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H Ishige

Publications and source records attributed to H Ishige.

31 records · Page 2Linked to original sources

Establishment and properties of a human choriocarcinoma cell line of ovarian origin.

A human nongestational choriocarcinoma cell line of ovarian origin (IMa) was established in vitro. This cell line had been subcultured serially more than 22 times over 18 months. Small polygonal cells with a prominent nucleus were dominant and a sparsity of cytoplasmic organelles was an ultrastructural characteristic of the IMa cells. The production and secretion of human chorionic gonadotropin and its subunits were identified by radioimmunoassay. The IMa cells were transplantable in the hamster cheek pouch and the histological diagnosis was choriocarcinoma. A newly established ovarian choriocarcinoma cell line can be considered useful for clarifying the biological differences between nongestational and gestational choriocarcinoma cells.

Animals↗

A newly established human gestational choriocarcinoma cell line and its characterization.

The cell biological characteristics of a newly established human gestational choriocarcinoma cell line, HM, were examined and compared with four other gestational and two nongestational choriocarcinoma cell lines. Striking heterogeneity in the production and secretion of hCG and its subunits was observed among the cell lines. The HM cell line consisted mainly of cytotrophoblast-like cells, and the hCG and its subunit values in both the cells and culture fluid were extremely low. The syncytiotrophoblast-like multinucleated giant cells which were occasionally seen in other cell lines were scarce in the HM cell line in vitro. On the other hand, deviation of the LDH isozyme pattern to the heart-type (LDH1) was characteristic of the HM cells in contrast to the other cell lines in which LDH3 was dominant. The HM cell line represents useful material for investigating the cell biological heterogeneity of human choriocarcinomas.

Adult↗

[Characterization of two choliocarcinoma cell lines and their sensitivity to MTX].

Both the sensitivity to MTX and hCG secretion were compared in two choriocarcinoma cell lines (BeWo and HCCM-5) and study on mechanisms about MTX-resistance was described. The uptake of nucleotides and protein precursors was decreased in dose-dependent manner in both cell lines when exposed to MTX, but HCCM-5 cells showed more sensitivity to MTX. In HCCM-5 cells, both hCG and hCG-beta levels in the medium were decreased with exposure to 10(-9)M MTX, but they tended to increase when exposed to higher concentration of MTX in contrast to the inhibition of 3H-thymidine uptake. However, in BeWo cells, an inverse relationship between the incorporation of 3H-thymidine and secretion of hCG was not clearly observed. The content of dihydrofolate reductase (DHFR) in HCCM-5 cells was about one-half of that in BeWo cells. Although the peak of 3H-MTX incorporation was observed at 120 minutes in both cell lines, HCCM-5 cells incorporated about 4 times higher 3H-MTX than BeWo cells. The difference of sensitivity to MTX between those two cell lines seems to be concerned with both the decrease of MTX transport and increase of intracellular DHFR levels.

Animals↗

Biochemical characterization of 1,25(OH)2D3 receptors in chick embryonal duodenal cytosol.

This study presents measurements of serum vitamin D metabolites, calcium and phosphorus as well as measurements of the equilibrium dissociation constant for duodenal 1,25(OH)2D3 receptor in 15-, 18-, 19-, and 20-day chick embryos in comparison to that in 1- and 118-day-old chicks and to vitamin D-deficient chicks. The present results showed that: (a) serum 1,25(OH)2D and 24,25(OH)2D levels rise from 15 and 18 to days 19 and 20 of embryonic development while serum phosphate levels are stable; (b) serum calcium levels rise at hatching to adult levels; (c) the duodenal 1,25(OH)2D3 receptor is detectable in 15-day-old embryo and has a Kd similar to that of 118-day-old vitamin D-replete chicks; and (d) the activity of 1,25(OH)2D3 receptor in chick duodenal cytosol is maximal at hatching.

Animals↗

[Study on the rationale for chemotherapy of refractory choriocarcinoma].

