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Biomedical subjects

I Nishiya

Publications and source records attributed to I Nishiya.

At least 19 recordsLinked to original sources

[Analysis of DNA synthetic cells in endometrial carcinoma cases treated with progestogen].

It is well known that the proliferation of endometrial adenocarcinoma is inhibited by progestogens. We often use medroxyprogesterone acetate (MPA) as endocrine therapy for advanced endometrial carcinoma. In the present study, we administered 400-600mg of MPA/day on 14 days as a progestogen challenge test (PCT) to 37 cases of endometrial carcinoma. We analysed the variation in the percentage of S phase cells by flow cytometry and also conducted an immunohistochemistry analysis with anti-BrdU monoclonal antibody before and after the administration of MPA. The percentage of S phase cells in endometrial carcinoma tended to decrease with much greater variation after PCT than before. The percentage of BrdU positive cells tended to decrease after PCT. The cases with a good histological effect such as 1) basal vacuolization 2) clear staining cytoplasm 3) homogenus finding of cells and nucleus by PCT had a better prognosis than the cases with no histological effect due to PCT.

Adenocarcinoma

[Phase III study of DWA2114R for ovarian cancer].

A phase III study of DWA2114R for ovarian cancer was carried out in CAP regimen by a cooperative study group consisting of 42 institutions. The response rate of 31 cases for DWA2114R regimen was 38.7% and out of 30 cases for CDDP regimen 46.7%. No significant differences were observed between the two regimens in efficacy, adverse reactions, and abnormalities in laboratory findings except for red blood cell and creatinine clearance, but the incidence of thrombocytopenia was likely to be lower in DWA2114R than in CDDP regimen. Since the DWA2114R regimen did not need hydration, or require diuretics, DWA2114R is more useful in the treatment of ovarian cancer than cisplatin.

Adult

Flow cytometric and biochemical analysis of dose-dependent effects of sodium butyrate on human endometrial adenocarcinoma cells.

Sodium butyrate (SB) treatment was previously shown to produce seven-fold increases in estrogen hormone receptor binding sites of human endometrial adenocarcinoma (IK) cells. Flow cytometric analysis and histone gel electrophoresis were used to examine cell cycle, cell metabolism, and nuclear histone fractions in IK cells treated with different concentrations of SB. SB-treated cells stained with fluorochromes specific for DNA, RNA, or general protein were analyzed by flow cytometry (FCM). Changes in accessibility to three DNA stains and gel electrophoresis were used to analyze rearrangements in chromatin structure. SB caused an accumulation of cells in the G1 phase and inhibited DNA synthesis, but not cellular levels of RNA and protein. Hoechst accessibility to A-T rich regions on DNA was dramatically increased after removal of SB. H1 histones were dephosphorylated and core histones were acetylated during SB-treatment. Information obtained in these studies may be useful for correlating cellular and biochemical events with SB-induced increases in nuclear steroid hormone binding sites.

Adenocarcinoma

Glucocorticoid-induced G1 arrest and the release effect of epidermal growth factor on the human salivary gland adenocarcinoma cell.

Dexamethasone (1 microM) decreased the distribution of cells in S phase (about 75%) and increased that of G1 cells (1.1-fold) in the DNA histogram of human submandibular salivary gland adenocarcinoma cells (HSG) reversibly. In synchronized cells at G1 phase, glucocorticoid delayed the initiation of DNA synthesis by about 3-4 h. The conditioned medium (50%) or exogenous human epidermal growth factor (EGF, 10 ng/ml) significantly nullified these effects by glucocorticoids. These results suggested that glucocorticoids arrested the cells at G1 phase, which implied the inhibition of production of some progressive factor, probably EGF, in the cell cycle of HSG.

Adenocarcinoma

Hepatoid carcinoma of the ovary: a case report.

A case of a right ovarian tumor in a 64-year-old patient showing high blood levels of alpha-fetoprotein (AFP) is reported. Histologically, the tumor resembled hepatocellular carcinoma with hyaline globules. Localization of AFP was detected by the immunoperoxidase method. Electron microscopically, the rough-surfaced endoplasmic reticulum had developed into a meshwork, and the mitochondria were present within this meshwork. Because a transition from adenocarcinoma to a region resembling hepatocellular carcinoma was observed, this tumor was considered to originate as a common epithelial carcinoma. In the blood, 67% of the AFP was bound with concanavalin A (Con A), and the fraction pattern obtained by lentil agglutinin affinity chromatography (LCA) was of the germ cell type. From these results, the current case may be labeled clinicopathologically a hepatoid carcinoma of the ovary as described by Ishikura and Scully.

Adenocarcinoma

[A clinical study of recombinant human G-CSF in gynecological tumor patients with neutropenia due to chemotherapy (rG.CSF Clinical Study Group)].

