Details of a Researcher - Kosaka, Takeo

Papers - Kosaka, Takeo

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Ets-1 and Hypoxia Inducible Factor-1 alpha Inhibition by Angiotensin II Type-1 Receptor Blockade in Hormone-Refractory Prostate

Kosaka, Takeo, Miyajima, Akira, Shirotake, Suguru, Kikuchi, Eiji, Hasegawa, Masanori, Mikami, Shuji, Oya, Mototsugu

PROSTATE 70 ( 2 ) 162 - 169 2010.02

Research paper (scientific journal), ISSN 0270-4137

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Activation of the aryl hydrocarbon receptor pathway enhances cancer cell invasion by upregulating the MMP expression and is associated with poor prognosis in upper urinary tract urothelial cancer

Ishida, Masaru, Mikami, Shuji, Kikuchi, Eiji, Kosaka, Takeo, Miyajima, Akira, Nakagawa, Ken, Mukai, Makio, Okada, Yasunori, Oya, Mototsugu

CARCINOGENESIS 31 ( 2 ) 287 - 295 2010.02

Research paper (scientific journal), ISSN 0143-3334

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Role of pelvic lymph node dissection in lymph node-negative patients with invasive bladder cancer

Shirotake Suguru, Kikuchi Eiji, Matsumoto Kazuhiro, Yazawa Satoshi, Kosaka Takeo, Miyajima Akira, Nakagawa Ken, Oya Mototsugu

Japanese Journal of Clinical Oncology 40 ( 3 ) 247 - 251 2009.11

ISSN 0368-2811

Objectives: The role of pelvic lymphadenectomy in patients with lymph node-negative bladder cancer at radical cystectomy (RC) has not yet been examined in detail. We retrospectively reviewed patients who underwent RC with pelvic lymphadenectomy for bladder cancer from January 1987 to March 2008. Methods: We identified consecutive data on 169 patients who underwent RC for bladder cancer. The mean follow-up was 64 months (range: 1-253 months). Node-positive status (pN(+)) was seen in 16 patients and 91 were diagnosed as node-negative (pN(-)). The lymph node status of the remaining 62 patients was unclear (pN(x)). We analysed the association between lymph node status and cancer-specific survival (CSS), and examined the role of the number of retrieved lymph nodes, particularly in pN(-). Results: The median number of retrieved nodes was 12.9 and 10.2 for stage pN(+) and stage pN(-), respectively. In 91 patients with pN(-), multivariate analysis revealed that pathological T3-4 (P = 0.0276) and less than nine retrieved lymph nodes (P = 0.0108) were independent risk factors for CSS. In a subgroup of 83 patients with pT3-4, Kaplan-Meier curves showed that the 5-year CSS rate in pN(-) patients with less than nine retrieved lymph nodes was 38.8%, which was extremely similar to the 40.8% in pN(+) and 45.1% in pN(x). Conclusions: Our results demonstrate that at least nine lymph nodes should be removed to improve the survival of pN(-) patients at RC and lymphadenectomy, and would provide information not only on prognosis but also on the therapeutic impact on pT3-4 invasive bladder cancer.

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Renal Damage Inhibited in Mice Lacking Angiotensinogen Gene Subjected to Unilateral Ureteral Obstruction

Uchida, Yasumitsu, Miyajima, Akira, Kikuchi, Eiji, Kozakai, Norihide, Kosaka, Takeo, Ieda, Masaki, Fukuda, Keiichi, Ohigashi, Takashi, Oya, Mototsugu

UROLOGY 74 ( 4 ) 938 - 943 2009.10

Research paper (scientific journal), ISSN 0090-4295

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Increased RANKL expression is related to tumour migration and metastasis of renal cell carcinomas

Mikami, Shuji, Katsube, Ken-ichi, Oya, Mototsugu, Ishida, Masaru, Kosaka, Takeo, Mizuno, Ryuichi, Mochizuki, Satsuki, Ikeda, Tohru, Mukai, Makio, Okada, Yasunori

JOURNAL OF PATHOLOGY 218 ( 4 ) 530 - 539 2009.08

Research paper (scientific journal), ISSN 0022-3417

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Brain metastasis of a papillary renal cell carcinoma, identified as type 2

