Search PubMed⌕ Search

Biomedical subjects

Takuya Moriya

Publications and source records attributed to Takuya Moriya.

At least 37 records · Page 2Linked to original sources
PubMed2006

MDM2: a novel mineralocorticoid-responsive gene involved in aldosterone-induced human vascular structural remodeling.

Aldosterone has been demonstrated to play an important role in the pathogenesis of various cardiovascular diseases. Vascular structural remodeling, including vascular smooth muscle cell (VSMC) proliferation, has been also reported in small resistance arteries of patients with primary aldosteronism. Therefore, in this study, we examined whether genes involved in the regulation of the cell cycle were induced by aldosterone alone in cultured human VSMCs and in human small resistance arteries. Results of these studies eventually demonstrated that MDM2, one of the genes involved in anti-apoptosis and cell growth, was markedly increased in mineralocorticoid receptor (MR)-positive VSMCs by aldosterone in all microarray, reverse transcriptase-polymerase chain reaction, immunoblotting, and immunofluorescence analyses. In addition, an analysis using small interfering RNA demonstrated that this gene product was involved in cell proliferation of VSMCs induced by aldosterone. Eplerenone, a specific MR antagonist, inhibited this gene induction by aldosterone in VSMCs. MDM2 protein was also more abundant in VSMCs of small resistance arteries in patients with primary aldosteronism compared with a control population. MDM2 is therefore considered one of the mineralocorticoid-responsive genes that regulates cell proliferation of VSMCs induced by MR-mediated aldosterone stimulation, possibly playing an important role in aldosterone-induced vascular structural remodeling.

Aldosterone↗
PubMed2006

Adjuvant chemotherapy with irinotecan hydrochloride and cisplatin for clear cell carcinoma of the ovary.

Clear cell carcinoma (CCC) of the ovary has distinct characteristics showing resistance to conventional platinum-based regimen. Our aim was to evaluate the effects of combination therapy with irinotecan hydrochloride and cisplatin (CPT-P), comparing to regimen with paclitaxel and platinum (TP). We retrospective reviewed 172 patients with complete surgical staging procedures including lymphadenenctomy. Forty-six patients received CPT-P and 126 patients were treated with TP. Survival of the two groups was compared. Between CPT-P group and TP group, there was no significant difference in median age, performance status, FIGO stage, rate of optimal cytoreduction, and follow-up period. There was no significant difference in progression-free survival of patients with stage I tumors (p=0.95) and suboptimally debulked stage II-IV tumors (p=0.92). Although there was no significant difference of overall survival, progression-free survival of CPT-P group was significantly better than that of TP group in optimally debulked stage II-IV (p=0.03). Multiple regression survival analysis revealed CPT-P regimen (p=0.02) and residual tumor diameter (p<0.01) were both independent prognostic factors in stage II-IV tumors. The combination of CPT-P was shown to have a potential therapeutic benefit for advanced CCC of the ovary, especially for cases with optimal debulking surgery. However, this is a limited retrospective study, therefore we recommend that the CPT-P regimen be evaluated in a larger prospective study.

Adenocarcinoma, Clear Cell↗
PubMed2005

Phenotypic and genetic characterization of the Atp7a(Mo-Tohm) mottled mouse: a new murine model of Menkes disease.

Mottled Tohoku (Atp7a(Mo-Tohm) or Mo(Tohm)) is an X-linked mutation with mottled pigmentation in heterozygous (Mo(Tohm)/+) females and is embryonic lethal at E11 in hemizygous (Mo(Tohm)/Y) males. Copper levels were low in the brain and high in the intestine of Mo(Tohm) mice. Two congenic strains with ICR or C57BL/6 (B6) background were produced for genetic and phenotypic analyses and revealed that Mo(Tohm)/+ females with ICR background survived until adulthood, while most with B6 background died within 2 days after birth. The Mo(Tohm)/Y males with both backgrounds died at around E11. Massive hemorrhage was shown in the yolk sac cavity with irregular attachment between the mesoderm and the endothelial cells of blood vessels in the embryos at E10.5, suggesting that this irregular attachment causes embryonic lethality. The Mo(Tohm) mutant had a 1440-bp deletion between intron 22 and exon 23 of the Atp7a gene. Mo(Tohm)/Y males with the wild-type Atp7a cDNA transgene were rescued from embryonic lethality, confirming that the Mo(Tohm) mutant is caused by the defect in the Atp7a gene. This mutant mouse is the most severe model of human Menkes disease in mottled mice established to date and one of the useful models for understanding the gene function of Menkes disease.

