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Biomedical subjects

S Shirotake

Publications and source records attributed to S Shirotake.

At least 19 recordsLinked to original sources
PubMed2001

Cyclophosphamide and 5-fluorouracil act synergistically in ovarian clear cell adenocarcinoma cells.

Chemosensitivity to the drugs plays a crucial role in the treatment of ovarian cancer. In this study, we evaluate the cytotoxicity of chemotherapeutic agents in six ovarian cancer cell lines; four clear cell adenocarcinoma and two serous papillary adenocarcinoma, using seven single drugs and seven sets of drug combinations with tetrazolium-based semiautomated colorimetric (MTT) assay. The drug concentration which produced 50% growth inhibition (IC50) of cisplatin was within clinically achievable range in five cell lines. The area under the curve (AUC) at IC50 of cyclophosphamide was below the clinically achievable AUC in two serous papillary cell lines. Paclitaxel was more effective in clear cells than serous papillary cells. The intensification of cytotoxicity was observed in the combinations of paclitaxel and cisplatin, and cyclophosphamide and cisplatin or 5-fluorouracil irrespective of histopathological characteristics of the original tumor. Our results indicate that ovarian cancer cell lines respond to chemotherapeutic agents heterogeneously depending upon histopathological features, indicating individualized regimens may improve survival in ovarian cancer patients.

Adenocarcinoma, Clear Cell↗
PubMed2001

Pharmacokinetics of acetaminophen from rapidly disintegrating compressed tablet prepared using microcrystalline cellulose (PH-M-06) and spherical sugar granules.

The aim of the present study was to evaluate the bioavailability of a drug from rapidly disintegrating tablets prepared using fine spherical crystalline cellulose (PH-M-06) and spherical sugar granules (Nonpareil, NP). Rapidly disintegrating tablets containing acetaminophen as the model drug in combination with a mixture of NP-108 (purified n-mannitol) and PH-M-06 were prepared. Plasma concentration profiles and pharmacokinetic parameters of acetaminophen in rabbits were investigated after oral administration of the prepared tablets. No significant difference in Cmax and AUC(0-infinity) of acetaminophen between rapidly disintegrating tablets and conventional tablets was observed after direct administration of these tablets into the stomach of rabbits. However, tmax (15 min) of acetaminophen from rapidly disintegrating tablets was significantly (p<0.05) shorter than that from conventional tablets (130 min). The same tmax was observed for rapidly disintegrating tablets and solution. When suitable excipients such as fine spherical microcrystalline cellulose (PH-M series) and spherical sugar granules (NP series) were used, rapidly disintegrating tablets could be prepared by the conventional direct compression method. According to the results of moment analysis, the mean residence time (MRT) obtained between both rapidly disintegrating and conventional tablets indicates that the mean absorption time (MAT) from these tablets is approximately 60 and 90 min, respectively. This difference in MAT between the two tablets may be caused by the difference in the sum of the mean dissolution time (MDT) and the mean disintegration time (MDIT) of these tablets. Rapidly disintegrating tablets allow rapid absorption of the drug compared with conventional tablets.

Acetaminophen↗
PubMed1999

[Effect of temperature on drug release and drug absorption in mixed type diclofenac sodium suppositories].

New types of diclofenac sodium suppositories known to control a drug release function for hospital preparations were developed based on a concept of the drug delivery system. Hard fat (Witepsol) used as a base of the suppository consists of a mixture of triglycerides, diglycerides and monoglycerides, and each Witepsol is characterized by its physicochemical properties. Authors disclosed that the amount of drug release measured in the commercially available diclofenac sodium suppositories decreased at a low temperature (36 degrees C). Mixed types of diclofenac sodium suppositories consisting of Witepsol W35 and Witepsol E85 as a base were also prepared and their drug release functions investigated in vitro and in vivo. The in vitro drug release properties changed with the mixing ratios of the two bases and with the temperature of the fluid tested. The amount of released diclofenac sodium increased with increases of both the ratio of Witepsol W35 in the suppository and the temperature of the test fluid. Moreover, several processes causing these phenomena were evidenced by the image analysis. The in vivo absorption of diclofenac sodium was found to be also influenced by these factors. Consequently, it is predicted that such factors as the ratio of Witepsol W35 in the suppository and the temperature will influence the drug absorption and the pharmacological effect of diclofenac sodium suppositories.

