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https://www.readbyqxmd.com/read/29778323/is-there-a-flare-phenomenon-on-bone-scintigraphy-in-men-with-advanced-prostate-cancer-treated-with-radium-223
#1
Gesa Isensee, Anne Péporté, Joachim Müller, Sabine Schmid, Silke Gillessen, Aurelius Omlin
INTRODUCTION: Radium-223 is an approved survival-prolonging treatment option in men with castration-resistant prostate cancer (mCRPC) and bone metastases. In the registration trial (ALSYMPCA), no regular imaging was mandated. We aimed to analyze men with metastatic mCRPC treated with radium-223 who had bone scintigraphy for staging and treatment monitoring. PATIENTS AND METHODS: Retrospective chart review was performed of mCRPC patients who received 6 cycles of radium-223 and who underwent bone scintigraphy before start of radium-223 and after 3 and 6 cycles of treatment...
April 23, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29777112/micrornas-as-potential-therapeutics-to-enhance-chemosensitivity-in-advanced-prostate-cancer
#2
Hui-Ming Lin, Iva Nikolic, Jessica Yang, Lesley Castillo, Niantao Deng, Chia-Ling Chan, Nicole K Yeung, Eoin Dodson, Benjamin Elsworth, Calan Spielman, Brian Y Lee, Zoe Boyer, Kaylene J Simpson, Roger J Daly, Lisa G Horvath, Alexander Swarbrick
Docetaxel and cabazitaxel are taxane chemotherapy treatments for metastatic castration-resistant prostate cancer (CRPC). However, therapeutic resistance remains a major issue. MicroRNAs are short non-coding RNAs that can silence multiple genes, regulating several signalling pathways simultaneously. Therefore, synthetic microRNAs may have therapeutic potential in CRPC by regulating genes involved in taxane response and minimise compensatory mechanisms that cause taxane resistance. To identify microRNAs that can improve the efficacy of taxanes in CRPC, we performed a genome-wide screen of 1280 microRNAs in the CRPC cell lines PC3 and DU145 in combination with docetaxel or cabazitaxel treatment...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29776913/-177-lu-psma-617-has-activity-in-castration-resistant-prostate-cancer
#3
(no author information available yet)
Radionuclide treatment with [177 Lu]-PSMA-617 (LuPSMA) reduced PSA levels by ≥50% in 57% of patients.
May 18, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29772621/-a-case-of-choroidal-and-brain-metastases-from-castration-resistant-prostate-cancer
#4
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
#5
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
#6
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/29765147/systemic-treatments-for-high-risk-localized-prostate-cancer
#7
REVIEW
Géraldine Pignot, Denis Maillet, Emmanuel Gross, Philippe Barthelemy, Jean-Baptiste Beauval, Friederike Constans-Schlurmann, Yohann Loriot, Guillaume Ploussard, Paul Sargos, Marc-Olivier Timsit, Sébastien Vincendeau, Gilles Pasticier, Delphine Borchiellini
The majority of patients with prostate cancer who later develop lethal metastatic disease have high-risk localized disease at presentation, emphasizing the importance of effective treatment strategies at this stage. Multimodal treatment approaches that combine systemic and local therapies offer a promising strategy for improving the clinical outcomes of patients with high-risk localized prostate cancer. Combinations of neoadjuvant and adjuvant chemotherapy, hormonal therapy, or chemohormonal therapy are considered to be the standard of care in most solid tumours and should be investigated in the future for the treatment of prostate cancer to improve patient outcomes...
May 15, 2018: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29764892/intense-exercise-for-survival-among-men-with-metastatic-castrate-resistant-prostate-cancer-interval-gap4-a-multicentre-randomised-controlled-phase-iii-study-protocol
#8
Robert U Newton, Stacey A Kenfield, Nicolas H Hart, June M Chan, Kerry S Courneya, James Catto, Stephen P Finn, Rosemary Greenwood, Daniel C Hughes, Lorelei Mucci, Stephen R Plymate, Stephan F E Praet, Emer M Guinan, Erin L Van Blarigan, Orla Casey, Mark Buzza, Sam Gledhill, Li Zhang, Daniel A Galvão, Charles J Ryan, Fred Saad
INTRODUCTION: Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC). METHODS AND ANALYSIS: Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC)...
May 14, 2018: BMJ Open
https://www.readbyqxmd.com/read/29764864/targeting-the-hsp40-hsp70-chaperone-axis-as-a-novel-strategy-to-treat-castration-resistant-prostate-cancer
#9
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/29762619/isolation-and-genome-sequencing-of-individual-circulating-tumor-cells-using-hydrogel-encapsulation-and-laser-capture-microdissection
#10
Emily S Park, Justin P Yan, Richard A Ang, Jeong Hyun Lee, Xiaoyan Deng, Simon P Duffy, Kevin Beja, Matti Annala, Peter C Black, Kim N Chi, Alexander W Wyatt, Hongshen Ma
Circulating tumor cells (CTCs) are malignant cells released into the bloodstream with the potential to form metastases in secondary sites. These cells, acquired non-invasively, represent a sample of highly relevant tumor tissue that is an alternative to difficult and low-yield tumor biopsies. In recent years, there has been growing interest in genomic profiling of CTCs to enable longitudinal monitoring of the tumor's adaptive response to therapy. However, due to their extreme rarity, genotyping CTCs has proved challenging...