Adenosine Triphosphatases↗
PubMed2005

Estrogen inhibits cell proliferation through in situ production in human thymoma.

PURPOSE: We showed previously estrogen receptor (ER) alpha as an independent prognostic marker in human thymoma. Estrogen sulfotransferase (EST), steroid sulfatase (STS), 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and aromatase are considered to play important roles in hormone metabolism of estrogen-dependent tumors. EXPERIMENTAL DESIGN: We examined estrogen production using primary cultures of human thymoma epithelial cells (TEC), intratumoral estradiol (E(2)) concentrations, and status of these enzymes above using immunohistochemistry or semiquantitative reverse transcription-PCR. We then correlated these findings with clinicopathologic variables and/or clinical outcome in 132 patients. RESULTS: E(2) inhibited cell proliferation via ERalpha in TEC, which synthesized estrone and E(2). Intratumoral E(2) concentrations were inversely correlated with EST, positively correlated with STS or 17beta-HSD type 1, and significantly higher in lower-grade or early-stage thymoma. EST status was positively correlated with tumor size, clinical stage, histologic differentiation, and Ki-67 labeling index and significantly associated with adverse clinical outcome and turned out to be a potent independent prognostic factor. STS and/or 17beta-HSD type 1 status was inversely correlated with Ki-67 labeling index and associated with lower histologic grade or early clinical stages. CONCLUSIONS: E(2) inhibits proliferation of TEC through ERalpha, which suggests that E(2) may be effective in treatment of thymoma, especially inoperable tumor, possibly through suppressing its cell proliferation activity. EST status is a potent prognostic factor in thymoma through inactivating estrogens. In situ estrogen synthesis through intracrine mechanism therefore may play important roles in tumorigenesis and/or development of thymoma through regulation of cell proliferation in an intracrine manner.

17-Hydroxysteroid Dehydrogenases↗
PubMed2005

Expression of estrogen-responsive finger protein (Efp) is associated with advanced disease in human epithelial ovarian cancer.

OBJECTIVE: The estrogen-responsive ring finger protein (Efp) gene, one of estrogen receptor (ER) target genes, is considered to be essential for estrogen-dependent cell proliferation. To understand the estrogenic action on ovarian cancer, we studied the relationships between Efp and ERs expressions and the correlations of Efp expression with clinicopathological parameters in epithelial ovarian cancer. METHODS: The protein expressions for Efp, ERalpha and ERbeta were examined by immunoblotting in 12 ovarian cancer cell lines. Efp mRNA expressions were evaluated by quantitative RT-PCR in 12 ovarian cancer cell lines. A total of 100 surgical specimens diagnosed as epithelial ovarian cancer were examined immunohistochemically using antibodies for Efp, ERalpha and ERbeta. RESULTS: Efp protein was detected in 8 out of 12 cell lines. In Efp protein-positive cell lines, Efp mRNA was expressed higher than that in negative (P=0.021). All of the Efp protein-positive cell lines simultaneously expressed either ERalpha or ERbeta protein. By immunohistochemical staining, Efp immunoreactivity was detected in 63 out of 100 ovarian cancer specimens and positive signals were in the cytoplasm of carcinoma cells. There were significant correlations between Efp and ERalpha, ERbeta immunoreactivity (Efp and ERalpha, P=0.022; Efp and ERbeta, P=0.032). Efp expression was significantly higher in a subgroup with serous adenocarcinoma (P=0.010) and with advanced disease (P=0.026). No significant relationship was detected between Efp immunoreactivity and overall survival. CONCLUSION: The expression of Efp was detected in human epithelial ovarian cancer and high expression of Efp was correlated with advanced disease and serous adenocarcinoma, and ERs status.

