Search PubMed⌕ Search

Biomedical subjects

Y Terashima

Publications and source records attributed to Y Terashima.

At least 109 records · Page 6Linked to original sources

[Effect of chemotherapy on the prognosis of ovarian cancer].

Through the collaboration of 22 institutions nationwide, a total of 1,185 cases of ovarian cancer treated between January, 1980 and December, 1987, were investigated as to their prognosis from the aspect of the chemotherapeutic effect. (1) An excellent effect of the remission-induction chemotherapy was observed in a group receiving combination therapy with CDDP as the main ingredient. In particular a significant effect was seen in stages III and IV. In addition, the effect on the remaining tumors by diameter also showed a significant difference in cases of tumors of not less than 2 cm in diameter. (2) As to the effect on histological types, a comparison in stage III showed a favourable effect on endometroid, serous and mucinous adenocarcinomas, while no effect was observed in clear cell adenocarcinoma. (3) The effect of the remission induction chemotherapy did not always give rise to an improvement in the long-term prognosis of ovarian cancer, and the establishment of a therapeutic method aimed at the prevention of recurrence was desired. (4) To improve the long-term prognosis, intermittent (or cyclic) chemotherapy with CDDP as the main ingredient was found to be very effective, but maintenance chemotherapy with orally administered of 5-Fluorouracil or Tegaful was not effective. (5) The effect of the conventional immunotherapy was not observed at all.

Adenocarcinoma↗

[Genetic alterations in the genesis and development of ovarian cancer].

Genetic alterations of various cancers have been clarified by recent development of molecular biology. Multiple genetic alterations occur through the development of cancer. Both activation of proto-oncogenes and inactivation of tumor suppressor genes are important for the development of cancer. Alterations of oncogenes such as K-ras, c-erbB-2/HER-2/neu and c-myc, and those of tumor suppressor genes such as p53, RB and DCC have been reported in ovarian cancer. Allelic losses of the specific chromosomes, which suggest the existence of tumor suppressor genes on those chromosomes, also have been reported in ovarian cancer. Further studies on genetic alterations of ovarian cancer will clarify the mechanisms for the development of ovarian cancer and also will develop new methods for prevention, diagnosis and treatment in clinical.

Female↗

[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↗

[A group study on prognosis of ovarian cancer in Japan].

An assessment has been made, with the cooperation of 22 institutes, of 1,185 cases of ovarian cancer as subjects who were treated in the period from January, 1980, to December, 1987. As a result, (1) As for distribution by clinical staging at the initial examination, the cases in Stage III were the most numerous, followed by those in Stage I, and if classified according to the histological type, serous cystadenocarcinoma was the most frequently observed in Stage III, and undifferentiated and unclassified carcinomata were observed in Stages III and IV. (2) In the examination of prognostic factors, it was confirmed that the clinical stage, histological type and diameter of the remaining tumor after the initial operation were important factors. (3) A significant difference was observed between the grade of histomorphological differentiation and prognosis, the difference was chiefly due to the deviated distribution of clinical staging in each group of differentiation. (4) A favorable trend was observed in the prognosis by patient's age toward the younger layer. (5) When the starting time of the therapy is considered, a trend toward improvement has been seen year by year, and it is considered that the beneficial effect of chemotherapy with CDDP contributes to this.

Adult↗

[Phase III study of DWA2114R for ovarian cancer].

A phase III study of DWA2114R for ovarian cancer was carried out in CAP regimen by a cooperative study group consisting of 42 institutions. The response rate of 31 cases for DWA2114R regimen was 38.7% and out of 30 cases for CDDP regimen 46.7%. No significant differences were observed between the two regimens in efficacy, adverse reactions, and abnormalities in laboratory findings except for red blood cell and creatinine clearance, but the incidence of thrombocytopenia was likely to be lower in DWA2114R than in CDDP regimen. Since the DWA2114R regimen did not need hydration, or require diuretics, DWA2114R is more useful in the treatment of ovarian cancer than cisplatin.

Adult↗

[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↗

[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↗

[A phase II clinical study of cis-diammine glycolato platinum, 254-S, for cervical cancer of the uterus].

