Article
Biochemistry & Molecular Biology
Dewei Jiang, Ting Qiu, Junjiang Peng, Siyuan Li, Tala, Wenlong Ren, Chuanyu Yang, Yi Wen, Chuan-Huizi Chen, Jian Sun, Yingying Wu, Rong Liu, Jun Zhou, Kongming Wu, Wen Liu, Xiaoyun Mao, Zhongmei Zhou, Ceshi Chen
Summary: Y-box binding protein 1 (YB-1) is highly expressed in various cancers, including basal-like breast cancer (BLBC), and functions as a transcription factor and an epigenetic regulator. The study reveals a positive correlation between YB-1 and Kruppel-like factor 5 (KLF5) expression in breast cancer patients, as well as a negative correlation with Dachshund homolog 1 (DACH1) expression. Mechanistically, YB-1 enhances KLF5 expression through transcription activation and mRNA stabilization, promoting cancer cell proliferation by regulating the expression of specific genes. The phosphorylation of YB-1 by ribosomal S6 kinase 2 (RSK2) promotes the formation of YB-1/KLF5 transcriptional complex and is involved in BLBC progression. These findings suggest that the RSK2-YB-1-KLF5-KRT16/Ly6D axis may serve as potential diagnostic markers and therapeutic targets for BLBC.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Pharmacology & Pharmacy
Joanna Jaworska, Arkadiusz Orchel, Anna Kaps, Marzena Jaworska-Kik, Anna Hercog, Mateusz Stojko, Jakub Wlodarczyk, Monika Musial-Kulik, Malgorzata Pastusiak, Marcelina Bochenek, Marcin Godzierz, Janusz Kasperczyk
Summary: Prostate cancer is the second most common cancer in males. Radical prostatectomy is a common treatment for locally advanced prostate cancer, but recurrence after surgery can occur. This study developed drug-eluting bioresorbable patches using electrospinning technology for local delivery, which showed potential for prostate cancer therapy.
Article
Oncology
Igor Tsaur, Anita Thomas, Michelle Monecke, Marion Zugelder, Jochen Rutz, Timothy Grein, Sebastian Maxeiner, Hui Xie, Felix K. -H. Chun, Florian Rothweiler, Jindrich Cinatl, Martin Michaelis, Axel Haferkamp, Roman A. Blaheta
Summary: The natural compound amygdalin has been shown to inhibit the growth and disseminative properties of taxane-resistant prostate cancer cells. This finding is important for identifying effective treatment options for metastatic prostate cancer.
Review
Biochemistry & Molecular Biology
Ryan Cronin, Greg N. Brooke, Filippo Prischi
Summary: Prostate cancer is the second most commonly occurring cancer in men, with standard treatments including androgen-deprivation therapy and AR signaling inhibitors. However, the development of therapy resistance can occur. The p90 ribosomal S6 kinase (RSK) family is a potential novel target for treatment, exhibiting roles in transcription and translation regulation.
Article
Multidisciplinary Sciences
Maria J. Martinez, Rolando D. Z. Lyles, Nahuel Peinetti, Alex M. Grunfeld, Kerry L. Burnstein
Summary: This study found that BUB1 kinase is over-expressed in taxane resistant prostate cancer and a specific BUB1 kinase inhibitor can overcome this resistance. The study also found that androgen receptor variant AR-V7 can increase BUB1 levels and reduce sensitivity to taxanes.
Article
Oncology
Shayan Khozooei, Soundaram Veerappan, Irina Bonzheim, Stephan Singer, Cihan Gani, Mahmoud Toulany
Summary: The study demonstrated that targeting RSK and AKT, as well as using fisetin, effectively inhibited phosphorylation of YB-1, affected DSB repair pathways, and increased radiosensitivity of colorectal cancer cells, regardless of the KRAS mutation status.
RADIOTHERAPY AND ONCOLOGY
(2023)
Article
Endocrinology & Metabolism
Olivia S. Chao, Oscar B. Goodman
Summary: This study indicates that DDR genes, particularly DNA-PKc, play a crucial role in promoting taxane resistance in mCRPC. Inhibiting DNA-PKc may provide a novel strategy to restore taxane sensitivity in taxane-refractory mCRPC.