Hasegawa, Masanori, Kikuchi, Eiji, Yasumizu, Yota, Hattori, Seiya, Takeda, Toshikazu, Morita, Shinya, Kosaka, Takeo, Miyajima, Akira, Horiguchi, Takashi, Mikami, Shuji, Oya, Mototsugu

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 14 ( 3 ) 270 - 272 2009.06

Research paper (scientific journal), ISSN 1341-9625

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A Case of Vesicocutaneous Fistula to the Thigh

Kosaka, Takeo, Asano, Tomohiko, Azuma, Ryuuichi, Yoshii, Hidehiko, Yamanaka, Yoshinori, Hayakawa, Masamichi

UROLOGY 73 ( 4 ) 2982 - 2992 2009.04

Research paper (scientific journal), ISSN 0090-4295

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Angiotensin II Type 1 Receptor Antagonist Enhances Cis-dichlorodiammineplatinum-Induced Cytotoxicity in Mouse Xenograft Model of Bladder Cancer

Kosugi, Michio, Miyajima, Akira, Kikuchi, Eiji, Kosaka, Takeo, Horiguchi, Yutaka, Murai, Masaru, Oya, Mototsugu

UROLOGY 73 ( 3 ) 655 - 660 2009.03

Research paper (scientific journal), ISSN 0090-4295

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

Miyajima Akira, Kikuchi Eiji, Kosaka Takeo, Oya Mototsugu

Reviews on Recent Clinical Trials 4 ( 2 ) 75 - 78 2009

ISSN 1574-8871

The potential for angiotensin II (AII) to promote tumor growth has been suspected based on its known hormonal actions and its vasoconstrictor effect. It has been suggested that angiotensin-converting enzyme (ACE) inhibitors may offer protection against cancer and may prevent carcinogenesis. Several studies report that AII can induce neovascularization in experimental systems by way of the AII type 1 receptor (AT1R). AT1R is also frequently expressed in such human tumors as skin cancer, renal cell carcinoma, and breast cancer. A growing number of recent studies focusing on treatment with an AT1R antagonist have demonstrated that angiotensin receptor blockade (ARB) appears to inhibit not only the growth of cancer cells but also tumor angiogenesis. We describe here the effects of AT1R blockade that implicate tumor angiogenesis in urogenital cancer since ARB may be an alternative modality for anti-cancer treatment.

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Expression of heparanase in renal cell carcinomas

Mikami Shuji, Oya Mototsugu, Shimoda Masayuki, Mizuno Ryuichi, Ishida Masaru, Kosaka Takeo, Mukai Makio, Nakajima Motowo, Okada Yasunori

Clinical Cancer Research 14 ( 19 ) 6055 - 6061 2008.10

ISSN 1078-0432

Purpose: Heparanase activity has been detected in many malignant tumors, showing a correlation with the metastatic potential. The present study was undertaken to investigate the expression of heparanase and its prognostic significance in renal cell carcinomas (RCC). Experimental Design: Nineteen RCCs and 6 nonneoplastic renal tissues were analyzed for heparanase mRNA expression by real-time PCR. Heparanase protein expression was semiquantitatively investigated by immunohistochemistry in 70 RCCs. Involvement of heparanase in the invasiveness of RCC cell lines, 786-O and Caki-2 cells, was examined by down-regulating the gene expression with small interfering RNA (siRNA) using the Matrigel invasion assay. Results: The expression level of heparanase mRNA was significantly higher in clear cell RCCs than in papillary RCCs, chromophobe RCCs, and nonneoplastic renal tissues. Heparanase was predominantly immunolocalized to cell surface and cytoplasm of clear cell RCCs and mean expression levels of heparanase were significantly higher in clear cell RCCs than in papillary and chromophobe RCCs. The protein expression levels were positively correlated with primary tumor stage, distant metastasis, and histologic grade. Targeting of heparanase mRNA expression in 786-O and Caki-2 cells with siRNA down-regulated the mRNA expression and inhibited the Matrigel invasion by these cells, whereas nonsilencing siRNA showed no effect. Multivariate Cox analysis revealed that elevated heparanase expression was a significant and an independent predictor of disease-specific survival (odds ratio, 8.814; P = 0.019). Conclusions: These data suggest that heparanase plays an important role in invasion and metastasis and silencing of the gene might be a potential therapeutic target in clear cell RCCs.