Adenocarcinoma↗
PubMed2005

Estrogen-responsive finger protein as a new potential biomarker for breast cancer.

PURPOSE: Estrogen-responsive finger protein (Efp) is a member of RING finger-B box-Coiled Coil family and is also a downstream target of estrogen receptor alpha. Previously, Efp was shown to mediate estrogen-induced cell growth, which suggests possible involvement in the development of human breast carcinomas. In this study, we examined expression of Efp in breast carcinoma tissues and correlated these findings with various clinicopathologic variables. EXPERIMENTAL DESIGN: Thirty frozen specimens of breast carcinomas were used for immunohistochemistry and laser capture microdissection/real-time PCR of Efp. Immunohistochemistry for Efp was also done in 151 breast carcinoma specimens fixed with formalin and embedded in paraffin wax. RESULTS: Efp immunoreactivity was detected in breast carcinoma cells and was significantly associated with the mRNA level (n = 30). Efp immunoreactivity was positively associated with lymph node status or estrogen receptor alpha status and negatively correlated with histologic grade or 14-3-3sigma immunoreactivity (n = 151). Moreover, Efp immunoreactivity was significantly correlated with poor prognosis of breast cancer patients, and multivariate analyses of disease-free survival and overall survival for 151 breast cancer patients showed that Efp immunoreactivity was the independent marker. CONCLUSIONS: Our data suggest that Efp immunoreactivity is a significant prognostic factor in breast cancer patients. These findings may account for an oncogenic role of Efp in the tumor progression of breast carcinoma.

14-3-3 Proteins↗
PubMed2005

Progesterone receptor in non-small cell lung cancer--a potent prognostic factor and possible target for endocrine therapy.

A possible involvement of gender-dependent factors has been postulated in development of human non-small-cell lung cancers (NSCLC), but its details remain unclear. In this study, we examined biological significance of progesterone receptor in NSCLCs. Progesterone receptor immunoreactivity was detected in 106 of 228 NSCLCs (46.5%). Progesterone receptor-positive NSCLC was frequently detected in female and adenocarcinoma, and was inversely associated with tumor-node-metastasis stage and histologic differentiation. Progesterone receptor status was also associated with better clinical outcome of the patients, and a multivariate analysis revealed progesterone receptor status as an independent prognostic factor. Progesterone-synthesizing enzymes were detected in NSCLCs, and tissue concentration of progesterone was higher in these cases (n = 42). Immunoblotting analyses showed the presence of progesterone receptor in three NSCLC cell lines (A549, LCSC#2, and 1-87), but not in RERF-LC-OK or PC3. Transcriptional activities of progesterone receptor were increased by progesterone in these three progesterone receptor-positive NSCLC cells by luciferase assays. Cell proliferation was inhibited by progesterone in these progesterone receptor-positive NSCLC cells in a dose-dependent manner, which was inhibited by progesterone receptor blocker. Proliferation of these tumor cells injected into nude mice was also dose-dependently inhibited by progesterone, with a concomitant increase of p21 and p27 and a decrease of cyclin A, cyclin E, and Ki67. Results of our present study suggested that progesterone receptor was a potent prognostic factor in NSCLCs and progesterone inhibited growth of progesterone receptor-positive NSCLC cells. Therefore, progesterone therapy may be clinically effective in suppressing development of progesterone receptor-positive NSCLC patients.

Adult↗
PubMed2005

Expression of core 2 beta1,6-N-acetylglucosaminyltransferase facilitates prostate cancer progression.

