Tsutomu Mure

Modulation of Membrane Permeability, Cell Proliferation and Cytotoxicity of Antitumor Agents by External ATP in Mouse Tumor Cells

External ATP causes a remarkable change in the passive permeability of the plasma membrane in several types of transformed cells. When mouse melanoma cells, Clone‐M3, were exposed to ATP in Tris‐buffered saline, a great increase in the passive permeability was induced within several minutes. Longer exposure of Clone‐M3 cells to external ATP led to a decrease in cell viability. Similar results were obtained with Ehrlich ascites cells, but none of these ATP effects were noted in untransformed cells such as NIH 3T3 cells or BALB/c mouse embryonic fibroblasts. The in vitro cytotoxic effects of antitumor agents (5‐fluorouracil, adriamycin, mitomicin C and nimustine hydrochloride) against Clone‐M3 cells were additively potentiated by treatment with external ATP, which also synergistically enhanced the cytotoxicity of vincristine. However, the effects of these drugs on mouse embryonic fibroblasts were not modulated by ATP. These results suggest that ATP‐treatment is a useful means of enhancing a selective toxicity for tumor cells.

Local Recurrence After Local Excision of Early Rectal Cancer

The advantage of local excision for early rectal cancer, excluding fiberscopic polypectomy, is that it allows preservation of the anal function of the sphincter. We treated 75 patients with early rectal cancer and carried out local excision in 29 of these cases during the period from 1974 to 1992. Three of these 29 patients were reoperated upon immediately because of massive invasion to the submucosa at the margin of the removed specimen. Two other cases experienced local recurrences and required additional surgery.

Cryosurgical Treatment For Local Recurrence Of Rectal Cancer

During the last 19 years we have used cryosurgery as part of a multidisciplinary therapy to treat 12 patients with local recurrence of rectal cancer. This treatment was chosen to provide these patients with the palliative benefits of minimal bleeding and to reduce tumor bulk. The survival time following resection therapy in 30 cases after relapse was significantly greater than that for the 12 cases receiving cryosurgical treatment. However, local destruction of the recurring cancer by cryosurgery resulted in effective control of the tumor.

Effect of ATP on antitumor activity of various antitumor drugs in mice tumor cells in vitro.

マウス培養細胞を用い, ATPの癌細胞および正常細胞の増殖, 膜透過性におよぼす影響を検討した. さらに本物質の癌化学療法への応用を目的として, 各種抗癌剤との併用実験を行った. ATPにより, 癌細胞では著明な細胞膜透過性の亢進, cell viabilityの低下がみられたのに対し, 非癌化細胞におけるこれらの変化は軽微で, ATP作用は癌細胞に特異的であった. ATP処理後の癌細胞における各種抗癌剤の抗腫瘍効果は, 5-FU, ADM, MMC, ACNUでは相加的, VCRでは相乗的に増強した. また, 正常細胞に対する抗癌剤の細胞毒性はATPの併用により増強されなかった. これらの結果からATPを用いることにより, 選択的癌化学療法が期待できるものと思われた.