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The novel NF-κB activation inhibitor dehydroxymethyl-epoxyquinomicin suppresses anti-thy1.1-induced glomerulonephritis in rats

Kosaka Takeo, Miyajima Akira, Kikuchi Eiji, Horiguchi Yutaka, Umezawa Kazuo, Ohigashi Takashi, Nakashima Jun, Asano Tomohiko, Oya Mototsugu

Nephron - Experimental Nephrology 110 ( 1 ) 2008.09

ISSN 1660-2129

Background: NF-κB participates in the transcriptional regulation of numerous genes, and many studies have confirmed the activation of NF-κB in inflammatory renal diseases. Therefore, NF-κB is a promising target for the treatment of these diseases. We tested the effects of dehydroxymethyl- epoxyquinomicin (DHMEQ), a novel NF-κB activation inhibitor, on anti-thy1.1 antibody-induced glomerulonephritis (Thy1.1 GN). Methods: Thy1.1 GN was induced in Sprague-Dawley rats (6/group) by intravenous injection of anti-thy 1.1 antibody. The effects of DHMEQ (8 mg/kg/day) on the glomerular disease were evaluated using periodic acid-Schiff and Masson trichrome stains, immunohistochemistry for proliferating cell nuclear antigen, fibronectin and CD45 (leukocyte common antigen) and TUNEL staining. NF-κB activation was analyzed by a fluorescent electrophoretic mobility shift assay. Results: On day 7, DHMEQ treatment resulted in marked inhibition of NF-κB, decreased proteinuria (223.2 ± 42.3 vs. 434.8 ± 16.5 mg/kg/day, p < 0.05), preserved creatinine clearance (1.93 ± 0.38 vs. 1.07 ± 0.29 l/day, p < 0.01), decreased glomerular cell proliferation (15.8 ± 1.2 vs. 31.2 ± 0.8 nuclei/glomerular cross-section) and mesangial matrix deposition, and an increase in glomerular and tubular apoptosis without inducing any obvious adverse effects. Conclusion: DHMEQ inhibited NF-κB and thereby suppressed the inflammatory renal responses in rats with Thy1.1 GN.

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Papillary renal cell carcinoma

Kosaka Takeo, Mikami Shuji, Miyajima Akira, Kikuchi Eiji, Nakagawa Ken, Ohigashi Takashi, Nakashima Jun, Oya Mototsugu

Clinical and Experimental Nephrology 12 ( 3 ) 195 - 199 2008.06

ISSN 1342-1751

Background: Two different subtypes of papillary renal cell carcinoma (PRCC) have so far been identified, type-1 with small cells and pale cytoplasm and type-2 with large cells and eosinophilic cytoplasm. It has generally been accepted that type-1 tumors have favorable features in comparison with type-2 tumors, suggesting that these subtypes could be different clinicopathological entities, and, as a result, that the subtypes need to be characterized. Forty cases of PRCCs were reviewed, with special attention to the distinct clinicopathological difference and the response to cytokine therapy. Methods: Thirty-five cases of PRCC diagnosed between January 1997 and August 2007 were reviewed. PRCCs were classified according to the criteria of Delahunt and Eble. Results: Of these 40 patients, 20 and 20 were diagnosed to be type-1 and type-2 PRCCs, respectively. No lymphatic or vascular invasion or distant metastasis were observed in patients with type-1 PRCC. The nuclear grade in all type-1 PRCCs was low grade. The nuclear grade (P ≤ 0.01) and the positive rate of vascular invasion (P ≤ 0.05) was significantly higher in type-2 than in type-1 PRCCs. Distant metastasis was detected preoperatively in three patients with type-2 PRCC. One patient with metastatic type-2 PRCCs demonstrated a response to IL-2 therapy. Conclusion: PRCCs include two distinct morphological types of tumor and type-2 PRCCs tends to have unfavorable features in comparison with type-1 PRCCs. These results support the clinical basis for the need to perform morphological subtyping of PRCCs when clinically evaluating such patients.