Cell surface carbohydrates expressed on epithelial cells are thought to play an important role in tumor progression. Previously, we have shown that expression of core 2-branched O-glycans is closely correlated with vessel invasion and depth of invasion in colon and lung carcinomas. In this study, we found that expression of core 2 beta1,6-N-acetylglucosaminyltransferase-1, Core2GnT, is positively correlated with the progression of prostate cancer in human patients. Statistical analysis demonstrated that Core2GnT is an independent predictor for progressed pathological stage (pT3) and for prostate-specific antigen (PSA) relapse. To determine directly the roles of Core2GnT in prostate cancer progression, we set up an experimental tumor model using the LNCaP prostate cancer cell line. Because this line does not express Core2GnT, we established an LNCaP line stably expressing Core2GnT, LNCap-Core2GnT, by transfecting cDNA encoding Core2GnT. When mock-transfected LNCaP cells and LNCaP-Core2GnT were inoculated in the prostate of nude mice, LNCaP-Core2GnT cells produced three times heavier prostate tumors than mock-transfected LNCaP cells. Furthermore, we found that LNCaP-Core2GnT cells adhered more strongly to prostate stromal cells, type IV collagen and laminin than did LNCaP-mock cells, but LNCaP and LNCaP-Core2GnT cells grew almost at the same rate on plates coated with type IV collagen or laminin. These results indicate that Core2GnT is an extremely useful prognostic marker for prostate cancer progression. The results also suggest that acquiring Core2GnT in prostate carcinoma cells facilitates adhesion to type IV collagen and laminin, and this increased adhesion may be a cause for aggressive tumor formation by prostate cancer cells expressing Core2GnT.

Aged↗
PubMed2005

Successful use of anti-CD20 monoclonal antibody (rituximab) for ABO-incompatible living-related liver transplantation.

BACKGROUND: Humoral rejection after ABO-incompatible liver transplantation often causes graft loss and a life-threatening situation. We used rituximab, which can eliminate B cells highly selectively, as an additional therapy for ABO-incompatible living-related liver transplantation. CASES: Patient 1 was a 1-year-old girl with biliary atresia. Her blood type was O, and the donor's was A. She underwent two plasma exchanges before liver transplantation and had triple immunosuppressants (mycophenolate mofetil, tacrolimus, and methylprednisolone). She was diagnosed with humoral rejection by needle biopsy on postoperative day 6. Rituximab was used for 3 days at 375, 187, and 187 mg/m(2) and successfully reduced the antibody titer, transaminase, and CD19(+) cells count in peripheral blood lymphocytes. The patient has not had any severe rejection, infection, or serious complications 2 years posttransplantation. Patient 2 was a 42-year-old woman with primary biliary cirrhosis. The blood type was O, and the donor's was B. She received three plasma exchanges, triple immunosuppressants, splenectomy, intraarterial anticoagulant therapy, and rituximab (375 mg/m(2) immediately after transplantation). The titer and CD19(+) cells count remained persistently low throughout the recovery course. She did not develop humoral rejection 1 year after transplantation. CONCLUSIONS: Rituximab efficiently reduces anti-ABO antibody titer by selectively eliminating B cells and is safe and effective against humoral rejection after ABO-incompatible liver transplantation.

ABO Blood-Group System↗
PubMed2005

Interactions between prostaglandin E(2), liver receptor homologue-1, and aromatase in breast cancer.

Local synthesis of estrogens within breast adipose tissue by cytochrome P450 aromatase contributes to the growth of postmenopausal breast cancers. One of the major stimulators of aromatase expression in breast is prostaglandin E(2) (PGE(2)) derived from tumorous epithelium and/or infiltrating macrophages. Recently, the orphan nuclear receptor, liver receptor homologue-1 (LRH-1), has also been shown to regulate aromatase expression in breast adipose tissue. We therefore examined the expression of, and correlations between, aromatase and LRH-1 mRNA in a panel of breast carcinoma tissues and adjacent adipose tissue. LRH-1 mRNA expression was low in normal breast tissue but markedly elevated in both breast carcinoma tissue and adipose tissue surrounding the tumor invasion (thereby paralleling aromatase expression). Laser capture microdissection localized the site of LRH-1 expression to tumor epithelial cells but not to intratumoral stromal cells. A strong correlation between LRH-1 and aromatase mRNA levels was observed in tumor-containing adipose tissue but not in tumor tissue. Ectopic expression of LRH-1 in primary human adipose stromal cells strongly activated endogenous aromatase mRNA expression and enzyme activity. Finally, treatment of adipose stromal cells with PGE(2) induced expression of both LRH-1 and aromatase. We suggest that PGE(2) derived from breast tumor tissue may increase aromatase expression in the surrounding adipose stroma in part by inducing LRH-1 in these cells. The roles of LRH-1 in breast cancer proliferation merit further study.

