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https://www.readbyqxmd.com/read/29772621/-a-case-of-choroidal-and-brain-metastases-from-castration-resistant-prostate-cancer
#1
Shuko Yoneyama, Takahiko Watanabe, Tatsuaki Onuki, Kazuro Yabuki, Kotaro Suzuki
Choroidal and central nervous system metastases from prostate cancer are extremely rare. We report a case of choroidal and brain metastases from castration-resistant prostate cancer (CRPC). A 75-year-old male patient with metastatic CRPC presented with a 1-week history of a decrease in visual acuity in his left eye. An ophthalmoscopic examination revealed a choroidal tumor, 4 disc diameters across with serious retinal detachment. He was diagnosed with metastatic choroidal tumor from examination and patient's background...
April 2018: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/29772102/novel-nomograms-for-castration-resistant-prostate-cancer-and-survival-outcome-in-patients-with-de-novo-bone-metastatic-prostate-cancer
#2
Jinge Zhao, Guangxi Sun, Banghua Liao, Xingming Zhang, Cameron M Armstrong, Xiaoxue Yin, Jiandong Liu, Junru Chen, Yaojing Yang, Peng Zhao, Qidun Tang, Zhenghao Wang, Zhibin Chen, Xiong Li, Qiang Wei, Xiang Li, Ni Chen, Allen C Gao, Pengfei Shen, Hao Zeng
OBJECTIVES: To develop nomograms predicting the incidence of castration resistant prostate cancer (CRPC) and overall survival (OS) for de novo metastatic prostate cancer (mPCa). MATERIALS AND METHODS: Data from 449 de novo mPCa patients were retrospectively analyzed. Patients were randomly divided into the training (n=314, 70%) and validation cohort (n=135, 30%). Predictive factors were selected by Cox-proportional model and further used for building predictive models...
May 17, 2018: BJU International
https://www.readbyqxmd.com/read/29765513/20-s-protopanaxadiol-regio-selectively-targets-androgen-receptor-anticancer-effects-in-castration-resistant-prostate-tumors
#3
Mohamed Ben-Eltriki, Subrata Deb, Mohamed Hassona, Gray Meckling, Ladan Fazli, Mei Yieng Chin, Nada Lallous, Takeshi Yamazaki, William Jia, Paul S Rennie, Artem Cherkasov, Emma S Tomlinson Guns
We have explored the effects of 20(S)-protopanaxadiol (aPPD), a naturally derived ginsenoside, against androgen receptor (AR) positive castration resistant prostate cancer (CRPC) xenograft tumors and have examined its interactions with AR. In silico docking studies for aPPD binding to AR, alongside transactivation bioassays and in vivo efficacy studies were carried out in the castration-resistant C4-2 xenograft model. Immunohistochemical (IHC) and Western blot analyses followed by evaluation of AR, apoptotic, cell cycle and proliferative markers in excised tumors was performed...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764864/targeting-the-hsp40-hsp70-chaperone-axis-as-a-novel-strategy-to-treat-castration-resistant-prostate-cancer
#4
Michael A Moses, Yeong Sang Kim, Genesis M Rivera-Marquez, Nobu Oshima, Matthew J Watson, Kristin Beebe, Catherine Wells, Sunmin Lee, Abbey D Zuehlke, Hao Shao, William E Bingman, Vineet Kumar, Sanjay Malhotra, Nancy L Weigel, Jason E Gestwicki, Jane Trepel, Leonard M Neckers
Castration-resistant prostate cancer (CRPC) is characterized by reactivation of androgen receptor (AR) signaling in part by elevated expression of AR splice variants (ARv) including ARv7, a constitutively active, ligand binding domain (LBD)-deficient variant whose expression has been correlated with therapeutic resistance and poor prognosis. In a screen to identify small molecule dual inhibitors of both androgen-dependent and androgen-independent AR gene signatures, we identified the chalcone C86. Binding studies using purified proteins and CRPC cell lysates revealed C86 to interact with heat shock protein 40 (Hsp40)...
