Details of a Researcher - Tanaka, Nobuyuki

Papers - Tanaka, Nobuyuki

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Significance of a frozen section analysis of the ureteral margin in bladder cancer patients treated with radical cystectomy and neoadjuvant chemotherapy

Hakozaki Kyohei, Kikuchi Eiji, Fukumoto Keishiro, Shirotake Suguru, Miyazaki Yasumasa, Maeda Takahiro, Kaneko Gou, Yoshimine Shunsuke, Tanaka Nobuyuki, Kanai Kunimitsu, Oyama Masafumi, Nakajima Yosuke, Momma Tetsuo, Oya Mototsugu

Medical Oncology 34 ( 12 ) 2017.12

Research paper (scientific journal), ISSN 1357-0560

Although the clinical utility of a frozen section analysis (FSA) at the time of radical cystectomy (RC) has already been established, its significance and utility in bladder cancer patients receiving neoadjuvant chemotherapy (NAC) have not yet been fully evaluated. We identified 458 patients (937 ureters) who underwent open RC for bladder cancer at our 7 Japanese institutions between 2004 and 2015. Among these patients, 139 (284 ureters) received NAC before RC (NAC group), while 319 (653 ureters) underwent RC alone (non-NAC group). FSA was performed on 356 out of 937 (38.0%) ureters and 179 out of 458 (39.1%) patients. FSA was positive in 30 out of 356 (8.4%) ureters and its sensitivity, specificity, and accuracy were 89.3, 98.5, and 97.8%, respectively. In the NAC group, FSA was performed on 138 out of 284 (48.6%) ureters and 68 out of 139 (48.9%) patients. FSA was positive in 8 out of 138 ureters (5.8%), and its sensitivity, specificity, and accuracy were 77.8, 99.2, and 97.8%, respectively. In the non-NAC group, FSA was performed on 218 out of 653 (33.4%) ureters and 111 out of 319 (34.8%) patients. FSA was positive in 22 out of 218 (10.1%) ureters, and its sensitivity, specificity, and accuracy were 94.7, 98.0, and 97.7%, respectively. No correlation was observed between preoperative clinical factors and FSA positivity in the NAC group; however, in the non-NAC group, the incidence of FSA positivity in the ureters of patients with concomitant CIS in TUR-BT specimens was 8/41 (19.5%), which was significantly higher than that in their counterpart (14/177, 7.9%, p = 0.033). Even in the era of NAC in the management of bladder cancer patients, the performance of FSA does not change and FSA at the time of RC may provide useful diagnostic information.

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Whole-tissue biopsy phenotyping of three-dimensional tumours reveals patterns of cancer heterogeneity

Tanaka, Nobuyuki, Kanatani, Shigeaki, Tomer, Raju, Sahlgren, Cecilia, Kronqvist, Pauliina, Kaczynska, Dagmara, Louhivuori, Lauri, Kis, Lorand, Lindh, Claes, Mitura, Przemyslaw, Stepulak, Andrzej, Corvigno, Sara, Hartman, Johan, Micke, Patrick, Mezheyeuski, Artur, Strell, Carina, Carlson, Joseph W., Moro, Carlos Fernandez, Dahlstrand, Hanna, Ostman, Arne, Matsumoto, Kazuhiro, Wiklund, Peter, Oya, Mototsugu, Miyakawa, Ayako, Deisseroth, Karl, Uhlen, Per

NATURE BIOMEDICAL ENGINEERING 1 ( 10 ) 796 - 806 2017.10

Research paper (scientific journal), ISSN 2157-846X

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Prognostic value of neutrophil-to-lymphocyte ratio in patients with metastatic renal cell carcinoma treated with first-line and subsequent second-line targeted therapy: A proposal of the modified-IMDC risk model

Tanaka, Nobuyuki, Mizuno, Ryuichi, Yasumizu, Yota, Ito, Keiichi, Shirotake, Suguru, Masunaga, Ayako, Ito, Yujiro, Miyazaki, Yasumasa, Hagiwara, Masayuki, Kanao, Kent, Mikami, Shuji, Nakagawa, Ken, Momma, Tetsuo, Masuda, Takeshi, Asano, Tomohiko, Oyama, Masafumi, Oya, Mototsugu

UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS 35 ( 2 ) E425 - E426 2017.02

Research paper (scientific journal), ISSN 1078-1439

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Acquired platinum-resistance involves epithelial-to-mesenchymal transition through ubiquitin ligase FBXO32 dysregulation.

