Biomedical subjects

Akira Miyajima

Publications and source records attributed to Akira Miyajima.

16 recordsLinked to original sources

PubMed2007

Angiotensin II type 1 receptor antagonist as an angiogenic inhibitor in prostate cancer.

BACKGROUND: Angiotensin II (AII) type 1 receptor (AT1R) antagonists are used widely as antihypertensive agents, and long-term AT1R blockade may have a protective effect against cancer. We previously demonstrated that specific AT1R blockade with candesartan, an AT1R antagonist, inhibited vascular endothelial growth factor (VEGF) production and dramatically decreased lung metastasis of renal cancer by inhibiting tumor angiogenesis. This study was then undertaken to investigate the effects of AT1R blockade using candesartan in prostate cancer (PCa). METHODS: We first determined whether hormone-independence is associated with tumor angiogenesis and AT1R expression. Accordingly, we postulated that AT1R blockade may affect angiogenesis in androgen-independent PCa rather than in androgen-dependent PCa, and investigated the effects of AII and candesartan on PCa cell lines and a tumor xenograft model. RESULTS: A human hormone-refractory PCa (HRPC) and C4-2 androgen-independent PCa cell line showed significantly higher expression of VEGF, MVD, and AT1R than did human androgen-dependent PCa and an LNCaP androgen-dependent PCa cell line. In vitro, AII and candesartan did not directly affect the proliferation of LNCaP and C4-2 cells, but candesartan significantly suppressed VEGF production in C4-2 cells. In vivo, candesartan significantly suppressed VEGF expression, serum PSA concentration and tumor growth (1.1 +/- 0.2, 45.0 +/- 17.6 ng/ml, 235.8 +/- 37.4 mm(3)) in C4-2 xenografts in castrated mice, compared with the controls (2.4 +/- 0.6, 376.7 +/- 74.2 ng/ml, 830.8 +/- 147.6 mm(3)). CONCLUSIONS: Candesartan exerted preventive effects on HRPC, rather than on androgen-sensitive PCa, through the inhibition of tumor angiogenesis.

Aged↗

PubMed2006

Assessment of long-term quality of life using the FACT-BL questionnaire in patients with an ileal conduit, continent reservoir, or orthotopic neobladder.

OBJECTIVE: To assess and compare quality of life (QOL) of patients followed for a long time who underwent an ileal conduit (IC), continent reservoir (CR) or ileal neobladder (NB) using FACT-BL, a bladder-cancer-specific questionnaire. METHODS: One hundred and forty-seven patients underwent radical cystectomy and urinary diversion for bladder cancer from 1987 to 2002 at our institution. Of them, 79 (54%) patients were asked to participate in this study. Forty-nine patients (20 IC, 14 CR and 15 NB) returned the answered questionnaire for a survey response rate of 62%. Mean follow-up was 83.0 months. RESULTS: Four categories (physical, social/familial, emotional and functional well-being) in FACT-G were equally favorable in these groups. Patients with IC had less trouble controlling urine but had a worse image on altered body appearance compared with NB patients. Interest in sex was extremely low in all patients and capability of maintaining an erection was also low in 39 male patients. The mean total value of FACT-BL in IC, CR and NB patients was 106.3+/-16.4, 104.0+/-14.2, and 110.9+/-18.0, respectively, showing no significant difference. Ten (77%) of 13 IC, seven (78%) of nine CR and six (86%) of seven NB patients answered that they would choose the same type of diversion if they had the choice again. CONCLUSIONS: The type of urinary diversion does not appear to be associated with a different QOL by general cancer-related assessment. Urinary function and body image are affected and related to the method used to reconstruct the urinary system.

Aged↗

PubMed2006

Angiotensin II type 1 receptor antagonist candesartan as an angiogenic inhibitor in a xenograft model of bladder cancer.

