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Biomedical subjects

H Takamizawa

Publications and source records attributed to H Takamizawa.

At least 19 recordsLinked to original sources
PubMed1992

CA54/61 as a marker for epithelial ovarian cancer.

Using a new one-step, double-determinant enzyme immunoassay, we performed quantitative measurements of a mucin-type glycoprotein antigen (CA54/61) that we recently detected in sera of ovarian carcinoma patients. When the cutoff value was set at 12 units/ml, at which a high diagnostic efficiency was demonstrated [or at 20 units/ml (mean + 3 SD of healthy females)], the positive rates of ovarian serous, mucinous, clear cell, and endometrioid carcinomas were 76% (or 63%), 63% (or 55%), 57% (or 52%), and 50% (or 38%), respectively. Even in mucinous cystadenocarcinoma, more than one-half of the cases were positive, indicating the potential utility of the assay in the diagnosis of mucinous tumors. In sera from patients with benign ovarian tumors, only 9% (or 4%) of the cases were positive, indicating the quite high specificity of this test for ovarian carcinomas. To make a comparison between CA54/61 and CA125, we set the cutoff level of CA125 at 110 units/ml, at which value a high diagnostic efficiency was demonstrated [or at 35 units/ml (mean + 3 SD of healthy females)]. When both CA54/61 and CA125 were assessed in sera from 36 patients with mucinous cystadenocarcinoma, the positive rates of CA54/61 and CA125 were 64% (or 56%) and 36% (or 56%), respectively, suggesting that CA54/61 is of clinical value as a new tumor marker for ovarian cancers, including mucinous tumors.

Adult↗
PubMed1992

Expression of a human multidrug resistance gene in human ovarian carcinoma cell lines.

To investigate the possible role of the multidrug resistance phenotype to chemoresistance in human ovarian carcinoma, we have analyzed human multidrug resistance gene (mdr 1) expression in 8 human ovarian adenocarcinoma cell lines. An increase in P-glycoprotein level specific to multidrug-resistant tumor cells was not apparently associated with the increase in resistance to vincristine (VCR) or doxorubicin (Adriamycin). Mdr 1 transcripts (4.5 kilobases) were observed in the RNA preparation obtained from only one cell line (SHIN-3) that showed the highest resistance to both drugs in vitro and in vivo. No cell lines showed mdr 1 DNA amplification. These results suggest that the insensitivity of human ovarian carcinoma to chemotherapy could be partly explained by the expression of mdr 1.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

The immunohistochemical localization of new membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) in human and cynomolgus monkey placentae.

New membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) were investigated by avidin-biotin immunoperoxidase technique in the human and cynomolgus monkey placentae, decidua and umbilical cords. In human early placentae, MP2 A, B, C, and E were localized mainly in the membrane of villous syncytiotrophoblasts and cytotrophoblasts. Histiocytes in the villous stroma were positive for MP2 A, B, D, and E. In human term placentae, obvious positive staining for MP2 A, B, C, and E was observed in the membrane of villous syncytiotrophoblasts, in the amniotic epithelium, and in the umbilical cord sheath. Histiocytes in the villous stroma were positive for MP2 A, B, C, E, and especially for MP2 D. Importantly, MP2 A, C, and E were positive in polymorphonuclear neutrophils, since most of these common antigens are also carcinoma-associated, suggesting clinical usage of MP2 proteins as a new tumor marker. In the cynomolgus monkey placentae, similar immuno-staining results were obtained. The monkey can thus serve as a experimental model for the investigation of the placental proteins.

Amnion↗
PubMed1992

[Studies of clinical usefulness of new tumor markers of ovarian cancer, CA 54/61 and CA 602--CA 602 assay reagent kit, performance its normal value and correlations with other tumor markers].

We made a preclinical study of a newly developed tumor maker, CA 602, and its clinical study using serum samples available from 58 institutions located throughout Japan. In the preclinical study, a CA 602 assay kit was investigated for the reproducibility and precision of assay results; and in the clinical study, the kit was investigated for the normal value of the marker, for variations in assay result with age, menstrual cycle and term of pregnancy, and for correlations of assay results with those of other tumor markers. The tests of the kit for simultaneous reproducibility and interval reproducibility of assay results, and the results of analytical recovery and dilution tests were all favorable; the kit proved to be reliable in both precision and reproducibility. For the study, 2 cutoff levels were set: mean + 2 SD of healthy subjects, i.e., 63 U/ml, and the level which permits the maximal efficiency of differential diagnosis of benign from malignant ovarian tumors, i.e., 90 U/ml. The assay results showed that CA 602 levels were low in women aged 50 and over; the levels were high in the first half of pregnancy, and also high in the menstrual period to the early follicular phase. The assay results of CA 602 also proved to be intimately correlated with those of CA 125, which suggested that the 2 markers might be analogous to each other. CA 602 proving to be of high reproducibility even in the range of concentrations below the cutoff value, the measurement with the marker appeared to be of high precision, capable of detecting even the slightest variations in the antigen. CA 602 therefore appears of great value in the early detection of recurrent ovarian cancers.

