapamil with 5-FU may provide better treatment for human cancer, although the mechanism still remains unknown

Cryosurgical Hemorrhoidectomy: Technique and Method

The key to gain successful results with cryosurgical hemorrhoidectomy is based on the prevention of prolapse of the edematous tissue after freezing. To prevent the edema, it is important to pull out the hemorrhoid as much as possible during freezing, to freeze only on the rectal side of the anal verge, to avoid freezing the anal verge, and to freeze the hemorrhoids in two or three separate stages when they are large such as the fourth-degree. The anal discomfort and discharge in these patients are related to prolapse of frozen tissue. Cryosurgery is an effective method of treatment for hemorrhoids if care is taken to use the proper techniques

A Cystic Lymphangioma of the Colon Seen in a Patient with Early Gastric Cancer

Lymphangiomas are very rare benign neoplasms of the gastrointestinal tract. A case of cystic lymphangioma in the hepatic flexure of the colon seen in patient with early gastric cancer is reported and the literature is reviewed

Lymphangioma of the Small Intestine : A Case Report

Lymphangiomas of the small intestine are rare tumors arising from masses of dilated lymphatic vessels in the submucosa. There are 11 cases of lymphangioma of the small intestine in the Japanese literature. We report a case of lymphangioma of the jejunum seen in a 76-year-old female and discuss with clinical feature