Tanaka, Nobuyuki, Kosaka, Takeo, Miyazaki, Yasumasa, Mikami, Shuji, Niwa, Naoya, Otsuka, Yutaro, Minamishima, Yoji Andrew, Mizuno, Ryuichi, Kikuchi, Eiji, Miyajima, Akira, Sabe, Hisataka, Okada, Yasunori, Uhlén, Per, Suematsu, makoto, Oya, Mototsugu.

Journal of Clinical Investigation Insight 1 ( 18 ) e83654 2016.11

Research paper (scientific journal)

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Plasma fibrinogen level: an independent prognostic factor for disease-free survival and cancer-specific survival in patients with localised renal cell carcinoma

Obata, Jun, Tanaka, Nobuyuki, Mizuno, Ryuichi, Kanao, Kent, Mikami, Shuji, Matsumoto, Kazuhiro, Kosaka, Takeo, Kikuchi, Eiji, Jinzaki, Masahiro, Oya, Mototsugu

BJU INTERNATIONAL 118 ( 4 ) 598 - 603 2016.10

Research paper (scientific journal), ISSN 1464-4096

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External Validation of the MSKCC and IMDC Risk Models in Patients Treated with Targeted Therapy as a First-line and Subsequent Second-line Treatment

Tanaka Nobuyuki, Mizuno Ryuichi, Ito Keiichi, Shirotake Suguru, Yasumizu Yota, Masunaga Ayako, Ito Yujiro, Miyazaki Yasumasa, Hagiwara Masayuki, Kanao Kent, Mikami Shuji, Nakagawa Ken, Momma Tetsuo, Masuda Takeshi, Asano Tomohiko, Oyama Masafumi, Oya Mototsugu

European Urology Focus 2 ( 3 ) 303 - 309 2016.08

Research paper (scientific journal), ISSN 2405-4569

Background Two risk models, the Memorial Sloan Kettering Cancer Center (MSKCC) model and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model, have been studied in metastatic renal cell carcinoma (mRCC) treated with targeted therapy. Objective To validate externally the predictive accuracies of the MSKCC and IMDC models for prognosis in mRCC patients treated with first-line and subsequent second-line targeted therapy. Design, setting, and participants A total of 311 patients were assessed retrospectively. Intervention All patients underwent targeted therapy. Outcome measurements and statistical analysis Survival outcomes were assessed using Kaplan-Meier analysis. The predictive ability was evaluated using the c-index. Results and limitations Regarding to the first-line targeted therapy, the 3-yr overall survival (OS) rates of the MSKCC (p < 0.001) and IMDC models (p < 0.001) were 76.2% and 77.3%, respectively, in the favorable-risk group; 46.7% and 47.9%, respectively, in the intermediate-risk group; and 13.4% and 15.6%, respectively, in the poor-risk group. The c-indexes were 0.68 for the MSKCC model and 0.69 for the IMDC model in a first-line setting. Regarding the second-line targeted therapy, the 1-yr OS rates of the MSKCC (p < 0.001) and IMDC models (p < 0.001) were 80.9% and 90.5%, respectively, in the favorable-risk group; 71.4% and 70.6%, respectively, in the intermediate-risk group; and 31.7% and 24.6%, respectively, in the poor-risk group. The c-indexes were 0.66 for the MSKCC model and 0.65 for the IMDC model in the second-line setting. The study is limited by its retrospective nature. Conclusions The results may assist physicians in providing more appropriate patient counseling and imply the need for a future prognostic tool in mRCC treated with targeted therapy. Patient summary Both risk models were useful for the risk stratification in metastatic renal cell carcinoma (mRCC) patients treated with first-line and second-line targeted therapy; however, it might be necessary to further update or optimize the models for our Japanese cohort of mRCC patients.