The combination chemotherapy consisting of methotrexate (MTX), actinomycin D (ACD), and an alkylating agent was applied to the high risk patients refractory to MTX and/or ACD. The remission rate of the high risk group was about 70% and that of low risk patients was 100%. It is important to seek an effective chemotherapy for patients refractory to the above combined chemotherapy; therefore, we tried out the following regimens: (1) Quadritherapy with MTX, ACD, CPM and vincristine; (2) CHAMOMA protocol; (3) cis-platinum, bleomycin and vinblastine therapy; (4) ultra high dose MTX therapy and (5) the combination chemotherapy without MTX. The last regimen was designed based on the experimental data chemotherapy using nude mice.

Antineoplastic Agents↗

[Studies on the recurrent trophoblastic disease].

We studied the remission and the recurrent of trophoblastic disease treated in our clinic, during 1973 to 1980. 1) The remission and recurrent rates of 168 cases were 91.1% (153/168) and 5.2% (8/153) respectively. In these percentages, high risk was 65.9% (29/44) and 20.7% (6/29), low risk was 100% (124/124) and 1.6% (2/124), choriocarcinoma was 58.3% (21/36) and 28.6% (6/21), invasive mole was 100% (44/44) and 0, and undetermined was 100% (88/88) and 2.3% (2/88). 2) The interval to recurrence: 5 cases appeared under a year, 3 cases did over a year. And remission rate of recurrent case was (4/8), high risk was (2/6), and low risk was (2/2). 3) HCG-beta titers when U-hCG decreased under the LH levels was higher until 3 months in the recurrent case of high risk than that unrecurrent, while we did not recognize any differences after 3 months. Therefore criteria of remission in high risk would occurred on continuous LH levels of U-hCG for 3 months. 4) High risk has been treated by 3 courses of additional chemotherapy, but that when hCG-beta titer over 1.0ng/ml require more chemotherapy.

Adult↗

Immunohistochemical detection of pregnancy-specific protein (SP1) and placenta-specific tissue proteins (PP5, PP10, PP11 and PP12) in ovarian adenocarcinomas.

By using an immunoglobulin-enzyme bridge method, pregnancy-specific beta 1-glycoprotein (SP1) and placenta-specific tissue proteins (PP5, PP10, PP11, PP12) were investigated in 15 cases of mucinous cystadenocarcinoma and 20 cases of serous cystadenocarcinoma. These proteins could be detected in the cytoplasm of some malignant cells. In mucinous cystadenocarcinomas, SP1, was present in 53.3% of cases, PP5 in 80.0%, PP10 in 20.0%, PP11 in 66.7% and PP12 in 46.7%. In serous cystadenocarcinomas, SP1 was present in 35.0% of cases, PP5 in 76.2%, PP10 in 9.5%, PP11 in 57.1% and PP12 in 23.8%. No proteins were detected in five normal ovaries. All control sections incubated with phosphate-buffered saline or normal, non-pregnant, non-immune rabbit serum in place of the first specific antiserum as well as with the antisera exhaustively absorbed with the corresponding purified antigens were negative for each protein. The detection rates are discussed in relation to the clinical stages and survival rates of the patients. This study suggests that these proteins, especially PP5 and PP11, may be useful as markers in monitoring patients with ovarian adenocarcinomas as well as for their early diagnosis.

Cystadenocarcinoma↗

[Effects of various agents on human choriocarcinoma transplanted to nude mice].

The effects of various anticancer agents on human choriocarcinoma transplanted to nude mice, specifically, inhibition effects on tumor growth and survival rate were studied to establish an appropriate chemotherapy for refractory choriocarcinoma. The agents studied were methotrexate (MTX), actinomycin D (ACD), cyclophosphamide (CPM), vincristine (VCR), L-PAM (MPI), bleomycin (BLM), carboquone (CQ), cisplatin (CDDP), ACNU, MCNU, vinblastine (VLB), VP16-213, OK-432, Maruyama vaccine (SSM) and metronidazole (ME), and the following results were obtained: 1) The inhibition effects on tumor growth were obtained in the groups of VCR, VP16-213, CDDP, MPL, CPM and CQ; 2) The survival rate was 100% in the groups of MPL, BLM, and CQ. In the groups of ACD VLB, VP16-213 and VCR, all mice died. 3) MPL was found to be the most effective agent in terms of inhibitory effect and survival rate. In the future, combination chemotherapy including MPL and maintenance chemotherapy with MPL to refractory choriocarcinoma should be studied.

