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Biomedical subjects

K Shiromizu

Publications and source records attributed to K Shiromizu.

At least 55 records · Page 3Linked to original sources
PubMed1986

[A case of primary malignant fibrous histiocytoma of the vagina].

A 52-year-old woman visited us complaining of a recurrent vaginal tumor, which was diagnosed histologically as malignant fibrous histiocytoma of the vagina. Computed tomography revealed multiple metastatic lesions in the liver, lymph nodes and vertebrae. The patient was treated with combination chemotherapy consisting of cyclophosphamide, adriamycin and cis-platinum, but the tumor did not yield readily to the treatment. We believe that this is the first reported case of this tumor in this location in Japan.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Murine oocyte destruction following intraovarian treatment with 3-methylcholanthrene or 7,12-dimethylbenz(a)anthracene: protection by alpha-naphthoflavone.

Bilateral or unilateral intraovarian injection with the polycyclic aromatic hydrocarbons 3-methylcholanthrene (3-MC), or 7,12-dimethylbenz(a)anthracene (DMBA) destroys oocytes in C57BL/6N and DBA/2N mice. The threshold for small oocyte destruction following bilateral intraovarian treatment with 3-MC was between 0.1 and 1 microgram/ovary in both DBA/2N amd C57BL/6N mice. After intraovarian treatment with DMBA, a more potent ovotoxin, the thresholds for small oocyte destruction were between 0.01 and 0.1 microgram/ovary. Calculated ED50's for small oocyte destruction following bilateral intraovarian treatment with 3-MC were C57BL/6N, 0.33 micrograms/ovary; DBA/2N, 1.02 micrograms/ovary--for DMBA the ED50's were C57BL/6N, 0.11 micrograms/ovary; DBA/2N, 0.03 micrograms/ovary. Unilateral intraovarian treatment also destroyed oocytes in the treated ovary. Treatment with intraperitoneal alpha-naphthoflavone (ANF), a competitive inhibitor of polycyclic aromatic hydrocarbon metabolism by microsomal monooxygenases, inhibited oocyte destruction. Intraovarian treatment with ANF decreased oocyte destruction produced by intraovarian DMBA. These data suggest that both 3-MC and DMBA are indirect acting ovotoxins requiring metabolic activation before oocyte destruction occurs. In addition, these data also suggest that the ovary contains the enzymes necessary to biotransform xenobiotics like 3-MC and DMBA to ovotoxic metabolites. Metabolic activation of xenobiotics to reactive products within the ovary may represent a special threat to the integrity of oocyte DNA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

The effect of intraovarian injection of benzo(a)pyrene on primordial oocyte number and ovarian aryl hydrocarbon [benzo(a)pyrene] hydroxylase activity.

The effect of intraovarian (io) injection of benzo(a)pyrene (BP) on primordial oocyte number, ovarian aryl hydrocarbon hydroxylase (AHH, EC 1.14.14.1) activity, and hepatic AHH activity and P-450 content was investigated in C57BL/6N (B6) and DBA/2N (D2) mice. Ovaries were exteriorized through dorsolumbar incisions under ether anesthesia, and 1.0 microliters of corn oil or corn oil containing BP was injected directly into the ovary. Bilateral io injection of BP was ovotoxic in a time and dose dependent manner. Primordial oocyte destruction was maximal 8 days after injection in both B6 and D2 mice. Unilateral io injection of BP destroyed oocytes only in the treated ovary. The threshold dose for primordial oocyte destruction was similar in both strains, approximately 50 ng/ovary. However, ED50's were different; 1.1 micrograms/ovary in B6 and 8.9 micrograms/ovary in D2 mice. Intraperitoneal treatment with alpha-naphthoflavone (80 mg/kg) inhibited the oocyte destruction by io treatment with BP (10 micrograms/ovary) in both B6 and D2 mice. In B6 mice, ovarian AHH activity was induced by BP in the treated ovary after either bilateral, or unilateral io treatment. However, io BP treatment did not change ovarian AHH activity in D2 mice. Hepatic AHH activity and P-450 content was not altered by io BP treatment in either mouse strain. These results strengthen the hypothesis that the ovary has the capability of metabolizing BP to ovotoxic products.