Adipose Tissue↗
PubMed2005

Hepatic resection of giant metastatic tumor from clear cell carcinoma of the ovary.

All cancer patients, particularly those treated for colorectal cancer, should be monitored for the presence of liver metastases, but liver metastases from ovarian clear cell carcinoma are quite rare. We report a patient subjected to extended left hepatectomy due to a giant metastasis 5 years after surgical treatment for an ovarian neoplasm that was histopathologically diagnosed as clear cell carcinoma. A 58-year-old woman had undergone hysterectomy and bilateral salpingo-oophorectomy due to ovarian cancer (stage Ic). Four years and 8 months after the operation, a computed tomography (CT) scan demonstrated a giant tumor in the left lobe of the liver. The tumor compressed the inferior vena cava (IVC), but it was not clear whether it invaded the vessel. She received chemotherapy for 4 months; however, the tumor did not decrease in size. She was subsequently referred to our institution and was submitted to operation after it was confirmed that there were no distant metastases. After being subjected to an extended left hepatectomy and cholecystectomy, the patient recovered from the surgery without any complications. She has been carefully followed for 17 months and has presented no evidence of recurrence.

Adenocarcinoma, Clear Cell↗
PubMed2005

Analysis for localization of steroid sulfatase in human tissues.

Human steroid sulfatase (STS) is an enzyme that hydrolyzes several sulfated steroids, such as estrone sulfate, dehydroepiandrosterone sulfate, and cholesterol sulfate, and results in the production of active substances. STS has been demonstrated in human breast cancer tissues and is considered to be involved in intratumoral estrogen production. It is very important to analyze the cellular distribution of STS with accuracy in human tissues in order to obtain a better understanding of the biological significance of STS. Therefore, this chapter describes several morphological approaches used to study the localization of STS, including immunohistochemistry, mRNA in situ hybridization, and laser capture microdissection/reverse transcription-polymerase chain reaction, in human tissues.

Breast Neoplasms↗
PubMed2005

Autoimmune pancreatitis with hepatic inflammatory pseudotumor.

We report a case of autoimmune pancreatitis (AIP) with hepatic inflammatory pseudotumor (IP). The patient was clinically diagnosed as having multiple metastatic tumors originated from cholangiocellular carcinoma as well as autoimmune pancreatitis and underwent left lobectomy of the liver. Histological examination showed a diffuse or dense lymphoplasmacytic infiltration with obliterating phlebitis but an absence of neoplastic proliferation both in the liver tumor and in the biopsy specimen of the pancreas. Abundant IgG4-positive plasma cells were seen in the lesions. This is the first case report that shows a simultaneous occurrence of hepatic IP and AIP, suggesting that these lesions appeared on the background of the recently proposed entity of IgG4-related systemic disease.

Autoimmune Diseases↗
PubMed2005

Immunolocalization of nuclear transcription factors, DAX-1 and Ad4BP/SF-1, in human common epithelial ovarian tumors: correlations with StAR and steroidogenic enzymes in epithelial ovarian carcinoma.

Intratumoral steroidogenesis is considered to play important roles in the biologic behavior of common epithelial ovarian carcinoma. Recent studies have demonstrated the important roles of Ad4BP/SF-1 and DAX-1 in regulation of steroidogenesis. In this study, we evaluated DAX-1, Ad4BP/SF-1, StAR, and steroidogenic enzyme expressions and their correlations in epithelial ovarian carcinomas to evaluate the possible roles of these factors in regulation of intratumoral steroid metabolism and/or production. Immunolocalization of DAX-1, Ad4BP/SF-1, StAR, and steroidogenic enzymes were examined in 90 epithelial ovarian carcinomas. mRNA expression of these proteins was evaluated using real-time polymerase chain reaction (PCR) in 23 cases for further characterization. DAX-1 and Ad4BP/SF-1 immunoreactivity was detected predominately in the nuclei of tumor cells, whereas that of StAR and steroidogenic enzymes was present in the cytoplasm. We detected a significant positive correlation between StAR and steroidogenic enzymes immunoreactivity and Ad4BP/SF-1 and statistically inversed correlation with DAX-1. A positive statistical correlation was detected between intratumoral stromal Ad4BP/SF-1 immunoreactivity and clinicopathologic parameters of carcinoma patients. Results of real-time PCR analysis were correlated with those of immunohistochemical studies. The status of intratumoral DAX-1, Ad4BP/SF-1, and StAR and steroidogenic enzymes in epithelial cells and intratumoral stromal cells of epithelial ovarian carcinoma may contribute in the progression and/or aggressiveness of these tumors.