PURPOSE: There have been several studies on the antitumor activity of angiotensin II type 1 receptor (AT1R) antagonists. In this study, we evaluated the efficacy of the AT1R antagonist candesartan in bladder cancer. EXPERIMENTAL DESIGN: For the study in vitro, human bladder cancer cells (KU-19-19) were cultured with or without angiotensin II and candesartan. Various cytokines and cell viability were analyzed. For the study in vivo, a tumor xenograft model was prepared in nude mice using KU-19-19 cells. Mice were given candesartan daily by oral gavage. Microvessel density, expression of vascular endothelial growth factor (VEGF), and apoptosis were assessed. RESULTS: Candesartan did not induce direct toxicity in KU-19-19 cells, but VEGF and interleukin-8 were significantly lower in candesartan-treated cells (2.55 +/- 0.25 and 6.58 +/- 0.48 pg/10(3) cells) than in the angiotensin II-treated control cells (3.16 +/- 0.42 and 7.91 +/- 0.69 pg/10(3) cells). In mice, candesartan both at doses of 2 and 10 mg/kg/d significantly suppressed tumor growth in mice (35.4% and 33.5% reduction in tumor volume). Microvessel density was significantly decreased by candesartan (9.8 +/- 2.8 per field) compared with the control group (17.6 +/- 6.0 per field), and VEGF expression was significantly suppressed by this AT1R antagonist. However, candesartan did not induce apoptosis of cancer cells in the tumor. CONCLUSIONS: Specific blockade of AT1R prevented bladder tumor growth by inhibiting angiogenesis. However, its antitumor effect was not due to direct toxicity. Because AT1R antagonists are widely used to treat hypertension, and a 2 mg/kg/d dose level of candesartan is clinically achievable, this AT1R antagonist could also be used to treat bladder cancer.

Aged↗

PubMed2006

Preoperative nomograms for predicting stone-free rate after extracorporeal shock wave lithotripsy.

PURPOSE: Extracorporeal shock wave lithotripsy is currently accepted as a first line treatment modality for urolithiasis. In obtaining informed consent it is important to inform patients of the stone-free rate with extracorporeal shock wave lithotripsy before surgery. The present study was performed to develop preoperative nomograms for predicting stone-free rates after extracorporeal shock wave lithotripsy. MATERIALS AND METHODS: A total of 435 patients with 507 urinary stones were treated with extracorporeal shock wave lithotripsy with a Dornier Lithotripter D. Patient age, sex, body mass index, number of stone(s) in each treatment, stone length, side and location were evaluated before extracorporeal shock wave lithotripsy, and treatment efficacies were evaluated at 3 months after each session. The treated stones were divided into 2 groups, those in cases that were stone-free with a single extracorporeal shock wave lithotripsy session and those in all other cases. Multivariate analysis was performed using a logistic regression model. The nomograms were developed by repeating the analysis on 200 bootstrap samples. RESULTS: Stone length, location and number were identified as significant variables on multivariate analysis, and a logistic regression model was developed using these variables. The nomograms predicting stone-free rate at 3 months after single extracorporeal shock wave lithotripsy treatment were finally developed from 200 bootstrap samples. In these nomograms the stone-free probability was highest for solitary proximal ureteral stones less than 5 mm in size (93.8%) and lowest for multiple caliceal stones greater than 21 mm (10.5%). CONCLUSIONS: This study demonstrated that stone size, location and number are significant predictors of extracorporeal shock wave lithotripsy outcome. We have developed nomograms for predicting the stone-free rate of extracorporeal shock wave lithotripsy, which is useful for counseling patients with urolithiasis before surgery.

Female↗

PubMed2006

Usefulness of alpha1-antichymotrypsin-PSA complex for predicting bone metastases of prostate cancer.

OBJECTIVES: To determine the usefulness of alpha1-antichymotrypsin-prostate-specific antigen (PSA) complex (PSA-ACT)-based parameters in predicting bone metastasis in patients with prostate cancer. METHODS: PSA-ACT, total PSA, free PSA, their volume-adjusted values, and alkaline phosphatase were evaluated in 220 consecutive patients with newly diagnosed prostate cancer. RESULTS: Bone metastases were detected by bone scan in 27 (12.3%) of the 220 patients. The serum levels of PSA-ACT, total PSA, free PSA, PSA density, PSA adjusted for transition zone volume, PSA-ACT density, PSA-ACT adjusted for transition zone volume, alkaline phosphatase, PSA-ACT/PSA ratio, and Gleason score in patients with bone metastases were each significantly greater than in those without bone metastases. On receiver operating characteristic analyses, PSA-ACT had the greatest area under the curve (0.88), but the receiver operating characteristic curve demonstrated that the sensitivity and specificity of PSA-ACT were marginally better than those of total PSA at only a few selected cutoff points. At a sensitivity of 93% (2 patients with bone metastasis missed), unnecessary bone scans would have been avoided in 107 and 102 patients using a PSA-ACT cutoff value of 10 ng/mL and total PSA cutoff value of 11.5 ng/mL, respectively. Multivariate logistic regression analysis demonstrated that PSA-ACT and Gleason score were significant independent predictors of bone metastasis. CONCLUSIONS: PSA-ACT is as useful as total PSA for identifying patients with a low probability of having bone metastasis. PSA-ACT could replace PSA for predicting negative bone scans in a clinical setting in which PSA-ACT is used for monitoring and screening patients for prostate cancer.