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Metastatic type-2 papillary renal cell carcinoma responded to interleukin-2 therapy

Kosaka Takeo, Mikami Shuji, Miyajima Akira, Oya Mototsugu

Clinical and Experimental Nephrology 12 ( 2 ) 155 - 158 2008.04

ISSN 1342-1751

This report documents a case of metastatic papillary renal cell carcinoma (PRCC) which successfully responded to interleukin-2 (IL-2) therapy. A 59-year-old male presented with a left renal mass measuring 3.0 cm in diameter and a right adrenal mass measuring 5.0 cm in diameter. He underwent a left partial nephrectomy and a right adrenalectomy. The histological findings revealed pT1bN1M1 type-2 PRCC and metastatic renal cell carcinoma in the right adrenal gland. The patient was given interferon-α (IFN-α) after the operation for 3 months. A CT scan revealed a metastatic nodule measuring 6.0 cm in diameter near the surface of the liver at 4 months after the opereation. The patient was given interleukin-2 (IL-2), 7 × 10⁵ units/day intravenously, for 3 days per week. A CT scan revealed this hepatic nodule to have decreased in size from 6.0 to 4.0 cm after 4 months of IL-2 therapy. However, a new metastatic nodule measuring 6.0 cm in diameter was found which came in contact with the spleen. Next, the patient was given an increased dose of IL-2 from 7 × 10⁵ to 1.4 × 10⁶ units/day intravenously, for 3 days per week. At 9 months of follow-up after the dose escalation, a CT scan revealed a dramatic decrease in the size of these two metastatic nodules to 1.5 and 0.5 cm, respectively. This is a very rare case in that it represents a type-2 PRCC which dramatically responded to low-dose IL-2 therapy.

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Giant lymphocele arising after extraperitoneal laparoscopic radical prostatectomy

Mikami Hiroshi, Ito Keiichi, Yoshii Hidehiko, Kosaka Takeo, Miyajima Akira, Kaji Tatsumi, Asano Tomohiko, Hayakawa Masamichi

Acta Urologica Japonica 54 ( 1 ) 23 - 27 2008.01

ISSN 0018-1994

A 68-year-old male visited our division with an elevation of PSA level. He underwent a needle biopsy of the prostate, and the histopathological diagnosis was poorly differentiated adenocarcinoma (Gleason score 4 + 3). The cancer was clinically diagnosed as T2aN0M0, and he underwent extraperitoneal laparoscopic radical prostatectomy and bilateral pelvic lymphadenectomy. Cystography 14 days after the operation still showed leakage at the vesico-urethral anastomosis and a dumbbell shaped bladder. A few days later, prominence of lower abdomen and a slight swelling of right leg presented with a high fever. Computed tomography revealed a giant lymphocele in the retroperitoneal space. We percutaneously punctured the lymphocele by using ultrasonography, inserted a pigtail catheter, and drained 1,000 ml of lymphatic fluid. After the puncture, sclerotherapy with minocycline was performed four times. Twenty days after the puncture, the lymphocele cavity was found to have shrunken and the pigtail catheter was removed. The lymphocele was diminished and did not recur thereafter.

Laparoscopic radical nephrectomy in acdk-associated renal cell carcinoma accompanied by duplicated IVC

Ito Keiichi, Asano Tomohiko, Kosaka Takeo, Yoshii Hidehiko, Kaji Tatsumi, Sumitomo Makoto, Hayakawa Masamichi

Acta Urologica Japonica 53 ( 12 ) 875 - 878 2007.12

ISSN 0018-1994

A 59-year-old male patent who had undergone chronic dialysis for 13 years presented with gross hematuria. Radiological examinations showed a cystic renal tumor in the left kidney, multiple renal cysts due to acquired cystic disease of the kidney (ACDK), and a duplicated inferior vena cava (IVC). Although we suspected that the branches of the left IVC might be anormalous with regard to number and location, we could not obtain information about the left renal vein by 3-dimensional computed tomography because of the decreased blood flow in the end-stage kidney. Laparoscopic radical nephrectomy was performed using a transperitoneal approach. We first identified the left IVC and then exposed its surface widely so that we could identify the veins draining into it. We identified and divided two renal veins and also identified an adrenal vein and a gonadal vein draining directly into the left IVC. The enlarged kidney with multiple renal cysts was removed in a purely laparoscopic procedure.