May 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29761841/prkar2b-promotes-prostate-cancer-metastasis-by-activating-wnt-%C3%AE-catenin-and-inducing-epithelial-mesenchymal-transition
#5
Jianjun Sha, Qing Han, Chenfei Chi, Yinjie Zhu, Jiahua Pan, Baijun Dong, Yiran Huang, Weiliang Xia, Wei Xue
Castration-resistant prostate cancers (CRPC) that occur after the failure of androgen-blocking therapies cause most of the deaths in prostate cancer (PCa) patients. In a previous study we identified that PRKAR2B expression is upregulated in CRPC and possesses potentials to develop CRPC. Here we further investigated the underlying mechanism of PRKAR2B in regulating prostate cancer metastasis. We established an androgen-independent LNCaPcell line (LNCaP-AI), and investigated the function of PRKAR2B on regulating cell invasion in vitro and in vivo...
May 15, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29760584/lsd1-inhibition-attenuates-androgen-receptor-v7-splice-variant-activation-in-castration-resistant-prostate-cancer-models
#6
Sergio Regufe da Mota, Sarah Bailey, Rosemary A Strivens, Annette L Hayden, Leon R Douglas, Patrick J Duriez, M Teresa Borrello, Hanae Benelkebir, A Ganesan, Graham Packham, Simon J Crabb
Background: Castrate resistant prostate cancer (CRPC) is often driven by constitutively active forms of the androgen receptor such as the V7 splice variant (AR-V7) and commonly becomes resistant to established hormonal therapy strategies such as enzalutamide as a result. The lysine demethylase LSD1 is a co-activator of the wild type androgen receptor and a potential therapeutic target in hormone sensitive prostate cancer. We evaluated whether LSD1 could also be therapeutically targeted in CRPC models driven by AR-V7...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29758518/benzoxazinone-containing-3-5-dimethylisoxazole-derivatives-as-bet-bromodomain-inhibitors-for-treatment-of-castration-resistant-prostate-cancer
#7
Xiaoqian Xue, Yan Zhang, Chao Wang, Maofeng Zhang, Qiuping Xiang, Junjian Wang, Anhui Wang, Chenchang Li, Cheng Zhang, Lingjiao Zou, Rui Wang, Shuang Wu, Yongzhi Lu, Hongwu Chen, Ke Ding, Guohui Li, Yong Xu
The bromodomain and extra-terminal proteins (BET) have emerged as promising therapeutic targets for the treatment of castration-resistant prostate cancer (CRPC). We report the design, synthesis and evaluation of a new series of benzoxazinone-containing 3,5-dimethylisoxazole derivatives as selective BET inhibitors. One of the new compounds, (R)-12 (Y02234), binds to BRD4(1) with a Kd value of 110 nM and blocks bromodomain and acetyl lysine interactions with an IC50 value of 100 nM. It also exhibits selectivity for BET over non-BET bromodomain proteins and demonstrates reasonable anti-proliferation and colony formation inhibition effect in prostate cancer cell lines such as 22Rv1 and C4-2B...
April 21, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29756415/the-expression-of-androgen-receptor-and-its-variants-in-human-prostate-cancer-tissue-according-to-disease-status-and-its-prognostic-significance
#8
Sung Woo Park, Jung Hee Kim, Hyun Jung Lee, Dong Hoon Shin, Sang Don Lee, Sik Yoon
PURPOSE: To evaluate changes in the expression of androgen receptor (AR) and its variants (ARVs) in human prostate cancer (PCa) tissues according to disease status, and its prognostic significance following radical prostatectomy (RP). MATERIALS AND METHODS: A total of 282 PCa cases were evaluated, which included 252 localized PCa, 8 metastatic castration resistant prostate cancer (CRPC), and 22 benign prostatic hyperplasia (BPH) cases. Samples were collected from patients who underwent RP or transurethral resection and were stored in ethically approved tissue banks...
