Biomedical subjects

K Ohama

Publications and source records attributed to K Ohama.

138 records · Page 8Linked to original sources

PubMedDate not supplied

Cyclin D1 overexpression and p53 mutation status in epithelial ovarian cancer.

OBJECTIVE: To examine the cyclin D1 mRNA expression level in ovarian tumor samples as compared with normal ovaries and to determine the relationship between cyclin D1 overexpression and p53 mutation status in ovarian tumors. METHODS: mRNA was isolated and cDNA was prepared from 27 epithelial ovarian tumors (3 tumors of low malignant potential (LMP) and 24 cancers) and 6 normal ovaries. The cyclin D1 sequences were amplified by using a thermal cycler in parallel with the beta-tubulin gene as an internal control. The cyclin D1 mRNA expression level relative to beta-tubulin was determined by 32P phosphoimager analysis. To confirm the overexpression of the cyclin D1 protein in ovarian tumor cells, immunostaining was performed. The p53 gene mutation status was examined by direct cDNA sequencing. RESULTS: mRNA levels of cyclin D1 were significantly higher in 21 (78%) of the 27 ovarian tumors than in normal ovaries. Cyclin D1 overexpression was detected in ovarian LMP tumors as well as in ovarian cancer cases. Positive immunostaining of cyclin D1 protein was observed in 10 of 18 (56%) ovarian tumors examined. p53 mutations were found in 11 (61%) of 18 ovarian tumors. Of 11 ovarian tumor cases with p53 mutations, 5 showed overexpression of cyclin D1. All 7 ovarian tumor cases without p53 mutations showed significant cyclin D1 mRNA overexpression. CONCLUSION: Cyclin D1 overexpression seems to be an early genetic event in ovarian tumor development. Although p53 may be one of the proteins whose function regulates the expression of G1 cyclins, ovarian tumors with no p53 mutation consistently showed cyclin D1 overexpression. Cyclin D1 overexpression may play an important role in the tumorigenesis of epithelial ovarian tumors.

Adenocarcinoma↗

PubMedDate not supplied

Expression of the protease inhibitor antileukoprotease and the serine protease stratum corneum chymotryptic enzyme (SCCE) is coordinated in ovarian tumors.

We have previously reported that the stratum corneum chymotryptic enzyme (SCCE) is overexpressed in ovarian cancers and that SCCE has potential as a useful marker and/or a therapeutic target for ovarian carcinoma. Antileukoprotease (ALP) has been shown to be a specific inhibitor of SCCE. The objective of this study was to investigate the potential cotranscription and overexpression of ALP in carcinoma of the ovary. The expression of ALP transcript was evaluated by Northern blot hybridization and by semiquantitative polymerase chain reaction (PCR) technique. The presence of the ALP protein in ovarian tumor cells was evaluated by immunohistochemistry. Northern blot hybridization showed that the ALP transcript was abundant in ovarian carcinomas but was not detected in the normal ovary. Semi-quantitative PCR examination revealed that the mRNA level of ALP was significantly elevated in low-malignant-potential tumors and in ovarian carcinomas compared with that in normal ovaries (P < 0.01). There was significant positive correlation between SCCE and ALP mRNA overexpression status in ovarian tumor cases (P < 0.01). Immunohistochemical expression of ALP protein was observed in ovarian tumor cells, whereas little or no staining was observed in normal ovarian surface epithelium. Like SCCE, ALP is highly overexpressed in ovarian tumor cells, which begs the question of whether it remains an effective inhibitor of SCCE or whether it is discordant in time or space and is ineffective as an inhibitor of the SCCE enzyme.

Adenocarcinoma, Clear Cell↗

PubMedDate not supplied

Villoglandular papillary adenocarcinoma of the uterine cervix responding to neoadjuvant chemotherapy with docetaxel and cisplatin: a case report.

Villoglandular papillary adenocarcinoma (VGPA) of the uterine cervix is a rare neoplasm, and its treatment has rarely been reported. We report a patient with VGPA stage IIA responding to neoadjuvant chemotherapy with docetaxel (60 mg/m2 as an intravenous infusion) and cisplatin (70 mg/m2 as an intra-arterial infusion). At 3 weeks after completing one course of this regimen, the tumor size was reduced from 5.3 x 4.0 cm to 2.0 x 2.0 cm (81.1% reduction), revealed by computed tomography. Accordingly, the patient underwent radical hysterectomy, and there have been no signs of recurrence. Thus, the combination of docetaxel and cisplatin is suggested to be useful for neoadjuvant chemotherapy of cervical adenocarcinoma.