A phase II clinical study of 254-S, a new anticancer platinum complex, for cervical cancer was conducted by the 254-S Cervical Cancer Study Group consisting of 10 institutions. 254-S was administered at 80 mg/m2 by intravenous drip infusion and this administration was repeated at least 2 times at 4-week intervals, in principle. Forty of 45 patients registered, were eligible and 38 were evaluable for tumor response (complete cases). Complete response (CR) and partial response (PR) were obtained in 4 (10.5%) and 9 patients (23.7%), respectively, for a 34.2% response rate. Against squamous cell carcinoma, a 38.2% response rate (4 CR and 9 PR in 34 patients) was obtained. The response rate obtained in patients with no prior chemotherapy was 40.0% (2 CR and 8 PR in 25 patients), while that in patients with prior chemotherapy was 23.1% (2 CR and 1 PR in 13 patients). Major toxic effects observed were hematotoxicity, including thrombocytopenia (35.1%), leukopenia (73.0%), anemia (75.7%), gastrointestinal toxicity such as nausea and vomiting (83.8%) and anorexia (83.8%). Nephrotoxicity observed was in the form of an elevation of serum creatinine with an incidence of 2.7% and a decrease in creatinine clearance with an incidence of 21.7%. In comparison with the results obtained in the phase II clinical study for gynecological cancers in which 254-S was administered at 100 mg/m2, the response rate obtained in this study was slightly lower but thrombocytopenia and leukopenia observed were less frequent and milder. Based on these results, it was concluded that 254-S is a very useful anticancer agent for the treatment of cervical cancer.

Adenocarcinoma↗

Allelic loss on chromosome 17p and p53 mutations in human endometrial carcinoma of the uterus.

To understand the involvement of allelic losses and inactivation of tumor suppressor genes for the development of endometrial carcinoma of the uterus (EC), 24 cases of EC were examined for loss of heterozygosity (LOH) using a total of 57 polymorphic DNA markers covering all 23 pairs of chromosomes. LOH was observed at 27 loci on 10 different chromosomes, i.e., chromosomes 1, 3, 6, 11, 13, 15, 17, 18, 20, and 21, but was not detected at loci on chromosomes 4, 5, 7, 9, 10, 12, 14, 16, and X. It was observed only in seven of 24 cases, and the other 19 cases did not show LOH at any loci examined, including five cases of tumors with a high proportion of adenomatous hyperplasia. Among seven tumors with LOH at one or more loci, five tumors showed LOH at loci on the short arm of chromosome 17. Furthermore, mutations of the p53 gene, which is located on the short arm of chromosome 17, were detected in three of these 24 tumors by a polymerase chain reaction-single strand conformation polymorphism analysis and subsequent DNA sequencing. In two of these three tumors, p53 mutations were accompanied by the loss of wild-type p53 alleles. These results suggest that inactivation of the p53 gene is involved in the development of EC as in the case of several other types of human cancers.

Alleles↗

Frequent allelic losses and mutations of the p53 gene in human ovarian cancer.

The p53 gene on chromosome 17p is considered to be a tumor suppressor gene, and frequent mutations of the p53 gene have been found in a wide variety of human cancers. We examined 31 ovarian cancers for allelic losses and mutations of the p53 gene by polymerase chain reaction-single strand conformation polymorphism analysis as well as restriction fragment length polymorphism analysis. Allelic loss of the p53 gene was detected in 16 of 20 cases (80%). Mutations were detected in 9 of 31 cases (29%): 2 cases in exon 4; 5 cases in exons 5-6; and 2 cases in exons 7-8. In 8 of 9 cases, p53 mutations were accompanied by losses of the normal allele. These alterations of the p53 gene were commonly detected from stage I to stage IV. These results suggest that alterations of the p53 gene play an important role in the development of human ovarian cancers.

Base Sequence↗

Serum levels of inhibin in maternal and umbilical blood during pregnancy.