April 16, 2018: World Journal of Men's Health
https://www.readbyqxmd.com/read/29755968/exploring-the-interaction-mechanism-between-cyclopeptide-dc3-and-androgen-receptor-using-molecular-dynamics-simulations-and-free-energy-calculations
#9
Huimin Zhang, Tianqing Song, Yizhao Yang, Chenggong Fu, Jiazhong Li
Androgen receptor (AR) is a key target in the discovery of anti-PCa (Prostate Cancer) drugs. Recently, a novel cyclopeptide Diffusa Cyclotide-3 (DC3), isolated from Hedyotisdiffusa , has been experimentally demonstrated to inhibit the survival and growth of LNCap cells, which typically express T877A-mutated AR, the most frequently detected point mutation of AR in castration-resistant prostate cancer (CRPC). But the interaction mechanism between DC3 and AR is not clear. Here in this study we aim to explore the possible binding mode of DC3 to T877A-mutated AR from molecular perspective...
2018: Frontiers in Chemistry
https://www.readbyqxmd.com/read/29752463/personalization-of-prostate-cancer-therapy-through-phosphoproteomics
#10
REVIEW
Wei Yang, Michael R Freeman, Natasha Kyprianou
Castration-resistant prostate cancer (CRPC) remains incurable despite the approval of several new treatments. Identification of new biomarkers and therapeutic targets to enable personalization of CRPC therapy, with the aim of maximizing therapeutic responses and minimizing toxicity in patients, is urgently needed. Prostate cancer progression and therapeutic resistance are frequently driven by aberrantly activated kinase signalling pathways that are amenable to pharmacological inhibition. Personalized phosphoproteomics, which enables the analysis of signalling networks in individual tumours, is a promising approach to advance personalized therapy by discovering biomarkers of pathway activity and clinically actionable targets...
May 11, 2018: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29749077/cabazitaxel-regimens-inhibit-the-growth-of-prostate-cancer-cells-and-enhances-the-anti-tumor-properties-of-pedf-with-various-efficacy-and-toxicity
#11
Courtney Jarvis, Thomas Nelius, Dalia Martinez-Marin, Souad R Sennoune, Stéphanie Filleur
BACKGROUND: Taxanes chemotherapies represent the major therapeutic alternative for symptomatic mCRPC. While docetaxel is the most commonly prescribed Taxane for mCRPC; cabazitaxel has been approved for patients unresponsive to docetaxel. Still mCRPC remains incurable and patients often experience severe side effects. Recently, the FIRSTANA trial first demonstrated the absence of superiority in overall survival between cabazitaxel and docetaxel in mCRPC patients. Inversely, different toxicity were reported suggesting that cabazitaxel may provide a first line treatment option for some patients urging for a deeper characterization of cabazitaxel mechanisms of action as well as a re-evaluation of cabazitaxel conventional dose and schedule...
May 10, 2018: Prostate
https://www.readbyqxmd.com/read/29748958/functional-roles-and-potential-clinical-application-of-mirna-345-5p-in-prostate-cancer
#12
Ilker Tinay, Mingyue Tan, Bin Gui, Lillian Werner, Adam S Kibel, Li Jia
BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs, which negatively regulate gene expression and impact prostate cancer (PCa) growth and progression. Circulating miRNAs are stable and detectable in cell-free body fluids, such as serum. Investigation of circulating miRNAs presents great potential in uncovering new insights into the roles of miRNAs in PCa diagnosis and therapy. METHODS: Using TaqMan miRNA quantitative reverse transcription polymerase chain reaction (RT-qPCR), we compared the expression levels of five miRNAs (miR-193a-3p, miR-9-3p, miR-335-5p, miR-330-3p, and miR-345-5p) in serum samples from 20 normal individuals without cancer, 25 patients with localized disease, 25 patients with hormone-naïve or hormone sensitive metastatic disease, and 25 patients with metastatic castration-resistant prostate cancer (CRPC)...