Adolescent↗
PubMed1992

Immunohistochemical and ultrastructural investigation of new membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) in gynecologic neoplasms.

New membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) were investigated immunohistochemically by avidin-biotin immunoperoxidase technique and immunoelectron microscopy in various gynecologic neoplasms and normal gynecologic tissues. MP2 A and MP2 B were not specific for malignant tumors. MP2 C was present in 67-100% of ovarian carcinomas, 100% of benign dermoid cysts, and 77% of endometrial carcinomas. Except for endocervical adenocarcinomas, MP2 D was hardly detectable in gynecologic malignancies. Although MP2 E was hardly detectable in benign gynecologic tumors, this protein was present in ovarian carcinomas, uterine squamous carcinomas, endocervical adenocarcinomas, and endometrial adenocarcinomas. These results suggest a possible clinical application of these MP2 proteins as a new tumor marker for gynecologic malignancies.

Biomarkers, Tumor↗
PubMed1992

[Phase II study of 254-S (cis-diammine glycolato platinum) for gynecological cancer].

A phase II study of 254-S was conducted in 134 patients with gynecological malignancies by the gynecology section of the 254-S cooperative study group. The drug was administered at least twice at a dose of 100 mg/m2 by intravenous infusion at 4 week intervals. Forty-two of the 102 evaluable patients responded, including 8 CRs and 34 PRs, with a response rate of 41.2%. The response rate was 37.7% for ovarian cancer and 46.3% for cervical cancer. The response rate of 46.3% for cervical cancer was the highest reported for any single anticancer agent available in Japan. The major side effect was hematotoxicity, in particular thrombocytopenia and leukopenia, while nephrotoxicity was rarely observed. These results suggest that 254-S is an active cisplatin analogue with reduced nephrotoxicity and is a very promising anticancer agent for the treatment of ovarian and cervical cancer.

Adult↗
PubMed1992

[A study of preclinical and clinical usefulness of new tumor markers of ovarian carcinoma, CA 54/61 and CA 602. 1. Evaluation of the diagnostic accuracy of CA 54/61, a study of the normal range of its values and its correlation with other tumor markers].

We made a preclinical study of CA 54/61, a recently developed marker of ovarian tumors, and also conducted a clinical study of it using serum samples collected from 58 institutions located throughout Japan. This paper describes the results of the preclinical study of the CA 54/61 marker that were obtained with a kit based on an enzyme immunoassay (EIA), and also the findings with the kit in the clinical study pertaining to the normal range of its values, its values relative to age, menstrual cycle, and pregnancy, and its correlations with other tumor markers. The tests for reproducibility of assay results, the analytical recovery test, and the dilution test all gave favorable results: the marker proved reliable in both precision and reproducibility. Two cut-off values were used: the mean + 2 S.D. of the mean for healthy subjects, or 20 U/ml; and the value for the maximum diagnostic efficacy, i.e., 12 U/ml. The assay results did not vary greatly with either age, menstrual cycle or pregnancy stage, which suggested that CA 54/61 might be a marker less liable to be affected by physiological conditions prevailing at the time of sample collection. The result correlated poorly with those of assays with other markers; thus CA 54/61 proved to differ in property from the previously recognized tumor markers.

Adolescent↗
PubMed1991

Neural rosette formation within in vitro spheroids of a clonal human teratocarcinoma cell line, PA-1/NR: role of extracellular matrix components in the morphogenesis.