Inhibin levels were measured by a double antibody heterologous radioimmunoassay in the peripheral serum of 75 pregnant women throughout gestation and in serum from the umbilical vein and artery, which was obtained at the time of delivery. For reference, samples were obtained from 20 nonpregnant women in the early (days 0 to 3), mid (days 4 to 8), and late (days 9 to 14) luteal or follicular phase. Maternal serum levels of inhibin (mean +/- SEM) in early (6 to 12 weeks) gestation (36.4 +/- 2.6 U/ml, n = 36) were significantly (p less than 0.01) higher than those in serum from nonpregnant women in the mid (23.9 +/- 2.5 U/ml, n = 19) or late (11.3 +/- 0.6 U/ml, n = 19) luteal phase. Inhibin levels in maternal serum fell to 15.9 +/- 1.4 U/ml (n = 24) in mid (14 to 20 weeks) gestation and then gradually increased during late (21 to 40 weeks) gestation to peak levels of 49.4 +/- 5.1 U/ml (n = 9) at 36 to 37 weeks. Inhibin levels declined in parallel with human chorionic gonadotropin concentrations during the first trimester (r = 0.587 at p less than 0.01). Significant positive correlations (p less than 0.001) were observed between serum levels of inhibin and 17 beta-estradiol (r = 0.560), progesterone (r = 0.648), and human placental lactogen (r = 0.715) during mid and late (20 to 40 weeks) gestation. Inhibin levels in umbilical vein serum (38.5 +/- 1.3 U/ml, n = 5) were not different from those in umbilical artery serum (39.4 +/- 3.6 U/ml) but were significantly (p less than 0.01) lower than those in maternal serum (50.9 +/- 5.3 U/ml), which was obtained at the time of delivery. By day 5 of puerperium, serum levels of inhibin in the maternal vein were extremely low (2.3 +/- 0.1 U/ml, n = 7); these levels were nearly one fifth lower than follicular phase levels of 10.9 +/- 3.4 U/ml (n = 38). We propose that maternal inhibin in early gestation is secreted from the corpus luteum of pregnancy but that increasing inhibin levels during mid and late gestation result from inhibin that is produced by the placenta. The lack of an umbilical arterial-venous gradient for inhibin and the higher levels of inhibin in maternal serum argue against a fetal source of inhibin in the maternal circulation. The physiologic function of inhibin that is produced by the corpus luteum and by the placenta remains to be determined.

Female↗

Human ovarian cancer cell lines resistant to cisplatin, doxorubicin, and L-phenylalanine mustard are sensitive to delta 7-prostaglandin A1 and delta 12-prostaglandin J2.

The antitumor activity of delta 7-prostaglandin A1 (delta 7-PGA1) or delta 12-prostaglandin J2 (delta 12-PGJ2) on human ovarian cancer cell lines resistant to cisplatin (CDDP), doxorubicin (ADR), and L-phenylalanine mustard (l-PAM) was studied in vitro. A2780AD, A2780 (parent cells of A2780AD), 2008DDP, and 2008 cells (parent cells of 2008DDP) were used. The antitumor activities of the drugs were defined with 50% inhibitory concentration (IC50) estimated from growth inhibition curves, which were obtained by an indirect colorimetric method. Drug-resistance ratios obtained from IC50 values, by comparing A2780AD and A2780 cells, were 62.5 for ADR, 4.6 for CDDP, 4.9 for l-PAM, 1.5 for delta 7-PGA1, and 1.8 for delta 12-PGJ2. Those obtained by comparing 2008DDP and 2008 cells were 1.1 for ADR, 16.0 for CDDP, 2.9 for l-PAM, 2.3 for delta 7-PGA1, and 3.2 for delta 12-PGJ2. Thus some human ovarian cancer cells resistant to ADR, CDDP, and l-PAM remain sensitive to antitumor PGs.

Antineoplastic Agents↗

An evaluation of ovarian carcinoma-associated antigen defined by murine monoclonal antibody CF511 in sera from patients with ovarian carcinoma.

Murine monoclonal antibody CF511, raised against human ovarian clear cell carcinoma, detects a glycoprotein (Mr 600 kDa) called CF511 antigen which is elevated in the serum of many patients with ovarian carcinoma. A competitive enzyme-linked immunosorbent assay was developed to detect CF511 antigen in human serum and used to detected CF511 antigen in subjects with ovarian carcinoma and other diseases. No raised levels (less than 18 unit (U) ml-1) of the antigen were found in the serum of 220 normal individuals or of patients with germ cell tumours (n = 6), granulosa theca cell tumour (n = 1), gastric carcinomas (n = 10) and colo-rectal carcinomas (n = 8). Raised serum levels of CF511 antigen were found in 6/46 patients (13.0%) with benign gynaecological tumours (including endometriosis or ovarian cyst), in 5/7 patients (71.4%) with breast carcinoma and 16/21 (76.2%) lung carcinoma patients. In patients with ovarian carcinoma, 42.3% (11/26) of stage I and II, and 96.0% (24/25) of stage III and IV had levels of greater than or equal to 18 U ml-1. In all patients with serial determination of CF511 antigen levels before and after the surgery, the levels of antigen correlated with the clinical course of disease. Determination of CF511 antigen levels may be useful for detection of ovarian carcinoma as well as lung and breast carcinomas and for monitoring progress of disease and response to therapy.