Article
Oncology
Samusi Adediran, Linbo Wang, Mohammad Afnan Khan, Wei Guang, Xiaoxuan Fan, Hancai Dan, Jianfei Qi, Steven M. Jay, France Carrier, Arif Hussain
Summary: The study explores the efficacy of targeting ErbB receptors and AKT in prostate cancer, finding that simultaneous targeting is more effective than individual targeting, especially in resistant cells. This provides a new avenue for treating refractory prostate cancer.
Article
Multidisciplinary Sciences
Derek K. Cheng, Tobiloba E. Oni, Jennifer S. Thalappillil, Youngkyu Park, Hsiu-Chi Ting, Brinda Alagesan, Nadia V. Prasad, Kenneth Addison, Keith D. Rivera, Darryl J. Pappin, Linda Van Aelst, David A. Tuveson
Summary: The study identified protein interactors of active KRAS in PDAC cells using proximity labeling, revealing that RSK1 selectively interacts with membrane-bound KRASG12D through NF1 and SPRED2. It was found that membrane RSK1 mediates negative feedback on WT RAS signaling and impedes the proliferation of pancreatic cancer cells upon the ablation of mutant KRAS in PDAC, highlighting the role of WT RAS signaling in promoting adaptive resistance to mutant KRAS-specific inhibitors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Hiroshi Hongo, Takeo Kosaka, Yoko Suzuki, Shuji Mikami, Junichi Fukada, Mototsugu Oya
Summary: The study identified etoposide as a promising treatment candidate for CBZ-resistant CRPC by inhibiting TOP2A expression, which could potentially be an optimal treatment for CRPC in the post-CBZ setting.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, Research & Experimental
Jin-Zhu Wang, Hong Zhu, Pu You, Hui Liu, Wei-Kang Wang, Xiaojuan Fan, Yun Yang, Keren Xu, Yingfeng Zhu, Qunyi Li, Ping Wu, Chao Peng, Catherine C. L. Wong, Kaicheng Li, Yufeng Shi, Nu Zhang, Xiuxing Wang, Rong Zeng, Ying Huang, Liusong Yang, Zefeng Wang, Jingyi Hui
Summary: In this study, the researchers found that overexpression of YB-1 protein is associated with activation of the mTOR signaling pathway in glioblastoma. YB-1 promotes the translation of CCT4, leading to mTOR activation, and also autoregulates its own translation to sustain mTOR signaling. Targeting YB-1 with RNA decoy therapy slows tumor growth and improves survival.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Pharmacology & Pharmacy
Jana B. B. Lampe, Priyanka P. P. Desai, Amit K. K. Tripathi, Nirupama A. A. Sabnis, Zhe Chen, Amalendu P. P. Ranjan, Jamboor K. K. Vishwanatha
Summary: We developed cabazitaxel-loaded nanoparticles using PLGA and introduced a bone-targeting moiety on the surface. These nanoparticles showed the ability to inhibit EMT, invasion and migration in prostate cancer cells. Treatment with targeted cabazitaxel-loaded nanoparticles led to decreased expression of EMT marker, Vimentin, and increased expression of E-cadherin, resulting in suppressed cancer progression. Furthermore, phosphorylated Src and cofilin levels were affected, potentially impacting migration and invasion pathways. The nanoparticles also showed increased expression of p-120 catenin and inhibition in IL-8 expression. Overall, targeted cabazitaxel-loaded nanoparticles hold promise for treating bone-metastatic prostate cancer.
Article
Oncology
Masaki Shiota, Yohei Sekino, Shigehiro Tsukahara, Tatsuro Abe, Fumio Kinoshita, Kenjiro Imada, Shohei Ueda, Miho Ushijima, Shohei Nagakawa, Takashi Matsumoto, Eiji Kashiwagi, Ario Takeuchi, Junichi Inokuchi, Takeshi Uchiumi, Yoshinao Oda, Masatoshi Eto
Summary: The study indicates that Y-box binding protein-1 (YB-1) is overexpressed in castration-resistant prostate cancer (CRPC) through gene amplification, which contributes to the progression of CRPC by regulating the expression of AR and AR V7. Additionally, YB-1 amplification is associated with poor prognosis in CRPC.
