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Biomedical subjects

Y Kikuchi

Publications and source records attributed to Y Kikuchi.

At least 685 records · Page 38Linked to original sources

Enhancement of antineoplastic effects of cisplatin by a calmodulin antagonist (W-7) in nude mice bearing human ovarian carcinoma.

The present study was designed to potentiate antineoplastic effects of cisplatin by combination with a calmodulin antagonist (W-7) using nude mice bearing human ovarian carcinoma. Tumor growth in nude mice treated with W-7 after (but not before) administration of cisplatin was significantly inhibited. Although treatment with cisplatin alone markedly inhibited lytic activity of the spleen cells in tumor-bearing nude mice against the tumor cells, the inhibitory effect was eliminated by subsequent treatment with W-7. There was no significant difference in the survival time between untreated and cisplatin-treated groups. Only when cisplatin was followed by W-7 was a significant enhancement by W-7 of the antitumor effect of cisplatin observed with respect to inhibition of the tumor growth as well as prolongation of the survival time.

Animals↗

[Ultrastructural study of the growth pattern in an experimental meningeal gliomatosis model].

We tried to examine the growth pattern of meningeal gliomatosis (MG) by using an experimental MG model. C6 rat glioma cells (3 X 10(5)/0.1 ml) were injected percutaneously into the cisterna magna of rats. Seven days after inoculation, the brains and spinal cords were removed and processed for morphological observation. Light microscopic findings showed that numerous tumor cells had invaded the spinal cord parenchyma directly and/or via the Virchow-Robin spaces. In contrast, a small amount of tumor cells had spread horizontally on the surface of the spinal cord. By transmission electron microscopy, discontinuity of the basal lamina (of the marginal glia) was found, and some tumor cells were found to have protruded their processes into the spinal cord parenchyma. A basal lamina-like granular material was observed in the vicinity of these areas, indicating the breakdown of the basal lamina. Scanning electron microscopic findings further supported the speculation concerning the penetration of the pia mater by tumor cells through the small pores which had blunt margins. From these ultrastructural observations, we speculated that some chemical membranolytic factors might play an important role in MG.

Animals↗

Lactic dehydrogenase isozyme patterns and alpha-hydroxybutyrate dehydrogenase activities in serum from newborns, patients with ovarian cancer or myocardial infarction.

Lactic dehydrogenase (LDH) and alpha-hydroxybutyrate dehydrogenase (HBD) and LDH isozyme patterns were studied in serum from newborns and patients with ovarian cancer or myocardial infarction. LDH and HBD activities from newborns and patients with ovarian cancer or myocardial infarction were significantly increased, compared with those from patients with benign ovarian tumor. These increases were accompanied with a decrease of LDH-H and an increase of LDH-M in serum from newborns and patients with ovarian cancer, while an increase of LDH-H in serum from patients with myocardial infarction was dominant. However, the raised HBD activities in serum from patients with benign ovarian tumor did not affect the LDH isozyme patterns. From analysis of linear regression, a negative correlation between LDH-1 or -2 and HBD activity in serum from patients with ovarian cancer was observed while there was a positive correlation between LDH-4 and HBD activity. Similar patterns in serum from newborns were observed. On the other hand, a positive correlation between LDH-1 and HBD activity and a negative correlation between LDH-4 and HBD activity were found in serum from patients with myocardial infarction.

Female↗

Interleukin-2 activity and the response of peripheral blood lymphocytes in patients with gynecologic malignancies.

The interleukin-2 (IL-2) production in peripheral blood lymphocytes (PBL), the response to IL-2, and the IL-2 absorption by PBL was studied in 34 patients with gynecologic malignancies. In addition measurement of the OKT 4/8 cell ratios were made. The OKT 4/8 cell ratio in patients with advanced gynecologic malignancies was significantly lower than that in patients with benign tumor. PBL from advanced cancer patients activated by phytohemagglutinin (PHA) had significantly lower IL-2 productivity than that from patients with benign tumors, while no significant difference was observed in its abilities to respond to IL-2 and to absorb IL-2. The OKT 4/8 cell ratio and IL-2 productivity in PBL of patients with good prognosis were significantly elevated after chemotherapy. On the other hand, PBL of patients with poor prognosis declined to about one-half of the preoperative levels. Although in patients with good prognosis the ability of PBL to respond to IL-2 was not changed before and after treatment, in patients with poor prognosis the response was significantly increased after chemotherapy. However, the ability to absorb IL-2 was not affected by treatment.

Antigens, Surface↗

[Potentiation of the antitumor effect of cisplatin by calmodulin antagonists (W-7 and W-5) in nude mice bearing human ovarian carcinoma].

The present study was designed to potentiate the antitumor effects of cisplatin by combination with calmodulin antagonists (W-7 and W-5) by using nude mice bearing human ovarian carcinoma. Tumor growth in nude mice treated with W-7 or W-5 combined with cisplatin was significantly inhibited, compared to that in nude mice treated with W-7 alone, W-5 alone or cisplatin alone. Although treatment with cisplatin alone markedly inhibited lytic activity of the spleen cells from tumor bearing nude mice against the tumor cells, the inhibitory effect was eliminated by combination with W-7 or W-5. There was no significant difference in the survival time among untreated, cisplatin-treated, W-7-treated and W-5-treated groups. Only when cisplatin was followed by W-7 or W-5, a significant enhancement by W-7 or W-5 of the antitumor effect of cisplatin was observed with respect to inhibition of the tumor growth as well as prolongation of the survival time.

Animals↗

[Establishment of a cisplatin-resistant human ovarian cancer cell line and the mechanism of resistance].