Adenocarcinoma, Papillary↗

PubMedDate not supplied

Telomerase activity in body cavity fluid and peritoneal washings in uterine and ovarian cancer.

The telomeric repeat amplification protocol (TRAP) assay was used to measure telomerase activity in body cavity fluid from 10 ovarian cancer patients (ascites 9; pleural fluid, 1), ascites and peritoneal washings from eight uterine corpus cancer patients, and ascites from one with cancer of the uterine cervix. Telomerase activity was observed in five of six (83.3%) samples with positive cytology, one of four (25%) samples with suspicious cytology and one of nine (11.1%) samples with negative cytology. A high level of activity was observed in samples containing large numbers of blood-cell components, which could be removed without inactivating the telomerase by treating the samples with Nycodenz (N,N1-Bis (2,3-dihydroxypropyl)-5-[N-(2,3-dihydroxypropyl) acetamide] 2,4,6-triiodo-isophtalamide). In two patients with ovarian cancer treated with anticancer drugs, 5 and 7 days after treatment, intracellular vacuoles and multinucleation were observed in ascites tumour cells, and telomerase activity decreased. At 14 to 21 days after treatment, the ascites tumour cell morphology was the same as before treatment, and telomerase activity rose once again. The TRAP assay is a sensitive method of detecting telomerase in cytological material and may provide a useful adjunct to cytological diagnosis.

Adult↗

PubMedDate not supplied

Prospective analysis of DNA ploidy, proliferative index and epidermal growth factor receptor as prognostic factors for pretreated uterine cancer.

For the purpose of identifying prognostic factors for pretreated uterine cancer, DNA ploidy, proliferative index (P.I.) and epidermal growth factor receptor (EGFR) expression were analyzed in a large prospective series of 76 cervical cancer and 64 endometrial cancer patients observed for 5 years or more (median 76 months). The frequency of aneuploid cells was 62.0% (44/71) in cervical cancer and 16.7% (10/60) in endometrial cancer. There was no association between DNA ploidy and the clinicopathological findings without clinical stage, in which aneuploid cervical and endometrial cancers were significantly more common among advanced tumors (cervical: p<0. 05, endometrial: p<0.01). The P.I. was significantly higher in the patients with aneuploid tumors (cervical: p<0.05, endometrial p<0. 01). EGFR expression was detected in 56.6% (30/53) in cervical cancer and 59.6% (34/57) in endometrial cancer, and the mean EGFR level was 17.8+/-37.7 and 9.5+/-42.5 fmol/mg. protein, respectively. There was no correlation between EGFR expression and DNA ploidy, P.I. and clinicopathological findings analyzed. Five-year survival rate in patients with aneuploid tumors tended to have a worse outcome in cervical cancer cases (p=0.1003, log-rank test), and was significantly worse in endometrial cancer (p=0.0048, log-rank test). No significant relationship was noted between P.I., EGFR expression and 5-year survival. Cox multivariate analysis showed that DNA ploidy, P.I., and EGFR expression are not association with the risk of death. Our data showed neither DNA ploidy, P.I. nor EGFR expression were independent prognostic factors for pretreated uterine cancer.

Adenocarcinoma↗

PubMedDate not supplied

Differential expression of matrix metalloprotease-7 in each component of uterine carcinosarcoma.

The aim of this study was to investigate the expression of matrix metalloprotease-7 (MMP-7) in each component of uterine carcinosarcoma. Surgical specimens of primary tumors of uterine carcinosarcomas were obtained from 13 patients. The carcinomatous component consisted of adenocarcinoma with or without squamous differentiation. The sarcomatous component consisted of spindle cell sarcoma, chondrosarcoma and rhabdomyosarcoma, either alone or in combination. The immunohistochemical expression of MMP-7 protein was examined using the avidin-biotin peroxidase complex technique employing the anti-MMP-7 monoclonal antibody. Expression of MMP-7 protein was detected in 9 (69.2%) of 13 adenocarcinoma components, while no staining was observed in any of the sarcomatous components examined. There was a statistically significant difference of the positive rate for MMP-7 between epithelial components and sarcomatous components of uterine carcinosarcoma (p<0.01). In some cases, MMP-7 was abundantly expressed at the invasive front of adenocarcinomas. It is concluded that MMP-7 protein is differentially expressed between the carcinomatous component and the sarcomatous component of uterine carcinosarcoma. Each component of carcinosarcoma may have its own potential for invasion and metastasis. MMP-7 may contribute to the invasive nature or growth capacity of the carcinomatous component of uterine carcinosarcoma, while it may not have a relation to that of the sarcomatous components.