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Effect of reclassification of the IMDC model in patients with metastatic renal cell carcinoma treated with targeted therapy in the first-line and second-line settings

Tanaka, Nobuyuki, Mizuno, Ryuichi, Shirotake, Suguru, Ito, Keiichi, Yasumizu, Yota, Masunaga, Ayako, Ito, Yujiro, Miyazaki, Yasumasa, Hagiwara, Masayuki, Kanao, Kent, Mikami, Shuji, Nakagawa, Ken, Momma, Tetsuo, Masuda, Takeshi, Asano, Tomohiko, Oyama, Masafumi, Oya, Mototsugu

UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS 34 ( 7 ) 554 - 559 2016.07

Research paper (scientific journal), ISSN 1078-1439

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Patient age was an independent predictor of cancer-specific survival in male patients with upper tract urothelial carcinoma treated by radical nephroureterectomy

Kobayashi, Hiroaki, Kikuchi, Eiji, Tanaka, Nobuyuki, Shirotake, Suguru, Miyazaki, Yasumasa, Ide, Hiroki, Obata, Jun, Hoshino, Katsura, Matsumoto, Kazuhiro, Kaneko, Gou, Hagiwara, Masayuki, Kosaka, Takeo, Oyama, Masafumi, Nakajima, Yosuke, Oya, Mototsugu

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 46 ( 6 ) 554 - 559 2016.06

Research paper (scientific journal), ISSN 0368-2811

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Refraining from Smoking for 15 Years or More Reduced the Risk of Tumor Recurrence in Non-muscle Invasive Bladder Cancer Patients

Ogihara, Koichiro, Kikuchi, Eiji, Yuge, Kazuyuki, Ito, Yujiro, Tanaka, Nobuyuki, Matsumoto, Kazuhiro, Miyajima, Akira, Asakura, Hirotaka, Oya, Mototsugu

ANNALS OF SURGICAL ONCOLOGY 23 ( 5 ) 1752 - 1759 2016.05

Research paper (scientific journal), ISSN 1068-9265

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Relationship Between Increased Expression of the Axl/Gas6 Signal Cascade and Prognosis of Patients with Upper Tract Urothelial Carcinoma

Hattori, Seiya, Kikuchi, Eiji, Kosaka, Takeo, Miyazaki, Yasumasa, Tanaka, Nobuyuki, Miyajima, Akira, Mikami, Shuji, Oya, Mototsugu

ANNALS OF SURGICAL ONCOLOGY 23 ( 2 ) 663 - 670 2016.02

Research paper (scientific journal), ISSN 1068-9265

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Impact of Second-Line Targeted Therapy Dose Intensity on Patients With Metastatic Renal Cell Carcinoma

Shirotake Suguru, Yasumizu Yota, Ito Keiichi, Masunaga Ayako, Ito Yujiro, Miyazaki Yasumasa, Hagiwara Masayuki, Kanao Kent, Mikami Shuji, Nakagawa Ken, Momma Tetsuo, Masuda Takeshi, Asano Tomohiko, Oyama Masafumi, Tanaka Nobuyuki, Mizuno Ryuichi, Oya Mototsugu

Clinical Genitourinary Cancer 2016.01

Research paper (scientific journal), ISSN 1558-7673

Background: Relative dose intensity (RDI) is a simple index for evaluation of the amount of drug administered per unit time. We retrospectively investigated the prognostic impact of RDI for patients with metastatic renal cell carcinoma (mRCC) treated with second-line targeted therapy. Methods: We enrolled 168 patients with mRCC. We assessed RDI at 4 weeks after second-line targeted therapy induction. Results: The median follow-up after second-line targeted therapy was 18.1 months. The median time-to-treatment-failure (TTF) and overall survival (OS) were 4.9 and 25.4 months, respectively. In the Kaplan-Meier analysis, the median OS of patients with second-line RDI <0.7 was significantly shorter than those with RDI ≥ 0.7 (12.1 vs. 31.3 months; P = .030). In the subgroup analysis, second-line RDI was definitely prognostic in the poor-risk group of the International Metastatic Renal Cell Carcinoma Database Consortium criteria, showing second-line RDI was an independent predictor for both TTF (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.6-8.0; P = .002) and OS (HR, 3.1; 95% CI, 1.1-8.4; P = .026). Also, assessing the type of second-line regimen, the multivariate analysis showed that second-line RDI was an independent prognostic indicator of TTF (HR, 1.7; 95% CI, 1.0-2.9; P = .040) and OS (HR, 2.7; 95% CI, 1.3-5.7; P = .009) in patients treated with everolimus. In this group, the median TTF and OS of patients with RDI <0.7 were 2.4 and 11.1 months, and those with RDI ≥ 0.7 were 5.3 and 25.9 months, respectively. Conclusion: The results suggest that second-line RDI may be a prognostic predictor for patients with mRCC treated with second-line targeted therapy, particularly in both the International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group and everolimus-treated group.

