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3. Immunohistochemical Expression of p53 and FGFR3 Predicts Response to Enfortumab Vedotin in Metastatic Urothelial Carcinoma.

Author

Nagata, Yujiro, Minato, Akinori, Aono, Hisami, Kimuro, Rieko, Higashijima, Katsuyoshi, Tomisaki, Ikko, Harada, Kenichi, Miyamoto, Hiroshi, and Fujimoto, Naohiro

Subjects
*TRANSITIONAL cell carcinoma, *BLADDER cancer, *URINARY organs, *IMMUNOHISTOCHEMISTRY, *BIOMARKERS
Abstract

Locally advanced or metastatic urothelial carcinoma is a genomically and molecularly heterogeneous disease associated with various clinical outcomes. We aimed to evaluate the association between the status of p53/FGFR3 expression and the efficacy of enfortumab vedotin (EV) in metastatic urothelial carcinoma. We evaluated the association between p53 (abnormal vs. wild-type) or FGFR3 (high vs. low) expression determined by immunohistochemistry and response to EV in 28 patients with metastatic urothelial carcinoma. Overall, 60.7% showed abnormal p53, and 17.9% had high FGFR3 expression. The rates of objective response to EV were statistically higher in patients with abnormal p53 than in those with wild-type p53 (p = 0.038). Patients with pure urothelial carcinoma (n = 18) and low FGFR3 showed significantly better response to EV than those with high FGFR3. When the statuses of p53 and FGFR3 were combined, abnormal p53/low FGFR3 (vs. wild-type p53/high FGFR3) was strongly associated with favorable outcomes in both the entire cohort (p = 0.002) and in cases of pure urothelial carcinoma only (p = 0.023). Immunohistochemically abnormal p53 tumors were found to respond well to EV, while high FGFR3 tumors had a poorer response. Thus, p53 and FGFR3 are potential biomarkers for predicting response to EV treatment in patients with urothelial carcinoma. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Prognostic Impact of Histologic Subtype and Divergent Differentiation in Patients with Metastatic Urothelial Carcinoma Treated with Enfortumab Vedotin: A Multicenter Retrospective Study

Author

Minato, Akinori, primary, Furubayashi, Nobuki, additional, Nagata, Yujiro, additional, Tomoda, Toshihisa, additional, Masaoka, Hiroyuki, additional, Song, Yoohyun, additional, Hori, Yoshifumi, additional, Kiyoshima, Keijiro, additional, Negishi, Takahito, additional, Kuroiwa, Kentaro, additional, Seki, Narihito, additional, Tomisaki, Ikko, additional, Harada, Kenichi, additional, Nakamura, Motonobu, additional, and Fujimoto, Naohiro, additional

Published
2024
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11. Efficacy and Tolerability of Enfortumab Vedotin for Metastatic Urothelial Carcinoma: Early Experience in the Real World

Author

MINATO, AKINORI, primary, KIMURO, RIEKO, additional, OHNO, DAICHI, additional, TANIGAWA, KENTAROU, additional, KURETAKE, KEISUKE, additional, MATSUKAWA, TAKUO, additional, TAKABA, TOMOHISA, additional, JOJIMA, KAZUMASA, additional, HARADA, MIRII, additional, HIGASHIJIMA, KATSUYOSHI, additional, NAGATA, YUJIRO, additional, TOMISAKI, IKKO, additional, HARADA, KENICHI, additional, FUJIMOTO, NAOHIRO, additional, and MIYAMOTO, HIROSHI, additional

Published
2023
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17. Differential impact of proton pump inhibitor on survival outcomes of patients with advanced urothelial carcinoma treated with chemotherapy versus pembrolizumab.