Animals↗
PubMed1984

Effect of cyclophosphamide on oocyte and follicle number in Sprague-Dawley rats, C57BL/6N and DBA/2N mice.

Oocyte and follicle destruction produced by cyclophosphamide was investigated in Sprague-Dawley (SD) rats, and inbred C57BL/6N (B6) and DBA/2N (D2) mice. Primordial oocytes were the most sensitive to destruction after intraperitoneal treatment with cyclophosphamide. A delayed decrease in the number of medium-sized follicles occurred between 1 and 2 weeks after treatment. No reduction in the number of large follicles was observed over the 3-week period of this experiment. Primordial oocyte destruction produced by cyclophosphamide occurred in a time-, dose-, strain-, and species-dependent fashion. The threshold for primordial oocyte/follicle destruction in B6 and D2 mice, and SD rats was less than 10, 40, and greater than 500 mg/kg, respectively. ED50S for primordial oocyte/follicle destruction were 49 and 137 mg/kg in B6 and D2 mice, respectively. The ED50 for oocyte destruction was greater than 500 mg/kg in SD rats. Primordial oocyte destruction occurred rapidly and was completed between 48 and 72 hours after treatment with cyclophosphamide in both murine strains. Oocyte destruction and premature ovarian failure is a significant side effect in women treated with alkylating agents. The rodent ovotoxicity model used in these experiments may be useful in elucidating mechanisms of ovotoxicity and evaluating treatment protocols designed to protect the ovary.

Animals↗
PubMed1983

Effects of toxic substances on female reproduction.

Successful reproduction requires a complex series of interdependent physiological, cellular and molecular events. In the female many of these interdependent events are vulnerable to interruption by xenobiotic compounds. The physiological steps in the female reproductive cycle are reviewed. Selected xenobiotics which interrupt this cycle are presented and their mechanisms and site of adverse effects are discussed. Finally, a more detailed discussion of chemically induced ovarian failure in the human and an experimental animal model system is presented.

Animals↗
PubMed1983

Oocyte destruction by polycyclic aromatic hydrocarbons.

Certain polycyclic aromatic hydrocarbons, ubiquitous environmental pollutants, destroy oocytes. Oocyte destruction by polycyclic hydrocarbons requires distribution of the parent hydrocarbon to the ovary where ovarian enzymes metabolize the compound to reactive intermediates responsible for ovotoxicity. Descriptive assays of polycyclic hydrocarbon metabolic activation such as the aryl hydrocarbon (benzo(a)pyrene) hydroxylase assay (AHH) are not good predictors of strain or species differences in sensitivity to polycyclic hydrocarbon ovotoxicity. Using benzo(a)pyrene as a probe of ovarian metabolic processing suggests that the rate of formation of metabolites along the metabolic pathway to the 7,8-dihydrodiol-9,10-epoxide may be the appropriate measure of the role of metabolic activation in strain or species differences in sensitivity to oocyte destruction. The multistep metabolic pathway involved in ovarian metabolic processing of benzo(a)pyrene may represent a useful model for exploring the roles of metabolic activation, detoxification, intrinsic sensitivity, and repair in reproductive toxicity.

Animals↗
PubMed1983

Ontogeny of ovarian glutathione and sensitivity to primordial oocyte destruction by cyclophosphamide.

Ovarian reduced glutathione concentration (microgram/mg wet ovarian weight) develops from levels of less than 0.2 microgram/mg in newborn Osborn Mendel rats to plateau at 0.7 microgram/mg between the ages of 3-7 weeks of age, finally reaching mature levels of approximately 1.0 microgram/mg between 7-8 weeks of age. Ovarian reduced glutathione concentration matures somewhat faster in Sprague Dawley rats, reaching mature levels of 1.0 microgram/mg between 4-6 weeks of age. The development of ovarian glutathione from immature (less than 0.2 microgram/mg) to mature levels (1.0 microgram/mg) was also observed over similar developmental time spans in DBA/2N and C57BL/6N mice. The sensitivity of primordial oocytes to destruction by cyclophosphamide in C57BL/6N mice was considerably different at 4 and 6 weeks of age. The ED50 for primordial oocyte destruction at 4 weeks of age in C57BL/6N mice was 140 mg/kg while at 6 weeks of age the ED50 was 260 mg/kg. The increase in ovarian reduced glutathione with age and the increasing resistance to primordial oocyte destruction over the same time period are consistent with the hypothesis that glutathione plays a major role in the modulation of primordial oocyte destruction.