Adenocarcinoma↗

PubMedDate not supplied

Radiotherapy combined with transcatheter arterial infusion of cisplatin versus oral fluoropyrimidine anticancer agent for locally advanced carcinoma of the uterine cervix: a prospective follow-up study.

We randomized patients with locally advanced cervical cancer to receive radiotherapy combined with transcatheter arterial infusion (TAI) of cisplatin or oral fluoropyrimidine anticancer agents, and compared the prognosis by a prospective follow-up study. Sixty patients were studied who completed their planned radiation therapy with chemotherapy at the Department of Obstetrics and Gynecology of Hiroshima University Hospital between January 1991 and December 1998. Patients were randomly assigned to receive (A) radiotherapy with TAI of 120 mg/body cisplatin twice a month at the interval of 4 weeks or (B) radiotherapy with 200 mg/day oral 5-FU or UFT every day. In both groups, radiotherapy is routinely 50 Gy of external beam irradiation to the whole pelvis and 18-20 Gy (point A dose) of intracavitary irradiation using a remote after loading system (RALS). Serious adverse reactions interfering with treatment did not appear in either group. The effective histologic response was 28/32 (87.5%) in group A and 25/28 (89.3%) in group B. The median follow-up period were 28.3 months and 25.4 months in group A and B, respectively. There was no significant difference in the overall survival and disease-free survival rates for all patients, clinical stage III and squamous cell carcinoma. We could not conclude that radiotherapy with TAI of cisplatin achieved superior therapeutic efficacy in locally advanced cervical cancer. To improve the therapeutic effects, it is important to establish a new cisplatin-containing chemoradiotherapy regimen.

Adenocarcinoma↗

PubMedDate not supplied

Semiquantitative analysis of telomerase activity in cervical cancer and precancerous lesions.

We investigated telomerase expression in cervical lesions and its diagnostic value for cervical cancer and the precancerous lesions. The subjects were 100 women who underwent cervical biopsy, comprising 16 normal cervix, 61 cervical intraepithelial neoplasia (CIN) and 23 invasive cervical cancer. Telomerase activity was detected by the telomerase repeat amplification protocol using a non-radioisotope system, and quantitated using a DNA image analyzing system. Telomerase was detected at 18.8% (3/16) in normal cervix, 32. 0% (8/25) in CIN I, 50.0% (3/6) in CIN II, 60.0% (18/30) in CIN III, and 91.3% (21/23) in invasive cervical cancer. Semiquantitation of telomerase activity was significantly higher in the subjects with invasive cancer than in those with CIN or a normal cervix (p<0.05). However, telomerase activity was not significantly different between the grades of CIN. Telomerase was detected in subjects with CIN, suggesting that telomerase expression is an early event in cervical carcinogenesis. Quantitation of telomerase activity may be helpful for the diagnosis of cervical cancer.

Biopsy↗

PubMedDate not supplied

Overexpression of testisin, a serine protease expressed by testicular germ cells, in epithelial ovarian tumor cells.

OBJECTIVE: In a continued effort to identify and characterize secreted proteases that are overexpressed in ovarian carcinomas, we discovered the testisin protease as such a candidate. When this discovery was originally made, no data existed in the literature or in the GenBank database that identified such a gene. Our main objective was to determine whether this gene was overexpressed exclusively in ovarian tumor tissues compared with normal ovary and whether it was expressed in any other normal tissues. METHODS: mRNA was isolated and cDNA was prepared from 34 ovarian tumors (four adenomas, three low malignant potential tumors, and 27 carcinomas) and seven normal ovaries. The testisin mRNA expression level relative to internal control, beta-tubulin, was determined by Northern blot analysis and semiquantitative polymerase chain reaction (PCR). RESULTS: Northern blot hybridization showed that the testisin transcript was abundant in ovarian carcinoma but was not detected in normal ovary. On examination of Northern blots from normal fetal and adult tissues, only adult testis showed abundant transcripts of testisin. Semiquantitative PCR examination showed that the testisin mRNA levels in ovarian tumors of low malignant potential and in ovarian carcinomas were significantly higher than in normal ovaries (P <.01). Testisin mRNA level in ovarian carcinomas was also significantly higher than in ovarian adenomas (P <.05). Testisin overexpression rates in advanced stage (stage 2 or 3) diseases were significantly higher than that in early stage diseases (stage 1) in ovarian carcinoma samples (P <.05). CONCLUSIONS: The induction of the testisin transcript might contribute to the development, progression, and invasive or metastatic capacity of ovarian carcinomas.