Administration, Rectal↗
PubMed1998

[Preparation and utility of glibenclamide suppository for hospital use].

Glibenclamide (GC) is widely used as an oral hypoglycemic drug in the treatment of non-insulin dependent diabetes mellitus (NIDDM). Since GC is usually taken for a long period, side effects and noncompliance are among the problems. In order to solve those problems, we prepared GC suppositories and examined their usefulness. Suppositories containing 4, 20, and 40 mg of GC were prepared and examined for drug release, drug absorption and blood glucose levels after the rectal administration of suppositories in rabbits. In the release test, GC suppositories released the drug continuously for 6 hours. The areas under the drug release time curve (ADT) of 20 and 40 mg GC suppositories were 3.5 and 6.2 times of 4 mg GC suppositories respectively. The plasma concentrations after administration of 4 and 20 mg GC suppositories showed about the same profiles for 6 hours. After administration of 40 mg GC suppositories, the maximum plasma concentration (Cmax) was observed at 2 hours. All the GC suppositories showed lower blood glucose levels compared with the control. The remainder of the area under the blood glucose concentration time curve between the control (RAUC) in the case of 40 mg GC suppository was 1.3 times larger than that of the 4 mg GC suppository. The GC suppositories sufficiently lowered the blood glucose levels. These results suggest that the GC suppositories should be useful in the hospital preparation for the treatment of NIDDM patients.

Animals↗
PubMed1997

[Trial for transdermal administration of sulfonylureas].

Sulfonylureas are widely used as oral hypoglycemic drugs in the treatment of non insulin dependent diabetes mellitus (NIDDM). Since sulfonylureas are usually taken for a long period, the compliance of the patients is very important. Therefore, for the improvement of the compliance of the patients, the development of a transdermal dosage form of sulfonylureas was attempted in this study. Glibenclamide (GLI) or chlorpropamide (CHL) was chosen as a principal agent and ointments were prepared by mixing 5% of GLI or CHL with a FAPG ointment base. Penetration and shearing stresses of the ointments were determined as physical characteristics of the ointments. There was no obvious difference of characteristics between the GLI ointment, or the CHL ointment and the FAPG ointment base. In drug release tests, the CHL ointment showed better release of the drug than the GLI ointment. In both ointments, comparatively rapid release of drug was observed in the initial 1 h, and continuous slow release was observed thereafter. When the ointments were applied on the back of male Wistar rats and the plasma glucose level was measured, both CHL and GLI ointments gave lower blood glucose levels than the control (FAPG base). At the all measuring points, the GLI ointment brought about significantly lower blood glucose levels than the control (p < 0.01). Thus, it was demonstrated that sulfonylureas were absorbed through the skin and lowered the blood glucose levels. The results suggest the possibility of transdermal administration of sulfonylureas for the treatment of NIDDM.

Animals↗
PubMed1997

[Sustained release double-layered progesterone suppository for luteal support therapy].

A sustained release suppository containing progesterone with a double-layered structure was prepared for the treatment of the luteal phase defect. Hydroxypropylcellulose-H (HPC) and Carbopol-934P (CP) were used as bases of the inner layer and Witepsol W35 was used as a base of the outer layer. The strength of the inner layer (stick) decreased with the increase of the rate of content of HPC component. The strength of the stick which was prepared from a mixture of HPC and CP in a ratio of 1:1, was inverse by proportional to the rate of the addition of crystalline cellulose (CC) and the amount of released drug was proportional to the rate of the addition of CC. The area under the drug release curve of the stick containing 60% of CC in the base was about 12 times of the stick containing no CC (control stick). Furthermore, the mean release time of the stick containing 60% of CC became about a half of the control stick. It was suggested that the drug release of progesterone from the stick could be controlled by changing the rate of the addition of CC. Two types of suppository which containing progesterone in both phases (suppository A) and in the stick alone (suppository B) were prepared. Both suppositories showed a sustained release property and suppository B had a lag time of two hours. When the suppositories were administered in to the vagina of rabbits, they showed a sustained release property and a rapid rise in the serum concentration was more suppressed than an ordinary Witepsol suppository. One hour after the administration of the two layered suppository, some parts of the suppository was identified macroscopically to be remained in the vagina. The usefulness of the double-layered suppository as a hospital preparation should be suggested after the attainment of the optimization of the formulation.