Author

Tomisaki, Ikko, Harada, Mirii, Sakano, Shigeru, Terado, Michikazu, Hamasuna, Ryoichi, Harada, Shuji, Matsumoto, Hiroomi, Akasaka, Soichiro, Nagata, Yujiro, Minato, Akinori, Harada, Ken‐ichi, and Fujimoto, Naohiro

Subjects
PROTON pump inhibitors, TRANSITIONAL cell carcinoma, SURVIVAL rate, OVERALL survival, TREATMENT effectiveness
Abstract

Objectives: We clarified the effect of concomitant proton pump inhibitor use on oncological outcomes in patients with advanced urothelial carcinoma treated either with chemotherapy or immune checkpoint inhibitor. Methods: We retrospectively reviewed patients with advanced urothelial carcinoma who received paclitaxel–gemcitabine therapy or pembrolizumab after platinum‐based chemotherapy. The patients were divided into four groups based on the treatment regimen and the concomitant use of proton pump inhibitor. We compared survival outcomes between the groups and determined which factors predicted overall survival. Results: Among the 60 and 75 patients treated with paclitaxel–gemcitabine and pembrolizumab, 15 and 29 used a concomitant proton pump inhibitor. Progression‐free and overall survival was significantly shorter in patients who were administered pembrolizumab with concomitant proton pump inhibitor compared to those without. The use of a concomitant proton pump inhibitor had no effect on survival outcomes in patients who received paclitaxel–gemcitabine therapy. Furthermore, progression‐free and overall survival were significantly shorter in patients treated with paclitaxel–gemcitabine therapy compared to those treated with pembrolizumab among patients without concomitant proton pump inhibitor. In contrast, there was no difference in survival outcomes between the two regimens among patients with concomitant proton pump inhibitor. Concomitant proton pump inhibitor use was associated with poor overall survival only in patients treated with pembrolizumab. Conclusion: The use of a concomitant proton pump inhibitor use had no impact on oncological outcomes in patients with advanced urothelial carcinoma treated with paclitaxel–gemcitabine therapy, different from those treated with pembrolizumab. [ABSTRACT FROM AUTHOR]

Published
2023
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18. Association Between Body Mass Index and Outcomes in Patients With Urothelial Carcinoma Treated With Pembrolizumab

Author

TOMISAKI, IKKO, primary, HARADA, MIRII, additional, SAKANO, SHIGERU, additional, TERADO, MICHIKAZU, additional, HAMASUNA, RYOICHI, additional, HARADA, SHUJI, additional, MATSUMOTO, HIROOMI, additional, AKASAKA, SOICHIRO, additional, NAGATA, YUJIRO, additional, MINATO, AKINORI, additional, HARADA, KEN-ICHI, additional, and FUJIMOTO, NAOHIRO, additional

Published
2022
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20. Protective role of mineralocorticoid receptor signaling in urothelial tumorigenesis

Author

Nagata, Yujiro, Matsukawa, Takuo, Goto, Takuro, Teramoto, Yuki, Jiang, Guiyang, Fujimoto, Naohiro, and Miyamoto, Hiroshi

Subjects
Original Article
Abstract

The expression status of mineralocorticoid receptor (MR) and its biological significance in human urothelial carcinoma remain unknown. The present study aimed to determine the functional role of MR in the development of urothelial cancer. In human normal urothelial SVHUC cells with exposure to a chemical carcinogen 3-methylcholanthrene (MCA), we assessed the effects of a natural MR ligand, aldosterone, and 3 MR antagonists, including spironolactone, eplerenone, and esaxerenone, as well as knockdown of MR via shRNA virus infection, on their neoplastic/malignant transformation. The in vitro system with carcinogen challenge showed that aldosterone and anti-mineralocorticoids significantly prevented and promoted, respectively, the neoplastic transformation of SVHUC cells. Similarly, MR knockdown in SVHUC cells considerably induced MCA-mediated neoplastic transformation, compared with a control subline. In addition, MR knockdown or antagonist treatment resulted in increases in the expression of β-catenin, c-Fos, and N-cadherin, and a decrease in that of E-cadherin. Meanwhile, spironolactone, which is known to possess anti-androgenic activity, rather suppressed the neoplastic transformation of a SVHUC subline stably expressing wild-type androgen receptor, indicating its dominant effect via the androgen receptor pathway. Immunohistochemistry in surgical specimens detected MR signals in 77 (98.7%; 23.1% weak/1+, 42.3% moderate/2+, and 33.3% strong/3+) of 78 non-invasive bladder tumors, which was significantly (P