Aged↗

PubMed2006

Endocytoscopy: novel endoscopic imaging technology for in-situ observation of bladder cancer cells.

BACKGROUND AND PURPOSE: Recent advances in endoscopy have enabled microscopic imaging of live bladdercancer cells in situ. The newly developed Endocystoscopy system (Olympus Medical Systems Co., Tokyo, Japan) is a flexible digital endoscope that has more than a 450-fold magnifying power on a video monitor. PATIENTS AND METHODS: This supermagnifying endoscope was used to evaluate bladder carcinoma in five patients through the working channel of a rigid cystoscope. RESULTS: The cell structure and nuclear morphology were imaged adequately compared with conventional hematoxylin and eosin staining of a biopsy specimen. The tumors were graded correctly in four of five cases. CONCLUSION: This novel technology appears to be useful for histologic diagnosis during endoscopic examinations, potentially allowing us to avoid a conventional biopsy.

Aged↗

PubMed2006

Retroperitoneoscopic partial nephrectomy using radiofrequency ablation.

Two patients with renal tumors underwent retroperitoneoscopic partial nephrectomy. The renal tumors were initially treated with radiofrequency ablation. This method allowed tumor excision to be achieved without clamping the renal pedicle. Residual renal function was well maintained as determined by enhanced computed tomography scanning and measurement of the serum creatinine level. There were no complications such as vascular damage or collecting system injury. The pathological diagnosis was clear cell carcinoma (pT1) in Patient 1 and was not determined in Patient 2 because of entire ablation. No recurrence has been observed after 3 years and 2 years of follow up, respectively. Radiofrequency ablation was useful for control of local bleeding during retroperitonaoscopic partial nephrectomy.

Adenocarcinoma, Clear Cell↗

PubMed2005

Prevention of cancer cachexia by a novel nuclear factor {kappa}B inhibitor in prostate cancer.

PURPOSE: To investigate the association between serum interleukin-6 (IL-6) and cachexia in patients with prostate cancer and the inhibitory effect of a new nuclear factor kappaB (NF-kappaB) inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on IL-6 production and cachexia in an animal model of hormone-refractory prostate cancer. EXPERIMENTAL DESIGN: The association between serum IL-6 levels and variables of cachexia was evaluated in 98 patients with prostate cancer. The inhibitory effects of DHMEQ on IL-6 secretion and cachexia were investigated in in vitro and in vivo studies using JCA-1 cells derived from human prostate cancer. RESULTS: Serum IL-6 levels were significantly elevated and cachexia developed in JCA-1 tumor-bearing mice as well as in prostate cancer patients with progressive disease. IL-6 secretion was significantly inhibited in JCA-1 cells exposed to DHMEQ. Intraperitoneal administration of DHMEQ (8 mg/kg) to tumor-bearing mice produced a significant amelioration of the reduction in body weight, epididymal fat weight, gastrocnemius muscle weight, hematocrit, and serum levels of triglyceride and albumin when compared with administration of DMSO or no treatment. DHMEQ caused a significant decrease of serum IL-6 level in JCA-1 tumor-bearing mice (all P < 0.05). CONCLUSIONS: These results suggested an association between serum IL-6 and cachexia in patients with prostate cancer and in JCA-1 tumor-bearing mice and that a new NF-kappaB inhibitor, DHMEQ, could prevent the development of cachexia in JCA-1 tumor-bearing mice presumably through the inhibition of IL-6 secretion. DHMEQ seems to show promise as a novel and unique anticachectic agent in hormone-refractory prostate cancer.

