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Biomedical subjects

Teruhiko Tamaya

Publications and source records attributed to Teruhiko Tamaya.

At least 19 recordsLinked to original sources
PubMed2007

Osteopontin in metastatic lesions as a prognostic marker in ovarian cancers.

Osteopontin (OPN) is expressed in various human cancers and associated with tumor progression, invasion and metastasis in many manners. The purpose of this study is to investigate the clinical significance of OPN expression in metastatic lesions of ovarian cancers, since the prognosis of the patients with peritoneal dissemination is extremely poor. In primary tumors and peritoneal metastatic lesions from 40 patients with stage III ovarian cancers, the protein levels of OPN and histoscores were determined by enzyme immunoassay and immunohistochemistry, respectively. Immunohistochemical staining revealed OPN was distributed in the cytoplasm and nuclear compartments of the cancer and stromal cells within and around the tumor. The OPN level was significantly (p < 0.05) increased in 32 of 40 metastatic lesions of ovarian cancers. The OPN increased cases identified by immunohistochemical staining were consistent with those identified by the sandwich immunoassay. The prognosis of the 32 patients with significant increase of OPN in ovarian cancers was extremely poor, whereas the 36-month survival rate of the 8 patients with no increase of OPN was 75%. Multivariate analysis revealed that the levels of OPN were independent predictors of prognosis from clinical characteristics (age, lesion size, histological types). OPN might be associated with peritoneal metastasis and its advancement, and that the OPN level in metastatic lesion may be a prognostic indicator in ovarian cancers.

Biomarkers↗
PubMed2007

Expression of protease activated receptor-2 related to angiogenesis in tumor advancement of uterine endometrial cancers.

Protease activated receptor-2 (PAR-2) is the second member of a novel family of G-protein coupled seven-transmembrane domain receptors. PAR-2 has been reported to be expressed in various tumors and play a vital role in the regulation of cancer cell growth. The purpose of this study was to clarify the roles of PAR-2 in the angiogenic pathway in uterine endometrial cancers. PAR-2 expression was analyzed in 61 uterine endometrial cancer and 15 normal endometrium tissue specimens. PAR-2 histoscores and mRNA levels were determined by immunohistochemistry and real-time RT-PCR, respectively. Microvessel counts were determined by immunohistochemistry for CD31 and factor VIII-related antigen. The localization of PAR-2 was dominant in the cancer cells of endometrial cancer tissues of all cases studied. PAR-2 histoscores highly correlated with PAR-2 mRNA levels in the same tissues (r=0.87, p<0.001). PAR-2 histoscores and mRNA levels both significantly increased in uterine endometrial cancers with clinical stages (I<II<III, p<0.001), dedifferentiation (G1<G2<G3, p<0.001) and myometrial invasion (A<B, p<0.001; B<C, p<0.05) in comparison to normal endometria. There were significant correlations between PAR-2 histoscores and mRNA levels with microvessel counts in uterine endometrial cancers. PAR-2 was upregulated during uterine endometrial cancer progression with dedifferentiation and myometrial invasion. Therefore, PAR-2 might work on tumor advancement of uterine endometrial cancers via angiogenic activity.

Adult↗
PubMed2006

Direct protection by a gonadotropin-releasing hormone analog from doxorubicin-induced granulosa cell damage.

BACKGROUND/AIMS: Recent clinical applications suggest a beneficial effect of gonadotropin-releasing hormone analog (GnRHa) as a gonadal protector from chemotherapy-induced premature ovarian failure. This study aimed to determine cellular mechanisms involved in the protective action of GnRHa against granulosa cell damage caused by doxorubicin. METHODS: Granulosa cells were obtained by ultrasound-guided follicular aspiration from patients undergoing in vitro fertilization, and screened for GnRH receptor expression prior to analyses. The cellular function was assessed by measuring the conversion of exogenously supplied androstenedione to estradiol-beta (E2) in response to follicle-stimulating hormone (FSH) (1 microM). RESULTS: Exposing to doxorubicin for 12 h before FSH stimulation caused a concentration-dependent inhibition of the E2 secretion to a minimum level of 20% of control. When the cells were incubated with a GnRHa for 12 h before and during exposure to doxorubicin, granulosa cells produced an equal level of E2 to that of control cells. The protective action of GnRHa was dose-dependent; a half-maximal effect occurred at 10 nM. Preincubation with GnRHa alone had no effect on FSH-induced E2 production. CONCLUSION: These findings demonstrate that a GnRHa may retard doxorubicin-induced granulosa cell damage, suggesting an additional GnRH activity to protect the gonads during chemotherapy through GnRH receptor-mediated mechanism(s).