May 10, 2018: Prostate
https://www.readbyqxmd.com/read/29748904/androgen-receptor-signaling-in-castration-resistant-prostate-cancer-alters-hyperpolarized-pyruvate-to-lactate-conversion-and-lactate-levels-in-vivo
#13
Niki Zacharias, Jaehyuk Lee, Sumankalai Ramachandran, Sriram Shanmugavelandy, James McHenry, Prasanta Dutta, Steven Millward, Seth Gammon, Eleni Efstathiou, Patricia Troncoso, Daniel E Frigo, David Piwnica-Worms, Christopher J Logothetis, Sankar N Maity, Mark A Titus, Pratip Bhattacharya
PURPOSE: Androgen receptor (AR) signaling affects prostate cancer (PCa) growth, metabolism, and progression. Often, PCa progresses from androgen-sensitive to castration-resistant prostate cancer (CRPC) following androgen-deprivation therapy. Clinicopathologic and genomic characterizations of CRPC tumors lead to subdividing CRPC into two subtypes: (1) AR-dependent CRPC containing dysregulation of AR signaling alterations in AR such as amplification, point mutations, and/or generation of splice variants in the AR gene; and (2) an aggressive variant PCa (AVPC) subtype that is phenotypically similar to small cell prostate cancer and is defined by chemotherapy sensitivity, gain of neuroendocrine or pro-neural marker expression, loss of AR expression, and combined alterations of PTEN, TP53, and RB1 tumor suppressors...
May 10, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29748619/eukaryotic-translation-initiation-factor-4-gamma-1-eif4g1-is-upregulated-during-prostate-cancer-progression-and-modulates-cell-growth-and-metastasis
#14
Praveen Kumar Jaiswal, Sweaty Koul, Prakash S T Shanmugam, Hari K Koul
eIF4G1, a critical component of the eIF4F complex, is required for cap-dependent mRNA translation, a process necessary for tumor growth and survival. However, the role of eIF4G1 has not been evaluated in Prostate Cancer (PCa). We observed an increased eIF4G1 protein levels in PCa tissues as compared to normal tissues. Analysis of the TCGA data revealed that eIF4G1 gene expression positively correlated with higher tumor grade and stage. Furthermore, eIF4G1 was over-expressed and or amplified, in 16% patients with metastatic PCa (SU2C/PCF Dream Team dataset) and in 59% of castration-resistant prostate cancer (CRPC) patients (Trento/Cornell/Broad dataset)...
May 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29748182/a-pdx-organoid-biobank-of-advanced-prostate-cancers-captures-genomic-and-phenotypic-heterogeneity-for-disease-modeling-and-therapeutic-screening
#15
Michael L Beshiri, Caitlin M Tice, Crystal Tran, Holly M Nguyen, Adam G Sowalsky, Supreet Agarwal, Keith H Jansson, Qi Yang, Kerry A McGowen, Juan Juan Yin, Aian Neil Alilin, Fatima H Karzai, William Dahut, Eva Corey, Kathleen Kelly
PURPOSE: Prostate cancer translational research has been hampered by the lack of comprehensive and tractable models   that represent the genomic landscape of clinical disease. Metastatic castrate-resistant prostate cancer (mCRPC) patient-derived xenografts (PDXs) recapitulate the genetic and phenotypic diversity of the disease. We sought to establish a representative, preclinical platform of PDX-derived organoids that is experimentally facile for high throughput and mechanistic analysis...
