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Hiromitsu Mimata

Publications and source records attributed to Hiromitsu Mimata.

At least 19 recordsLinked to original sources
PubMed2006

Beta2-microglobulin promotes the growth of human renal cell carcinoma through the activation of the protein kinase A, cyclic AMP-responsive element-binding protein, and vascular endothelial growth factor axis.

PURPOSE: Beta(2)-microglobulin (beta2M), a soluble protein secreted by cancer and host inflammatory cells, has various biological functions, including antigen presentation. Because aberrant expression of beta2M has been reported in human renal cell carcinoma, we investigated the effects of beta2M overexpression on cancer cell growth and analyzed its molecular signaling pathway. EXPERIMENTAL DESIGN: We established clonal cell lines that overexpressed beta2M in human renal cell carcinoma (SN12C) cells and then examined cell growth in vitro and in vivo and studied the beta2M-mediated downstream cell signaling pathway. RESULTS: Our results showed that beta2M expression positively correlates with (a) in vitro growth on plastic dishes and as Matrigel colonies, (b) cell invasion and migration in Boyden chambers, and (c) vascular endothelial growth factor (VEGF) expression and secretion by cells. We found, in addition, that beta2M mediates its action through increased phosphorylation of cyclic AMP-responsive element-binding protein (CREB) via the protein kinase A-CREB axis, resulting in increased VEGF expression and secretion. In convergence with this signal axis, beta2M overexpression also activated both phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways. Beta2M overexpression induced accelerated growth of SN12C in mouse subcutis and bone. Interrupting the beta2M signaling pathway using small interfering RNA led to apoptosis with increased activation of caspase-3 and caspase-9 and cleaved poly(ADP-ribose) polymerase. CONCLUSIONS: Our results showed for the first time that the beta2M-protein kinase A-CREB-VEGF signaling axis plays a crucial role in support of renal cell carcinoma growth and progression and reveals a novel therapeutic target.

Animals↗
PubMed2006

IFNgamma-dependent, spontaneous development of colorectal carcinomas in SOCS1-deficient mice.

Approximately 20% of human cancers are estimated to develop from chronic inflammation. Recently, the NF-kappaB pathway was shown to play an essential role in promoting inflammation-associated cancer, but the role of the JAK/STAT pathway, another important signaling pathway of proinflammatory cytokines, remains to be investigated. Suppressor of cytokine signaling-1 (SOCS1) acts as an important physiological regulator of cytokine responses, and silencing of the SOCS1 gene by DNA methylation has been found in several human cancers. Here, we demonstrated that SOCS1-deficient mice (SOCS1-/- Tg mice), in which SOCS1 expression was restored in T and B cells on a SOCS1-/- background, spontaneously developed colorectal carcinomas carrying nuclear beta-catenin accumulation and p53 mutations at 6 months of age. However, interferon (IFN)gamma-/- SOCS1-/- mice and SOCS1-/- Tg mice treated with anti-IFNgamma antibody did not develop such tumors. STAT3 and NF-kappaB activation was evident in SOCS1-/- Tg mice, but these were not sufficient for tumor development because these are also activated in IFNgamma-/- SOCS1-/- mice. However, colons of SOCS1-/- Tg mice, but not IFNgamma-/- SOCS1-/- mice, showed hyperactivation of STAT1, which resulted in the induction of carcinogenesis-related enzymes, cyclooxygenase-2 and inducible nitric oxide synthase. These data strongly suggest that SOCS1 is a unique antioncogene which prevents chronic inflammation-mediated carcinogenesis by regulation of the IFNgamma/STAT1 pathways.

Animals↗
PubMed2006

Striated muscle fiber compositions of human male urethral rhabdosphincter and levator ani.

PURPOSE: We clarified the contractile properties of human male periurethral striated muscle fibers to better understand how the rhabdosphincter and the levator ani maintain urinary continence. MATERIALS AND METHODS: Muscle specimens were obtained from 52 male patients who underwent radical prostatectomy or radical cystectomy. The specimens were frozen in liquid nitrogen. Frozen sections (10 microm thick) were stained with myofibrillar ATPase at different pH values (pH 4.2, 4.6 and 10.6), and evaluated for quantitative parameters and fiber type distribution. Myosin heavy chain analysis was performed using SDS-PAGE. RESULTS: Of all 52 cases 37 provided specimens that could be divided into the 2 major fiber types, type 1 (slow twitch) and type 2 (fast twitch). Although type 1 muscle fibers were predominant in RS and LA muscle groups (RS 69.6 +/- 2.7%, LA 67.0 +/- 2.0%), mean muscle fiber size was significantly smaller in RS (mean area 906 +/- 86 microm(2)) than in LA (mean area 2,967 +/- 170 microm(2)) (p <0.0001). In 11 specimens type 2 muscle fibers could be subdivided into types 2A (fast fatigue resistant) and 2B (fast fatigable). Type 2A fibers were significantly more prevalent than type 2B fibers (p <0.05). Likewise, MHC analysis of these 11 specimens found a significantly higher percentage of fiber type 2A expression products (MHC 2A) than of fiber type 2B expression products (MHC 2X) (p <0.05). CONCLUSIONS: RS and LA contribute to urinary continence mechanism by slow contraction. Moreover, the smaller mean size of muscle fibers in RS suggests more fatigue resistance compared with muscle fibers in LA because small fibers have a shorter diffusion distance for metabolic substrates. These results should help contribute to a more detailed understanding of the function of periurethral striated muscles in the human male.

