Review
Cell Biology
Vincenza Conteduca, Alessandra Mosca, Nicole Brighi, Ugo de Giorgi, Pasquale Rescigno
Summary: Prostate cancer is a common cancer in men and patients may develop metastatic disease after radical treatments. Prognostic biomarkers are urgently needed to define patients' risk of cancer-related death.
Review
Oncology
Claudia Mosillo, Maria Letizia Calandrella, Claudia Caserta, Serena Macrini, Annalisa Guida, Grazia Sirgiovanni, Sergio Bracarda
Summary: This review summarizes and discusses new therapeutic approaches for metastatic castration-resistant prostate cancer, including the prognostic and predictive role of molecular alterations, investigation techniques, and potential clinical implications. Despite the approval of several drugs, metastatic castration-resistant prostate cancer remains a lethal disease.
Article
Oncology
Xun Shangguan, Zehua Ma, Minghao Yu, Jie Ding, Wei Xue, Jun Qi
Summary: This study reveals a dependence on SQLE-mediated cholesterol metabolism in castration-resistant prostate cancer with PTEN and p53 deficiency, providing insights for new therapeutic strategies.
Article
Oncology
Xueliang Gao, Yubao Wang, Caroline F. Ribeiro, Cherubin Manokaran, Hyeyoun Chang, Thanh Von, Silvia Rodrigues, Onur Cizmecioglu, Shidong Jia, Manav Korpal, Joshua M. Korn, Zhigang Wang, Fabienne Schmit, Lan Jiang, Raymond Pagliarini, Yi Yang, Isha Sethi, Sabina Signoretti, Guo-Cheng Yuan, Massimo Loda, Jean J. Zhao, Thomas M. Roberts
Summary: Research findings suggest that blocking p110 beta can slow down the progression of castration-resistant prostate cancer and reduce tumor growth. Combining p110 beta with other inhibitors shows potential for treating CRPC.
MOLECULAR CANCER RESEARCH
(2022)
Article
Oncology
Jian Pan, Jinou Zhao, Xudong Ni, Hualei Gan, Yu Wei, Junlong Wu, Tingwei Zhang, Qifeng Wang, Stephen J. Freedland, Beihe Wang, Shaoli Song, Dingwei Ye, Chang Liu, Yao Zhu
Summary: The study evaluated the prevalence and prognostic value of therapeutic targets (TTs) in Chinese mCRPC patients, finding that metastatic volume was an independent factor influencing TT positivity, and patients with positive PET/CT and HRR defects had shorter PFS after receiving abiraterone. Precision treatments based on specific TTs criteria could be beneficial for improving outcomes in patients with mCRPC who had poor prognosis on abiraterone.
MOLECULAR ONCOLOGY
(2022)
Article
Oncology
Kumar Nikhil, Mohini Kamra, Asif Raza, Kavita Shah
Summary: This study uncovers a novel mechanism of PTEN downregulation triggered by LIMK2, which significantly contributes to the pathogenesis of CRPC. Depletion of LIMK2 fully reverses tumorigenesis, and its phosphorylation of PTEN promotes the development of highly aggressive oncogenic phenotypes in cells and in vivo. LIMK2 serves as the missing link between hypoxia and PTEN degradation in CRPC, providing a potential therapeutic target to halt the progression to CRPC, ADT-resistance, and drug-resistance.
Article
Cell Biology
Mayao Luo, Yifan Zhang, Zhuofan Xu, Chenwei Wu, Yuedian Ye, Rui Liu, Shidong Lv, Qiang Wei
Summary: The combination therapy of tautomycin and enzalutamide could achieve a more comprehensive inhibition of androgen receptor (AR) signaling in castration-resistant prostate cancer (CRPC). Enzalutamide enhanced tautomycin-induced AR degradation by competing with residual androgens, while tautomycin decreased ARv7 levels through AR degradation. This combination therapy may represent a new therapeutic strategy for CRPC.
CELL DEATH DISCOVERY
(2022)
Article
Medicine, General & Internal
Christopher Sweeney, Sergio Bracarda, Cora N. Sternberg, Kim N. Chi, David Olmos, Shahneen Sandhu, Christophe Massard, Nobuaki Matsubara, Boris Alekseev, Francis Parnis, Vagif Atduev, Gary L. Buchschacher, Rustem Gafanov, Luis Corrales, Michael Borre, Daniil Stroyakovskiy, Gustavo Vasconcelos Alves, Evangelos Bournakis, Javier Puente, Marie-Laurence Harle-Yge, Jorge Gallo, Geng Chen, Justin Hanover, Matthew J. Wongchenko, Josep Garcia, Johann S. de Bono
Summary: The combination of ipatasertib and abiraterone significantly improved radiographical progression-free survival in patients with mCRPC with PTEN-loss tumors, but there was no significant difference between the groups in the intention-to-treat population. Adverse events were consistent with the known safety profiles of each agent, suggesting a potential treatment for men with PTEN-loss mCRPC.
