STUDIES ON CULTIVATION OF HUMAN BLADDER TUMORS AND SENSITIVITY TESTS OF ANTI-CANCER DRUGS FOR HUMAN BLADDER TUMORS

Abstract

For the selection of optimal anti-cancer drugs, the sensitivity test using egg culture has been attempted. The use of chorioallantoic membrane of the chick embryo for heterogenous tumor growth dates back to the classic studies of Murphy. (1912) Since then this method of egg culture has been modified by various investigators. Fertile white leghorn eggs incubated at 37°C from nine to thirteen days were used in the present study. Human bladder tumor was surgically obtained, which was cut into fragments approximately 1mm³ in size.
A single fragment of tumor tissue was placed on the major blood vessel branches in the chorioallantoics. Two days after tumor plantation, anti-cancer drugs such as 5-Fluorouracil (5FU), Mitomycin C (MMC) and Carbazilpuinone (CQ) were injected into the yolk sack, and two days later the tumor was removed and examined with a light microscope and electron microscope.
The following results were obtained. Bladder tumors from 48 patients were implanted and examined, and their successful plantation rate was 83.4%. Sensitivity tests of anti-cancer drugs for 30 patients were performed. Subsequently the drug was chosen according to this result, 28 patients were successfully treated during the past 18 months.
The changes of cultured human bladder tumors due to anti-cancer drugs observed with a light microscope were nuclear degeneration, vague surrounding of the cell, decreased intensity of cell staining, cell infiltration arround tumor cells and fibrotic change arround tumor cells.
The electronmicroscopical effects of anti-cancer drugs on cultured human bladder tumors were irregular nuclear profilers, swollen mitochondria, a decrease in number and low electron density of rough endoplasmic reticulum, an increase in number of acuole and lysosome and changes of cell junction.
There was no relation between successful plantation rate and patient age, sex, pre-operation chemotherapy, methods of tumor removal, macroscopic features, and malignancy. But there was significant relation between the survival rate of inplanted tumors and the macroscopic features and malignancy. Sensitivity tests of single anti-cancer drug such as CQ, MMC and 5 FU for 14 patients were attempted. And their mean cell survival rates were 87.6% (control), 51.8% (MMC), 44.8% (CQ) and 23.5% (5FU). 5FU was the most effective in this case.
In addition to these drugs, sensitivity test of combination drugs such as CQ & MMC, CQ & 5FU & MMC, and these 3 drugs were tested to 9 patients. And their mean cell survival rate were 86.5, 86.6% (control), 59.1% (MMC), 37.0% (CQ), 25.4% (5FU), 39.4% (CQ & MMC), 43.6% (CQ 5FU), 50.3% (MMC & 5FU), and 43.1% (3 drugs).