膀胱癌患者におけるβ-GlucuronidaseおよびそのInhibitor投与の影響について

Abstract

Urinary p-glucuronidase activity and glucaric acid level were biochemically determined, and tissue p-glucuronidase in the removed bladder tumor was histochemically investigated. SLA, diacetyl-type of glucaro-(1--, 4)(6–, .3)-dilactone, was orally administered to the postoperative patients, and its effects on urinary p-glucuronidase and glucaric acid were studied. Moreover, SLNA, sodium salt of SLA, was directly injected into the tumor tissue, and its effects on tissue p-glucuronidase were investigated. Urinary p-glucuronidase wa s measured using a part of 24-hour urine with phenolphthalein monoglucuronide as the substrate. Urinary glucaric acid was isolated and measured by Ishidate's method with use of anion exchange resin column chromatography. Tissue p-glucuronidase was studied by Hayashi's method which is the histochemistry with naphthol AS-BI glucuronide as the substrate on the frozen section. The following results were obtained. 1) Urinary p-glucuronidase activity of the patients with carcinoma of the bladder was 520-3, 067 pg/hr/dl, which was generally higher than that of the normal persons, 250-688p g/ hr/dl. Urinary p-glucuronidase in acute pyelonephritis measured as a control was also high and showed 1, 0672, 333 pg/hr/dl. 2) The urinary gluc a ric acid of the patients with carcinoma of the bladder was 1.9-10.2 mg/day. Most of all the cases had the low level as compared with the control group which showed 2.3-21.0 mg/day. SLA-glucaric acid conversion rate was lower than 18 % except one patient. 3) Distribution of p-glucuronidase activity in the tissue of transitional cell carcinoma was not even but was striking in the vicinity of the papillary growth. The activity, however, was variable according to grade of anaplasia. Namely, in the more anaplastic area, the more activity was seen. 4) The c h aracter of p-glucuronidase positive granules seemed to be correlated with grading. The 'p-glucuronidase staining granules in the tissue of higher malignancy were larger and denser. Histochemical investigation of p-glucuronidase in the tumor tissue seems to be quite significant to determine its grade just like Broders' classification. 5) Under oral administration of SLA, both the urinary level and tumor tissue activity of i3-glucuronidase were inhibited. At the present time, no final conclusion could be made as to the prophylactic effects of SLA on the recurrence of the bladder tumor. 6) Local injection of SLNA into the tumor inhibited 8-glucuroni d ase activity of cancer tissue and produced the vacuolization of the tissue. Some tumors underwent shrinkage or even disappeared after SLNA injection, although its mechanism could not be elucidated.