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Biomedical subjects

J Hirata

Publications and source records attributed to J Hirata.

At least 37 records · Page 2Linked to original sources
PubMed1995

Dysgerminoma of the ovary with hypercalcemia associated with elevated parathyroid hormone-related protein.

The purpose of the present paper is to present a rare case of dysgerminoma of the ovary with hypercalcemia showing elevation of multiple serum tumor markers including parathyroid hormone-related protein (PTH-rP). An 18-year-old unmarried woman, with ovarian dysgerminoma showing hypercalcemia and elevated serum PTH-rP, received six courses of a combination chemotherapy consisting of bleomycin, etoposide and cisplatin after her first surgery, and had no evidence of recurrence approximately 30 months after completing the chemotherapy.

Adolescent↗
PubMed1995

[Circumvention of cisplatin resistant ovarian cancer cells by antiestrogens].

Antiestrogens (AEs) have been considered to elicit antitumor effects via estrogen receptor. However, recent reports have demonstrated that AEs had an antitumor effect even in cases without estrogen receptor, and that AEs caused various kinds of biological behavior such as a chemosensitizing effect. We therefore investigated the possibility of circumvention of cisplatin (CDDP) resistance due to the chemosensitizing effect of AEs by using 5 ovarian cancer cell lines. They were named KF, MH, KK, KFra and KFrb cell lines. KF and MH were derived from serous cystadenocarcinomas, and KK from a clear cell carcinoma. KFra and KFrb were CDDP-resistant cell lines developed from the KF cell line. MCF-7 cell line derived from breast cancer was used as a control. The study of a 50% inhibitory concentration (IC50) revealed that clomiphene (CLO) had the most potent antiproliferative effect among the AEs used, and was followed by tamoxifen (TAM) and toremifene (TOR) with a similar effect. On the whole, the degree of CDDP sensitivity was not correlated with the degree of AE sensitivity. KFra cell line which had the highest CDDP-resistance among the 5 ovarian cancer cell lines used was the most sensitive to AEs, especially to CLO. In the study on the combined administration of CDDP and AEs, 1 microM of CLO significantly reduced the IC50 of CDDP to KFrb, KK and MCF-7 cell lines. Similarly, 1 microM of TAM significantly reduced the IC50 of CDDP to KF, KFra and MCF-7 cell lines, and 1 microM of TOR significantly reduced it to KFra, KK and MCF-7 cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Cisplatin↗
PubMed1994

Preclinical studies of antitumor prostaglandins by using human ovarian cancer cells.

Pleiotropic actions of antitumor prostaglandins (PGs) on tumor cells are reviewed including our preclinical results focused on human ovarian cancer. Regarding inhibition of cell proliferation, antitumor PGs exerts its action as a G1 blocking agent. The cyclopentenone PGs inhibit myc oncogene expression while inhibiting the cell cycle progression and results in apoptotic cell death and growth inhibition. Cyclopentenone PGs inhibit growth of various tumors transplanted to mice or nude mice and show adjuvant effects to cis-diamminedichloroplatinum(II) (CDDP). In order to elucidate a role of antitumor PGs in immune systems, relevance of effects on tumor growth with those on the immune systems are also discussed with our results.

Animals↗
PubMed1994

New human oral squamous carcinoma cell line and its tumorigenic subline producing granulocyte colony-stimulating factor.

A new human carcinoma cell line, MISK81-5, was established from a metastatic lymph node of oral squamous cell carcinoma. Immunocytochemical and ultrastructural observations revealed an obvious epithelial origin of the cell line. Chromosome analysis revealed a hypertriploid karyotype with numerical and structural anomalies. MISK81-5 cells could form a tumor mass in the subcutaneous tissue of recipient BALB/c athymic mice only when coinjected with Matrigel. A stem cell assay revealed that conditioned medium (CM) of MISK81-5 contained granulocyte colony-stimulating factor (G-CSF) or interleukin-6 activity. Quantitation by ELISA disclosed a higher concentration of G-CSF in the CM of MISK81-5 than in the CM of other squamous and gastric carcinoma cell lines. The sMISK, that was derived from MISK81-5 as a subpopulation of the cell line having higher tumorigenicity, also showed a similar hematopoietic stimulating activity to that of MISK81-5. These characteristics of the MISK81-5 cell line and its subpopulation, sMISK will be useful for studying the biological behavior of oral squamous cell carcinomas and its relation to hematopoietic stimulating factors.