May 15, 2018: Lab on a Chip
https://www.readbyqxmd.com/read/29762244/brca2-mutation-as-a-possible-cause-of-poor-response-to-177lu-psma-therapy
#11
Hojjat Ahmadzadehfar, Florian Gaertner, Philipp S Lossin, Bettina Schwarz, Markus Essler
We present the case of a 66-year-old man with castration-resistant prostate cancer, with an increasing prostate-specific antigen level, and a progressive disease during Lu-PSMA radionuclide therapy. Because the patient had a BRCA2 mutation, poly-ADP ribose polymerase inhibitor therapy was started. The patient showed a dramatic subjective and biological response to this therapy with a progression-free survival of 5 months.
May 14, 2018: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29762238/diagnostic-performance-of-18f-fluciclovine-in-detection-of-prostate-cancer-bone-metastases
#12
Albert Chau, Peter Gardiner, Patrick M Colletti, Hossein Jadvar
PURPOSE: 18F-fluciclovine is a synthetic amino acid radiotracer that has recently been approved in Europe and the United States for PET imaging in men with biochemical recurrence (BCR) of prostate cancer after prior definitive treatment. Accurate identification of the sites of disease in patients presenting with BCR of prostate cancer is important in determining the appropriate treatment. Bone is the most frequent site of metastatic disease in patients with prostate cancer. METHODS: We conducted a comprehensive review of the available preclinical and clinical data on the diagnostic performance of 18F-fluciclovine PET/CT in an attempt to draw practical and general conclusions on the utility and limitations of 18F-fluciclovine PET/CT in localization of osseous metastatic disease in prostate cancer...
May 14, 2018: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29761841/prkar2b-promotes-prostate-cancer-metastasis-by-activating-wnt-%C3%AE-catenin-and-inducing-epithelial-mesenchymal-transition
#13
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
#14
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
#15
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/29757697/molecular-drivers-of-metastatic-castrate-resistant-prostate-cancer-new-roads-to-resistance
#16
Phoebe A Huang, Douglas K Price, William D Figg
Numerous growth-inducing signaling pathways have been implicated in the development of metastatic castrate-resistant prostate cancer, but their cross-talk with androgen receptor functions remains poorly understood. A recent study published in Science Signaling by Chen et al. 1 has identified a novel androgen-mediated signaling axis driven by loss of SPDEF and gain of TGFBI to facilitate metastasis, which may explain the acquisition of resistance to androgen deprivation therapy. These findings suggest that therapeutic inhibition of androgen signaling may inadvertently promote castrate resistance by inhibiting tumor suppressive functions of the androgen receptor...
May 14, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29757368/the-long-noncoding-rna-landscape-of-neuroendocrine-prostate-cancer-and-its-clinical-implications
#17
Varune Rohan Ramnarine, Mohammed Alshalalfa, Fan Mo, Noushin Nabavi, Nicholas Erho, Mandeep Takhar, Robert Shukin, Sonal Brahmbhatt, Alexander Gawronski, Maxim Kobelev, Mannan Nouri, Dong Lin, Harrison Tsai, Tamara L Lotan, R Jefferey Karnes, Mark A Rubin, Amina Zoubeidi, Martin E Gleave, Cenk Sahinalp, Alexander W Wyatt, Stanislav V Volik, Himisha Beltran, Elai Davicioni, Yuzhuo Wang, Colin C Collins
Background: Treatment induced neuroendocrine prostate cancer (tNEPC) is an aggressive variant of late-stage metastatic castrate resistant (mCRPC) prostate cancer that commonly arises through neuroendocrine transdifferentiation (NEtD). Treatment options are limited, ineffective, and for most patients, results in death in less than a year. We previously developed a first-in-field patient-derived xenograft (PDX) model of NEtD. Longitudinal deep transcriptome profiling of this model enabled monitoring of dynamic transcriptional changes during NEtD and in the context of androgen deprivation...
May 10, 2018: GigaScience
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
#18
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
#19
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/29755405/dual-paraneoplastic-endocrine-syndromes-heralding-onset-of-extrapulmonary-small-cell-carcinoma-a-case-report-and-narrative-review
#20
Jill B Feffer, Natalia M Branis, Jeanine B Albu
Objective: Extrapulmonary small cell carcinoma (EPSCC) is rare and frequent metastases at presentation can complicate efforts to identify a site of origin. In particular, SCC comprises <1% of prostate cancers and has been implicated in castration resistance. Methods: Clinical, laboratory, imaging, and pathology data are presented. Results: A 56-year-old man with locally advanced prostate adenocarcinoma on androgen deprivation therapy presented with a clogged nephrostomy tube...
2018: Frontiers in Endocrinology
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