May 10, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29743949/favourable-response-of-serum-prostate-specific-antigen-to-conjugated-oestrogen-in-castrate-resistant-prostate-cancer-in-jamaica
#16
Andrew Condappa, Maxine Gossell-Williams, William Aiken
Conjugated oestrogen is one of the more affordable secondary hormonal options available for castrate-resistant prostate cancer (CRPC) in Jamaica. The present study was conducted to examine the disease response in Jamaican men with CRPC treated with conjugated oestrogen. This study retrospectively reviewed the medical notes of patients who attended the urologic clinic of the University Hospital of the West Indies from 1 January 2009 to 31 December 2013 and a private urology clinic from 2 November 2005 to 3 June 2015 to identify patients diagnosed with CRPC treated with conjugated oestrogen (Premarin ®) as secondary therapy...
2018: Ecancermedicalscience
https://www.readbyqxmd.com/read/29743605/p53-dependent-cd51-expression-contributes-to-characteristics-of-cancer-stem-cells-in-prostate-cancer
#17
Xin Sui, Jianye Cai, Hongyu Li, Chenchen He, Congya Zhou, Yiping Dong, Li Chen, Bin Zhang, Yingnan Wang, Yanan Zhang, Yuan Qiu, Yuanyuan Zhang, Yang Zhao, Yinong Huang, Yutian Shen, Haoxiang Wu, Jiaqi Xiao, Clifford Mason, Qing Zhu, Suxia Han
Castration-resistant prostate cancer (CRPC), which is considered to contain cancer stem cells (CSCs), leads to a high relapse rate in patients with prostate cancer (PCa). However, the markers of prostate CSCs are controversial. Here we demonstrate that CD51, in part, correlates with the poor prognosis of PCa patients. Further, we find that CD51 is a functional molecule that is able to promote the malignancy of PCa through enhancing tumor initiation, metastatic potential, and chemoresistance. Moreover, we find that elevated CD51 expression in PCa specimens correlates with p53 loss of function...
May 9, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29738189/-bipolar-androgen-therapy-a-novel-therapeutic-strategy-for-castration-resistant-prostate-cancer
#18
REVIEW
Yong-Hui Hu, Jian-Chao Guo, Meng Zhang
Bipolar androgen therapy (BAT), as a new therapeutic strategy for castration-resistant prostate cancer (CRPC), can significantly reduce the level of prostate-specific antigen (PSA) for prostate cancer patients and has exhibited an excellent safety profile with no serious adverse events. Based on the clinical trials recently published at home and abroad, this article reviews the background, action mechanism, development, and prospect of BAT.
December 2017: Zhonghua Nan Ke Xue, National Journal of Andrology
https://www.readbyqxmd.com/read/29736376/a-rare-case-of-isolated-castrate-resistant-bilateral-testicular-metastases-in-advanced-prostate-cancer
#19
Jiarui Su, Edwin Jonathan Aslim, Hakan Aydin, Puay Hoon Tan, Henry Sun Sien Ho
Testicular metastasis is rare with the prostate being the most common site of primary cancer. We report a case of a 72-year-old man with castration-resistant prostate cancer (CRPC) and known metastases to bone and lymph nodes, who developed bilateral painful swollen testes 3 years after the initial diagnosis of prostate cancer. He had first presented with lower urinary tract symptoms (LUTS) with suspicious findings on digital rectal examination of the prostate, and an elevated serum prostate specific antigen (PSA) level of 129 ng/mL...
April 2018: Asian Journal of Urology
https://www.readbyqxmd.com/read/29735818/treatment-strategy-for-metastatic-prostate-cancer-with-extremely-high-psa-level-reconsidering-the-value-of-vintage-therapy
#20
Yasutaka Yamada, Shinichi Sakamoto, Yoshiyasu Amiya, Makoto Sasaki, Takayuki Shima, Akira Komiya, Noriyuki Suzuki, Koichiro Akakura, Tomohiko Ichikawa, Hiroomi Nakatsu
The prognostic significance of initial prostate-specific antigen (PSA) level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows: low (<100 ng ml-1 ), intermediate (100-999 ng ml-1 ), and high (≥1000 ng ml-1 ). All patients received androgen deprivation therapy (ADT) immediately...
May 4, 2018: Asian Journal of Andrology
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