Development of a miniaturized, improved nucleic acid precursor incorporation assay for chemosensitivity testing of human solid tumors.

Two technological problems limit the usefulness of chemosensitivity assays: low success rates (generally 30-60%); and the requirement for large numbers of tumor cells (5 X 10(5)/dish). To solve these problems, we developed a miniaturized, improved, nucleic acid precursor incorporation assay (MINI-assay). In this new assay, 0.

[Current status of the human tumor clonogenic assay for gastrointestinal cancer].

The author reviewed his experience to date with chemosensitivity testing of 162 gastric and 144 colorectal cancers. All human tumor clonogenic assays were performed using a double-layer soft agar system with continuous exposure of cells to one concentration of standard anticancer drugs. Significant growth was defined as greater than or equal to 30 colonies/control plate.

[In vitro chemosensitivity of lung cancer and other chest tumors evaluated by human tumor colony assay].

In vitro chemosensitivity of lung cancer and other chest tumors was evaluated by human tumor colony assay (HTCA). From 61 specimens 33 (54%) grew more than 30 colonies from which evaluation of chemosensitivity could be performed. Of 41 specimens of lung cancer, 26 (63%) yielded adequate growth for drug testing.

[Local administration of anti-cancer drugs].

Anti-cancer drugs in the forms of an emulsion, a microsphere, and of conjugates with high molecular dextran have been developed in our laboratories, namely a fat emulsion of anticancer drug, MMC-microsphere, or MMC-dextran conjugates. The main advantages of these forms of pharmaceutical preparation are that they give prolongation of pharmacological actions by slow release and that they are applicable for topical use because of their reduced toxicities to local tissue yet maintaining local therapeutic potency. In this study we found that the rate of sustained release of drugs and antitumor effects were enhanced when used in such modified forms of drugs for topical injections.

Clonogenic assay for urologic malignancies.

An in vitro double soft agar technique was used to culture 91 human urologic tumors including 37 renal cell, 40 uroepithelial, 7 prostatic and 7 testicular cancers. Cells from 31 of 37 renal, 32 of 40 uroepithelial, 3 of 7 prostatic and 4 of 7 testicular cancer specimens grew to the extent that they could be used in chemosensitivity testing in soft agar (greater than or equal to 30 colonies per control plate). With this assay system, a very high growth rate (70/91; 77%) was obtained.

[Clinical correlations of drug sensitivity in the human tumor clonogenic assay--heterogeneity in drug sensitivity of human tumors].

The method of the human tumor clonogenic assay and its clinical correlations have been reported here. True positive rate for predicting of sensitivity to cytostatic drugs has been characteristically low. Results of our studies indicate that discrepancy of in vitro and in vivo results in clinical trials with the tumor clonogenic assay may be due to therapeutic heterogeneity among tumor colony-forming units within a primary tumor and between primary tumor and metastases.

Comparison of drug sensitivity among tumor cells within a tumor, between primary tumor and metastases, and between different metastases in the human tumor colony-forming assay.

The human tumor colony-forming assay was used to compare chemosensitivity among tumor cells within a primary tumor, between primary tumor and metastases, and between different metastases. No significant differences in cloning efficiency were found in any of the three comparison studies. However, considerable differences in chemosensitivities were observed between different parts of the same tumor and between the primary tumor and metastases.

Clinical correlations with chemosensitivities measured in a rapid thymidine incorporation assay.

A rapid assay for in vitro chemosensitivity testing measuring [3H]thymidine incorporation has been developed. Results of this assay correlate highly with chemosensitivities determined by the soft-agar clonogenic assay. A correlative study was carried out on 219 solid tumor specimens to assess the ability of the rapid assay to predict clinical response to antineoplastic therapy.

[Heterogeneity in drug sensitivity of human tumors in the human tumor colony-forming assay].

The human tumor colony-forming assay was used to compare chemosensitivity among tumor cells within a primary tumor, between primary tumor and its metastasis, and between different metastases. The results indicate that the reported discrepancies of in vitro and in vivo results in clinical trials with TCFA for predicting of resistance or sensitivity to cytostatic drugs may be due to therapeutic heterogeneity among tumor colony-forming units within a primary tumors and between primary tumor and metastases, and that the results from a metastatic lesion may have more profound implications in planning treatment of other metastatic lesions of the same patient.

The effects of lidocaine and verapamil on overdrive-induced suppression of pacemakers in dogs with complete atrioventricular block.

When the ventricle is electrically stimulated at a faster rate, the cessation of the drive is followed by a temporary suppression of automaticity (overdrive suppression). The effects of lidocaine and verapamil on overdrive suppression were studied in dogs. Lidocaine slowed the ventricular escape rate and prolonged the pause following overdrive; occasionally, it was about twice the next succeeding RR interval.

[Experimental studies on the genesis of low-frequency vibrations (M-sound) of the first heart sound using a miniature accelerometer].

We studied eight mongrel dogs, weighing 15 to 35 kg, in which an initial low-frequency vibration of the first heart sound (M-sound) was recognized on the chest wall. A miniature accelerometer weighing 0.5 gm was used to record surface velocity signals and surface acceleration signals as well as phonocardiograms over the cardiac apex of the closed chest wall and over the pericardium or epicardium.

Experimental study on lymphatic vascular changes in the development of cancer.

Sudan Black B and Sudan Blue can partly enter the lymphatics of the small intestine from the lumen with long chain fatty acids. By use of a fat emulsion saturated with them small intestinal and mesenteric lymphatics were clearly delineated. Subserosal and mesenteric lymphatics of the small intestine appeared as blue lines.

Antitumor activity of mitomycin C-dextran conjugate against various murine tumors.

The antitumor activity of a high molecular weight pro-drug of mitomycin C(MMC), MMC-dextran conjugate (MMC-D), was examined against various murine tumors under different experimental conditions. A single intraperitoneal injection of MMC-D exhibited higher antitumor activity against intraperitoneally inoculated B16 melanoma, Ehrlich ascites carcinoma, and P388 leukemia than MMC, but lower activity against BDF1 mouse-transplanted L1210 leukemia. Intratumoral injection of MMC-D showed a superior effect on subcutaneously implanted B16 melanoma, while intravenous injection of MMC-D exhibited reduced activity against P388 and L1210 leukemia compared with MMC.