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Are the Formulas Used to Estimate Renal Function Adequate for Patients Treated With Cisplatin-Based Chemotherapy After Nephroureterectomy for Upper Tract Urothelial Carcinoma?

Niwa Naoya, Kikuchi Eiji, Masashi Matsushima, Tanaka Nobuyuki, Nishiyama Toru, Miyajima Akira, Saito Shiro, Oya Mototsugu

Clinical Genitourinary Cancer 2015.12

Research paper (scientific journal), ISSN 1558-7673

Objective: The relationship between endogenous creatinine clearance (eCrCl) and renal function values obtained using mathematical formulas has not yet been fully elucidated, especially in patients with upper tract urothelial carcinoma that are treated with radical nephroureterectomy followed by cisplatin-based chemotherapy. Methods: Sixty patients who received cisplatin-based chemotherapy for locally advanced or metastatic upper tract urothelial carcinoma after radical nephroureterectomy between 2000 and 2012 were retrospectively identified. eCrCl was measured based on 24-hour urine specimens obtained immediately prior to each cycle of chemotherapy. Renal function was estimated with 4 different formulas: the Cockcroft-Gault, Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration, and Wright formulas. We evaluated the relationship between eCrCl and the renal function values obtained with each formula using the Pearson correlation coefficient and κ statistics. Results: The median eCrCl was 53.9 mL/min. The Pearson correlation coefficients and κ statistics for the relationships between eCrCl and the renal function values obtained with each of the mathematical formulas ranged from 0.600 to 0.763 and from 0.29 to 0.67, respectively. Among the patients with eCrCl of ≥ 60 mL/min, 70%, 60%, 50%, and 20% were estimated to have the renal function values of <60 mL/min by the Cockcroft-Gault, Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration, and Wright formulas, respectively. Conclusions: All 4 of the tested formulas underestimated eCrCl. The values obtained with the Wright formula were most closely associated with eCrCl.

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Nicotine induces tumor growth and chemoresistance through activation of the PI3K/Akt/mTOR pathway in bladder cancer

Yuge Kazuyuki, Kikuchi Eiji, Hagiwara Masayuki, Yasumizu Yota, Tanaka Nobuyuki, Kosaka Takeo, Miyajima Akira, Oya Mototsugu

Molecular Cancer Therapeutics 14 ( 9 ) 2112 - 2120 2015.09

Research paper (scientific journal), ISSN 1535-7163

Continued smoking is highly associated with not only a higher incidence but also greater risk of tumor recurrence, progression, and acquired chemoresistance of urothelial carcinoma. We investigated whether nicotine affects urothelial carcinoma, and the detailed mechanism by which nicotine could induce tumor growth and any associated chemoresistance. Cell viability was evaluated in the human bladder cancer cell line T24 exposed to nicotine with or without cisplatin (CDDP) and NVP-BEZ235 as a PI3K/mTOR dual inhibitor by the WST-1 assay. Protein expression of the PI3K/Akt/mTOR pathway was investigated by Western blotting or immunohistochemical analysis. The influence of nicotine on tumor growth was also evaluated with or without CDDP and/or NVP-BEZ235 in a subcutaneous bladder tumor model. The result demonstrated that cell proliferation was increased in T24 cells after exposure to nicotine. Phospho-specific Akt (pAkt) and phospho-specific p70 S6 kinase (pS6) were significantly upregulated by nicotine exposure. Tumor growth in vivo was significantly induced by nicotine exposure in accordance with increased pS6 expression. Nicotine attenuated inhibition of T24 cell growth by CDDP and further upregulated pS6 expression in vitro and in vivo. NVP-BZE235 inhibited T24 cell proliferation and pAkt and pS6 expression induced after exposure to nicotine and/or CDDP. In conclusion, nicotine increases tumor growth and induces acquired chemoresistance through activation of the PI3K/Akt/mTOR pathway in bladder cancer.