Adrenal metastasis of lung adenocarcinoma with unusual sites of lymph node metastasis and concomitant renal cell carcinoma

Otsuki Hideo, Ito Keiichi, Kosaka Takeo, Mikami Hiroshi, Yoshii Hidehiko, Asakuma Junnichi, Kaji Tatsumi, Asano Tomohiko, Hayakawa Masamichi

Acta Urologica Japonica 53 ( 12 ) 879 - 882 2007.12

ISSN 0018-1994

A 58-year-old male presented to a clinic with general weakness. Right adrenal tumor was found by computed tomography and he was referred to our hospital. Imaging studies revealed right adrenal tumor (8 cm) with marked swelling of surrounding lymph nodes and synchronous left renal tumor (2 cm) that was weakly enhanced by contrast media. Needle biopsy of the left kidney proved to be clear cell type renal cell carcinoma (RCC) and the preoperative diagnosis was left RCC and right primary adrenal cancer with lymph node metastasis. We performed right adrenalectomy, lymph node dissection and left radical nephrectomy. Pathological findings of right adrenal tumor and lymph nodes were both metastatic adenocarcinoma, which was not consistent with RCC or adrenal-derived carcinoma. Then, we extensively reviewed preoperative radiological examinations and found a small lesion in the left upper lung. This lesion was attached to the mediastinal shadow and there was no obvious lymph node swelling around this lesion. According to pathological findings and an elevation of carcinoembryogenic antigen, the adrenal lesion was diagnosed as adrenal metastasis of lung adenocarcinoma.

Effect of angiotensin II type 1 receptor antagonist on tumor growth and angiogenesis in a xenograft model of human bladder cancer

Kosugi, Michio, Miyajima, Akira, Kikuchi, Eiji, Kosaka, Takeo, Horiguchi, Yutaka, Murai, Masaru

HUMAN CELL 20 ( 1 ) 1 - 9 2007.02

Research paper (scientific journal), ISSN 0914-7470

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

Kosaka, Takeo, Miyajima, Akira, Takayama, Eiji, Kikuchi, Eiji, Nakashima, Jun, Higashi, Takashi, Asano, Tomohiko, Sakamoto, Michiie, Okita, Hajime, Murai, Masaru, Hayakawa, Masamichi

PROSTATE 67 ( 1 ) 41 - 49 2007.01

Research paper (scientific journal), ISSN 0270-4137

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Atorvastatin ameliorates renal tissue damage in unilateral ureteral obstruction

Mizuguchi Yasunori, Miyajima Akira, Kosaka Takeo, Asano Takako, Asano Tomohiko, Hayakawa Masamichi

Journal of Urology 172 ( 6 I ) 2456 - 2459 2004.12

ISSN 0022-5347

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-β (TGF-β) 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-β 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-β bioassay showed that the obstructed kidney in the control group contained significantly higher TGF-β 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-β 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-β, 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.

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Novel nuclear factor κB activation inhibitor prevents inflammatory injury in unilateral ureteral obstruction

Miyajima Akira, Kosaka Takeo, Seta Kaori, Asano Tomohiko, Umezawa Kazuo, Hayakawa Masamichi

Journal of Urology 169 ( 4 ) 1559 - 1563 2003.04

ISSN 0022-5347

Purpose: We determined whether the novel nuclear factor κB 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 κB activity and transforming growth factor-β 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 κB, 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 μmol. hydroxyproline per gm. tissue versus 3.4 ± 0.1, respectively). Conversely daily administration of DHMEQ (8 mg./kg.) significantly inhibited nuclear factor κB 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 μmol. hydroxyproline per gm. tissue) in the obstructed kidney. Conclusions: Specific inhibition of nuclear factor κB can prevent inflammatory renal responses, suggesting that targeting nuclear factor κB activation may be feasible for preventing inflammatory kidney diseases.

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