Article
Oncology
Debashis Sarker, Nancy A. Dawson, Ana M. Aparicio, Tanya B. Dorff, Allan J. Pantuck, Ulka N. Vaishampayan, Lynn Henson, Lakshmi Vasist, Sumita Roy-Ghanta, Michele Gorczyca, Whitney York, Gopinath Ganji, Jerry Tolson, Johann S. de Bono
Summary: The study investigated the combination of enzalutamide and the PI3K beta inhibitor GSK2636771 in patients with PTEN-deficient mCRPC. Results demonstrated acceptable safety and tolerability of the drug combination, but limited antitumor activity was observed.
CLINICAL CANCER RESEARCH
(2021)
Review
Oncology
Asta Juzeniene, Vilde Yuli Stenberg, Oyvind Sverre Bruland, Roy Hartvig Larsen
Summary: There is currently no cure for late stage metastatic prostate cancer, but targeted alpha therapy focusing on the overexpressed protein PSMA may offer a promising treatment option. This therapy utilizes radionuclides emitting alpha-particles to target PSMA, potentially providing a more effective and selective treatment option for patients.
Article
Biochemistry & Molecular Biology
Yun Zhao, Xiaoxia Peng, Hope Baldwin, Chao Zhang, Zhongmin Liu, Xin Lu
Summary: Despite advancements in AR antagonists, CRPC remains incurable and requires further study in animal models. Prostate-specific deletion of Pten and Smad4 in mice mimics human prostate adenocarcinoma, with Pten/Smad4 tumors promoting an immunosuppressive microenvironment. Combination therapy of surgical castration and enzalutamide in Pten/Smad4 mice slows tumor growth and prolongs survival. RNA profiling reveals transcriptomic alterations in CRPC, particularly related to immune-related and coagulation-related pathways in lung metastatic CRPC.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Review
Biochemistry & Molecular Biology
David Ka-Wai Leung, Peter Ka-Fung Chiu, Chi-Fai Ng, Jeremy Yuen-Chun Teoh
Summary: The management of castration-resistant prostate cancer has seen significant progress, with three novel hormonal agents showing survival benefits in non-metastatic patients and a wider range of management options being investigated for metastatic disease.
Article
Oncology
Elahe A. Mostaghel, Brett T. Marck, Orpheus Kolokythas, Felix Chew, Evan Y. Yu, Michael T. Schweizer, Heather H. Cheng, Phillip W. Kantoff, Steven P. Balk, Mary-Ellen Taplin, Nima Sharifi, Alvin M. Matsumoto, Peter S. Nelson, R. Bruce Montgomery
Summary: This study found that low levels of circulating adrenal androgens before starting abiraterone acetate were associated with faster progression in metastatic castration-resistant prostate cancer. In addition, low circulating androgens were strongly correlated with an androgen-poor tumor microenvironment and poor response to abiraterone acetate, suggesting potential benefit for patients with higher serum DHEAS levels from dual androgen receptor pathway inhibition.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Valentine M. Macaulay, Simon Lord, Syed Hussain, Jose Pablo Maroto, Robert Hugh Jones, Miguel Angel Climent, Natalie Cook, Chia-Chi Lin, Shian-Shiang Wang, Diletta Bianchini, Mark Bailey, Laura Schlieker, Thomas Bogenrieder, Johann de Bono
Summary: This study evaluated the combination therapy of xentuzumab and enzalutamide in patients with metastatic castrate-resistant prostate cancer. The results showed that the combination treatment had some efficacy in certain patients.
BRITISH JOURNAL OF CANCER
(2023)
Article
Biotechnology & Applied Microbiology
Zhe Yu, Wei Wei, Hongruo Liu, Evenki Pan, Peng Yang, Kui Jiang
Summary: mCRPC, the advanced stage of PCa, develops resistance to ADT, associated with AR and PI3K-Akt-mTOR signaling pathway. A 64-year-old male mCRPC patient with AKT1 and AR mutations received everolimus treatment, resulting in stable disease progression with a significant drop in PSA level.