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Comparison of outcomes between ultrasonography and cystoscopy in the surveillance of patients with initially diagnosed TaG1-2 bladder cancers: A matched-pair analysis

Niwa, Naoya, Matsumoto, Kazuhiro, Hayakawa, Nozomi, Ito, Yujiro, Maeda, Takahiro, Akatsuka, Seiya, Masuda, Takeshi, Nakamura, So, Tanaka, Nobuyuki

UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS 33 ( 9 ) E13 - E13 2015.09

Research paper (scientific journal), ISSN 1078-1439

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Impact of Combined Use of Blood-based Inflammatory Markers on Patients with Upper Tract Urothelial Carcinoma Following Radical Nephroureterectomy

Tanaka Nobuyuki, Kikuchi Eiji, Kanao Kent, Matsumoto Kazuhiro, Shirotake Suguru, Miyazaki Yasumasa, Kobayashi Hiroaki, Kaneko Gou, Hagiwara Masayuki, Ide Hiroki, Obata Jun, Hoshino Katsura, Hayakawa Nozomi, Kosaka Takeo, Hara Satoshi, Nakagawa Ken, Jinzaki Masahiro, Oya Mototsugu

European Urology Focus 1 ( 1 ) 54 - 63 2015.08

Research paper (scientific journal)

Background: Previous studies showed the prognostic impact of preoperative levels of neutrophil-to-lymphocyte ratio (NLR), plasma fibrinogen, and serum C-reactive protein (CRP) in surgically treated upper tract urothelial carcinoma; however, few papers have discussed the proper use of these indices. Objective: To investigate whether combinations of these three markers, as a cumulative marker score (CMS), improve the accuracy of prognostic models following radical nephroureterectomy (RNU). Design, setting, and participants: A total of 394 patients from multiple institutions were included. Median follow-up was 30 mo. Intervention: All patients underwent RNU without neoadjuvant chemotherapy. Outcome measurements and statistical analysis: Associated outcomes were assessed using multivariate analysis. The CMS was defined as the number of elevated levels of preoperative NLR, plasma fibrinogen, and serum CRP. Results and limitations: Multivariate analyses revealed that an increasing CMS was independently associated with high rates of disease recurrence, cancer-specific mortality, and all-cause mortality following RNU. Addition of the CMS to a model that included standard clinicopathologic predictors significantly improved predictive accuracy by 2.7% for disease recurrence, 3.9% for cancer-specific mortality, and 4.0% for all-cause mortality, which were the highest among other prognostic models using each marker alone or combinations of two. The study is limited by its retrospective nature. Conclusions: Although the use of each inflammatory marker alone may be as predictive as clinicopathologic indices for prognosis, combinations like CMS can provide more accurate prognostic models following RNU. Patient summary: Elevation of blood-based inflammatory markers may be useful for predicting prognosis because of their low cost and accessibility. Among blood-based indices, we examined the efficacy of preoperative neutrophil-to-lymphocyte ratio, plasma fibrinogen, and serum C-reactive protein levels. Although use of each marker alone provides additional prognostic information, the combination of all three markers would be more predictive than any single marker or combinations of two.

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Down-regulation of NF kappa B activation is an effective therapeutic modality in acquired platinum-resistant bladder cancer

Ito, Yujiro, Kikuchi, Eiji, Tanaka, Nobuyuki, Kosaka, Takeo, Suzuki, Eriko, Mizuno, Ryuichi, Shinojima, Toshiaki, Miyajima, Akira, Umezawa, Kazuo, Oya, Mototsugu

BMC CANCER 15 2112 - 2120 2015.04

Research paper (scientific journal), ISSN 1471-2407

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Impact of an Adjuvant Chemotherapeutic Regimen on the Clinical Outcome in High Risk Patients with Upper Tract Urothelial Carcinoma: A Japanese Multi-Institution Experience

