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Biomedical subjects

N Tanigawa

Publications and source records attributed to N Tanigawa.

At least 163 records · Page 9Linked to original sources

[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. Clinical responses were determined according to standard criteria. Forty-six per cent of gastric cancer specimens and 67% of colorectal cancer specimens plated produced significant growth in vitro. When greater than or equal to 50% inhibition of colony formation was used as the criterion for differentiating sensitivity from resistance, the assay was 67% (8/12) reliable for predicting in vivo sensitivity, and 91% (10/11) reliable for in vivo resistance.

Animals↗

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, 0.3-1.5 X 10(5) tumor cells were plated in double-layer agarose in 16-mm wells of a Costar (No. 3524) 24-well cluster dish. After 72 h of incubation, 5 microCi [3H]thymidine were added to each well. After an additional 24 h of incubation, the trichloroacetic acid-precipitable material was collected and counted by liquid scintillation. We found that 280 of 351 (80%) human solid tumors gave evaluable chemosensitivity results. Labeling efficiency was optimum when the plating density was between 1.5 and 3 X 10(4) cells/well. Radioisotope uptake was less efficient in 35-mm Petri dishes and in the 7-mm wells. The MINI-assay was particularly suitable for small specimens (less than 1 g) and for tumor types that usually yield small numbers of viable tumor cells (19 of 30 breast cancers and 56 of 71 sarcomas were evaluable). The artifacts of colony counting (cell clumps, debris, clots) were also eliminated with this assay. With high evaluability rates, the requirement of fewer cells, a short duration (5 days), and ease of quantitation, the MINI-assay is widely applicable to chemosensitivity testing in human tumors.

Agar↗

[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. Nine out of 26 specimens of non-small cell lung cancer showed more than 50% reduction in colony formation, and in 4 of the 26 specimens, more than 70% reduction was obtained with more than one of the drugs tested. Specimens obtained from metastatic lesions of lung cancer showed higher plating efficiency and drug sensitivity than those from primary lesions. Plating efficiency of non-epithelial tumors was lower than that of epithelial tumors. HTCA has a potential value for screening anticancer agents against lung cancer and other chest tumors. However, the assay still has many problems to be resolved, such as difficulty in obtaining single-cell suspensions and poor plating efficiency.

Adenocarcinoma↗

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. Two different parts of the same tumor were comparably assayed for nine primary tumors. In nine paired samples which allowed in vitro drug sensitivity testing, there was no satisfactory correlation of sensitivity to cytostatic drugs. Cell suspensions were prepared from 28 primary tumors and from metastases taken from the same patient. In 14 paired samples which formed sufficient colonies for determination of drug effect, the data showed no satisfactory correlation of chemosensitivity between a primary tumor and its metastases. Both tumor samples from different metastatic sites of the same patient formed sufficient colonies in seven of eight instances. In the seven paired samples, there was strong association of chemosensitivity (p less than 0.005). The results indicate that the reported discrepancies of in vitro and in vivo results in clinical trials using the tumor colony-forming assay for predicting resistance or sensitivity to cytostatic drugs may be due to therapeutic heterogeneity among tumor colony-forming units within a primary tumor and between a primary tumor and its metastases.

Antineoplastic Agents↗

[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. Results of clinical trials of those drugs have been promising. However, the number of trials has been limited so far. Further studies would be required for evaluating on of their clinical utilities.

Adult↗

[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.

Antineoplastic Agents↗

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. The in vitro response rates of greater than or equal to 10% were noted with mitomycin C, 5-fluorouracil, cisplatin, bleomycin and vincristine in renal cell cancers, and with vincristine and cisplatin in uroepithelial cancers. Drug sensitivity studies showed that the rates of in vitro sensitivity of uroepithelial cancers were close to those obtained in general clinical experience, while the rates of the vitro sensitivity of renal cell cancers were considerably higher than the rates found clinically. It is concluded from this study that in vitro chemosensitivity testing by clonogenic assay is likely to be a useful tool in the treatment of urologic cancers, but that a simple definition of sensitivity cannot be applied for all types of tumors.

Antineoplastic Agents↗

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. One hundred forty-two of 219 tumors (65%) yielded chemosensitivity data. Of these, 33 were evaluable for in vitro-in vivo correlations. In vitro sensitivity (greater than or equal to 80% inhibition of thymidine uptake) was associated with clinical response in 6 of 13 patients. In vitro resistance was associated with progressive disease in 20 of 20 patients. The rapid assay offers several advantages over the soft-agar clonogenic assay, including higher success rate, avoidance of clumping artifact, shorter time course (5 days), and very low false-negative rate. Further refinement may be necessary, but the rapid assay appears to have potential for individualizing solid tumor chemotherapy.

Antineoplastic Agents↗

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. On the contrary, verapamil influenced neither the ventricular escape rate nor the pause following overdrive. It is suggested that lidocaine not only suppresses the automaticity of ventricular escape pacemaker but also induces exit block and that the spontaneous depolarization of the ventricular pacemaker is not slow channel-dependent.

Animals↗

[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. The frequency response of accelerometer was essentially flat (+/- 1.5 dB) from 1 to 200 Hz. The accelerometer mounted was such that its sensitive axis was perpendicular to the recording surface. Equisensitive phonocardiograms were obtained to compare the signal size of M-sound on the epicardium at several positions including the cardiac apex, the left ventricular anterior wall near the interventricular septum, the left ventricular antero-lateral wall and the right ventricular anterior wall. Intraventricular phonocardiograms and pressure curves were obtained by a Millar catheter directly inserted through the left ventricular wall near the apex to keep the tip near the apex. Furthermore, the relationship between M-sound and the shortening of the myocardium at the apex was investigated by means of ultrasonic dimension system and phonocardiography. Studies of M-sound were performed not only in sinus rhythm, but also in atrio-ventricular dissociation and ventricular pacing after crushing sinus node or electrical vagus stimulation. The results were as follows: The M-sounds over the chest wall, pericardium and epicardium were recorded coincidentally with the onsets of the left ventricular pressure curve, its dP/dt, low-frequency vibration of the first heart sound of intraventricular phonocardiogram, positive velocity, and acceleration of myocardial surface. The M-sound on the epicardium was maximal in intensity at or near the cardiac apex, in comparison with those recorded on the left ventricular anterior wall near the interventricular septum, left ventricular antero-lateral wall, and right ventricular anterior wall. The M-sound was observed between A and C points of the mitral valve echogram. There was no effect of atrial contraction on the M-sound in cases of atrio-ventricular dissociation. The onset of the M-sound on the epicardium at the apex was not always coincident with the onset of shortening of the myocardium at the same position.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