Albumins↗

PubMed2005

[Clinical experience of laparoscopic adrenalectomy: the National Defense Medical College experience].

Twenty-seven laparoscopic adrenalectomies (LapAdx) were performed at the National Defense Medical College between 1999 and 2004. We evaluated the results of LapAdx (group L) compared to the results of open adrenalectomy (group O). Twenty-six of the 27 LapAdx were successfully performed, but one patient with a large pheochromocytoma required open surgey because of arterial bleeding in the renal hilus. The mean operating time in group L (185 +/- 19 min) was not significantly different from that in group O (206 +/- 13 min). The mean estimated blood loss in group L (111 +/- 61 g) was significantly lower than that in group O (308 +/- 67 g). The starting time for oral feeding and for ambulation was significantly earlier in group L than in group O. There was a major complication (intraoperative bleeding) in which a group L patient required a blood transfusion. We also compared the surgical results of 26 patients in LapAdx divided chronologically into the first half and the last half to determine the surgical skill acquired. The operating time was significantly shorter and blood loss significantly less for patients in the last half. In addition, the operating time and blood loss for the first-time LapAdx operators were comparable with those of experienced surgeons. Our results support the efficacy and the minimal invasiveness of LapAdx. The accumulated experience and knowledge regarding laparoscopic surgery in our institute were important in improving surgical procedures and results.

Adrenal Gland Neoplasms↗

PubMed2004

Differential expression of activator protein-2 isoforms in renal cell carcinoma.

OBJECTIVES: To investigate the expression of activator protein-2 (AP-2) in renal cell carcinoma (RCC) by immunohistochemistry. Three AP-2 isoforms alpha (alpha), beta (beta), and gamma (gamma) are known to exhibit a highly homologous structure; however, their functions are considered to be different. AP-2 has been implicated to play a role in carcinogenesis, as well as in the development of the kidney. METHODS: The expression of the three AP-2 isoforms, alpha, beta, and gamma, was determined in 58 patients with RCC by immunohistochemistry. Epidermal growth factor receptor and erbB2 expression in 42 patients with RCC was also evaluated to investigate the correlation with AP-2 isoforms. RESULTS: AP-2 isoforms are differentially expressed in normal renal tubules. Of 58 RCC tissue specimens, 15 (25.9%) demonstrated nuclear and cytoplasmic expression of AP-2alpha. Clear cell RCC had a significantly greater rate of AP-2alpha expression than the nonclear subtypes (14 of 41 clear versus 1 of 17 nonclear subtypes). Of the 58 specimens, 8 (13.8%) showed nuclear staining for AP-2beta; notably, localized small cases had a significantly greater rate of nuclear staining for AP-2beta (5 of 13 in pT1a versus 3 of 45 in pT1b or greater). In addition, only 2 cases (3.5%) demonstrated nuclear staining for AP-2gamma. Epidermal growth factor receptor and erbB2 expression did not correlate with expression of the AP-2 isoforms. CONCLUSIONS: AP-2 isoforms were differentially expressed in RCC, as well as in the adult normal kidney. AP-2alpha was dominantly expressed in clear cell RCC. AP-2beta expression was observed in the low-stage subtypes of RCC, and this transcription factor may be related to early carcinogenesis.

Adenocarcinoma↗

PubMed2004

Suppression of lung metastasis of renal cell carcinoma by the intramuscular gene transfer of a soluble form of vascular endothelial growth factor receptor I.

PURPOSE: We clarified whether adenovirus mediated intramuscular gene transfer of soluble vascular endothelial growth factor receptor 1 (sFlt-1) can inhibit lung metastasis of renal cell carcinoma. MATERIALS AND METHODS: We constructed the adenovirus vector AdsFlt-1, which expresses soluble Flt-1 protein. Functional validation of the vector was determined by HUVEC (in vitro human umbilical vein endothelial cell) proliferation inhibition assay. The efficacy of AdsFlt-1 was tested in a Renca murine renal cell carcinoma lung metastasis model. BALB/c mice were injected with Renca cells, followed by the intramuscular administration of AdsFlt-1 24 hours later. Lung specimens were harvested 17 days later and the number of lung metastases was counted. Immunohistochemical analysis of the specimen for angiogenesis and apoptosis was done. RESULTS: Treatment with adenovirus expressed sFlt-1 inhibited HUVEC proliferation. The intramuscular administration of AdsFlt-1 significantly inhibited lung metastasis of Renca cells. Immunohistochemical analysis of the lung specimen showed fewer neovessel formations and more apoptotic cells in AdsFlt-1 treated tumors in mice. CONCLUSIONS: The intramuscular administration of AdsFlt-1 effectively inhibited lung metastasis in a murine model of renal cell carcinoma. Because of the simplicity of this therapy, it may well be useful as an effective adjuvant therapy for renal cell carcinoma.