Age Factors↗
PubMed1981

The effects of cyclophosphamide, azathioprine, and 6-mercaptopurine on oocyte and follicle number in C57BL/6N mice.

Cyclophosphamide, azathioprine and 6-mercaptopurine were studied for oocyte and follicle toxicity in a murine ovarian toxicity assay system. Seven days after a single treatment with cyclophosphamide (100 mg/kg ip), 63% of the primordial follicles and 0% of the growing or large follicles and their oocytes were destroyed in four week old C57BL/6N mice. Treatment with azathioprine (100 mg/kg/day ip x 9 days) or 6-mercaptopurine (100 mg/kg/day ip x 9 days) suppressed weight gain and increased mortality but had no effect on the number of oocytes or follicles in these mice. These data are consistent with previous observations on the effects of cyclophosphamide, azathioprine and 6-mercaptopurine on human ovarian toxicity. This suggests that the murine ovarian toxicity assay system may be useful in evaluating xenobiotics, including drugs, for human ovarian toxicity.

Animals↗
PubMedDate not supplied

Independence of the prognostic value of tumor suppressor protein expression in ovarian adenocarcinomas: A multivariate analysis of expression of p53, retinoblastoma, and related proteins.

Accurate estimation of prognosis of ovarian cancer is difficult. For this report, in a group of 73 patients with ovarian adenocarcinomas, clinical factors and protein expression status of p53, retinoblastoma (Rb), and related proteins were evaluated for potential prognostic values. Clinical factors included FIGO stage, age, histopathologic type, and protein expression of p53, Rb, MDM2, p14ARF, p21WAF(1)/CIP(1) was determined by an immunohistochemical technique. Univariate Cox proportional hazard regression analysis was used to determine the significant prognostic value of FIGO stage (P < 0.0001), p53 status (0.0021), and patient age (P = 0.0255), and we report here, for the first time, the significant (P = 0.0072) prognostic value of Rb status. Histopathologic type and MDM2, p14ARF, p21WAF(1)/CIP(1) status did not show any prognostic value. To examine further the independence of prognostic values, we next applied multivariate analysis: We found that FIGO stage (P < 0.0001) and p53 status (P = 0.0108) were independent prognostic factors, while age and Rb status were not. Independence of prognostic value of p53 has heretofore been controversial, but we found a definite independent prognostic value for p53 status in ovarian adenocarcinomas. We also found that selection of appropriate antibodies for immunohistochemistry was essential to obtain significant results. We used five kinds of antibodies for p53 immunolocalization, and correlation with prognosis was obtained by three of these with different grades of statistical significance.

Adenocarcinoma↗
PubMedDate not supplied

Fine needle aspiration cytology of adenocarcinoma of the rectovaginal septum. A case report.

BACKGROUND: Adenocarcinoma arising in the rectovaginal septum is exceedingly rare and is difficult to diagnose by pathologic examination prior to surgery because of the anatomic position of the tumor. CASE: A 42-year-old woman presumed to have adenocarcinoma of the rectovaginal septum underwent fine needle aspiration for diagnosis. Although a previously performed biopsy from the posterior vaginal fornix was unsuccessful, fine needle aspiration cytology via the posterior vaginal wall detected adenocarcinoma cells. The cell clusters were composed of cells with enlarged and hyperchromatic nuclei. The nuclei themselves demonstrated round and/or irregular morphologic patterns, with high nuclear/cytoplasmic ratios, and often contained an enlarged, round nucleolus and sometimes multiple ones in a single nucleus. Aniso-nucleosis was severe, and the chromatin patterns ranged from coarse to finely granular. The cytoplasm was narrow and lightly stained. Following fine needle aspiration, the patient underwent posterior exenteration on the basis of the cytologic diagnosis. CONCLUSION: Fine needle aspiration cytology was useful in establishing the preoperative diagnosis of adenocarcinoma of the rectovaginal septum, and curative exenterative surgery could be then performed. To our knowledge, this is the first report of fine needle aspiration cytology of adenocarcinoma at this location.

