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Biomedical subjects

H Tokita

Publications and source records attributed to H Tokita.

At least 19 recordsLinked to original sources
PubMed1991

A newly developed in vitro chemosensitivity test (nuclear damage assay): application to ovarian cancer.

With a newly developed in vitro chemosensitivity test based on the morphological changes of nuclear damage (nuclear damage assay) described here, we were able to screen currently available anticancer drugs within 24 hr with a 100% success rate. In preclinical chemotherapy using four human ovarian epithelial tumor cell lines and their xenografts in nude mice, the in vitro/in vivo response (sensitive/sensitive and resistant/resistant) rate was 94%. The nuclear damage assay was used to determine the chemosensitivity in 49 patients (60 assays) with ovarian cancer. The response rate of the 13 patients with measurable tumors, 9 of whom showed resistance to CAP (cyclophosphamide, adriamycin, and cisplatin) therapy, was 46% when the patients were given various combination chemotherapy protocols consisting of more than one active agent selected from group A and B agents by the nuclear damage assay. The newly developed in vitro chemosensitivity test proved to be useful when selecting a second-line combination chemotherapy for patients with CAP-resistant ovarian cancer.

Animals↗
PubMed1991

[Comparative studies on the antitumor activity of fluorinated pyrimidine derivatives against human bladder, cervical and ovarian cancer xenografts in nude mice].

Fluorinated pyrimidines given orally were examined for their antitumor activity with 11 human cancer xenograft models (4 bladder, 4 cervical and 3 ovarian cancers). The drugs were evaluated to be effective when they inhibited tumor growth over 58%. UFT was not effective against all of 11 cancer xenografts tested. 5-Fluorouracil (5-FU) was effective against only one bladder cancer xenograft among 6 cancer xenografts tested. On the other hand, 5'-deoxy-5-fluorouridine (5'-DFUR) was effective against one bladder, 3 cervical and one ovarian cancer xenografts. The Antitumor activity of 5'-DFUR was correlated with the enzyme activity of pyrimidine nucleoside phosphorylase, which is an essential enzyme for phosphorolysis of 5'-DFUR to 5-FU.

Administration, Oral↗
PubMed1991

[Antitumor spectra of ranimustine against various human tumors].

Ranimustine (MCNU) has been shown to exhibit high antitumor activity and broad antitumor spectra against various experimental tumors. These effects were comparable to those of nimustine (ACNU). However, clinical applications of ACNU are indicated to various types of malignancies including solid tumors, while those of MCNU are almost limited to hematological ones. Therefore, the antitumor activity of MCNU was examined against 55 specimens from 15 types of solid tumors and compared with those of ACNU and 8 other drugs. Drug sensitivity was examined by a morphological method measuring the proportion of degenerative changes in the nucleus of drug-treated and untreated tumor cells. MCNU showed antitumor activities (measured by karyorrhexis) against adenocarcinoma of the lung, squamous cell carcinoma of the lung, renal cell carcinoma, bladder tumor, ovarian cancer and brain tumor. In addition, MCNU and ACNU showed a similar positive rate (15-16%) in this experiment and this was the highest among all drugs examined. Although MCNU and ACNU showed similar antitumor spectra, a clear difference was observed when the antitumor activities of both drugs were compared in each identical specimen. These results clearly suggest that MCNU is worthy of clinical study to examine the antitumor activity against various solid tumors.

Antineoplastic Agents↗
PubMed1991

[Result of individualized chemotherapy with a newly developed in vitro chemosensitivity testing in ovarian cancer].

By means of a newly developed in vitro chemosensitivity test based on the morphological changes in the nucleus (nuclear damage assay) as previously described, we were able to screen currently available anticancer drugs within 24 hr with a 100% success rate. The nuclear damage assay was used to determine the chemosensitivity in 50 patients (66 assays) with ovarian cancer. The response rate for the 13 patients with measurable tumors, 8 of whom showed resistance to CAP (cyclophosphamide, adriamycin, and cisplatin) therapy, was 46 percent when they were given various combination chemotherapy protocols consisting of more than one active agent selected from group A and B agents by the nuclear damage assay. The newly developed in vitro chemosensitivity test proved to be useful when selecting a second line combination for patients with CAP-resistant ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

[Basic study on in vitro chemosensitivity tests].