Aged↗
PubMed1994

Late-appearing Philadelphia chromosome in a patient with acute nonlymphocytic leukaemia derived from myelodysplastic syndrome: detection of P210- and P190-type bcr/abl fusion gene transcripts at the leukaemic stage.

We describe a patient with acute nonlymphocytic leukaemia (ANLL) derived from myelodysplastic syndrome in whom the Philadelphia chromosome (Ph1) first emerged at the late stage of ANLL transformation. Cytogenetically, the Ph1 chromosome was not detected until the late stage of ANLL transformation, 14 months after the transformation following a 3-month history of refractory anaemia with excess of blasts. The cells with and without the Ph1 chromosome had a common abnormal chromosome, t(3;3) (q21;q26). The reverse transcription-polymerase chain reaction analysis showed no bcr/abl message at diagnosis. However, the mRNA encoding P210bcr/abl was detected in the early stage of ANLL transformation. Furthermore, the mRNAs encoding both P210bcr/abl and P190bcr/abl were detected in the late stage of ANLL transformation when the Ph1 chromosome was detected by cytogenetic analysis. These evidences support a multistep pathogenesis of leukaemias, and the products of bcr/abl fusion gene may influence the course of disease.

Adult↗
PubMed1994

Endometriotic tissues produce immunosuppressive factors.

In order to study the possible role of the immune functions in the pathogenesis of endometriosis, effects of supernatants from endometrial and endometriotic tissue cultures on the natural killer (NK) activity were examined by determining the lymphocyte cytotoxicity toward an erythroleukemic cell line (K562). Endometrial and endometriotic tissues were obtained at the time of operation from patients with ectopic endometriosis or uterine myoma. The normal peritoneum and myoma tissues were used as controls. The supernatants obtained by culturing the ectopic endometriotic tissues for 24-48 h had significant (p < 0.01) suppressive effects on NK activity of peripheral blood lymphocytes (PBL) from a healthy woman, compared to the supernatants from the normal peritoneum and the myoma tissues. There was no significant difference between NK activities of PBL from patients with ectopic endometriosis and age-matched healthy women. However, the NK activity in patients with low NK status before surgery was significantly elevated after surgery while that in patients with normal NK status before surgery was not changed. Although PBL from the same healthy women could significantly lyse the endometrial cells, the ability was about-one-third the level at which they could lyse K562 cells. These results suggest that the immunosuppressive factors secreted by endometriotic tissues may be involved in the local implantation and development of ectopic endometriosis.

Adult↗
PubMed1994

Cord blood levels of calcium-regulating hormones and osteocalcin in premature infants.

We measured cord blood levels of calcium-regulating hormones and osteocalcin in 34 premature infants of various gestational ages. 1,25(OH)2D levels were low in mid-gestation and increased with advancing gestation. Parathyroid hormone levels were low, and calcitonin levels were high in mid-gestation. Both of them declined with advancing gestation. Osteocalcin levels were high in mid-gestation. They increased from 22 weeks through 27 weeks of gestational age, and decreased thereafter. Circulating osteocalcin is considered as a clinical marker of bone turnover. However, cord blood osteocalcin decreased between 27 and 36 weeks of gestation during which period calcium accumulation by the fetus increases. Therefore, cord blood osteocalcin does not appear to reflect fetal bone formation.