Article
Oncology
Edoardo Francini, Fang-Shu Ou, Justin Rhoades, Eric G. Wolfe, Edward P. O'Connor, Gavin Ha, Gregory Gydush, Kaitlin M. Kelleher, Rupal S. Bhatt, Steven P. Balk, Christopher J. Sweeney, Viktor A. Adalsteinsson, Mary-Ellen Taplin, Atish D. Choudhury
Summary: This study aimed to evaluate the association between ABC transporter gene ABCB1 amplification and primary resistance to docetaxel or cabazitaxel in mCRPC patients using sparse whole genome sequencing, but no significant correlation was found. Future studies with larger sample sizes including ABCB1 amplification and a suite of putative biomarkers are needed to draw definitive conclusions.
Article
Urology & Nephrology
Vicenc Ruiz de Porras, Xieng C. Wang, Luis Palomero, Mercedes Marin-Aguilera, Carme Sole-Blanch, Alberto Indacochea, Natalia Jimenez, Sara Bystrup, Martin Bakht, Vincenza Conteduca, Josep M. Piulats, Oscar Buisan, Jose F. Suarez, Juan Carlos Pardo, Elena Castro, David Olmos, Himisha Beltran, Begona Mellado, Eva Martinez-Balibrea, Albert Font, Alvaro Aytes
Summary: The study identified the anticancer efficacy of taxane-platinum combinations in metastatic castration-resistant prostate cancer through patient data and preclinical models. Taxanes reduce cancer cell escape mechanisms, making the cells more vulnerable to platinum-based treatments.
Article
Oncology
Kazuo Nishimura, Masaki Shiota, Masatoshi Eto, Takefumi Satoh, Angela Stroupe, Caroline Seo, Alyssa Uzumcu, Dianne Athene Ledesma
Summary: This study aimed to understand the perspectives of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) on their quality of life, including unmet needs and what they consider most important in treatment outcomes. A gap analysis was conducted to identify the missing elements from the patient perspective and guide the development of patient-reported outcomes (PROs) for nmCRPC in Japan.
Article
Urology & Nephrology
Takashi Matsumoto, Yoshifumi Hori, Masaki Shiota, Leandro Blas, Motonobu Nakamura, Narihito Seki, Kentaro Kuroiwa, Akira Yokomizo, Futoshi Morokuma, Keijiro Kiyoshima, Masatoshi Eto
Summary: This study evaluated the safety and effectiveness of Ra-223 treatment for bone-metastatic castration-resistant prostate cancer in real-world practice. The study found that the number of treatment cycles, baseline anemia, and bone pain were associated with overall survival.
INTERNATIONAL JOURNAL OF UROLOGY
(2023)
Article
Urology & Nephrology
Ken Lee, Masaki Shiota, Dai Takamatsu, Miho Ushijima, Leandro Blas, Ayami Okabe, Shunichi Kajioka, Shunsuke Goto, Fumio Kinoshita, Takashi Matsumoto, Keisuke Monji, Eiji Kashiwagi, Junichi Inokuchi, Yoshinao Oda, Masatoshi Eto
Summary: This study investigated the impact of extended pelvic lymph node dissection (ePLND) on urinary incontinence (UI) after robot-assisted radical prostatectomy (RARP). The results showed that the urinary continence rate at 1 month postoperatively was lower among patients who underwent ePLND, but there was no significant difference at 3, 6, and 12 months after RARP. Additionally, ePLND and larger prostate volume were associated with an increased UI rate.
INTERNATIONAL JOURNAL OF UROLOGY
(2023)
Article
Pharmacology & Pharmacy
Masaki Shiota, Ryo Inoue, Kojiro Tashiro, Keita Kobayashi, Shizuyo Horiyama, Hiromi Kanji, Masatoshi Eto, Shin Egawa, Jun Haginaka, Hideyasu Matsuyama
Summary: This study aimed to evaluate the efficacy and safety of adding dutasteride, a 5 alpha-reductase inhibitor, to abiraterone for the treatment of castration-resistant prostate cancer. The results showed that the combination therapy achieved a significant reduction in prostate-specific antigen levels without severe adverse events. Genotype analysis revealed that HSD3B1 and SRD5A2 genotypes were associated with drug metabolism and efficacy. These findings provide valuable insights for further investigation and randomized trials.
JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Review
Oncology
Masaki Shiota, Satoshi Endo, Leandro Blas, Naohiro Fujimoto, Masatoshi Eto
Summary: Castration resistance is caused by the abnormal activation of androgen receptor (AR) signaling through intracrine activation of androgen precursors from adrenal glands. To address this, novel AR pathway inhibitors (ARPIs) have been developed to suppress androgen synthesis or AR activation. However, resistance to these ARPIs can occur due to the persistent androgen environment despite intensive AR signaling suppression.