By means of 3 different kinds of in vitro chemosensitivity testings--(1) a nuclear damage assay developed by us, (2) MTT assay, and (3) colony formation inhibition assay--we examined the sensitivity of 8 kinds of human ovarian cancer cell lines to various anticancer drugs. The sensitivity of in vivo xenografts of the cell lines in nude mice to anticancer drugs was also examined by inhibition of the tumor growth. The in vitro--in vivo correlation of sensitivity was studied in respect to both sensitivity and specificity rates. 1. Different active anticancer drugs were screened among the 3 in vitro chemosensitivity testings in the same human ovarian cancer cell line. 2. The in vitro--in vivo correlation of the nuclear damage assay (sensitivity 50%, specificity 94%) was the highest among the 3 testings. The nuclear damage assay which we developed therefore seemed to be the most useful assay method for clinical use.

Animals↗
PubMed1988

A rapid in vitro assay for predicting thermochemosensitivity of human cancer: comparison with clonogenic assay.

We previously reported a rapid in vitro assay based on morphological changes in the nucleus in order to predict response to thermochemotherapy. It was strongly suggested that this simple method may be clinically useful. In the present study, a comparison with the clonogenic assay was carried out on eight different human tumors (three malignant melanomas, two lung carcinomas, two colon carcinomas and one leukemia). Melphalan, mitomycin C and vincristine were tested. Correlation between the two test systems was dependent upon the criteria for each test system. At the level of less than 50% survival of colony as compared with normothermic dishes in clonogenic assay, there was a high correlation between the two test systems for sensitive tumor to 43 degrees C. In respect of response to thermochemotherapy, when only karyorrhexis changes in the nucleus were selected as an activity criteria in our cytotoxic test, parallel data between the two test systems were obtained.

Antineoplastic Agents↗
PubMed1988

Predicting the sensitivity of human cancers to combined chemotherapy and hyperthermia.

In order to estimate its ability to predict the thermochemosensitivity of human cancers, a rapid in vitro assay based on morphological changes in the nucleus was performed on eight different human tumors (four malignant melanomas, two lung tumors, one renal carcinoma, and leukemia K-562). Nude mice, implanted with tumors, supplied the tumor material, with the exception of leukemia. Nimustine, melphalan, mitomycin C, vincristine and vinblastine were tested. Tumor cells developed karyorrhectic changes after incubation for 4 h with each of the aforementioned five drugs. An increase in the karyorrhectic changes was observed with hyperthermia at 43 degrees C. The individual tumors showed different sensitivities to 43 degrees C. Five of the eight tumors were significantly sensitive to 43 degrees C. However, in two thermosensitive tumors no drug enhancement was recognized at 43 degrees C. In four tumors several drugs were synergistically enhanced by hyperthermia at 43 degrees C. This study suggests that this simple method may be of clinical use in predicting response to thermochemotherapy.

Animals↗
PubMed1988

Experiments with tissue cultures from a human ovarian serous cystadenocarcinoma producing cancer antigen 125 (CA125), tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA).