Acrylic Resins↗
PubMed1990

Enzyme immunoassay for placental protein 4 (PP4) and its possible diagnostic significance in patients with genital tract cancer.

We have established an enzyme immunoassay for placental protein 4 (PP4), by using avidin-biotin binding reaction, and set its normal range below 10.9 ng/ml (mean + 2 sigma). Throughout the menstrual cycle, the serum PP4 profile was similar to that of serum progesterone. In the follicular and ovulatory phase, PP4 remained relatively low, with the mean levels of 1.5 ng/ml and 1.8 ng/ml, respectively. In the luteal phase, the mean level was 3.2 ng/ml. In normal pregnancy, serum PP4 levels were low irrespective of gestational age, with a mean level of 3.0 ng/ml. There was only one case in which the serum PP4 level over 10.9 ng/ml. Mean serum PP4 levels and the frequencies of elevated serum PP4 levels were respectively 6.3 ng/ml and 11% in patients with benign ovarian neoplasms, 4.7 ng/ml and 6% in patients with endometriosis, and 5.5 ng/ml and 18% in patients with uterine myomata. The frequency of raised PP4 levels was 48% and the mean value was 13.3 ng/ml in patients with endometrial carcinoma, and the values were 44% and 13.4 ng/ml respectively in patients with cervical carcinoma. In patients with ovarian malignancy, the respective values were 15% and 7.0 ng/ml. The results did not relate to clinical stages of disease (FIGO), while the frequencies of elevated serum PP4 in patients with uterine carcinoma was over 40% in stage I diseases. Compared with other tumor markers such as carcino-embryonic antigen (CEA), tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125), PP4 seems to be more promising as a marker of endometrial carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Annexin A5↗
PubMed1989

Clinical significance of a solid-phase immunoradiometrical assay for sialyl SSEA-1 antigen in obstetrics and gynecology.

The clinical usefulness of sialyl SSEA-1 antigen was evaluated in obstetrics and gynecology. Serum levels of sialyl SSEA-1 were measured in patients with benign or malignant gynecologic diseases, and in normal pregnant women. Moreover, in 10 cases of full term delivery, samples of maternal sera immediately prior to delivery, soon after delivery and 5-day-puerperium, cord sera from the umbilical artery and vein, and amniotic fluid were taken to measure its concentration. During the course of pregnancy, serum SSEA-1 levels were within the normal range (below 38 U/ml), showing no significant correlation with gestational weeks. Of patients with gynecologic diseases, those with malignant ovarian neoplasms, uterine cervical carcinoma and benign ovarian neoplasms exhibited elevated (over 38 U/ml) levels in 26%, 15% and 6% of all cases, respectively. In cases of full term delivery, the concentrations of sialyl SSEA-1 in the maternal and cord sera were within the normal range. Concentrations were extremely high, however, in the amniotic fluid.

Amniotic Fluid↗
PubMed1989

Immunochemical measurement and immunohistochemical detection of membrane-associated placental tissue protein 1.

Using the avidin-biotin binding system, an enzyme immunoassay procedure was developed to measure the membrane-associated placental tissue protein 1 (MP1) in serum. The standard curve covered the range from 10 to 1000 ng/ml of MP1. The intra- and inter-assay coefficient of variations (C.Vs) were less than 5 and 10%, respectively. Recoveries of MP1 added to serum ranged between about 96 and 101%. The MP1 serum level was over 10 and under 112 ng/ml in non-pathological men, and under 240 ng/ml in non-pathological women. The MP1 level in the ovulatory phase was higher than in other phases of the menstrual cycle. In pregnancies during 6-39 weeks, the MP1 level ranged from 10 to 540 ng/ml, and it increased during the third trimester of gestational age. In benign gynecologic diseases, the MP1 concentration in serum ranged from 10 to 215 ng/ml. The MP1 levels in benign diseases were compared with those in ovarian malignancies, in endometrial carcinoma, and in uterine cervical cancer. The immunohistochemical location of MP1 was detected in the cell membrane of ovarian cystadenocarcinoma.