Aged↗
PubMed2006

Source of plasma adrenomedullin in a patient with pheochromocytoma receiving hemodialysis.

A 45-year-old man on long-term hemodialysis (HD) was incidentally discovered to have a pheochromocytoma and underwent successful resection. This patient was normotensive, and had no symptoms suggesting pheochromocytoma. The plasma concentrations of total adrenomedullin (AM-T) and mature AM (AM-m) were higher than those in normal controls. To elucidate the source of AM, we measured plasma AM levels by immunoradiometric assay before and 3 weeks after surgery in addition to plasma adrenaline, noradrenaline and dopamine. AM expression was also assessed by immunoblot and immunohistochemical analyses on normal adrenal and tumor tissues. After surgery, elevated plasma adrenaline levels returned to the normal range; however, the levels of AM-T and AM-m remained almost the same as the preoperative values. Furthermore, although AM was expressed in both normal adrenal and tumor tissues, the AM expression level was less in tumor. In this case, it was suggested that elevation in plasma AM level might be a factor associated with normotensive blood pressure; however, adrenal pheochromocytoma was not a major source of circulating AM. To our knowledge, this is the first case of pheochromocytoma in patient with HD associated with AM in the literature.

Adrenal Gland Neoplasms↗
PubMed2006

Transitional cell carcinoma of the navicular fossa detected human papillomavirus 16.

We present a rare case of transitional cell carcinoma of the navicular fossa in an elderly man. We detected the expression of human papillomavirus type 16 specific DNA sequence in the tumor using polymerase chain reaction. Human papillomavirus dissemination into the urethra by urethral instrumentation might cause urethral tumors, such as squamous cell carcinoma or condyloma acuminatum, and also transitional cell carcinoma as seen in the present case.

Aged, 80 and over↗
PubMed2006

Molecular basis for the involvement of thymidine phosphorylase in cancer invasion.

Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), has been implicated in bladder cancer angiogenesis and invasion. However, the molecular basis of its role in invasion remains unclear. We investigated the expression of TP and 10 invasion-related genes in bladder cancers from 72 randomly selected patients by real-time two-step RT-PCR assay. We found that the expression levels of TP, MMP-9, uPA, and MMP-2 were significantly higher in invasive tumors than those in superficial tumors. Also, the expression level of TP significantly correlated with that of uPA, MMP-1, MMP-9, PAI-1 and VEGF. KK47/TP cells, bladder cancer cells that overexpress TP, had a higher expression of MMP-7 and MMP-9 than KK/CV cells that express lower level of TP in hypoxic condition. PC/TP cells, prostate cancer cells that overexpress TP, also had a higher expression of MMP-1 and MMP-7 than PC/CV cells that express no detectable TP. Taken together these data indicate that TP enhances the invasion of tumor cells through the induction of invasion-related genes.

Cell Line, Tumor↗
PubMed2005

Sp1 and Sp3 transcription factors upregulate the proximal promoter of the human prostate-specific antigen gene in prostate cancer cells.

The serum level of prostate-specific antigen (PSA) is useful as a clinical marker for diagnosis and assessment of the progression of prostate cancer, and in evaluating the effectiveness of treatment. We characterized four Sp1/Sp3 binding sites in the proximal promoter of the PSA gene. In a luciferase assay, these sites contributed to the basal promoter activity in prostate cancer cells. In an electrophoretic mobility shift assay and chromatin immunoprecipitation assay, we confirmed that Sp1 and Sp3 bind to these sites. Overexpression of wild-type Sp1 and Sp3 further upregulated the promoter activity, whereas overexpression of the Sp1 dominant-negative form or addition of mithramycin A significantly reduced the promoter activity and the endogenous mRNA level of PSA. Among the four binding sites, a GC box located at nucleotides -53 to -48 was especially critical for basal promoter activity. These results indicate that Sp1 and Sp3 are involved in the basal expression of PSA in prostate cancer cells.