The patient was a 57-year-old woman with ovarian serous cystadenocarcinoma in FIGO clinical stage IV. Cancer antigen 125 (CA125), tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA) were immunohistochemically demonstrated in tumor cells, and the variations of serum CA125 and TPA levels reflected the clinical course. The tumor tissue obtained at exploratory laparotomy was minced with scissors, and transplanted subcutaneously into female nude mice for in vivo maintenance. The tumor cells from 5th generation nude mice were dispersed in Eagle's minimal essential medium supplemented with 10% fetal calf serum, and incubated in Falcon tissue culture dishes at 37 degrees C in 5% CO2 in air for in vitro maintenance. The results were as follows: Histopathologically the tumor transplanted into nude mice showed a cystadenocarcinoma, which closely resembled the original human tumor. Immunohistochemically CA125, TPA and CEA were demonstrated in the tumor transplanted into nude mice as well as in the original human tumor. From the growth curve in nude mice, the doubling time was estimated to be about 3.5 days. Serum TPA levels in nude mice were increased in proportion to the tumor growth after transplantation, but serum levels CA125 and CEA were normal. The concentrations of CA125 and TPA were increased in the conditioned media compared with the control media, although the elevated values were decreased with subsequent passages. CEA concentrations in the conditioned media were unchanged.

Animals↗
PubMed1988

[An in vitro chemosensitivity test indicating regressive changes in the nucleus in cases of human ovarian cancer].

A simple in vitro sensitivity test of oncolytic drugs has been applied in 60 cases of human ovarian cancer. Tumor tissue blocks were minced with a razor blade, after which the cell clumps were poured into a tissue culture medium, containing an anticancer drug with a certain concentration, and incubated at 37 degrees C. Nine to 16 kinds of drugs were tested for each specimen. After incubation, the cell clumps were dispersed for providing smear specimens. Typical morphological changes appeared in the nucleus, characterized by karyorrhexis and karyopyknosis. The individual tumors displayed different sensitivities to the various drugs. The positive rate of alkylating agents ranged around 30%, and specimens examined after oncolytic treatment displayed low sensitivity.

Antineoplastic Agents↗
PubMed1986

[An in vitro chemosensitivity test for human breast cancer based on morphological changes in the nucleus].

We have developed a simple in vitro chemosensitivity test for breast cancer. Tumor tissues were chopped finely with razor blade. The cell clumps were pounced into tissue culture medium, which contained a specified level of concentration of anticancer drugs, and incubated at 37 degrees C for four to eight hours. Nine to 10 kinds of drugs were tested on each specimen. After incubation, the clumps were pumped down. The cells were smeared and stained with Giemsa for microscopic examination. The individual tumors showed different sensitivities towards various drugs, and the typical morphological changes observed in their nuclei; were karyorrhexis and karyopyknosis.

Adult↗
PubMed1985

Thermochemotherapy for malignant melanoma: overcoming heterogeneity in drug sensitivity.

Endo B (melanotic) and W (amelanotic) human malignant melanomas originated from the same tumor, both known to be heterogeneous in drug sensitivity to ACNU [( 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitroso- urea hydrochloride]), were treated experimentally with a combination therapy of ACNU and hyperthermia in mice. Whereas Endo W melanoma has no sensitivity, Endo B melanoma is sensitive to ACNU alone. However, in both types of melanomas, a marked synergistic effect of the combination therapy was noted. Histologically, marked degeneration of both tumor cells was detected. These results strongly suggest that thermochemotherapy may overcome the tumor heterogeneity in drug sensitivity.

Animals↗
PubMed1985

[A new in vitro chemosensitivity test. Individualized chemotherapy against ovarian cancer and its clinical effect].

A new in vitro chemosensitivity test was developed from comparative studies on the cytotoxicity of anticancer drugs against human tumor tissues xenografted into nude mice and their cultivated cells in vitro. Half a gram of the material was sufficient to examine the sensitivity of the tissues to 10 kinds of potential anticancer drugs and the results were obtained within 24 hours. The test was applied to all of 20 patients with advanced ovarian cancer. The predictive accuracy was 58% in 12 evaluable patients. This response rate was higher than those of conventional combination chemotherapy with or without cisplatin and adriamycin. Individual ovarian cancers showed different sensitivities to the drugs. These results indicate that heterogeneity of sensitivity to anticancer drugs exists among individual ovarian cancers and that our new type of in vitro chemosensitivity test is useful for selecting the most effective drugs for each individual type of ovarian cancer.

Adult↗