From the human teratocarcinoma-derived cell line PA-1, we established a clonal line, PA-1/NR, that stably produced a distinct cellular arrangement of neural rosettes when cultured as in vitro multicellular spheroids for 3 weeks. On immunofluorescence staining and fluorescence-activated cell sorter analyses, PA-1/NR cells in monolayer expressed the neuroectoderm-associated antigens HNK-1, NC-1, and A2B5 and the neuroblastoma-associated antigens KP-NAC8 and KP-NAC10 but lacked human embryonal carcinoma antigens, SSEA-3 or K21 antigen. Here, we investigated the developmental process of rosette formation with respect to morphological features, distribution of mitotic cells, and expression of multiple lineage-related markers and extracellular matrix (ECM) components. Ultrastructural examination of these rosettes disclosed a well-defined cavity radially surrounded by wedge-shaped or pseudostratified cells, apical microvilli and junctional complexes, and basal laminae and collagen fibrils at their basal surface. In these rosettes, many proliferating cells were detected by the immunohistochemical staining of cells incorporating bromodeoxyuridine. PA-1/NR spheroids consistently displayed neuron-specific enolase, S-100 protein, and vimentin but not glial fibrillary acidic protein, neurofilament proteins, or myelin basic protein. The rosette formation accompanied a strikingly polarized and overlapped deposition of ECM components including tenascin-carrying HNK-1 epitopes, laminin, type IV collagen, heparan, and chondroitin sulfate proteoglycans. Immunoblotting analyses showed that laminin B1 and B2 chains were constitutively expressed, whereas a fully assembled form of laminin and type IV collagen appeared only after spheroid development, suggesting that these ECM components play a morphogenetically important role in rosette formation. Close similarities between these rosettes and the neural tube of humans and experimental animals in the morphogenetic process and ECM formation lead us to propose that the PA-1/NR spheroids provide an in vitro model for the study of the earliest stage of human neurogenesis.

Antibodies↗
PubMed1991

Genetic identification of pregnancies responsible for choriocarcinomas after multiple pregnancies by restriction fragment length polymorphism analysis.

The pregnancies responsible for two cases of choriocarcinomas were determined by the restriction fragment length polymorphism of human leukocyte antigen-DQ genes in the tumors and leukocytes from the patients, their husbands, and their children. The first case was preceded by three normal pregnancies, and the second case was preceded by two normal pregnancies and a complete hydatidiform mole. Comparison of the restriction fragment length polymorphism patterns revealed that the first case of choriocarcinoma carried the parental genome and originated from the third normal pregnancy, whereas the second case was of androgenetic origin from the complete mole. By choosing an appropriate probe (or probes), restriction fragment length polymorphism analysis is shown to be a useful method for identification of the pregnancy responsible for choriocarcinoma.

Adult↗
PubMed1991

A newly developed in vitro chemosensitivity test (nuclear damage assay): application to ovarian cancer.

With a newly developed in vitro chemosensitivity test based on the morphological changes of nuclear damage (nuclear damage assay) described here, we were able to screen currently available anticancer drugs within 24 hr with a 100% success rate. In preclinical chemotherapy using four human ovarian epithelial tumor cell lines and their xenografts in nude mice, the in vitro/in vivo response (sensitive/sensitive and resistant/resistant) rate was 94%. The nuclear damage assay was used to determine the chemosensitivity in 49 patients (60 assays) with ovarian cancer. The response rate of the 13 patients with measurable tumors, 9 of whom showed resistance to CAP (cyclophosphamide, adriamycin, and cisplatin) therapy, was 46% when the patients were given various combination chemotherapy protocols consisting of more than one active agent selected from group A and B agents by the nuclear damage assay. The newly developed in vitro chemosensitivity test proved to be useful when selecting a second-line combination chemotherapy for patients with CAP-resistant ovarian cancer.

Animals↗
PubMed1991

Characterization of a 54 kDa, alpha 1-antitrypsin-like protein isolated from ascitic fluid of an endometrial cancer patient.

A protein factor which stimulated [3H]thymidine uptake into free hepatocytes prepared from normal mouse liver was detected in the ascitic fluid of gynecological cancer patients. The factor was subsequently further purified from the ascitic fluid of an endometrial cancer patient by DEAE-Sephacel, Sephadex G-150 and Phenyl-Sepharose CL-4B column chromatographies, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed a single protein band of 54,000 Da, designated tentatively as 54K ascitic protein (54K-AP). 54K-AP was similar to human alpha 1-antitrypsin (alpha 1-AT) in terms of SDS-PAGE and immunological behavior, but was slightly different in terms of amino acid sequence and isoelectric point. Although 54K-AP inhibited the activities of bovine trypsin and alpha-chymotrypsin as did human alpha 1-AT, 54K-AP inhibited the plasminogen activator released from human endometrial cancer Ishikawa cells more efficiently than alpha 1-AT. Because, in contrast to normal serum, the serum from the endometrial cancer patients stimulated [3H]thymidine uptake into hepatocytes, the possibility arises that 54K-AP could be produced by the cancer host as a defence mechanism against the cancer.

Amino Acid Sequence↗
PubMed1991

A study of adult T-cell leukemia virus (ATLV) infection in the field of obstetrics: its epidemiology, vertical transmission and familial clustering.