Adenoma↗

PubMedDate not supplied

Cyclin E mRNA overexpression in epithelial ovarian cancers: inverse correlation with p53 protein accumulation.

OBJECTIVE: We investigated the relationship between cyclin E mRNA overexpression and p53 protein accumulation in epithelial ovarian cancers. METHODS: mRNA was isolated and cDNA was prepared from 36 epithelial ovarian tumors (three adenomas, three low malignant potential tumors, and 30 carcinomas), and six normal ovaries. The cyclin E mRNA expression levels relative to an internal control, beta-tubulin, were determined by semiquantitative polymerase chain reaction (PCR). Cyclin E and p53 protein expression in ovarian cancer tissues were examined by immunohistochemistry using the same series of samples. Fisher exact test of significance and an unpaired t test were used for statistical analysis. RESULTS: Considerable levels of cyclin E mRNA were detected in all normal ovaries and ovarian tumor samples examined by semiquantitative PCR amplification. mRNA levels of cyclin E were significantly higher in nine of 30 (30%) ovarian cancers compared with those in normal ovaries. The immunohistochemical expression of cyclin E protein was confirmed in the nuclei of tumor cells in 13 of 30 (43%) ovarian cancers. p53 protein accumulation was detected in 12 of 30 (40%) ovarian cancers examined. There was a significant inverse correlation between cyclin E mRNA overexpression and p53 protein accumulation (P <.01, Fisher exact test). CONCLUSIONS: Cyclin E mRNA overexpression frequently occurs in ovarian cancers without p53 protein accumulation. Cyclin E might have an important effect on the development of a limited number of ovarian cancers.

Adenoma↗

PubMedDate not supplied

Adenovirus-mediated p16 gene transfer changes the sensitivity to taxanes and Vinca alkaloids of human ovarian cancer cells.

BACKGROUND: Deletions and point mutations of the p16 gene are detectable in more than 50% of ovarian cancer cells. In this study, we examined the effect of p16 gene transduction on the growth of ovarian cancer cells and on the effect of anti-cancer agents. MATERIALS AND METHODS: p16-null human ovarian cancer cell lines, SKOV-3 and OVCAR-5, were used in this study. We transduced the full-length human p16 gene using recombinant adenovirus (AxCA-hp16). RESULTS: The spontaneous growth of these cells was significantly inhibited by hp16 transduction. MTT assay revealed that AxCA-hp16 infection induced chemoresistance in both cell lines. Flow cytometric analysis revealed that only hp16 -transduced SKOV-3, were arrested at the G1-phase for 3 days whereas those infected with AxCA-mock and OVCAR-5 infected with both recombinant viruses did not. Western blot analysis showed increased microtubule-associated proteins 4 (MAP4) in both cell lines. CONCLUSION: These results suggest that in SKOV-3 cells, G1-arrest induced by p16-transduction prevents paclitaxel- and vindesine-induced cell death, and in OVCAR-5 cells, the other unknown mechanisms play a role of chemoresistance.

Adenoviridae↗

PubMedDate not supplied

Characteristic ultrasonographic appearance of the Krukenberg tumor.

We studied the value of ultrasonography in the differential diagnosis of Krukenberg tumors (N = 15) and primary ovarian cancers (N = 15) using the echo pattern of the tumor wall, solid component and cystic component. Fourteen of the 15 Krukenberg tumors had a clear tumor margin, an irregular hyperechoic solid pattern, and moth-eaten cyst formation. In contrast, the primary ovarian cancers had unclear tumor margins, an irregular hypoechoic solid pattern, clear cyst formation, papillary proliferation, and irregular thickness of the septum. These data suggest that Krukenberg tumors can be distinguished ultrasonographically from primary ovarian cancers.

Adult↗