A cisplatin-resistant cell line was established by using KF-1 cells derived from human serous cystadenocarcinoma of the ovary. This resistant cell line, designated "KFr", was capable of proliferating in the presence of 1.0 microgram/ml cisplatin. It had doubling times of 24.8 and 27.2 hr in the presence of 0.5 and 1.0 microgram/ml cisplatin, respectively. The morphologic characteristics of the KFr cells were an enlarged nucleus and prominent nucleoli, unlike the nucleus and nucleoli of the parent KF-1 cells. The degree of resistance to cisplatin of the KFr cells was about 20 times as great as that of the KF-1 cells, with regard to the concentrations of cisplatin required for 50% inhibition of cell proliferation. Although the cisplatin content in the KF-1 cells incubated with 10 micrograms/ml cisplatin was increased in a time-dependent manner, that in the KFr cells reached the plateau level after 1.5 hr incubation with cisplatin. After about 4 hr incubation, the cellular content in the KFr cells was about a half of that in the KF-1 cells. When 0.5 mg cisplatin was administered i.p. to nude mice with KF-1 or KFr tumor, the cisplatin content in the KFr tumor was significantly lower than that in the KF-1 tumor. The KFr cells showed a cross-resistance to melphalan, while no cross-resistance to vincristine or 5-fluorouracil was observed. When 5 microM W-5 or W-7 was added in the presence of concentrations of cisplatin that hardly inhibited cell proliferation, the KFr cell proliferation was markedly inhibited. These findings suggest that the cisplatin resistance in the KFr cells may be due to an impaired cisplatin-transport mechanisms and can be overcome by calmodulin antagonists.

Animals↗

Enhancement of antineoplastic effects of cisplatin by calmodulin antagonists in nude mice bearing human ovarian carcinoma.

The present study was designed to potentiate the antineoplastic effects of cisplatin by combination with calmodulin antagonists [N-(6-amino-hexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5)] in nude mice bearing human ovarian carcinoma. Tumor growth of nude mice treated with W-7 or W-5 combined with cisplatin was significantly inhibited, compared to that of nude mice treated with W-7 alone, W-5 alone, or cisplatin alone. Although treatment with cisplatin alone markedly inhibited lytic activity of spleen cells from tumor-bearing nude mice against the tumor cells, the inhibitory effect was eliminated by combination with W-7 or W-5. There was no significant difference in survival time among untreated, cisplatin-treated, W-7-treated, and W-5-treated groups. Only when cisplatin was followed by W-7 or W-5 was a significant enhancement by W-7 or W-5 of the antitumor effect of cisplatin observed with respect to inhibition of tumor growth as well as prolongation of survival time.

Adenocarcinoma↗

Desmosine and isodesmosine as cross-links in the hinge-ligament protein of bivalves. 3,3'-Methylenebistyrosine as an artefact.

Desmosine and isodesmosine were detected in an invertebrate molluscan species, i.e. in an insoluble protein in the hinge ligament of a bivalve species, Sakhalin surf clam (Pseudocardium sachalinensis, in family Mactridae). The protein is rich in glycine and methionine S-oxide but devoid of hydroxyproline and hydroxylysine. 3,3'-Methylenebistyrosine was also detected in the HCl hydrolysate of the hinge-ligament protein, but it was found to be an artefact produced from tyrosine and formaldehyde derived from methionine S-oxide during the HCl hydrolysis of the protein.

Amino Acids↗

Chemical taxonomy of the hinge-ligament proteins of bivalves according to their amino acid compositions.

The proteins in the hinge ligaments of molluscan bivalves were subjected to chemotaxonomic studies according to their amino acid compositions. The hinge-ligament protein is a new class of structure proteins, and this is the first attempt to introduce chemical taxonomy into the systematics of bivalves. The hinge-ligament proteins from morphologically close species, namely mactra (superfamily Mactracea) or scallop (family Pectinidae) species, showed high intraspecific homology in their compositions. On the other hand, inconsistent results were obtained with two types of ligament proteins in pearl oyster species (genus Pinctada). The results of our chemotaxonomic analyses were sometimes in good agreement with the morphological classifications and sometimes inconsistent, implying a complicated phylogenetic relationship among the species.

Amino Acids↗

Establishment of a human ovarian cancer cell line capable of forming ascites in nude mice and effects of tranexamic acid on cell proliferation and ascites formation.

The present study was designed to obtain an experimental tumor model as similar as possible to human ovarian cancer which often had a large amount of ascites and to assess the therapeutic value of tranexamic acid. Human tumor cell lines which form ascites in nude mice were established from ascites of patient with serous cystadenocarcinoma of the ovary. Two cloned cell lines designated HRA and HR-1 were obtained from the parent cell line designated HR. All of these cultured cell lines had about 2.5-3.5 times higher lactate dehydrogenase activities than the original tumor. The original tumor and the tumor grown in nude mice had all 5 bands of lactate dehydrogenase isoenzymes, while all cultured cell lines had only a marked lactate dehydrogenase-3 in addition to a faint lactate dehydrogenase-2. Modal chromosome numbers of HR cells ranged from 50-76, while that of HRA cells ranged widely from 40-140. The DNA histograms of HR and HRA cells were similar to each other, showing predominant G1 and S phases. Although these cell lines had ability to produce ascites in the nude mice when the cells were inoculated i.p., the HRA cell inoculation made ascites most rapidly and brought about the shortest median survival (39 days). The proliferations of all three cell lines were dose-dependently inhibited by tranexamic acid. However, the concentration of this drug required for 50% inhibition of the proliferation of HRA cells was about one-half of that of HR and HR-1 cells. In addition, i.p. injections of tranexamic acid to nude mice treated with cisplatin resulted in a significant inhibition of the ascites formation and prolongation of 50% survival.

Animals↗