Androstenedione↗
PubMed2006

Expression of cyclooxygenase-2 related to angiogenesis in uterine cervical cancers.

Angiogenesis is essential for development, growth and advancement of solid tumors. Cyclooxygenase (COX)-2 is recognized as an angiogenic factor in various tumors. This prompted us to study the clinical implications of COX-2 expression related to angiogenesis in uterine cervical cancers. There was a significant correlation between microvessel counts and COX-2 levels in uterine cervical cancers. COX-2 localized in the cancer cells, but not in the stromal cells of uterine cervical cancer tissues. COX-2 levels increased with advancement, and the prognosis of the 30 patients with high COX-2 expression in uterine cervical cancers was poor (60%), while the 24-month survival rate of the other 30 patients with low COX-2 expression was 90%. Furthermore, COX-2 levels significantly correlated with VEGF levels in uterine cervical cancers. VEGF associated with COX-2 might work on angiogenesis in advancement. Therefore, long-term administration of COX-2 inhibitors might be effective on the suppression of regrowth or recurrence after intensive treatment for advanced uterine cervical cancers.

Cyclooxygenase 2↗
PubMed2006

Plausible linkage of hypoxia inducible factor-1alpha in uterine cervical cancer.

Angiogenesis is essential for the development, growth and advancement of solid tumors. Angiogenesis is induced by hypoxia with angiogenic transcription factor hypoxia inducible factors (HIF). This prompted us to study the clinical implications of HIF relative to angiogenesis in uterine cervical cancers. Although there was no significant difference in HIF-1alpha histoscores and mRNA levels according to histopathological type or lymph node metastasis, HIF-1alpha histoscores and mRNA levels increased significantly with advancing cancer stages. The prognosis of 30 patients with high HIF-1alpha in uterine cervical cancers was poor (73% survival), whereas the 24-month survival rate of the other 30 patients with low HIF-1alpha was 93%. HIF-1alpha histoscores and mRNA levels were correlated with the levels of the angiogenic factors thymidine phosphorylase and interleukin-8, and HIF-1alpha might be linked with these factors in cervical cancer tissue. HIF-1alpha is a candidate for prognostic indicator as an angiogenic mediator in uterine cervical cancer.

Adult↗
PubMed2006

Clinical implications of osteopontin in metastatic lesions of uterine cervical cancers.

Osteopontin (OPN) is a glycophosphoprotein that has variety of physiological functions. OPN is expressed in various human cancers and associated with tumor progression, invasion and metastasis in many manners. The purpose of this study is to investigate the clinical significance of OPN expression in metastatic lymph node of uterine cervical cancers, since the prognosis of the patients with lymph node metastasis is extremely poor. Immunohistochemical staining revealed OPN was distributed in the cytoplasm and nuclear compartments of the cancer and stromal cells within and around the tumor. In 25 of the 40 cases, stronger staining for OPN was found in the cancer cells or stromal cells of the metastatic lymph node lesion than in those of the primary tumor. The OPN level was significantly (P<0.05) increased in 25 of 40 metastatic lymph node lesions of uterine cervical cancers. The OPN increased cases identified by immunohistochemical staining were consistent with those identified by the sandwich immunoassay. The prognosis of the 25 patients with significant increase of OPN in uterine cervical cancers was extremely poor, whereas the 24-month survival rate of the 15 patients with no increase of OPN was 67%. This indicates that OPN may contribute to lymph node metastasis and its advancement, and that the OPN level in metastatic lesion may be a prognostic indicator in uterine cervical cancers.

Adult↗
PubMed2006

Clinical implications of expression of cyclooxygenase-2 related to angiogenesis in ovarian cancer.