Adenoviridae↗

PubMed2004

Atorvastatin ameliorates renal tissue damage in unilateral ureteral obstruction.

PURPOSE: The current study was done to determine whether atorvastatin, the HMGCoA (3-hydroxy-3-methylglutaryl CoA) reductase inhibitor, could decrease renal transforming growth factor-beta (TGF-beta) levels in unilateral ureteral obstruction (UUO) and concomitantly affect renal tissue damage in UUO. MATERIALS AND METHODS: Atorvastatin (20 mg/kg) was administered to rats 1 day prior to UUO and every day thereafter. Kidneys were harvested at day 14 after UUO. Tissue TGF-beta was measured by bioassay using mink lung epithelial cells. Renal tubular proliferation and apoptosis were detected by immunostaining proliferating cell nuclear antigen and polyclonal antisingle strand DNA antibody, respectively. Fibrosis was assessed by measuring collagen deposition with trichrome stained slides. Interstitial leukocyte was detected by immunostaining CD45. RESULTS: TGF-beta bioassay showed that the obstructed kidney in the control group contained significantly higher TGF-beta than the unobstructed kidney in the control group (mean +/- SD 79.1 +/- 48.5 vs 28.7 +/- 13.7 pg/mg tissue) and atorvastatin significantly decrease tissue TGF-beta in the obstructed kidney (53.4 +/- 37.0 pg/mg tissue). Immunostaining polyclonal antisingle strand DNA antibody demonstrated that the obstructed kidney in the control group has significantly more tubular apoptosis than the unobstructed counterpart (4.8 +/- 2.8 vs 2.1 +/- 1.2 nuclei per high power field) and atorvastatin significantly decreased renal tubular apoptosis in the obstructed kidney (1.1 +/- 0.7 nuclei per high power field). In addition, immunostaining proliferating cell nuclear antigen showed that the obstructed kidney in the atorvastatin group had significantly more renal tubular proliferation than the obstructed kidney in the control group (48.7 +/- 20.8 vs 17.3 +/- 10.6 per high power field). Control obstructed kidney showed significantly more fibrosis, which was also blunted by atorvastatin. CONCLUSIONS: Atorvastatin significantly decreases tissue TGF-beta, resulting in a decrease in tubular damage and interstitial fibrosis. This suggests that atorvastatin is a promising agent for preventing renal tubular damage in UUO.

Animals↗

PubMed2003

Loss of expression of transforming growth factor-beta receptor as a prognostic factor in patients with renal cell carcinoma.

OBJECTIVES: To determine the clinical implication of the loss of transforming growth factor-beta (TGF-beta) receptor (TbetaR) expression for the pathologic features in renal cell carcinoma (RCC) and the prognosis of 62 patients (Stage I, 4; Stage II, 28; Stage III, 11; and Stage IV, 19) who underwent radical nephrectomy for RCC. Loss of expression in TbetaR could result in escape from the growth inhibitory effect of TGF-beta in TGF-beta-secreting cancer. METHODS: TbetaR and apoptosis in the tumor were detected by immunohistochemistry using samples from 62 patients. We statistically investigated the relationship among the TbetaR expression pattern, pathologic features, and the prognosis of patients with RCC. RESULTS: A loss of expression of TbetaR-I and TbetaR-II was identified in 29 patients (46.7%) and 31 patients (50.0%), respectively. Although the loss of TbetaR-I was not associated with clinical stage, the loss of TbetaR-II was associated with clinical stage (P <0.01). Univariate analysis of all patients demonstrated that Stage T3 or greater, clinical Stage III or greater, loss of TbetaR-II, and a tumor apoptotic index of less than 35 were associated with a significantly lower survival rate than their respective counterparts. Multivariate analysis showed that the only two significant prognostic factors were clinical stage and loss of TbetaR-II. In addition, TbetaR-negative RCC had significantly lower apoptosis than did TbetaR-positive RCC. CONCLUSIONS: These results suggest that a loss of TbetaR-II expression in the primary tumor is a significant prognostic factor in patients with RCC.