Adenocarcinoma↗
PubMedDate not supplied

Malignant squamous cell elements in the ovarian cancer: report of 5 cases and review of the literature.

Five cases of ovarian cancer are presented in which malignant squamous cell elements were present. Three of the cases were adenosquamous carcinoma without composite endometriosis, mature cystic teratoma or with mixed mesodermal tumor. The other two cases were squamous cell carcinoma which arose in mature cystic teratoma, one of them being in situ carcinoma. Among cases of adenosquamous carcinoma, one composed predominantly of squamous cell element and foci of endometrioid adenocarcinoma was found. In this case, transitional figures between the two components were found. In other cases of adenosquamous carcinoma, components of adeno- and squamous cell carcinoma were intermingled in each carcinoma cell nests. Thus a large variety of histogenesis and microscopic figures were seen in malignant squamous cell elements in the ovarian cancer.

Adult↗
PubMedDate not supplied

Immunohistochemical detection of ras p21 oncoprotein in undifferentiated and well-differentiated epithelial carcinomas of the human ovary.

Expression of ras p21 oncoproteins in human ovarian carcinomas was examined immunohistochemically by using a monoclonal antibody(clone RAS 10) with respect to the degree of their histological differentiation. To achieve this, the intensity of staining for the protein was compared between undifferentiated and well differentiated carcinomas, i.e. extreme subtypes of common epithelial carcinomas. The former was composed of 8 "solid" carcinomas and the latter, 11 serous, 8 mucinous, 4 endometrioid and 4 clear cell carcinomas. All the cases examined, including both undifferentiated and well-differentiated carcinomas, showed a positive reaction to this antibody. Staining intensity and the number of positive cells somewhat varied among the cases. Additionally, 2 cases of ovarian epithelial tumors of low malignant potential (I,MP) were stained with this antibody. Both the cases were positive, but the number of positive cells seemed to be rather less than that found in the carcinoma groups. Thus, no differences in ras p21 expression were observed between the cases examined in spite of the differences in the degree of differentiation of the epithelial ovarian carcinomas. However, the possibility remained that the number of positive cells could be an indicator of malignant potential, enabling us to distinguish LMPs from carcinomas.

Adenocarcinoma↗
PubMedDate not supplied

Tamoxifen mediated human endometrial carcinogenesis may not involve estrogenic pathways: a preliminary note.

Seven cases of endometrial adenocarcinoma patients who had experienced long-term tamoxifen treatments as adjuvant therapy of breast carcinoma, were investigated with respect to estrogen receptor (ER) status. Four cases of endometrial adenocarcinoma without tamoxifen treatment but with a previous history of breast carcinoma were investigated for comparison. One of the 7 and two of the 4 cases were positive for ER immunohistochemically. Thus, the frequency of ER positivity in secondary endometrial adenocarcinoma seemed to be at random among tamoxifen-treated and non-treated breast cancer patients. These results suggest that tamoxifen-mediated human endometrial carcinogenesis may not involve estrogenic pathway(s) but may involve other carcinogenic mechanisms such as DNA adduct formation as shown in rat liver tumorigenesis.

Adenocarcinoma↗
PubMedDate not supplied

Expression of bcl-2 and apoptotic DNA fragmentation in human endometrial adenocarcinoma cells.

Immunohistochemical detection of bcl-2 products and in situ estimation of DNA fragmentation during apoptosis by the nick and labelling method were performed to establish any correlation between these two apparently opposing processes in human solid tumors. Serial sections, one micrometer in thickness, from formalin-fixed and paraffin-embedded tissues of 10 cases of human endometrial adenocarcinoma were examined using the two techniques. A significant fraction of carcinoma cells were found to be stained by both methods, although there existed a general tendency for bcl-2 expression to be negatively correlated with DNA fragmentation in carcinoma tissue. The results thus suggest that bcl-2 expression does not always block apoptosis, and that simultaneous application of bcl-2 immunostaining and DNA nick end labeling is useful for showing the complex nature of apoptosis in histologic slides, especially in gynecological cancers.

Adenocarcinoma↗