Localization and regulation of ovarian carbonyl reductase in rats.
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Aging↗
Biomedical subjects
N Inaba
Publications and source records attributed to N Inaba.
Physiological role of ovarian carbonyl reductase and effect of antiestrogen on its activity in rats.
In order to clarify physiological role of carbonyl reductase in rat ovary and effect of antiestrogen on its activity, we investigated effects of five antiestrogens on changes in ovarian enzyme activities towards three carbonyl compounds. All of five antiestrogens tested, significantly decreased 13,14-dihydro-15-ketoprostaglandin F2 alpha 4-benzoylpyridine and menadione reducing activities in ovarian cytosol by both consecutive treatments and single treatment. This inhibition of ovarian enzyme activities by antiestrogen was dramatically antagonized by human chorionic gonadotropin treatment at 3:00 p.m. on the day of proestrus. These results suggest that antiestrogen inhibits LH surge at afternoon of proestrus in rats and that the ovarian enzyme catalyzing reduction of carbonyl compounds is involved in ovulatory process.
Alcohol Oxidoreductases↗
[The evaluation of CA54/61 in the diagnosis of ovarian cancer--with special reference to the cooperative results of 5 institutes].
The clinical usefulness of a newly developed one-step enzyme-immunoassay, MKS-15, in the diagnosis of ovarian cancer was evaluated with 1,563 serum samples collected at five institutes. In this assay, two monoclonal antibodies, MA54 and MA61, which both recognize the carbohydrate chain in a high molecular weight mucin-type glycoprotein, were used as the immobilized antibody on beads and peroxidase-labeled antibody, respectively. When the cut-off value was set at 20 IU/ml (mean + 3SD), 56% of the sera from ovarian cancer patients were positive, and the positive rates for serous, mucinous, mesonephroid, endometrioid, undifferentiated, and metastatic cancers were 63%, 55%, 52%, 38%, 55%, and 62%, respectively. In sera from patients with benign ovarian tumors, only 4% of the cases were positive, but 7% of benign and low potential malignant cases of mucinous cystadenoma were positive, indicating that CA54/61 cannot distinguish benign mucinous cystadenoma from malignant ones. Since the positive rate for CA125 is rather low in mucinous cyst-adenocarcinoma, CA54/61 may be of clinical value.
Adolescent↗
[Diagnosis of precancerous lesions of the endometrium].
Cytodiagnosis of the precancerous lesions of the endometrium has remained unclear compared to that for cervical lesions. Endometrial cytology and biopsy have been performed for patients with atypical genital bleeding, who were over fifty, postmenopausal or nulliparous, We studied cytologic findings in cystic glandular, adenomatous and atypical hyperplasia, and compared to them in early cancer. Differential diagnosis was somewhat difficult between cystic glandular hyperplasia and benign lesions. Cytological diagnosis becomes gradually easier with progress of the lesions. A few cases with endometrial hyperplasia developed endometrial carcinoma for several years. Endometrial carcinoma has been detected even in the patients with suspicious endometrial cytology, so endometrial biopsy is still an important method. However, endometrial cytology is very easy, so we need to clarify the cytological cytological characteristics in precancerous lesions of the endometrium.
Cytodiagnosis↗
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↗
Immunohistochemical study of tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125) in the human and cynomolgus monkey placenta, umbilical cord and decidua.
Tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125) were studied immunohistochemically by the avidin-biotin immunoperoxidase technique in human and cynomolgus monkey placentae, membranes, umbilical cords and decidua. In early human placentae, TPA was localized mainly in the cell membranes of villous syncytio- and cyto-trophoblast. The cytoplasm of those trophoblastic cells were weakly stained with TPA. The membrane of basal chorionic trophoblast cells was strongly stained with TPA and the cytoplasm stained weakly. In early cynomolgus placentae, similar immunostaining results were obtained. However, the positive stainings for TPA was more marked in the cytoplasm of villous syncytiotrophoblast and basal chorionic trophoblast, and less marked in the cell membrane of villous cytotrophoblast. In early human and cynomolgus placentae, CA125 was not demonstrated immunohistochemically in the villi and basal chorion. In human and cynomolgus term placentae, the villous syncytiotrophoblast and basal and reflected chorionic trophoblast showed similar immunostaining as the early placentae. In addition, TPA was found in the amniotic epithelium in both sorts of placentae. TPA was not detected immunohistochemically in the umbilical cord and decidual cells. While weakly positive stains for CA125 were observed in decidual cells, CA125 was localized mainly in the membrane and cytoplasm of amniotic epithelium in both human and cynomolgus term placentae. TPA and CA125 are thus oncoplacental antigens and the monkey could serve as a model for their investigation.
Animals↗
Immunoradiometrical measurement of tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125) in pregnancy and at delivery.