Adult↗

PubMed2003

Novel nuclear factor kappa B activation inhibitor prevents inflammatory injury in unilateral ureteral obstruction.

PURPOSE: We determined whether the novel nuclear factor kappa B activation inhibitor dehydroxymethylepoxyquinomicin (DHMEQ), which is derived from epoxyquinomicin C, affects renal inflammatory responses in unilateral ureteral obstruction. MATERIALS AND METHODS: DHMEQ (8 mg./kg.) was administered to rats 1 day after unilateral ureteral obstruction and every day thereafter. Kidneys were harvested at day 7 after unilateral ureteral obstruction. Tissue nuclear factor kappa B activity and transforming growth factor-beta were determined by electrophoretic mobility shift assay and bioassay using mink lung epithelial cells, respectively. Renal tubular proliferation and apoptosis were detected by immunostaining proliferating cellular nuclear antigen and the TUNEL (Intergen, Purchase, New York) assay, respectively. Leukocyte infiltration was detected by immunostaining for CD45. Fibrosis was assessed by measuring tissue hydroxyproline content. RESULTS: Unilateral ureteral obstruction for 7 days significantly activated nuclear factor kappa B, induced tubular apoptosis, proliferation and interstitial fibrosis in the obstructed kidney of the control group compared with their unobstructed counterparts (30.3 +/- 4.5 nuclei per high power field versus 1.7 +/- 0.4, 25.7 +/- 3.3 nuclei per high power field versus 3.2 +/- 0.4 and 6.2 +/- 0.3 micromol. hydroxyproline per gm. tissue versus 3.4 +/- 0.1, respectively). Conversely daily administration of DHMEQ (8 mg./kg.) significantly inhibited nuclear factor kappa B activation and decreased mean tubular apoptosis (9.5 +/- 2.1 nuclei per high power field), proliferation (10.2 +/- 2.4 nuclei per high power field) and interstitial fibrosis (4.9 +/- 0.4 micromol. hydroxyproline per gm. tissue) in the obstructed kidney. CONCLUSIONS: Specific inhibition of nuclear factor kappa B can prevent inflammatory renal responses, suggesting that targeting nuclear factor kappa B activation may be feasible for preventing inflammatory kidney diseases.

Animals↗

PubMed2002

Angiotensin II type I antagonist prevents pulmonary metastasis of murine renal cancer by inhibiting tumor angiogenesis.

Angiotensin II (AII) is a potent vasoconstrictor peptide from the renin-angiotensin system in the kidney. The AII type 1 receptor (AT1R) is reportedly expressed in several tumors including renal cell carcinoma, and AII is involved in tumor angiogenesis. We p.o. administered the long-acting AT1R antagonist, candesartan (10 mg/kg), to the 16 days mouse renal cancer lung metastasis model to test the preventive effects in tumor metastasis. Pulmonary metastases of renal cancer showed prominent AT1R expression in both mice and humans, and candesartan treatment dramatically prevented lung metastatic nodules (14.9 +/- 1.8; P < 0.0001; n = 12) in mice along with the inhibition of neovascularization and vascular endothelial growth factor expression, compared with control metastatic mice (123.3 +/- 8.6; n = 13). Candesartan is widely used clinically, so it seems to be a reasonable therapy for patients with lung metastases of renal cell carcinoma.

Adult↗

PubMed2002

[Carcinosarcoma of the renal pelvis and ureter: a case report].

We report a case of carcinosarcoma of the renal pelvis and ureter arising in an 89-year-old man who presented at our hospital with gross hematuria. Abdominal computed tomography, excretory pyelography, and retrograde pyelography demonstrated that left hydronephrosis was caused by an ureteral tumor. Left urine cytology indicated transitional cell carcinoma. The patient underwent chemotherapy and radiation therapy. However, gross hematuria recurred, and the patient underwent left nephroureterectomy. The surgical specimen showed carcinosarcoma in the renal pelvis and ureter histologically. He has been free of cancer for 1.5 years.

Aged↗