Calcitonin↗
PubMed1994

[Potentiation of cisplatin sensitivity of cisplatin-resistant human ovarian cancer cell lines by L-buthionine-S,R-sulfoximine].

We established two human ovarian cancer cell lines (KK and MH) from the ascites of patients who did not respond to cisplatin (CDDP)-based combination chemotherapy. These cell lines showed higher resistance to CDDP in vitro than HRA cells which were established previously in our laboratory, and also have cross resistance with its analogues. The amount of intracellular glutathione (GSH) in these cells correlated with the degree of resistance to CDDP and was high, but the intracellular platinum (Pt) uptake was unchanged. Preincubation with L-buthionine-S,R-sulfoximine (BSO) reduced cellular GSH in these cells to 9-25%, while the Pt uptake remained unchanged. When the CDDP-resistant KK and MH cells were incubated in the presence of 10 microM BSO, they were sensitized to CDDP and its analogues showing a decrease to 79-38% in the IC50 values. On the basis of these results, we conclude that GSH may be involved in the mechanisms of resistance to CDDP and its analogues in the KK and MH cells.

Adenocarcinoma↗
PubMed1994

Establishment of a human myeloma cell line with growth-promoting activity for bone marrow-derived fibroblastoid colony-forming cells.

A human myeloma cell line, PCM6, was newly established from peripheral blood of a patient with advanced IgG myeloma by addition of recombinant interleukin-6 (IL-6) in culture. PCM6 cells had a morphology typical of mature plasma cells. Cytogenetic and surface marker studies confirmed that PCM6 cells were identical to fresh myeloma cells. Coculture of PCM6 cells with normal bone marrow mononuclear cells resulted in increased colony size of bone marrow-derived fibroblastoid colony-forming cells (CFU-F). Conditioned medium of PCM6 (PCM6-CM) cells increased the CFU-F colony size in a dose-dependent manner. The activity was labile to trypsin treatment but was heat stable (60 degrees C, 30 minutes). Molecular weight of the activity was approximately 165 kd by Sephacryl S-300 gel filtration. Platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), and IL-1 beta were not detectable in the conditioned medium. These findings suggest that in some myeloma cases, bone marrow stroma may be affected by CFU-F growth-promoting activity.

Antigens, Surface↗
PubMed1993

Modulation of sensitivity of human ovarian cancer cells to cis-diamminedichloroplatinum(II) by 12-O-tetradecanoylphorbol-13-acetate and D,L-buthionine-S,R-sulphoximine.

The ability of 12-O-tetradecanoylphorbol-13-acetate (TPA) and D,L-buthionine-S,R-sulphoximine (BSO) to modulate cis-diamminedichloroplatinum(II) (CDDP) sensitivity was investigated in human ovarian cancer cell lines sensitive (KF) or with intrinsic resistance (KK and MH) to CDDP. The KK and MH cell lines were derived from ascites of patients with clear-cell carcinoma and serous cystadenocarcinoma of the ovary who both showed clinical resistance to CDDP. The CDDP IC50 value of KK and MH cells was about 4.6- and 10.2-fold higher than that of KF cells. PKC activities in the cytosol and membrane of KK and MH cells were also about 4- to 5-fold higher than those of KF cells. Proliferation of KF, KK and MH cells was inhibited in a dose-dependent manner by TPA. The membrane PKC activities in the KF cells were rapidly activated and down-regulated 24 hr after exposure to TPA, while those in the KK and MH cells were not down-regulated even after exposure to TPA for 24 hr, suggesting that the membrane form of PKC may be involved in the intrinsic resistance. Continuous exposure to 10 nM TPA for 5 days significantly reduced the CDDP sensitivity of KF and KK cells, while exposure to 10 nM TPA for 1 hr significantly elevated that of KK and MH cells. Interestingly, 1-hr exposure to 1 microM TPA induced CDDP-resistance in KK cells. Such changes in CDDP sensitivity by TPA seemed to be linked with those of cellular PKC activity, i.e., when the CDDP sensitivity was reduced by TPA, the cellular PKC rose.(ABSTRACT TRUNCATED AT 250 WORDS)

Buthionine Sulfoximine↗
PubMed1993

CD7+ stem cell leukemia/lymphoma. Features of a subgroup without circulating blast cells.