Animals↗

[Study for the experimental chemotherapy and clinical application (author's transl)].

Experimental chemotherapy has been studying with choriocarcinoma in nude mice transplanted from drug resistant patients. The following results: 1) the combined therapy with MTX and ACD was not always effective and in place of one of them, the combination of CPM was effective 2) addition of VCR was effective; were obtained. These results were applied to two patients in clinic. 1) The first patient failed to obtain complete remission by the course of ACD, MTX + ACD, and MTX + ACD + CPM (MAC) therapy. Then the combination therapy with ACD + CPM made her HCG titer regressed to negative immediately. She is free from disease now. 2) The HCG titer and pulmonary metastasis of the second patient showed resistance to MAC therapy, CHAMOMA therapy, and the combined therapy with MTX. The combination chemotherapy with ACD + CPM + VCR made her HCG titer become to regressed and the pulmonary metastasis reduce to 1/4 in size. The clinical application of the results from experimental chemotherapy was defined to be possible. The experimental model will contribute to establish the schedule of the rational chemotherapy for drug-resistant choriocarcinoma.

Adult↗

[Characteristics of human choriocarcinoma transplanted in nude mice (author's transl)].

Experimental chemotherapy with choriocarcinoma transplanted in nude mice has been studying to improve the prognosis of drug resistant choriocarcinoma. In this paper the characteristics of transplanted tumors were presented. Two tumors, CC-HM-I (HM) and CC-I-JCK (JCK), were used. The characteristics of the tumors were studied in macroscopical findings, histological findings, growth curves, DNA amount analysis, LDH activity, alkaline phosphatase activity, and their isozyme patterns. Both tumors well maintained the characteristics of original and/or the beginning ones. Some differences between two tumors were pointed out. In morphology, HM was yellowish and hard tumor and the growth rate was rather slow. While, JCK was dark and soft tumor and contained a lot of bleeding and necrotic tissue. Its growth rate was quick and all of nude mice with JCK died of tumors around 50 days after transplantation. The serum level of HCG of HM was 75.8 +/- 2.8 ng/ml/g tumor and that of JCK was 117.4 +/- 6.2 ng/ml/g tumor. The good correlation between the tumor weight and the serum level of HCG was obtained in both groups. The activities of LDH and alkaline phosphatase in the tissues of JCK were about 3 times as higher as the one of HM. It was confirmed that the transplanted choriocarcinoma in nude mice was useful model for the study the nature of human choriocarcinoma and it will contribute to the establishment of the rational chemotherapy for drug resistant choriocarcinoma.

Animals↗

[Experimental chemotherapy with drug-resistant choriocarcinoma transplanted to nude mice (author's transl)].

Serial transplantation in nude mice of human choriocarcinoma showed the drug resistance in clinic was succeeded and experimental chemotherapy has been studied to improve the prognosis of the patients with choriocarcinoma. The experimental tumors were two lines. CC-I-JCK (JCK) and CC-HM-I- (HM). In this paper, single and/or combination chemotherapy with methotrexate (MTX), actinomycin D (ACD), cyclophosphamide (CMP), and vincristine (VCR) were discussed. 1) Effects of the single agent: In JCK, the suppressive effects against tumor growth under administration of CPM or VCR, and some responses in histological finding were obtained. While, in HM, few suppressive effects against tumor growth and some responses in histological findings were obtained. 2) Effects of the combined agents: In JCK, the suppressive effects against tumor growth were as follows; nontreatment group less than MTX + ACD less than MTX + CPM less than MTX + ACD + CPM less than ACD + CPM less than ACD + CPM + VCR. The complete disappearance of tumors were gained under administration of the combination therapy with ACD and CPM. While in in HM, the effects were as follows; nontreatment group less than MTX + ACD less than ACD + CPM less than MTX + ACD + CPM less than MTX + CPM less than MTX + CPM + VRC. But no complete disappearance of tumor was obtained. 3) The good relationship between the results of experimental chemotherapy and the response of clinical patients who provided the tissues could be seen. It has been defined that the experimental chemotherapy with the tumors transplanted to nude mice in useful models for the establishment of rational chemotherapy for drug resistant choriocarcinoma.

Animals↗