We evaluated clinical efficacy of recombinant human granulocyte colony stimulating factor (rG-CSF), successfully expressed in Chinese hamster ovarian cell, in gynecological tumor patients (pts) with neutropenia due to chemotherapy (CT). Fifty-eight pts with advance or relapsed gynecological malignancy were entered into this study. These pts had neutropenia below 1,000/cmm by CT and in the next cycle of CT they were treated with daily rG-CSF (2 micrograms/kg/day, subcutaneously) starting from the next day of CT for 14 days. The activities of rG-CSF were evaluated using following indices calculated for each cycle: a) the absolute neutrophil count (ANC) at nadir, b) the period for restoration in ANC above 1,500/cmm, and c) the total area below the 1,000/cmm level in ANC calculated by a computer. Forty-seven out of 52 evaluable pts (90.4%) showed good response to rG-CSF. Only adverse events considered possibly due to rG-CSF were transient fever and anorexia, one case each. In conclusion, rG-CSF appears to be well tolerated by gynecological tumor patients and to considerably rescue them from neutropenia caused by intensive chemotherapy.

Adolescent

[Quenching effect and analysis of cell proliferation in dual-laser flow cytometry with human endometrial adenocarcinoma cells in vitro].

We analyzed the characterization of DNA synthesized cells (S phase cells) in the proliferation. It is important that the fixation and cell cycle time of S phase cells and DNA qualitative changes, etc., be examined. We used the dual-laser FCM system of the Los Alamos National Laboratory in New Mexico and analyzed the cell cycle, especially changes in S phase cells both quantitatively and qualitatively. By the bromodeoxyuridine (BrdU)/Hoechst Quenching effect, we could detect differences in electric signals by adopting the differential fluorescence correction method. (1) The effects of sodium butyrate in gene expression were dose-dependent at human endometrial adenocarcinoma cells. (2) After double staining with Mithramycin and Hoechst33342, S phase cells incorporating BrdU under quenching gave from linear relative to arched bivariate contour histograms. (3) At 24 hours G1 phase synchronization of SB 1,3 and 5mM appeared in slow cycling cells after BrdU was added. These results suggest that the effect of sodium butyrate in human endometrial adenocarcinoma cells might be understood not only from the quantitative change, but also by the qualitative change in S phase cells.

Adenocarcinoma

[Hyperamylasemia in endometrial adenocarcinoma].

Two patients suffering from endometrial adenocarcinoma (endometrial type) showed hyperamylasemia. The elevated level of amylase in the serum dropped to the normal range after operation in case 1. Case 2 had a recurrent tumor and continued to have a high amylase concentration in the blood. Isozyme analysis of serum-amylase showed predominant patterns of the salivary type. Tumor homogenates contained only salivary type amylase. Immunohistochemical staining revealed localizations of amylase in these tumor tissues. So it was clear that the production and secretion of salivary type amylase caused hyperamylasemia. Further study was done immunohistochemically to find the incidence of amylase-productive endometrial adenocarcinoma (endometrial type). It was shown that 56% of these tumors had amylase in neoplastic cells. Well differentiated adenocarcinoma showed a high frequency of amylase-positive findings. It was suggested that amylase measurement would provide useful information in checking the recurrence and in monitoring the therapeutic effects of endometrial adenocarcinoma.

Adenocarcinoma

[Combination chemotherapy of ovarian cancer with cisplatinum, aclarubicin and tegafur].

Two hundred fifty-nine patients with ovarian cancers were treated with the combination of CDDP, aclarubicin and tegafur. Ninety-seven of them had macroscopic diseases during the combination chemotherapy, and the overall anti-tumor response rate (CR + PR) for these patients was 54.6%. It was 60.0% for the 80 cases with epithelial ovarian cancer among them. The median survival time for the antitumor responders was 18 months, against 7 months for the non-responders and 18 months for 103 patients with advanced ovarian cancer (stage III-IV).

Aclarubicin

[Cell kinetic effects of cis-platinum on cancer cells in a culture system and in cases of cervical cancer using monoclonal antibody of BrdU].

Flow cytometric analyses were done in cervical squamous cell carcinoma cell line (SKG-IIIa) and in cancer cells of cervical cancer cases treated with CDDP using monoclonal antibody of BrdU. 1) In fundamental studies using culture system, accumulation of late S phase cells and of mid S phase cells was observed after 48 hours at the dose of 0.2 micrograms/ml and 0.5 micrograms/ml of CDDP, respectively. 2) Accumulation of early S phase cells was observed at the condition of 1 microgram/ml and 3 micrograms/ml of CDDP. All S phase cells decreased gradually thereafter 3) In clinical studies, accumulation of early S phase cells was observed in cancer cells of cervical cancer cases after intra-arterial infusion of CDDP. However, cell cycle recycling was observed in tumor cells which retained their low sensitivity to CDDP after 21-day treatment with intra-arterial infusion of CDDP.