Published
2023

26. Prognostic Value of Squamous Differentiation in Upper Tract Urothelial Carcinoma Treated With Radical Nephroureterectomy

Author

AKINORI MINATO, HIROTSUGU NOGUCHI, RIEKO KIMURO, HARADA MIRII, NAGATA YUJIRO, YOSHITAKA HASEGAWA, IKKO TOMISAKI, KENICHI HARADA, and NAOHIRO FUJIMOTO

Subjects
Aged, 80 and over, Male, Cancer Research, Cell Differentiation, General Medicine, Kaplan-Meier Estimate, Prognosis, Nephroureterectomy, Disease-Free Survival, Oncology, Predictive Value of Tests, Carcinoma, Squamous Cell, Humans, Female, Neoplasm Metastasis, Urothelium, Aged, Proportional Hazards Models
Abstract

This study retrospectively investigated the impact of squamous differentiation on the prognosis of patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU).Among the 244 consecutive patients who underwent RNU at our Institution from May 2005 to October 2019, 224 were analysed. Metastasis-free (MFS) and overall (OS) survival rates were evaluated using Kaplan-Meier analysis and Cox regression analysis.With a median follow-up time of 58 months, the groups with pure UTUC (n=197) and UTUC with squamous differentiation (n=27) had 5-year MFS rates of 65.2% and 40.9% (p=0.005) and 5-year OS rates of 74.4% and 49.0% (p=0.002), respectively. Multivariate analyses revealed that the presence of squamous differentiation was significantly associated with poor MFS (hazard ratio=1.88; p=0.027) and OS (hazard ratio=1.70; p=0.048).Squamous differentiation in UTUC appears to be an independent predictor of poor prognosis after RNU for UTUC.

Published
2021

30. Clinical significance of early kinetics of C‑reactive protein in patients with advanced urothelial carcinoma treated with pembrolizumab: Flare response and baseline levels predict oncological outcomes.

Author

Tomisaki, Ikko, Harada, Mirii, Sakano, Shigeru, Terado, Michikazu, Hamasuna, Ryoichi, Harada, Shuji, Matsumoto, Hiroomi, Akasaka, Soichiro, Nagata, Yujiro, Minato, Akinori, Harada, Ken-Ichi, and Fujimoto, Naohiro

Subjects
DRUG side effects, TRANSITIONAL cell carcinoma, C-reactive protein, OVERALL survival, PROGRESSION-free survival
Abstract

Data on the C-reactive protein (CRP) flare response in patients with metastatic and unresectable urothelial carcinoma (mUC) are limited. The present study aimed to clarify the clinical significance of the CRP flare response in patients with mUC who received pembrolizumab. Between March 2018 and December 2022, patients with mUC who received pembrolizumab following chemotherapy were retrospectively reviewed. Patients were categorized into three groups based on the early kinetics of CRP: i) Flare-responders, in which CRP levels increased >2-fold from baseline (BL) within 1 month after pembrolizumab administration (CRP flare) and decreased to below-BL levels within 3 months; ii) responders, in which CRP levels decreased ≥30% from baseline within 3 months without CRP flare; and iii) non-responders, which included the remaining patients. Tumor response, survival and incidence of immune-related adverse events (AEs) were compared between the groups. Of the 108 eligible patients, 17 (16%), 27 (25%) and 64 (59%) were classified as CRP flare-responders, CRP responders and CRP non-responders, respectively. Objective response rate was higher in CRP flare-responders and CRP responders than in CRP non-responders. Progression-free survival and overall survival were longer in CRP flare-responders and CRP responders than in CRP non-responders. Among CRP flare-responders, patients with low BL CRP levels had a better tumor response and survival than patients with high BL CRP levels. Notably, there was no difference in the incidence of immune-related AEs. In patients with mUC who received pembrolizumab, CRP flare-responders showed favorable oncological outcomes; therefore, BL CRP levels could predict oncological outcomes in CRP flare-responders. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Identification of BXDC2 as a Key Downstream Effector of the Androgen Receptor in Modulating Cisplatin Sensitivity in Bladder Cancer