Female↗
PubMed1988

Relation between serum levels of tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125) and their immunohistochemical identification in benign and malignant gynecological disease.

We studied immunohistochemical stains for TPA and CA125 in patients with benign and malignant gynecologic diseases. The results were as follows: (1) CA125 was not found in ovarian mucinous cystadenocarcinoma but was demonstrated immunohistochemically in 82% of ovarian serous cystadenocarcinomas and 83% of Krukenberg's tumors. (2) TPA was demonstrated in 65% of ovarian serous and 75% of ovarian mucinous cystadenocarcinomas, and in 58% of endometrial carcinomas. (3) TPA was found in all trophoblastic tumors examined, while CA125 was found in none. Eighty-three percent of patients with trophoblastic diseases had raised serum TPA levels. (4) When serum CA125 levels were raised CA125 was demonstrated immunohistochemically in 71% of patients with ovarian serous cystadenocarcinomas, 67% of patients with Krukenberg's tumors and 100% of patients with tubal carcinomas. (5) Despite elevated serum levels, CA125 and TPA were not identified by immunohistochemistry in 64% cases of benign ovarian disease and in 80% of patients with uterine myomata. (6) It would seem that CA125 was more easily released from tumor cells than TPA.

Antigens, Neoplasm↗
PubMed1988

Serum levels of six tumor markers in patients with benign and malignant gynecological disease.

We studied the pretreatment serum levels of 6 tumor markers in gynecological patients with and without malignant disease. The tumor markers were carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), ferritin, Schwangerschaftsprotein 1 (SP1), Schwangerschaftsprotein 3 (SP3) and cancer antigen 125 (CA125). The results were as follows: (1) Serum CA125 and TPA levels were raised in 81% and 57% of patients with ovarian serous cystadenocarcinoma; CEA and SP3, in 52% and 43% respectively of patients with ovarian mucinous cystadenocarcinoma; CA125, TPA and SP3, in 76%, 48% and 48% respectively of patients with other ovarian malignancies; and TPA and SP3, in 56% and 40% respectively of patients with endometrial carcinoma. (2) Serum levels of TPA, ferritin and CA125 were more often raised with advancing stages of malignant disease. (3) Serum TPA levels were elevated in 55% of patients with stage I endometrial carcinoma, and serum SP3 levels were elevated in 35% of patients with a stage I malignant ovarian neoplasm and in 45% of patients with endometrial carcinoma. (4) One of the 6 tumor markers showed a raised level in 84% of patients with gynecologic malignancy as against 56% in those with benign gynecologic diseases.

Antigens↗
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↗
PubMed1987

The immunocytochemical localization of new soluble placental tissue proteins (PP14, 16, 17, 19, 20 and PP21) in human and cynomolgus monkey placentae.

Apparently Placenta-specific placental tissue proteins (PP14 and PP17) and solitary tissue proteins (PP16, 19, 20 and PP21) were investigated by avidin-biotin immunoperoxidase technique in the human and cynomolgus monkey placentae, membranes, decidua and umbilical cords. In human early placentae, PP14, 16, 17, 19 and PP21 were localized mainly in the cytoplasm of villous syncytiotrophoblast. PP20 was localized in the cytoplasm of basal chorionic trophoblasts. In human term placentae, positive stainings for PP16, 19 and PP21 were observed mainly in all kinds of trophoblastic cells, while positive stainings for PP14, 17 and PP20 were weakened in the trophoblastic cells. PP20 was clearly localized in the cytoplasm of Hofbauer-like cells in the villous stroma. The membrane of villous syncytiotrophoblast showed strongly positive stainings for PP21. PP21 was also localized in the membrane of amniotic and umbilical epithelium. The umbilical epithelium was cytoplasmically positive for PP14, 16 and PP20. Clear positive stainings for PP14 and PP21 were found in the cytoplasm of fetal polymorphonuclear neutrophils. All of the placental proteins were immunocytochemically positive in the decidual large cells. In the cynomolgus monkey placentae, similar immunostaining results were obtained. The monkey could, thus, serve as a model for the investigation of the placental proteins.