Using conventional radioimmunoassay kits, we measured concentrations of two cancer-related antigens, tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125) throughout gestation and at delivery. The maternal serum was collected from 147 pregnant women between 5 and 43 weeks gestation and 27 women were studied at delivery at which time samples of maternal blood, umbilical artery and vein blood as well as amniotic fluid were collected. The various concentrations of TPA and CA125 were compared with placental weight and infant birth weight. The results are summarized as follows: (1) Mean TPA levels in maternal serum increased with advancing gestation and rose above 110 U/l (upper non-pregnant limit) from 35 weeks onwards. Mean CA125 levels rose above 35 U/ml (normal non-pregnant upper limit) before 9 weeks gestation and thereafter fell. Both levels were markedly raised immediately after delivery. (2) In umbilical artery and vein serum, mean TPA levels were slightly raised. However, there were no significant differences between TPA levels in maternal serum and matched serum from the umbilical artery and vein. Mean umbilical CA125 levels were below 35 U/ml, while mean CA125 levels were significantly higher in the corresponding maternal serum. (3) The concentrations of TPA and CA125 were extremely high in amniotic fluid. The mean values reached 3604 U/l and 2187 U/ml, respectively. (4) None of the concentrations of TPA and CA125 in those pregnancy-related body fluids correlated significantly with birth weight, placental weight or fetal sex. These findings suggest that the production of these two cancer-related antigens is not by the fetus but the placenta.
Amniotic Fluid↗
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↗
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↗
The capacity for differentiation and production of human chorionic gonadotropin and alpha-fetoprotein in human embryonal carcinoma cell lines.
The capacity for differentiation of five human embryonal carcinoma (EC) cell lines was studied by examination of the morphology of xenograft tumors in nude mice. In addition to morphology, differentiation into extraembyronic elements was studied by examining the evidence of human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) production. The EC cell lines can be divided into two groups: pluripotent (NEC 14 and Tera 2) and nullipotent (NEC 8, NEC 15, and ITO-II) cell lines. In nude mice, the pluripotent NEC 14 and Tera 2 cells produced EC mixed with various somatic elements such as glandular, neuronal, and cartilaginous tissue. However, typical extraembryonic elements, such as choriocarcinoma and yolk sac elements, were not usually observed. Production of hCG and/or AFP was identified in the tumors by both radioimmunoassay and the immunoperoxidase reaction. These results indicate that some human EC cell lines retain the capacity for differentiation into somatic and extraembryonic elements and that hCG and/or AFP appears to be produced by transitional types of cells that still retain the morphology of EC cells.
Animals↗
Establishment and characterization of a human cell strain, KT, with high sensitivity to UV-killing and to cell proliferation inhibition by interferon.
We have established a human cell line, designated KT, with high susceptibility to both cell proliferation inhibition by interferon and UV-killing, from a metastatic breast carcinoma. A tumor marker, a pregnancy-specific glycoprotein (Schwangerschaftsprotein 1; SP1), and carcinoma characteristics compatible with ductal carcinoma of the breast were seen in KT cells by electron microscopic observation. KT cells were slightly more resistant to X-ray-induced toxicity than fibroblastic cells, termed KS, from the scalp of the patient. But, KT cells had lower cloning efficiency after UV irradiation than did KS cells: D0 values of 1.5 J/m2 and 7.2 J/m2, respectively. KT cells also appeared more susceptible to human interferon (HuIFN) preparations (alpha, beta, gamma and natural or recombinant) than did KS cells, as measured by cell colony formation ability, proliferation rates, and [3H]deoxythymidine incorporation levels into acid-insoluble cell materials. The sensitivity of KT cells to UV and HuIFN was greater than that of human RSa cells, a cell line with high sensitivity to both agents. KT cells had more capacity for UV-induced DNA-repair replication synthesis than did RSa cells, the capacity being much the same as that of KS cells. There was no significant difference in levels of antiviral activity induced by HuIFN and binding capacity for 125I-labeled IFN-alpha A between KT and KS cells. KT cells appeared refractory to cell proliferation inhibition by tumor necrosis factor (TNF) preparations.
Brain Neoplasms↗
[The immunohistochemical localization of CA 15-3 in human breasts and their tumors].
The tissue distribution of CA 15-3, a breast carcinoma associated antigenic determinant, has been investigated by an avidin-biotin immunoperoxidase technique in the human breasts and in their tumors. In cases of scirrhous carcinoma, positive stainings for CA 15-3 were observed in almost all carcinoma cells. In cases of solid-tubular carcinomas and papillotubular carcinomas, the reaction was various and there was no correlation between the distribution of CA 15-3 and the clinical stage. Apical staining was recognized in both solid-tubular and papillotubular carcinomas, in benign breast tumors, and in normal breast tissues. CA 15-3 appears to be related to the degree of differentiation of the breast tissue.
Adenocarcinoma↗
In vitro and in vivo studies of the production of placental proteins (HCG, SP1, PPs) in human choriocarcinoma cell lines.