Binding Sites↗
PubMed2005

Recto-peritoneal fistula following transperineal prostate biopsy.

A recto-peritoneal fistula is an extremely rare complication after prostate biopsy. We report herein on a peritonitis arising from a recto-peritoneal fistula 5 days after undergoing prostate biopsy. To our knowledge, this is the first case of recto-peritoneal fistula following transperineal needle biopsy of the prostate in the published literature.

Abdominal Abscess↗
PubMed2005

Spontaneous recovery from renal infarction resulting from renal artery dissection.

A 31-year-old, previously normotensive healthy man developed right flank pain and was admitted to a medical service. Right renal infarction was suspected by enhanced abdominal computed tomography (CT) and arteriography. Fourteen days after the onset, he was transferred to the Oita University Hospital, Oita, Japan. Renal angiography revealed an isolated renal artery dissection causing renal atrophy due to main stem narrowing of the right renal artery. Renogram and renal scintigram with (99m)Tc-diethylene triamine pentaacetic acid revealed a remarkable decline in the glomerular filtration rate and almost no uptake in the right kidney. Four months later, in spite of our belief that functional recovery could not be expected, intravenous pyelography and enhanced abdominal CT scans revealed a functioning right kidney that had spontaneously recovered from the renal artery dissection through conservative management.

Adult↗
PubMed2005

Lower incidence of inguinal hernia: minilaparotomy radical retropubic prostatectomy compared with conventional technique. A preliminary report.

INTRODUCTION: The purpose of the present study was to compare the incidence of inguinal hernias after conventional and minilaparotomy (minilap) radical retropubic prostatectomy (RRP). PATIENTS AND METHODS: In this retrospective study, we review our experience with 70 consecutive patients with prostate cancer who underwent prostatectomy from April 1995 through March 2001. Of these, 35 patients had conventional RRP, and 35 patients had minilap RRP. RESULTS: Conventional RRP and minilap RRP groups were similar in body mass index (mean 24.4 and 23.5), operative time (mean 260 and 241 min), previous lower abdominal operation record (mean 37.1 and 25.7%), and post-prostatectomy anastomotic strictures (mean 11.4 and 14.3%). The volume of the estimated blood loss was significantly less for minilap RRP (mean 1,220 ml) than for conventional RRP (mean 1,666 ml; p = 0.0194). The incidence of postoperative inguinal hernias was 17.1% (6 of 35), 2.9% (1 of 35), and 3.2% (1 of 31) in conventional RRP, minilap RRP, and unoperated groups, respectively. The incidence of inguinal hernias after minilap RRP was significantly lower than after conventional RRP (p = 0.0464). Seven patients with postoperative inguinal hernias had a high incidence of postoperative strictures (42.9%), while 63 patients without hernia had a low incidence (9.5%). There was a significant difference in developing postoperative strictures between patients with hernia and those without (p = 0.0124). While postoperative stricture and operative technique were different in the hernia and hernia-free groups on univariate analysis, multivariate logistic analysis revealed that the operative technique was an independent factor for the occurrence of inguinal hernias (p = 0.0419). CONCLUSION: Minilap RRP compares favorably with conventional RRP in view of the postoperative inguinal hernia development.

Aged↗
PubMed2005

Expression of the inhibitors of apoptosis proteins in cisplatin-resistant prostate cancer cells.

Acquired multi-drug resistance remains a major obstacle in the management of prostate cancer. The objective of this study was to examine whether chemoresistance could be due in part to the expression of the inhibitors of apoptosis proteins (IAPs). We established cisplatin-resistant LNCaP sublines. We examined the effects of cisplatin on cell growth and apoptosis in LNCaP cells and LNCaP sublines by 2-(4-lodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-1) assay and Hoechst 33258 staining, and analyzed cross-resistance to adriamycin, 5-fluorouracil, taxol, taxotere, and etoposide. In addition, the expression of IAP-1, IAP-2, X-linked IAP (XIAP), neuronal apoptosis inhibitory protein, and survivin was investigated by immunoblot analysis in LNCaP sublines. Although the growth rates were reduced in a dose-dependent manner by cisplatin in LNCaP sublines, the anti-proliferative effects of cisplatin were significantly decreased in LNCaP sublines compared to LNCaP cells. Cisplatin-resistant sublines, LNCaP/C1, LNCaP/ C2, and LNCaP/C3 cells, were 6.3-, 9.1-, and 22.3-fold more resistant to cisplatin than LNCaP cells, respectively, and this resistance was paralleled with reduced induction of apoptosis. LNCaP/C3 cells showed cross-resistance to adriamycin, 5-fluorouracil, and etoposide whereas those cells exhibited no or only weak cross-resistance against taxol and taxotere. With the exception of survivin, all the IAPs were identified in LNCaP cells by immunoblot analysis. Interestingly, the expression of IAP-2, XIAP, and survivin gradually increased with the extent of cisplatin-resistance. Altered expression of IAP-2, XIAP, and survivin was involved in these phenotypes of cisplatin-resistant LNCaP sublines. IAPs may make an important contribution to the resistance to the apoptotic effect of cisplatin in prostate cancer.

