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Biomedical subjects

N Inaba

Publications and source records attributed to N Inaba.

At least 91 records · Page 5Linked to original sources

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↗

[Combined passive and active immunization for preventing the development of the infantile carrier state in hepatitis B virus vertical transmission].

By applying hepatitis B (HB) immunoglobulin (HBIG) and HB vaccine (vaccine) to 43 infants born to HB e antigen (HBeAg)-positive HB surface antigen (HBsAg) carrier women intramuscularly, and sub-and/or intra-cutaneously, respectively, the clinical usefulness of combined passive and active immunization in preventing infantile development of the carrier state was evaluated. The results obtained in this study are summarised as follows: Of the 43 infants, 5 (11.6%) developed the carrier state and 38(88.4%) were persistent HBsAb-positive. This carrier-rate was found to be significantly lower than that of 78 non-treated infants (73.1%) born to HBeAg-positive carrier women (control). Four of 15 infants (26.7%), who received HBIG every 4 months, developed carrier state, while only one case (3.6%) fell into carrier state in 28 infants who received HBIG every 3 months. In 30 infants whose vaccination was started at 2 or 4 months of age, 93.3% of the cases became persistent HBsAb-positive within 12 months, while 76.9% of 13 infants who underwent the first vaccination at 12 months of age became persistent HBsAb-positive. No adverse effects of HBIG and HB vaccine were observed in this study. In addition, the mean values for serum glutamic pyruvic transaminase (SGPT) were 35 and 69mu/ml in the treated and control groups, respectively. Thus, the present study demonstrates that the infantile development of HBsAg carrier state by HB virus-vertical transmission could be safely, economically and easily prevented by early initiation of vaccination and re-administration of HBIG within 3 months.

Carrier State↗

AFP-producing Sertoli-Leydig cell tumor of the ovary.

A tumor of the right ovary in a 21-year-old single woman is reported. Secondary amenorrhea, hirsutism, acne and deepening of the voice were associated with the tumor. Light and electron microscopic examinations showed that the tumor was composed of cells resembling Sertoli and Leydig cells of the testis in their cytology features and growth patterns. High levels of circulating dehydroepiandrosterone, androstenedione, testosterone and alpha-fetoprotein (AFP) were found preoperatively. Preoperative estrogen and progesterone levels were all slightly above the upper limits of normal for females. These hormone and AFP levels fell to within the normal range after removal of the tumor. Direct hormone and AFP production of this tumor was confirmed by immunohistochemical techniques and long-term cell cultures in vitro. This is possibly the first report on a Sertoli-Leydig cell tumor in which AFP has been identified in the patient's plasma, in part of the tumor cells and the culture fluid.

Adult↗

Characterization of human embryonal carcinoma cell lines derived from testicular germ-cell tumors.

Four human embryonal carcinoma (EC) cell lines (ITO, NEC 8, NEC 14, NEC 15) derived independently from testicular germ-cell tumors were established in vitro. In their xenografted tumor tissues, all of them exhibited histological characteristics consistent with EC. The cell-biological characterization of these human EC cell lines was investigated with reference to well-known murine EC cell lines. This included examination of their morphology, growth, tumorigenic potential, karyotype, cell-aggregate formation, HLA expression, large glycopeptides, AFP and HCG production, plasminogen-activator secretion, and LDH profiles. Three (ITO, NEC 14, NEC 15) of these human EC cell lines shared cell-biological characteristics consistent with typical EC, but one of them (NEC 8) differed from the others with respect to its rapid growth, high tumorigenic potential, formation of solid cell aggregates, and less differentiated, solid histological pattern. Thus, it is suggested that there are several developmentally different types of human EC cells. The relationship between the properties of these human EC cell lines and their differentiation potential is discussed.

Adult↗