Recent advances in immunology have clarified the cellular origin of hematopoietic neoplasms. Blast cells with a CD7+ CD4- CD8- phenotype are demonstrated to originate from malignant pluripotent hematopoietic stem cells. In this article, the authors describe three rare cases, designated as a lymphoma type of CD7+ stem cell leukemia/lymphoma, with clinical features described below. All three patients were admitted with non-Hodgkin lymphoma with a 2-month to 4-month history of lymphadenopathy. Histologic examination of lymph nodes showed lymphoblastic lymphoma (LBL) in all patients. Bone marrow blast cells had an immunophenotype consistent with CD7+ CD4- CD8- acute leukemia, although abnormal cells were not observed in the peripheral blood during the course of the disease. One patient had a recurrence in the bone marrow, with myeloperoxidase-positive blast cells expressing myeloid differentiation antigens. Chromosomal analysis detected a common abnormal karyotype initially and at relapse. Furthermore, the same T-cell receptor gene rearrangement was found initially and at relapse, suggesting that these blast cells originated from the same pluripotent leukemic clone. Additional studies on more patients are required to determine the clinical significance of this group, including the difference from CD7+ stem cell leukemia/lymphoma with circulating blast cells (leukemic type) or LBL.

Acute Disease↗
PubMed1993

Enhancement of antiproliferative effect of cis-diamminedichloroplatinum(II) by clomiphene and tamoxifen in human ovarian cancer cells.

In this study, we examined antiproliferative effect of clomiphene and tamoxifen alone and their combined effect on cis-diamminedichloroplatinum(II) (CDDP) by using human ovarian cancer cells (KF, KK, and MH cells) with different sensitivity to CDDP and MCF-7 cells derived from human breast cancer. KF, KK, and MH cells did not have estrogen receptor while MCF-7 cells had it. The KF cells were most sensitive to CDDP followed by KK, MCF-7, and MH cells. Similarly, the KF cells among three human ovarian cancer cell lines were most sensitive to clomiphene and tamoxifen alone. The MCF-7 cells had similar high sensitivity to both clomiphene and tamoxifen. When effects of clomiphene and tamoxifen on the protein kinase C (PKC) activity in the cancer cells were examined, the degree of inhibition of the PKC activity in the KF cells by clomiphene and tamoxifen was most marked and that by clomiphene was followed by those by KK, MH, and MCF-7 cells, while that by tamoxifen was, in increasing order, MH, MCF-7, and KK cells. Analyses of effects of clomiphene or tamoxifen on concentrations of CDDP required for 50% inhibition of cell proliferation (IC50) revealed that although the combined effects, in the KF and KK cells were only marginal, marked enhancement of antiproliferative effects of CDDP on the MH cells resistant to CDDP was obtained. When 5 x 10(6) cells were incubated with 100 microM CDDP for 3 hr, uptake of CDDP by MCF-7 cells was lowest, followed by MH, KK, and KF cells. The CDDP uptake by KF and KK cells was increased about 30-40% in the presence of clomiphene or tamoxifen. The CDDP uptake by the MH cells in which most marked enhancement of antiproliferative effect of CDDP was observed by a combination with clomiphene or tamoxifen was increased about 80-90% in the presence of clomiphene or tamoxifen. These results suggest that not only tamoxifen but also clomiphene can potentiate antiproliferative effect of CDDP in the ER-negative CDDP-resistant cancer cells by enhancing the CDDP uptake.

Adenocarcinoma↗
PubMed1993

Inhibitory effects by oral administration of ginsenoside Rh2 on the growth of human ovarian cancer cells in nude mice.