Angiogenesis is essential for the development, growth and advancement of solid tumors. Cyclooxygenase (cox)-2 is recognized as an angiogenic factor in various tumors. This prompted us to study the clinical implications of cox-2 expression and angiogenesis in ovarian cancer. There was a significant correlation between microvessel counts and cox-2 levels. Cox-2 localized in the cancer cells, but not in the stromal cells of ovarian cancer tissue. Cox-2 levels increased with the advancement, and the prognosis of the 30 patients with high cox-2 expression was extremely poor (33%), while the 24-month survival rate of the other 30 patients, those with low cox-2 expression, was 67%. Furthermore, cox-2 levels significantly correlated with VEGF levels. VEGF associated with cox-2 might work on angiogenesis with advancement. Therefore, long-term administration of cox-2 inhibitors might be effective on the suppression of regrowth or recurrence after intensive treatment for advanced ovarian cancer.

Adult↗
PubMed2006

PTEN sensitizes epidermal growth factor-mediated proliferation in endometrial carcinoma cells.

The fact that the genetic alterations of PTEN are frequently found in hormone-dependent cancers, such as endometrial, breast, and prostate cancers, might suggest the involvement of PTEN in the hormone-dependent cell growth of such tumors. Estrogen promotes the cell growth of the tumors by inducing peptide growth factors in part. We analyzed the possible involvement of PTEN in peptide-growth factor-dependent cell growth in endometrial carcinoma cells. PTEN-null Ishikawa cells were efficiently infected with recombinant adenovirus at 20 MOI (multiplicity of infection) to express PTEN protein. In PTEN-IK cells, phospho-Akt/PKB was down-regulated regardless of the consistent expression of Akt/PKB. The cell growth of parental IK cells was significantly stimulated by EGF and IGF-I, and PTEN-IK cells were further sensitized to the EGF-or IGF-I-growth stimulation. EGFR antibody could completely compromise the stimulatory effects of EGF in both cell lines. Wortmannin, a PI3K inhibitor, or UO126, a MAPK inhibitor, partly suppressed EGF-mediated cell growth stimulation in both cell lines. EGF augmented the level of phospho-Akt/PKB of PTEN-IK cells more effectively than that of parental IK cells. These results imply that the dysfunction of PTEN leads cells into a less-sensitive phenotype to peptide growth factors by constitutive activation of the PI3K/Akt/PKB signaling pathway in endometrial carcinoma.

Adenoviridae↗
PubMed2006

Anti-tumor effects of herbal medicines on endometrial carcinomas via estrogen receptor-alpha-related mechanism.

This study was performed to examine the relationship between the anti-tumor effects of herbal medicine and endometrial carcinoma with ER-related mechanisms. An endometrial cancer cell line (Ishikawa) was used for this study. The cell viability and expression of estrogen receptors (ER) were determined by MTT and RT-PCR. A dose-dependent decrease of viability and apoptosis of the cancer cells was generated by exposure to the herbal medicines, Juzen-taiho-to or Shimotsu-to. The expression of ER-alpha mRNA, but not ER-beta mRNA was suppressed by Juzen-taiho-to or Shimotsu-to in an endometrial cancer cell line. The anti-tumor effect of these herbal medicines against endometrial carcinoma might be correlated to the ER-alpha related mechanism.

Antineoplastic Agents↗
PubMed2006

[Prevalence and treatment of pharyngeal Chlamydia trachomatis infections].

In recent years, the number of the patients with pharyngeal infection caused by Chlamydia trachomatis is believed to be on the rise due to diversification in sexual behaviors. In addition, pharyngeal infection by C. trachomatis is often asymptomatic, and this is also believed to be a major factor for the increase of the disease. In this study, we conducted a survey among general females and commercial sex workers (CSWs) to study their sexual behavior and prevalence of chlamydial infections (in uterine cervix and pharynx). The results showed that orogenital contact has become a common act, even for general females. Chlamydial infections of uterine cervix were found in 33.3% and 7.9% of CSWs and general females, respectively. Chlamydial infections of pharynx were found in 22.5% and 5.2% of CSWs and general females, respectively. The evaluation of treatments of these infections with clarithromycin, levofloxacin, and azithromycin showed that 7, 10, and 14 days administrations of 400 mg clarithromycin, 7, 10, and 14 days administrations of 300 mg levofloxacin, and a single dose of 1000 mg of azithromycin, would eradicate 100% of C. trachomatis for infections of uterine cervix. For pharyngeal infections, 10 and 14 days administrations of clarithromycin and levofloxacin were shown to eradicate 100% of C. trachomatis. However, the eradication rates for 7 days administrations of clarithromycin and levofloxacin were 83.9% and 86.2%, respectively, and the rate for a single dose of azithromycin was 85.0%. From these results, it was thought that more than 10 days of administrations of clarithromycin or fluoroquinolone antibacterial agents such as levofloxacin are necessary to treat pharyngeal chlamydial infection. Clinical significance of pharyngeal chlamydial infection is still not clear; however, this study have shown the need for more detailed investigations using culture assay, in corporation with doctors in otolaryngology and internal medicine.