Nine hundred and seventy-one healthy individuals in Iwate Prefecture, 659 pregnant women in Ishigaki Island, 487 pregnant women in Chiba Prefecture and 108 familial members of the ATLA-Ab-positive pregnant women (pregnant carrier women) were tested for ATLA-Ab by the PA, EIA and WB tests. 1) The rate of agreement of EIA with the PA test was 88.4% and there were no false negative sera by both examinations. These results indicate the both tests are available for mass screening. 2) In Iwate and Chiba Prefectures, the ATLA-Ab-positive rates of pregnant women were 5.3 and 0.6%, respectively. In addition, the incidences for healthy individuals ranged from 5.3 to 21.1% by age in Iwate Prefecture. Thus, Iwate Prefecture was found to equal Ishigaki Island (7.1%) in ATLA-Ab detection rates. 3) Forty-five (41.7%) out of 108 familial members of 15 pregnant carrier women were found to be seropositive for ATLA-Ab, which confirms a certain familial clustering of ATLV.

Adolescent↗
PubMed1991

[Changes in various differentiation-related markers after differentiation induction of a pluripotent human embryonal carcinoma (EC) cell line by hexamethylene bisacetamide].

A pluripotent human EC cell line (NEC14) could be induced to morphologically differentiate by treatment with 10(-2) M HMBA for 3 days in vitro. The changes in various differentiation-related markers (cell surface antigens, lectin binding sites, intermediate filaments, secreted products and extracellular matrix proteins) after induction of differentiation were examined in order to clarify the differentiation lineage. The results were as follows: 1) The most conspicuous changes in cell surface antigens after differentiation were the expression of major human histocompatibility antigens (HLA-A,B,C) and the changes in stage specific embryonic antigens (SSEA-1-/SSEA-3(+)----SSEA-1+/SSEA-3-). 2) Vimentin, mesenchymal intermediate filament, was only detected after the differentiation. 3) Tenascin, an extracellular matrix protein produced in mesenchymal cells, was produced after the differentiation. These results indicate that HMBA can induce NEC14 cells to differentiate into mesenchymal elements of embryonal mesoderm.

Acetamides↗
PubMed1991

[Transforming activity of human papillomavirus 16 DNA].

A HPV16DNA integrated in a human cancer cell line of the uterine cervix (QG-U) was isolated and cloned. Three kinds of cells (mouse Balb/3T3, Detroit 551 and human keratinocyte) were co-transfected with HPV16DNA and neo DNA with calcium phosphate co-precipitates. Selection of the Transformants and their characteristics were examined. Transformants of mouse Balb/3T3 cells were able to be obtained about 2 weeks after co-transfection. HPV16DNA was integrated in the transformants. The most characteristic change observed in the transformants was the ability to proliferate in serum-free medium. In contrast, two kinds of human diploid cells (Detroit 551 and human keratinocyte) were not transformed by transfection, and ceased growing at almost the same time as nontransfected cells. These results indicate that HPV-DNA transformants are easily selected in cell lines rodents but selection of transformants from human diploid cells is relatively difficult.

Animals↗
PubMed1991

[Analysis of prognostic factors in high risk gestational trophoblastic disease with respect to remission and recurrence].

Sixty-nine patients with high risk gestational trophoblastic disease (excluding invasive mole) were treated at Chiba University from 1973 to 1988. The clinical features and results of treatment which influenced remission and recurrence in these high risk patients were analyzed statistically. The factors analyzed were (1) the height of pretreatment urinary hCG titer, (2) the type of antecedent pregnancy, (3) the time interval from pregnancy to treatment, (4) the metastatic site, (5) age, (6) the type of chemotherapy, (7) the time of operation and (8) the number of additional chemotherapy courses. With respect to the remission rate and the metastatic site, the type of chemotherapy was statistically significant. In addition, the factors related to the time of operation were significant in relation to recurrence.

Adult↗
PubMed1991

[Fundamental studies on differentiation inducers using a human embryonal carcinoma model].

A human embryonal carcinoma (EC) cell line, NEC14, was pluripotent and the tumors formed in nude mice contained differentiated somatic and extra-embryonic elements in addition to EC. The NEC14 cells could be induced to differentiate with 5 differentiation inducers in vitro, and N,N'-hexamethylene bisacetamide (HMBA) showed the most potent differentiator induction among them. All of the NEC14 cells were morphologically differentiated when exposed to 10(-2) M HMBA for 3 days. The differentiated derivatives ceased to proliferate in vitro and became non-tumorigenic in nude mouse. Several differentiation markers appeared in the differentiated derivatives. When the tumor-bearing nude mice were injected intraperitoneally with HMBA (10mg, twice a week), the tumor growth was inhibited. These results show that human EC is a useful model of differentiation-induction in cancer therapy.

Acetamides↗