Biomarkers, Tumor↗
PubMed2005

StAR and progesterone producing enzymes (3beta-hydroxysteroid dehydrogenase and cholesterol side-chain cleavage cytochromes P450) in human epithelial ovarian carcinoma: immunohistochemical and real-time PCR studies.

Steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage enzyme (P450scc) and 3 beta-hydroxysteroid dehydrogenase enzyme (3beta-HSD) are all involved in the transport of cholesterol and production of progesterone. In situ production of sex steroids including progesterone have been considered to play important roles in pathogenesis and/or development of common epithelial ovarian carcinomas. In this study, StAR, P450scc, and 3beta-HSD were immunolocalized in 100 cases of ovarian carcinoma and results were then correlated with clinicopathological and prognostic parameters of individual patients including status of progesterone receptor (PR) in tumor cells. Results of immunohistochemistry were further characterized by real-time PCR analysis in 20 cases of epithelial ovarian carcinomas in which frozen tissues were available for examination. StAR, P450scc, and 3beta-HSD immunoreactivity was detected predominately in the cytoplasm of carcinoma cells. Results of real-time PCR analysis were correlated with those of immunohistochemical studies. StAR, P450scc, and 3beta-HSD H scores demonstrated significant inversed statistical correlation with FIGO stage, residual size of the tumor, and Ki67 LI. A positive statistically significant correlation was detected between StAR H score and PR-B LI. Multivariate statistical analysis demonstrated that the status of intratumoral StAR, FIGO stage, and residual tumor size all turned out to be independent prognostic factors for the clinical outcome of the patient. The presence of StAR, a cholesterol transporter for steroidogenesis in human epithelial ovarian carcinoma, may reflect the ability of these tumors to produce progesterone in situ that could influence biological behavior of these tumors, especially through progesterone dependent inhibition of tumor cell proliferation.

17-Hydroxysteroid Dehydrogenases↗
PubMed2005

3beta-Hydroxysteroid dehydrogenase in human aorta.

3beta-Hydroxysteroid dehydrogenase (3beta-HSD) is known to be involved in steroid production and/or metabolism and to be expressed in many tissues including adrenal cortex. Expression of this enzyme has also been elucidated in human cardiovascular system but its details remain largely unknown. Therefore, in this study, we examined the status of 3beta-HSD in postmortem human aorta utilizing RT-PCR and immunohistochemical analysis. Both mRNAs and immunoreactivity for the enzyme were detected predominantly in female aorta, and in those with mild atherosclerotic changes. In addition, immunohistochemical study demonstrated that immunoreactivity for 3beta-HSD was detected in vascular smooth muscle cells (VSMCs) of aorta. These findings all indicated that steroidogenesis via 3beta-HSD may occur in VSMCs of human aorta, possibly related to gender differences and/or the degree of atherosclerosis.

3-Hydroxysteroid Dehydrogenases↗
PubMed2005

Progesterone receptor subtypes in vascular smooth muscle cells of human aorta.

Progesterone is involved in various functions of the cardiovascular system, including those of vascular smooth muscle cells (VSMCs) via progesterone receptor (PR). Progesterone has also been postulated to be involved in inhibition of VSMC proliferation via PR. However, the details of PR expression have remained largely unknown in human cardiovascular VSMCs. Therefore, we first examined the relative levels of PR isoform (PR-A and PR-B) expression in VSMCs, using both immunohistochemistry and quantitative RT-PCR analysis. PR-B was equally expressed between male and female aorta, but PR-A was more abundant in female than in male aorta. This finding demonstrated that the status of PR subtype expression was associated with the difference of genders.

Adult↗