Amnion↗
PubMed1987

[Anticancer effect of VP16-213 (etoposide) on three choriocarcinoma cell lines].

A new anticancer drug, VP16-213 was studied in vitro to determine its effect upon 3H-thymidine uptake and the survival rate of choriocarcinoma cells in comparison with the effect of MTX and Act-D. Three human choriocarcinoma cell lines, BeWo, HCCM-5 and SCH were used. The results were as follows; Serum VP16-213 levels were 10.3 +/- 1.19 micrograms/ml and 1.35 +/- 0.38 micrograms/ml at one hour and 12 hours after the administration of 100mg of VP16-213, respectively. In those three cell lines, VP16-213 suppressed cellular 3H-thymidine uptake by 70% as compared with the control. On the sixth day after exposure to VP16-213, the survival rate of choriocarcinoma cells was less than 10% in each of the three cell lines. One of the most prominent pharmacodynamic characteristics of VP16-213 was a rapid influx and efflux mechanism as seen in MTX. From the above, the anticancer effect of VP16-213 upon those three cell lines was supposed to be equal to or more than those of MTX and Act-D.

Cell Line↗
PubMed1987

[Synergistic effect of amphotericin B and actinomycin-D against two human choriocarcinoma cell lines].

The sensitivity to actinomycin-D (Act-D) and the changes in survival rate of two human choriocarcinoma cell lines (BeWo and SCH) were studied in vitro and the following results were obtained. BeWo was shown to be more sensitive to Act-D than SCH, when the survival rate was compared in the two cell lines. 3H X Act-D uptake was 39 pmol/10(6) cells in BeWo and 12 pmol/10(6) cells in SCH after a two hours treatment. Those results suggested that the sensitivity to Act-D of choriocarcinoma cells was positively correlated with the intracellular Act-D concentration. The intracellular Act-D concentration was increased depending upon the concentrations of amphotericin B (AMB). After a two hours treatment with Act-D and AMB, the intracellular Act-D concentrations were twice in BeWo, and 2.3 times in SCH comparing with those treated with Act-D alone. The synergistic effects of Act-D and AMB on the survival rate were 1,000 times in BeWo and 100 times in SCH compared with those treated with Act-D alone. From the above, combination therapy with Act-D and AMB was supposed to be one of the trial methods in the treatment of drug resistant choriocarcinoma.

Amphotericin B↗
PubMed1987

[Fundamental and clinical study of chemotherapy of refractory choriocarcinoma].

Since the introduction of MAC therapy in 1973, choriocarcinoma has become one of the most curable gynecologic malignancies. But in MAC resistant cases, the therapeutic results have been unsatisfactory. To establish the proper therapy for MAC resistant choriocarcinoma, fundamental experiments with MTX resistant HM cell lines were carried out with the aim of their clinical application. The effective combination in the treatment of choriocarcinoma appeared to be 10 to the minus 5th power mol of MTX and 10 to the minus 8th power mol of Act-D, considering its effect in cell proliferation inhibition, deoxyuridine uptake inhibition and dihydrofolate reductase activity suppression. Taking the effects of Oncovin confirmed by the experiments with nude mice into consideration, a combined moderate dose of MTX, Oncovin and Act-D, namely MOA therapy was used. The protocol of MOA therapy is as follows: The first day, MTX 150mg bolus, 300mg drip infusion for 4 hours, Oncovin 2mg bolus and Act-D 0.5mg bolus. From the second to the fifth day, Act-D bolus. MAC was effective in only one of the eight recurrent cases, but on the other hand, MOA was effective in five cases of choriocarcinoma including two MAC resistant cases. Therefore, MOA seemed to be a more effective therapy than MAC.

Adult↗