Antibodies, Monoclonal

Diagnosis of benign and malignant cervical specimens by multifiberoptic microspectrophometry and by flow cytometry.

Two techniques for the automation of mass screening for cervical cancer were studied. Microspectrophotometry was tried first, using a novel multifiberoptic scanning system that measured the nuclear size and DNA content of cells in routine smears restained by the Feulgen technique. Specimen diagnoses were based on the percentages of cell types present, as determined by thresholds set for the two parameters. While this method gave good results in the automated detection of severe dysplasias and carcinomas, with only 3 of 72 cases misdiagnosed as negative (4.2%), it had a 22.9% false-positive rate (misdiagnosing 24 of 105 "benign" cases) and a 30.3% false-negative rate for adenocarcinomas (10 of 33 cases misclassified). The second approach involved flow cytometric measurements of specimens that were double stained for the assessment of both the DNA and RNA content, with the results analyzed by preset windows in a two-dimensional plane. This technique gave a 6.1% false-negative rate in 49 positive specimens and a 32.3% false-positive rate in 102 benign specimens, with an overall correct classification rate of 76.2%, including adenocarcinomas.

Female

Relationship between changes of the steroid receptor and synchronization in human endometrial adenocarcinoma cells in vitro.

It has been reported that the response of target cells to steroid hormone (SH) stimulation may depend on their position in the cell cycle. The DNA and RNA contents of malignant cells of the endometrium cultured in vitro were measured using flow cytometry (FCM). We also measured estrogen receptor (ER) and progesterone receptor (PR) levels of cells at different positions in the cell cycle. The G1 and S phases of the cell cycle were investigated using cells synchronized by sodium n-butyrate (G1 block), methotrexate (S block), and excess thymidine (S block). For DNA measurements, the cells were stained with propidium iodide following RNase treatment. For RNA measurements (double-stranded RNA) the cells were treated with DNase. We found that S phase synchronization by methotrexate was 136.2% of control (100%). Using the excess thymidine block and release procedure, the S phase fraction was 185.1% of control. G1 phase synchronization by sodium n-butyrate was 134% of control. The estrogen receptor level in G1 phase synchronized cells increased to 5.94 fmol/micrograms DNA in the cytosol and 12.35 fmol/micrograms DNA in the nuclear fraction. These levels represent a sevenfold total increase over that of the control estrogen receptor level. Cells in S phase showed no significant increase in estrogen receptor levels over control cells. Based on this study, the functional increase of the steroid receptor was most significant in the G1 phase.

Adenocarcinoma

[Cytokinetic effects of carboplatin and cisplatin on a human ovarian cancer cell line].

The cytokinetic effects of carboplatin(CBDCA) on a human ovarian cancer cell line(KF-1) were examined by means of cell survival rate and flow cytometry in comparison with cisplatin(CDDP). CBDCA and CDDP exhibited dose dependent cytotoxicity on KF-1, and CBDCA showed compatible cell growth inhibition to that of 15 times concentration of CDDP in comparison with IC50 of 72 hrs after drug addition. From the analysis of cell cycle, CBDCA and CDDP inhibited cell cycle progression at G2 + M phase. CBDCA exhibited G2 + M phase block to that of 15 to 20 times the concentration of CDDP. We suggested that CBDCA had potential therapeutic activity against ovarian cancer, but should be evaluated carefully in the clinical use.

Carboplatin

[Phase II study of carboplatin in ovarian cancer].

A phase II study of carboplatin was conducted in ovarian cancer by a cooperative study group consisting of 22 institutions nationwide. The overall response rate of 50 evaluable cases was 38.0%. The response rate in cases with no prior chemotherapy was 54.2% and that with prior chemotherapy was 23.1%. In addition, the response rate was 26.3% in cases that received prior CDDP-based chemotherapy. Histologically, the response rate was high in serous cystadenocarcinoma and endometrioid adenocarcinoma. Hematologic toxicities, particularly leukopenia and thrombocytopenia, were frequently observed, but well tolerated, while renal and neurologic toxicities were rare. These results suggested that carboplatin is useful in the treatment of ovarian cancer.

Adenocarcinoma

[Phase III study of carboplatin in ovarian cancer].

A phase III study of carboplatin vs cisplatin in CAP regimen for ovarian cancer was conducted by a cooperative study group consisting of 22 institutions nationwide. The response rate for 23 cases allocated to carboplatin regimen group was 34.8% and 42.1% for 19 cases allocated to cisplatin regimen group. No significant difference was observed between these two regimens in response rates, and no significant differences were noted between the two regimens in each of the clinical toxicities and abnormalities in laboratory findings. Since the carboplatin regimen group did not require hydration, or the use diuretics or antiemetics, these results suggested that carboplatin is more useful in the treatment of ovarian cancer than cisplatin.

Adult