The production of human chorionic gonadotropin (hCG), pregnancy-specific beta-1 glycoprotein (SP1), and the various placental tissue proteins (PP4, PP5, PP10, PP11, PP12, MP1) was examined in human choriocarcinoma cell lines using radioimmunoassay (RIA) and an immunoperoxidase (PAP) staining method. In 6 gestational and 2 nongestational choriocarcinoma cell lines, hCG was produced in vitro. A significant heterogeneity of hCG production was noted among the cell lines. Production of hCG in the xenograft tumors was consistent with the hCG production of the same cell lines in vitro. SP1 was demonstrated both in the culture supernatants and the xenograft tumors of 3 cell lines, and the production was found to be inversely correlated with the hCG production of the cell lines. Positive staining for PP4 and MP1, and weakly positive staining for PP5, PP10, and PP12 was found in the xenograft tumors by immunoperoxidase (PAP) stain, but the staining for PP11 was negative. These placental proteins showed positive staining in portions of choriocarcinoma cells. These results indicate that placental proteins are not equally produced in heterogeneous choriocarcinoma cells.
Animals↗
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↗
Human chorionic gonadotropin and alpha-fetoprotein in sera and tumor cells of a patient with pure dysgerminoma of the ovary. A case report with radio-immunoassay and immunoperoxidase.
One of 7 patients with pure dysgerminoma had slightly elevated serum human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) levels as determined by radio-immunoassay before operation. The values returned to the normal range after the removal of the tumor. The cells that produced the HCG or AFP were identified by immunohistochemical staining of the tumor tissues. HCG proved positive both in the multinucleated giant cells with eosinophilic cytoplasm and in the spindle-shaped cells with a hyperchromatic nucleus. AFP was positively stained in the round cells. These results suggest that HCG and AFP are produced by the cells which constitute pure dysgerminoma.
Adolescent↗
[Mixed ductal and acinar cell cancer of the pancreas head; report of a case].
A 63 year old Japanese man was admitted in Feb. 1983, with his chief complaint of upper abdominal pain. Physical examination showed only resistance in the right hypochondrium on palpation, but no icteric conjunctiva and skin. A large global tumor of the pancreas head was visualised as a hyperechoic mass with irregularly shaped cystic cavity in ultrasonography, as a hypervascular mass with lucent area in celiac arteriography, and as a mass lesion with low density area in body computerized tomography. Cancer cells were histologically confirmed on specimens taken by fine needle aspiration biopsy under ultrasonic guidance. Cancer of 6.5 X 6.0 X 4.0 cm in size was resected by pancreaticoduodenectomy. Four months after operation, two liver metastatic nodules were resected by right hepatic lobectomy. Histologically, tumor was composed of two characteristic patterns, acinar cell cancer and duct cell cancer, which were confirmed by immunohistochemical techniques. The patient is doing well 3 years and 3 months postoperatively without evidence of recurrent cancer. To our best knowledge, this case is the seventh of mixed ductal and acinar cancer in the world, but the previous 6 cases were reported on autopsy specimens.
Carcinoma, Intraductal, Noninfiltrating↗
[Production of monoclonal antibody against a newly established human endometrial cancer cell line SNG-II].
A cell line designated SNG-II was established from the operation specimen of human endometrial adenocarcinoma, and by means of an immunization procedure using intact SNG-II cells, a monoclonal antibody (Mab) named MSN-1 which reacts immunohistochemically with endometrial cancers was obtained. The cell line grew well without interruption for over 5 years, and, SNG-II cells produced tumors of cell differentiated adenocarcinoma in nude mice. The modal chromosomal number was diploid without a marker chromosome. The production of human chorionic gonadotropin and its beta-subunit, CA-125, tissue polypeptide antigen, and placental proteins such as PP6 and PP7 in SNG-II was confirmed. MSN-1 was of IgM subclass. As the antigenic reactivity was unchanged by trypsin treatment, but lost by periodic treatment, it was suggested that the antigen corresponding to MSN-1 was a carbohydrate sequence. Immunohistochemically MSN-1 reacted with about 70% cases of endometrial adenocarcinoma, but seldom with normal endometrium. Furthermore, the staining pattern of MSN-1 was different in benign cells from that in malignant cells: only the luminal surface of the normal endometrium was positive, whereas the cytoplasma was also stained in many of adenocarcinoma cells.
Adenocarcinoma↗
[Establishment and characteristics of a new human choriocarcinoma cell line and its production of tumor markers].
A human gestational uterine choriocarcinoma cell line (NJG) was established in vitro. The NJG cell line had been subcultured more than 73 times over 7 years. The cells consisted mainly of Langhans-like cells, while multinucleated cells were occasionally seen. The cells grew in a monolayered sheet, showing a tendency to pile up, with the population doubling in 80 hrs. Electron-microscopically, desmosomes were characteristically observed, which suggested that the cultured cells were of epithelial origin. Chromosomal analysis revealed aneuploidy with a hypertriploid mode and 4 marker chromosomes. Immunocyto- and-histochemical staining for tumor markers of the cultured cells and the transplanted tumors to nude mice showed close similarity. SP1 was occasionally demonstrated and PP5 was faintly stained only in the heterotransplanted tumors, although PP10 and PP12 were not demonstrable. HCG was localized not only in syncytial cells, but also in Langhans cells, and syncytial cells without hCG were also observed in the tumors. A single cell clone was also established from the original NJG cells by a limiting dilution method. The heterotransplanted tumor consisted of Langhans and syncytial cells, indicating that both cells originated from the same cell.
Animals↗