ONCOTARGETS AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Yurika Hata, Takahiro Shimizu, Suo Zou, Masaki Yamamoto, Yohei Shimizu, Hideaki Ono, Takaaki Aratake, Shogo Shimizu, Youichirou Higashi, Nobutaka Shimizu, Takashi Karashima, Motoaki Saito
Summary: This study investigated the effects of central CRF on micturition and the involvement of CRF receptor subtypes and glutamatergic receptors. The results suggest that stimulation of brain CRFR1 may facilitate rat micturition via brain NMDA/AMPA receptors.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Urology & Nephrology
Kazutoshi Fujita, Makoto Matsushita, Eri Banno, Marco A. De Velasco, Koji Hatano, Norio Nonomura, Hirotsugu Uemura
Summary: The gut microbiome is associated with various diseases and the modulation of immune function. It is influenced by lifestyle, diet, sex, race, genetic background, and country.
INTERNATIONAL JOURNAL OF UROLOGY
(2022)
Review
Endocrinology & Metabolism
Makoto Matsushita, Kazutoshi Fujita, Koji Hatano, Marco A. De Velasco, Hirotsugu Uemura, Norio Nonomura
Summary: This study highlights the association between increased levels of circulating IGF-1 and the risk of developing prostate cancer. It also demonstrates that gut microbiota-derived short-chain fatty acids (SCFAs) can promote prostate cancer progression by increasing IGF-1 production. Furthermore, specific bacteria in the gut microbiome are associated with high-grade prostate cancer. These findings suggest that dietary interventions and supplements targeting the gut-IGF-1-prostate axis may be effective for preventing prostate cancer.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Nobutaka Shimizu, Tetsuichi Saito, Naoki Wada, Mamoru Hashimoto, Takahiro Shimizu, Joonbeom Kwon, Kang Jun Cho, Motoaki Saito, Sergei Karnup, William C. de Groat, Naoki Yoshimura
Summary: This article summarizes the current progress in fundamental studies of lower urinary tract dysfunction (LUTD) after spinal cord injury (SCI). Animal models of SCI have allowed researchers to investigate the effects of SCI on micturition control and the underlying neurophysiological processes. SCI disrupts the normal reflex circuits that regulate bladder and urethral sphincter function, leading to involuntary and inefficient voiding. These findings provide a better understanding of the pathophysiological mechanisms of LUTD after SCI and may contribute to the development of novel therapies for SCI patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Kazutoshi Fujita, Makoto Matsushita, Marco A. A. De Velasco, Koji Hatano, Takafumi Minami, Norio Nonomura, Hirotsugu Uemura
Summary: The gut microbiome plays a crucial role in the development of diseases like prostate cancer. Gut dysbiosis caused by factors like diet leads to the leakage of gut bacterial metabolites, resulting in prostate cancer growth. Lifestyle factors, especially diet, impact the gut microbiome and are associated with prostate cancer risk. Alterations in the gut microbiome have been identified in patients with prostate cancer, highlighting the importance of considering the gut-prostate axis in screening and treating prostate cancer patients.
Article
Urology & Nephrology
Takahira Kuno, Kenji Tamura, Nobutaka Shimizu, Hideo Fukuhara, Satoshi Fukata, Shingo Ashida, Takashi Karashima, Hirofumi Satake, Kohji Sawada, Ichiro Yamasaki, Fumito Komatsu, Hajime Kuroiwa, Motoaki Saito, Keiji Inoue
Summary: In this study, the treatment effects of vibegron on elderly Japanese patients with overactive bladder were evaluated. The results showed that vibegron significantly improved OABSS and OAB-q SF, especially in patients aged 80 and above. Furthermore, switching from mirabegron to vibegron also resulted in significant improvements to residual urine volume.
RESEARCH AND REPORTS IN UROLOGY
(2023)
Article
Pharmacology & Pharmacy
Nobutaka Shimizu, Takahiro Shimizu, Youichirou Higashi, Suo Zou, Hideo Fukuhara, Takashi Karashima, Keiji Inoue, Motoaki Saito
Summary: In our previous study, we found that & alpha;7 nicotinic acetylcholine receptors in the brain inhibited the rat micturition reflex, and we investigated the relationship between & alpha;7 nicotinic acetylcholine receptors and hydrogen sulphide (H2S) as H2S also inhibits the rat micturition reflex in the brain. Through cystometry in male Wistar rats, we examined the effects of H2S and H2S synthesis inhibitor on the activation of & alpha;7 nicotinic acetylcholine receptors in prolonging intercontraction intervals. Our results suggest that brain H2S may be involved in inhibiting the rat micturition reflex induced by activation of brain & alpha;7 nicotinic acetylcholine receptors.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Takahisa Suzuki, Takahiro Shimizu, Sergei Karnup, Nobutaka Shimizu, Jianshu Ni, William C. de Groat, Naoki Yoshimura
Summary: This study found that p38 MAPK activity plays an important role in the electrophysiological properties of capsaicin-sensitive bladder afferent neurons in SCI mice, especially in the changes in KA currents. Evaluating the changes in KA currents is crucial for understanding the hyperexcitability of these neurons in SCI mice.