Antibodies, Monoclonal↗

Resistance to anticancer drugs in NIH3T3 cells transfected with c-myc and/or c-H-ras genes.

NIH3T3 cells transfected with c-H-ras and/or c-myc genes were examined for differences in drug sensitivity. The five transfectants used were N8, NIH3T3-nm-1, pT22-3-nm-2, pP1-4 and pT22-3. They were transfected with pKOneo alone, pKOneo and c-myc, pKOneo and c-myc plus activated c-H-ras, normal c-H-ras and activated c-H-ras genes, respectively. The IC50s of cisplatin, 4-hydroperoxycyclophosphamide, adriamycin, melphalan, and CPT-11 were significantly higher for NIH3T3-nm-1 abd pT22-3-nm-2 than for the parental NIH3T3 and N8 cells. Transfection with normal and activated C-H-ras oncogenes only led to increases in the IC50s of alkylating agents. There was no significant difference between the IC50s of N8 and those of NIH3T3 parental cells to any of these anticancer agents. These results strongly suggest that the expression of the c-myc gene plays a role in the acquisition of drug resistance. The c-myc gene may therefore provide us with an important clue in determining the mechanism of drug resistance.

Animals↗

Effect of estrogen and progesterone on the growth of human ovarian dysgerminoma heterotransplanted to athymic nude mice.

The effects of estrogen and progesterone on the growth of dysgerminoma of ovary heterotransplanted to ovariectomized athymic nude mice (OVX-NUs) were examined. OVX-NUs were divided into 6 groups and a subcutaneous injection of either 1 micrograms or 10 micrograms of estradiol (E1 or E10), 0.1 mg or 1 mg of progesterone (P0.1 or P1), or a combination treatment of E1 and P1 (E1 + P1), or sesame oil as a vehicle control (oil) was given every other day for 2 weeks. Tumor size was recorded every day and the volume doubling time (VDT) was calculated. Tumor bearing OVX-NUs were killed on day 21 and tumor tissue was excised for retransplantation, histological examination and cytosol receptor assay. E10 treatment accelerated tumor growth and shortened VDT to 25 hours compared to 44 hours for the control group. P1 treatment delayed the tumor growth (VDT: 71 hrs) and E1 + P1 treatment further inhibited it (VDT: 197 hrs). E1 or P0.1 did not have any effect on the tumor growth. The levels of both the estrogen receptor (ER) and progesterone receptor (PR) of the original tumor were 5 fmol/mg protein, respectively. Hormone treatment had no remarkable effect, except for a significant increase in PR after estrogen treatment and this result seems to be responsible for the enhanced inhibitory effect of E + P on tumor growth. These effects were also observed histologically. In conclusion, the dysgerminoma used in this study was sex steroid hormone dependent and P alone or in combination with E could be a choice for the treatment of such ovarian dysgerminoma.

Analysis of Variance↗

Risk determination in cases with an extra minute chromosome: prenatal diagnosis.

The interpretation of an extra minute chromosome (EMC) detected in utero presents both diagnostic and prognostic problems. Two EMC cases are presented and a flow-chart guideline is proposed for the determination of developmental risk. A prenatally detected EMC was familially inherited through a normal phenotype father. The pregnancy was continued and a normal baby boy was delivered. At one year his development was within normal ranges. The second EMC case was a mentally retarded girl examined at 4 years and 7 months of age. The EMC was identified with a combination of various staining techniques to be an inversion duplication (15). The importance of differential diagnosis of EMCs by DA/DAPI staining is emphasized.

Adult↗

Study of macrophages in prostatic fluid from nonbacterial prostatitis patients. V. Relation between activation of macrophages and stage of prostatitis.

Relationship between activation of macrophages in prostatic fluid and stage of nonbacterial prostatitis was studied by observing the rate of adherence of leukocytes, percentage of macrophages among adherent leukocytes and presence of spreading of macrophages. As a result, it was found that macrophages in the early stage of NBP were more activated than macrophages in the chronic stage.

Adult↗