Adult↗
PubMed2006

Inhibitory effects of Hochu-ekki-to on endometrial carcinogenesis induced by N-methyl-N-nitrosourea and 17beta-estradiol in mice.

An evaluation of the effects of a traditional Chinese herbal medicine, Hochu-ekki-to (Bu-zong-yi-qi-tang) on endometrial carcinogenesis was performed in experiments with female mice. In the short-term experiment, dietary exposure of Hochu-ekki-to (0.2% for 2 weeks) decreased the estradiol-17beta (E2)-stimulated expression levels of c-jun (P<0.001), tumor necrosis factor (TNF)-alpha (P<0.005), estrogen receptors (ER)-alpha (P<0.001) and ER-beta (P<0.005), as determined by reverse transcription-polymerase chain reaction and a Southern blot analysis in the uteri of the ovarectomized mice. In the long-term experiment, the mice were given N-methyl-N-nitrosourea (MNU) solution (1 mg/100 g body weight) and normal saline (as controls) into their left and right uterine corpora, respectively, and then were divided into four groups. Group 1 (25 mice) was given a diet with Hochu-ekki-to and 5 ppm E2. Group 2 (25 mice) was given a diet with E2 alone. Group 3 (25 mice) was given a diet with Hochu-ekki-to alone. Group 4 (25 mice) was kept on the basal diet alone and treated as a control. The incidence of uterine endometrial cancer in the group with Hochu-ekki-to treatment was substantially lower than of the control group. The inhibitory effect of Hochu-ekki-to on endometrial carcinogenesis is thus suggested to decrease the expressions of c-jun, TNF-alpha, ER-alpha and -beta.

Animals↗
PubMed2006

[Clinical investigation on administration method of gatifloxacin based on PK/PD theory].

There have not been sufficient clinical studies based on pharmacokinetics/pharmacodynamics (PK/PD) theory, on which many clinical doctors have recently focused. To consider the optimized administration method based on PK/PD theory for gatifloxacin (GFLX), which was one of the oral fluoroquinolone antibacterial, we influenzae investigated clinical efficacies and adverse events for pelvic inflammatory disease (PID) in giving GFLX daily 400 mg divided twice a day or four times a day. The number of leukocyte and the value of CRP were significantly reduced by chemotherapy in twice a day group, compared with four times a day group. We were able to measure the blood level in 4 cases. The AUC/MIC values for presumption causative bacteria (causative bacteria in both cases: Escherichia coli) in cured patients were 142.28 and 280.16, however, in therapy-failed patients, the AUC/MIC value to presumption causative bacterium were 4.10 (causative bacteria: Prevotella bivia) and 4.35 (causative bacteria: Pseudomonas aeruginosa). These results suggested the importance of the therapeutic method based on PK/PD theory.

Anti-Infective Agents↗
PubMed2005

Efficacy of micafungin against deep-seated candidiasis in cyclophosphamide-induced immunosuppressed mice.

OBJECTIVES: We investigated the effects of fluconazole and micafungin for the therapy of deep-seated candidiasis in a cyclophosphamide-induced immunosuppressed mouse model. METHODS: We used the experimental model of intraperitoneal fungal abscess caused by Candida albicans, as described previously. RESULTS AND CONCLUSIONS: Micafungin efficacy was equal to that of fluconazole in one-tenth dosage even in peritonitis. We also assessed the short-term (24 h) and long-term (8 days) therapeutic effects after the end of therapy. Although the therapeutic effect of fluconazole was similar to that of micafungin at 24 h after the end of therapy, the effect of micafungin was superior to that of fluconazole at 8 days after the end of therapy.

Animals↗