Review
Andrology
Makoto Matsushita, Kazutoshi Fujita, Koji Hatano, Marco A. De Velasco, Akira Tsujimura, Hirotsugu Uemura, Norio Nonomura
Summary: The gut microbiota, influenced by both environmental and genetic factors, has been found to have a significant impact on human health. Research has shown a close association between the gut microbiome and various non-intestinal diseases, particularly in the field of cancer biology and therapy. Prostate cancer cells are directly affected by the microbiota in local tissues and urine, suggesting a relationship between prostate cancer cells and the gut microbiota. The bacterial composition of the gut microbiota differs depending on prostate cancer characteristics, such as histological grade and castration resistance. Additionally, certain intestinal bacteria have been shown to be involved in testosterone metabolism, indicating a potential influence on prostate cancer progression and treatment. Basic research suggests that the gut microbiome plays a crucial role in prostate cancer biology through microbial-derived metabolites and components. This review focuses on the emerging relationship between the gut microbiome and prostate cancer, referred to as the gut-prostate axis.
WORLD JOURNAL OF MENS HEALTH
(2023)
Article
Urology & Nephrology
Mamoru Hashimoto, Nobutaka Shimizu, Saizo Fujimoto, Ken Kuwahara, Mitsuhisa Nishimoto, Shogo Adomi, Eri Banno, Takafumi Minami, Kazutoshi Fujita, Kazuhiro Yoshimura, Akihide Hirayama, Hirotsugu Uemura
Summary: This study aimed to elucidate the pathophysiology of post-micturition dribble (PMD) by analyzing pressure flow study (PFS) findings and symptoms questionnaire. The results showed that PMD was significantly associated with larger prostate volume (PV) and higher bladder outlet obstruction index (BOOI) evaluated by PFS. Furthermore, PMD was found to significantly exacerbate the quality of life (QOL). The severity of PMD and other m-IPSS sub-scores (except nocturia) could have intercorrelation with each other.
INTERNATIONAL UROLOGY AND NEPHROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Suo Zou, Takahiro Shimizu, Atsushi Kurabayashi, Masaki Yamamoto, Shogo Shimizu, Youichirou Higashi, Nobutaka Shimizu, Takashi Karashima, Motoaki Saito
Summary: In this study, it was found that hydrogen sulfide pretreatment can prevent bladder dysfunction caused by cyclophosphamide treatment by suppressing the activity of bladder afferent nerves, rather than by inhibiting bladder inflammation. Therefore, hydrogen sulfide may be a new candidate as a protective drug for bladder dysfunction induced by cyclophosphamide chemotherapy.
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2022)
Review
Urology & Nephrology
Naoki Wada, Sergei Karnup, Katsumi Kadekawa, Nobutaka Shimizu, Joonbeom Kwon, Takahiro Shimizu, Daisuke Gotoh, Hidehiro Kakizaki, William C. de Groat, Naoki Yoshimura
Summary: This review article summarizes the recent advancements in basic research on lower urinary tract dysfunction following spinal cord injury, focusing on neurophysiologic mechanisms and changes in micturition control in animal models of SCI. It discusses how SCI impairs voluntary control of voiding and normal reflex pathways, leading to bladder hyperreflexia but inefficient bladder emptying.
UROLOGICAL SCIENCE
(2022)
Meeting Abstract
Urology & Nephrology
K. Fujita, M. Matsushita, D. Motooka, H. Hase, E. Banno, M. A. De Velasco, T. Kato, K. Hatano, A. Kawashima, M. Uemura, S. Nakamura, K. Tsujikawa, E. Morii, H. Uemura, N. Nonomura
Meeting Abstract
Oncology
Hirotsugu Uemura, Yurie Kura, Eri Banno, Mamoru Hashimoto, Kazuko Sakai, Kazutoshi Fujita, Masahiro Nozawa, Kazuhiro Yoshimura, Kazuto Nishio, Marco A. Develasco
Meeting Abstract
Oncology
Chisato Wakamori, Marco A. Develasco, Yurie Kura, Kazuko Sakai, Mamoru Hashimoto, Eri Banno, Kazutoshi Fujita, Masahiro Nozawa, Kazuhiro Yoshimura, Kazuto Nishio, Hirotsugu Uemura