Apoptosis↗
PubMed2004

Placenta percreta invading the urinary bladder.

INTRODUCTION: Placenta percreta is a rare obstetric complication causing life-threatening hemorrhage. CASE REPORT: The case of a woman with a placenta percreta invading the urinary bladder treated by cesarean hysterectomy and partial bladder resection is presented. Overall estimated blood loss was 11,130 ml, and 59 units of various blood products were transfused. CONCLUSION: Obstetricians and urologists should be aware of this rare condition.

Adult↗
PubMed2004

Intestinal perforation after cadaveric renal transplantation.

We performed cadaveric renal transplantation on a 46-year-old man on long-term hemodialysis. Methicillin-resistant Staphylococcus aureus (MRSA) enterocolitis occurred on the fifth postoperative day and severe intestinal ulceration and perforation followed. Subtotal abdominal colectomy and the simultaneous removal of the transplant were performed. Postoperatively, disseminated intravascular coagulopathy with pancytopenia and cerebral hemorrhagic infarction developed and the patient died 40 days later.

Cadaver↗
PubMed2004

Urethral condyloma acuminata following urethral instrumentation in an elderly man.

A 70-year-old man had undergone urethral dilatation with bougie for 8 months following transurethral resection of the prostate and complained papillary masses at the urethral meatus. Physical and endoscopic examination revealed multiple tumors from the urethral meatus to the bulbous urethra. These tumors were resected transurethrally and 5-FU cream was instilled into urethra. Microscopic examination revealed urethral condyloma acuminata. Human papillomavirus types 6/11 were detected in the condylomas. As high prevalence rate of genital human papillomavirus was reported in penile skin of healthy men, urethral instrumentation including transurethral surgery might cause dissemination of penile skin human papillomavirus into the urethral lumen.

Aged↗
PubMed2003

The X-linked inhibitor of apoptosis protein inhibits taxol-induced apoptosis in LNCaP cells.

To clarify the roles of the X-linked inhibitor of apoptosis protein (XIAP), we investigated the effects of XIAP overexpression on taxol-induced cell growth arrest and apoptosis in the prostate cancer cell line (LNCaP). After the transfection of XIAP cDNA into LNCaP cells, we established clonal cell lines that overexpressed XIAP and examined the taxol effects on growth and apoptosis by 2-(4-lodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt and flow cytometric analysis. The effects of XIAP overexpression on caspase-3 were examined by immunoblot analysis and activity assay. The interaction between XIAP and caspase-3 in LNCaP cells was examined by cotransfection with myc-XIAP and caspase-3-HA cDNAs followed by immunoprecipitation and immunoblot analysis. Large amounts of XIAP were expressed in the established cell lines. Although the growth rates were reduced in a dose- and time-dependent manner by taxol, these effects were significantly decreased in XIAP stably overexpressing cell lines. In addition, we found that taxol treatment induced the cleavage of pro-caspase-3, followed by apoptosis, and that the overexpression of XIAP inhibited apoptosis by attenuating the cleavage of pro-caspase-3 and caspase-3 activity. Interestingly, XIAP bound to pro-caspase-3 in LNCaP cells transiently cotransfected with myc-XIAP and caspase-3-HA cDNAs, and this interaction was inhibited by taxol treatment. These results suggest that the overexpression of XIAP inhibits taxol-induced apoptosis through the decrease of caspase-3 activity and inhibition of the processing of pro-caspase-3.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Suppressor of cytokine signaling-1 is essential for suppressing dendritic cell activation and systemic autoimmunity.

Suppressor of cytokine signaling-1 (SOCS1/JAB) negatively regulates not only the cytokine-signaling pathway but also lipopolysaccharide (LPS)-induced macrophage activation. We found that SOCS1-deficient dendritic cells (DCs) were also hyperresponsive to interferon-gamma and interleukin-4. To define the role of SOCS1-deficient DCs in vivo, we generated mice in which the SOCS1 expression was restored in T and B cells on a SOCS1(-/-) background. In these mice, DCs were accumulated in the thymus and spleen and produced high levels of BAFF/BLyS and APRIL, resulting in the aberrant expansion of B cells and autoreactive antibody production. SOCS1-deficient DCs efficiently stimulated B cell proliferation in vitro and autoantibody production in vivo. These results indicate that SOCS1 plays an essential role in the normal DC functions and suppression of systemic autoimmunity.

Animals↗