Recently two new compounds, ginsenosides Rh1 and Rh2, have been isolated from an ethanol extract of the processed root of Panax ginseng CA Meyer, and Rh2 (but not Rh1) has been found to cause growth inhibition of cultured B16 melanoma cells. We have also demonstrated that Rh2 caused inhibition of cultured human ovarian cancer cell (HRA) proliferation. The effect of oral administration of Rh2 on tumor growth and survival of nude mice bearing HRA cells was examined. Nude mice were inoculated subcutaneously in the right flank with 10(6) HRA cells. After 7 days of tumor inoculation 2 mg/kg cis-diamminedichloroplatinum(II) (cisplatin) was administered intraperitoneally once a week for 5 weeks. In Rh2-treated groups. Rh2 was dissolved in absolute ethanol, adjusted with distilled water to 1, 15, and 120 microM, and 0.4 ml of each concentration was administered orally by canula every day for 90 days, from the next day of tumor inoculation. The tumor volume, hematocrit and body weight were measured every week. On days 56 and 63 after tumor inoculation, the tumor volumes in all groups treated with Rh2 were significantly less than those in an ethanol-treated control group and also in cisplatin treated group. After 70 days, the tumor growth in nude mice treated with 15 microM and 120 microM Rh2 was significantly inhibited compared to that in a cisplatin treated group as well as a control group. Consequently, the survival of nude mice treated with 15 microM and 120 microM Rh2 was also significantly prolonged, compared to that of cisplatin treated mice. No toxic effects were observed in any of the mice.

Administration, Oral↗
PubMed1993

Thrombosis and hormone replacement therapy in postmenopausal women.

OBJECTIVE: The effects of postmenopausal hormone replacement therapy on thrombosis remain controversial. We tested the hypothesis that estrogen or progesterone has no significant effect on thrombosis by means of newly developed markers of blood clotting, specifically prothrombin fragment 1 + 2, a marker of factor Xa generation, and thrombin-antithrombin III complex, a marker of thrombin generation. STUDY DESIGN: A prospective study that included 106 women, 68 postmenopausal women on hormone replacement therapy and 38 postmenopausal controls, was performed. Plasma levels of prothrombin fragment 1 + 2 and thrombin-antithrombin III complex were measured by enzyme-linked immunosorbent assay. Multivariate analysis of the covariance was used for statistical analysis, controlling for patient's age because the hormone replacement therapy group was older. RESULTS: There were no statistically significant differences between the hormone replacement therapy and control groups in either of the clotting parameters measured. A comparison of the levels of prothrombin fragment 1 + 2 and thrombin-antithrombin III complex in patients receiving estrogen alone or estrogen plus progestin also revealed no differences. CONCLUSIONS: Current doses of postmenopausal hormone replacement therapy do not appear to enhance in vivo clotting. Thromboembolic complications among postmenopausal women receiving hormone replacement therapy may therefore be secondary to congenital or other acquired coagulation defects.

Adult↗
PubMed1993

Double t(1;7)(p36;p11) in a megakaryocytic crisis of chronic myelogenous leukemia with variant t(5;9;22).

A 56-year-old man with chronic myelogenous leukemia (CML) who presented with a variant Ph chromosome, t(5;9;22)(q13;q34;q11), developed a unique additional chromosomal change of a double reciprocal t(1;7)(p36;p11) during the accelerated phase. A minor clone that had two copies of 1p+ and a copy of 7p- with a normal chromosome 7 was observed simultaneously. The patient underwent a megakaryocytic crisis. Surface marker of the blasts was positive for CD13, CD33, HLA-DR, CD41a, and CD42b, and negative for CD14 and lymphoid markers. Sequential chromosome analysis suggests that the double t(1;7) was caused by a multistep event consisting of duplication of both derivative chromosomes accompanied by loss of normal chromosomes 1 and 7. This may be the first report of a double reciprocal chromosomal translocation in a hematopoietic neoplasm.

Chromosome Banding↗