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
(2023)
Article
Oncology
Masashi Kaitsumaru, Masaki Shiota, Dai Takamatsu, Leandro Blas, Takashi Matsumoto, Junichi Inokuchi, Yoshinao Oda, Masatoshi Eto
Summary: A 67-year-old man with metastatic prostate cancer showed radiographic progression after 1 year of leuprorelin and enzalutamide treatment. Liver metastasis and elevation of nerve-specific enolase were observed. Biopsy confirmed neuroendocrine carcinoma with BRCA1 mutation detected in the prostate sample. Olaparib treatment achieved significant remission, but was associated with interstitial pneumonia.
INTERNATIONAL CANCER CONFERENCE JOURNAL
(2023)
Article
Oncology
Masaki Shiota, Shuichi Tatarano, Toshiyuki Kamoto, Hideyasu Matsuyama, Hideki Sakai, Tsukasa Igawa, Tomomi Kamba, Naohiro Fujimoto, Yuya Sekine, Hiroko Kimura, Shintaro Narita, Naoki Terada, Yukihide Momozawa, Shusuke Akamatsu, Tomonori Habuchi, Akira Yokomizo, Seiji Naito, Masatoshi Eto
Summary: This study aimed to identify genetic markers that could predict the outcome of androgen-deprivation therapy (ADT) for advanced prostate cancer. Through a genome-wide association study (GWAS), single-nucleotide polymorphisms (SNPs) associated with radiographic progression-free survival (rPFS) and adverse events (AEs) were identified. Validation studies confirmed the association of these SNPs with ADT outcomes, and a genetic prognostic model using these SNPs showed excellent predictive efficacy for progression-free survival and overall survival. The study also revealed SNPs associated with AEs in ADT, such as de novo diabetes mellitus, arthralgia, and de novo dyslipidemia.
ENDOCRINE-RELATED CANCER
(2023)
Article
Urology & Nephrology
Leandro Blas, Masaki Shiota, Shigehiro Tsukahara, Shunsuke Goto, Fumio Kinoshita, Takashi Matsumoto, Keisuke Monji, Eiji Kashiwagi, Junichi Inokuchi, Masatoshi Eto
Summary: This study aimed to compare the detection of clinically significant prostate cancer (csPC) between MRI/ultrasound fusion-targeted prostate biopsy and systematic biopsy (SBx) in biopsy-naive Japanese men. The results showed that MRI/ultrasound fusion-targeted biopsy had better performance in detecting csPC and reduced the detection of non-csPC. However, performing MRI/ultrasound fusion-targeted biopsy alone would miss some csPC, indicating the need for a combination with SBx.
INTERNATIONAL JOURNAL OF UROLOGY
(2023)
Article
Oncology
Kazuyuki Numakura, Makito Miyake, Mizuki Kobayashi, Yumina Muto, Yuya Sekine, Nobutaka Nishimura, Kota Iida, Masanori Shiga, Shuichi Morizane, Takahiro Yoneyama, Yoshiaki Matsumura, Takashige Abe, Takeshi Yamada, Kazumasa Matsumoto, Junichi Inokuchi, Naotaka Nishiyama, Rikiya Taoka, Takashi Kobayashi, Takahiro Kojima, Hiroshi Kitamura, Hiroyuki Nishiyama, Kiyohide Fujimoto, Tomonori Habuchi
Summary: Upper urinary tract urothelial carcinoma (UTUC) is rare after intravesical bacillus Calmette-Guerin (BCG) therapy, and its incidence, clinical impact, and risk factors are not fully understood. This retrospective cohort study aimed to investigate the clinical implications of UTUC after intravesical BCG therapy. A total of 3226 patients diagnosed with non-muscle-invasive bladder cancer (NMIBC) and treated with intravesical BCG therapy were included. UTUC impact was assessed by comparing recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) rates. Factors associated with UTUC after BCG therapy were analyzed. Among the 2873 patients with medical history analysis, UTUC was detected in 175 patients (6.1%) during the follow-up period. Patients with UTUC had worse survival rates. Tumor multiplicity, Connaught strain treatment, and intravesical recurrence were identified as predictive factors for subsequent UTUC diagnosis after BCG therapy.