Shirotake, Suguru, Kikuchi, Eiji, Tanaka, Nobuyuki, Matsumoto, Kazuhiro, Miyazaki, Yasumasa, Kobayashi, Hiroaki, Ide, Hiroki, Obata, Jun, Hoshino, Katsura, Kaneko, Gou, Hagiwara, Masayuki, Kosaka, Takeo, Kanao, Kent, Kodaira, Kiichiro, Hara, Satoshi, Oyama, Masafumi, Momma, Tetsuo, Miyajima, Akira, Nakagawa, Ken, Hasegawa, Shintaro, Nakajima, Yosuke, Oya, Mototsugu

JOURNAL OF UROLOGY 193 ( 4 ) 1122 - 1128 2015.04

Research paper (scientific journal), ISSN 0022-5347

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Prognostic Impact of Renin–Angiotensin System Blockade on Renal Cell Carcinoma After Surgery

Miyajima Akira, Yazawa Satoshi, Kosaka Takeo, Tanaka Nobuyuki, Shirotake Suguru, Mizuno Ryuichi, Kikuchi Eiji, Oya Mototsugu

Annals of Surgical Oncology 22 ( 11 ) 3751 - 3759 2015.02

Research paper (scientific journal), ISSN 1068-9265

Background: Angiotensin 2 is a key biologic peptide in the renin–angiotensin system (RAS) that regulates blood pressure and renal hemodynamics. The potential role of the RAS in the promotion of tumor growth, angiogenesis, and metastasis also has been shown in the past few decades. This study investigated the prognostic impact of RAS blockade on patients with renal cell carcinoma (RCC) after surgery. Methods: The study identified 557 patients with pathologically diagnosed RCC (pT1-4 N0M0) and evaluated the prognostic factors after surgery for patients administered or not administered angiotensin-converting enzyme inhibitors (ACEs) or angiotensin 2 receptor blockers (ARBs). Results: The median follow-up period was 5.1 years. Radical nephrectomy was performed for 349 patients (62.7 %), whereas the remaining 208 patients (37.3 %) underwent partial nephrectomy. A total of 104 patients (18.7 %) were administered RAS inhibitors: ACEs (n = 22) or ARBs (n = 82). Multivariate analysis showed that administration of RAS inhibitors (P = 0.044; HR 2.69), longer tumor length (P < 0.001; HR 1.02), high-grade tumor (P < 0.001; HR 3.55), and positive microvascular invasion (P < 0.003; HR 3.13) were not independent risk factors for a decrease in subsequent disease-specific survival after surgery for RCC. The 5-year disease-specific survival rate was 96.8 % among the patients administered RAS inhibitors and 89.8 % among their counterparts (P = 0.019). Conclusions: The authors propose renin–angiotensin blockade as a possible potent choice for effective treatment after surgical treatment of RCC.

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A Multi-Institutional Validation of the Prognostic Value of the Neutrophil-to-Lymphocyte Ratio for Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy

Tanaka, Nobuyuki, Kikuchi, Eiji, Kanao, Kent, Matsumoto, Kazuhiro, Shirotake, Suguru, Miyazaki, Yasumasa, Kobayashi, Hiroaki, Kaneko, Gou, Hagiwara, Masayuki, Ide, Hiroki, Obata, Jun, Hoshino, Katsura, Hayakawa, Nozomi, Kosaka, Takeo, Hara, Satoshi, Oyama, Masafumi, Momma, Tetsuo, Nakajima, Yosuke, Jinzaki, Masahiro, Oya, Mototsugu

ANNALS OF SURGICAL ONCOLOGY 21 ( 12 ) 4041 - 4048 2014.11

Research paper (scientific journal), ISSN 1068-9265

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Ductal Adenocarcinoma of the Prostate Forming a Mass in the Retrovesical Space

Niwa, Naoya, Tanaka, Nobuyuki, Horinaga, Minoru, Hayashi, Yuichiro, Hisazumi, Hiromi, Masuda, Takeshi

UROLOGY 84 ( 4 ) E9 - E10 2014.10

Research paper (scientific journal), ISSN 0090-4295

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