Author

Jiang, Guiyang, primary, Teramoto, Yuki, additional, Goto, Takuro, additional, Mizushima, Taichi, additional, Inoue, Satoshi, additional, Ide, Hiroki, additional, Nagata, Yujiro, additional, Kashiwagi, Eiji, additional, Baras, Alexander S., additional, Netto, George J., additional, Yang, Zhiming, additional, and Miyamoto, Hiroshi, additional

Published
2021
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36. Abstract 2071: Identification of FOXO1 as a tumor suppressor modulated by androgen receptor/estrogen receptor-βsignals: Implications for bladder cancer promotion and chemoresistance

Author

Ide, Hiroki, primary, Inoue, Satoshi, additional, Mizushima, Taichi, additional, Jiang, Guiyang, additional, Goto, Takuro, additional, Nagata, Yujiro, additional, Teramoto, Yuki, additional, Netto, George J., additional, Oya, Mototsugu, additional, and Miyamoto, Hiroshi, additional

Published
2020
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38. MP17-11 IDENTIFICATION OF FOXO1 AS A TUMOR SUPPRESSOR MODULATED BY ANDROGEN RECEPTOR/ESTROGEN RECEPTOR-β SIGNALS: IMPLICATIONS FOR BLADDER CANCER PROMOTION AND CHEMORESISTANCE

Author

Ide*, Hiroki, primary, Inoue, Satoshi, additional, Mizushima, Taichi, additional, Jiang, Guiyang, additional, Goto, Takuro, additional, Nagata, Yujiro, additional, Teramoto, Yuki, additional, Oya, Mototsugu, additional, Netto, George, additional, and Miyamoto, Hiroshi, additional

Published
2020
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39. FOXO1 as a tumor suppressor inactivated via AR/ERβ signals in urothelial cells

Author

Ide, Hiroki, primary, Mizushima, Taichi, additional, Jiang, Guiyang, additional, Goto, Takuro, additional, Nagata, Yujiro, additional, Teramoto, Yuki, additional, Inoue, Satoshi, additional, Li, Yi, additional, Kashiwagi, Eiji, additional, Baras, Alexander S, additional, Netto, George J, additional, Kawahara, Takashi, additional, and Miyamoto, Hiroshi, additional

Published
2020
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43. Epitaxial AB[O.sub.3]-type oxide films prepared by the sol-gel method

Author

Taniguchi, Takashi, Fukuoka, Naoto, Ozawa, Tadashi C., Nagata, Yujiro, Noro, Yoshihiko, and Samata, Hiroaki

Subjects
Epitaxy -- Research, Epitaxy -- Magnetic properties, Electromagnetism -- Research, Dielectric films -- Research, Dielectric films -- Magnetic properties, Thin films -- Research, Thin films -- Magnetic properties, Business, Electronics, Electronics and electrical industries
Abstract

Epitaxial thin films of AB[O.sub.3] (A = Ca, Sr; B = 3d, 4d transition metal) were fabricated on a (100)-SrTi[O.sub.3] substrate by spin coating an organic metal and subjecting it to successive heal treatments. Results of X-ray diffraction and transmission electron microscopy indicate that the growth is pseudomorphic and the [001] axis of the AB[O.sub.3] film is perpendicular to the (100) plane of the SrTi[O.sub.3] substrate and that its pseudocubic axes align parallel to the cubic axes of the SrTi[O.sub.3] crystal. Epitaxial AB[O.sub.3] thin films have similar transport and magnetic properties to those of bulk materials. Index Terms--Coatings, epitaxial growth, sol-gel, transition metal oxides.

Published
2005

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