Review
Pharmacology & Pharmacy
Masaki Shiota, Miho Ushijima, Shigehiro Tsukahara, Shohei Nagakawa, Leandro Blas, Dai Takamatsu, Satoshi Kobayashi, Takashi Matsumoto, Junichi Inokuchi, Masatoshi Eto
Summary: This study explored the cellular mechanisms involved in steroidogenesis that lead to resistance to the antiandrogen agent darolutamide in prostate cancer. The overexpression of HSD3B1 and its upstream regulator NR5A2 were found in darolutamide-resistant cells, and they were induced by darolutamide treatment and AR knockdown. Inhibiting the NR5A2/HSD3B1 pathway can increase cellular sensitivity to darolutamide, suggesting it as a potential therapeutic strategy to overcome resistance.
DRUG RESISTANCE UPDATES
(2023)
Article
Urology & Nephrology
Masaki Shiota, Naoki Terada, Takahiro Kimura, Hiroshi Kitamura, Toshiyuki Kamoto, Masatoshi Eto, Japanese Urological Oncol Grp JUOG
INTERNATIONAL JOURNAL OF UROLOGY
(2023)
Article
Urology & Nephrology
Leandro Blas, Masaki Shiota, Takashi Matsumoto, Yoshifumi Hori, Motonobu Nakamura, Narihito Seki, Kentaro Kuroiwa, Akira Yokomizo, Futoshi Morokuma, Keijiro Kiyoshima, Masatoshi Eto
Summary: This study investigated the effect of bone-modifying agents (BMA) on the occurrence of symptomatic skeletal events (SSE) in patients with bone metastatic castration-resistant prostate cancer (CRPC) treated with Radium-223 (Ra-223). The results showed that BMA use was associated with favorable SSE-free survival.
INTERNATIONAL JOURNAL OF UROLOGY
(2023)
Article
Urology & Nephrology
Leandro Blas, Masaki Shiota, Hideaki Miyake, Masayuki Takahashi, Mototsugu Oya, Norihiko Tsuchiya, Naoya Masumori, Hideyasu Matsuyama, Wataru Obara, Nobuo Shinohara, Kiyohide Fujimoto, Masahiro Nozawa, Kojiro Ohba, Chikara Ohyama, Katsuyoshi Hashine, Shusuke Akamatsu, Tomomi Kamba, Koji Mita, Momokazu Gotoh, Shuichi Tatarano, Masato Fujisawa, Yoshihiko Tomita, Shoichiro Mukai, Keiichi Ito, Tokiyoshi Tanegashima, Shoji Tokunaga, Masatoshi Eto, SNiP RCC Investigators
Summary: The study aimed to identify clinical factors associated with tumor response, progression, and survival in nivolumab therapy for advanced clear cell renal cell carcinoma (RCC) in Japanese patients. The results showed that pancreas metastasis, lung metastases, prior cytokine therapy, and serious adverse events were related to objective response. Liver metastases, age >= 75, previous resection of primary sites, and serious adverse events were independent prognostic factors for progression-free survival (PFS). Karnofsky Performance Status < 70, high platelets, previous resection of primary sites, and pathological grade were independent prognostic factors for overall survival (OS). Serious adverse events were associated with objective response, PFS, and OS in patients with prior nephrectomy.
INTERNATIONAL JOURNAL OF UROLOGY
(2023)
Article
Urology & Nephrology
Leandro Blas, Masaki Shiota, Shigehiro Tsukahara, Shohei Nagakawa, Takashi Matsumoto, Masatoshi Eto
Summary: This study aimed to compare the adverse event profiles of abiraterone and enzalutamide using a large data set. Adverse event data sets were obtained from the FDA Adverse Event Reporting System database and analyzed using logistic regression. The results showed that abiraterone had a higher incidence of serious adverse events compared to enzalutamide.
Article
Urology & Nephrology
Leandro Blas, Masaki Shiota, Dai Takamatsu, Fumio Kinoshita, Takashi Matsumoto, Ken Lee, Keisuke Monji, Eiji Kashiwagi, Junichi Inokuchi, Masatoshi Eto
Summary: This study analyzed the evolution of BCR-free survival after radical prostatectomy and developed a nomogram incorporating postoperative PSA to predict BCR-free survival.
WORLD JOURNAL OF UROLOGY
(2023)