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https://www.readbyqxmd.com/read/29757368/the-long-noncoding-rna-landscape-of-neuroendocrine-prostate-cancer-and-its-clinical-implications
#1
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/29734647/recent-advances-in-prostate-cancer-treatment-and-drug-discovery
#2
REVIEW
Ekaterina Nevedomskaya, Simon J Baumgart, Bernard Haendler
Novel drugs, drug sequences and combinations have improved the outcome of prostate cancer in recent years. The latest approvals include abiraterone acetate, enzalutamide and apalutamide which target androgen receptor (AR) signaling, radium-223 dichloride for reduction of bone metastases, sipuleucel-T immunotherapy and taxane-based chemotherapy. Adding abiraterone acetate to androgen deprivation therapy (ADT) in order to achieve complete androgen blockade has proven highly beneficial for treatment of locally advanced prostate cancer and metastatic hormone-sensitive prostate cancer (mHSPC)...
May 4, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29580149/a-novel-brca2-mutation-in-prostate-cancer-sensitive-to-combined-radiotherapy-and-androgen-deprivation-therapy
#3
Qiuli Liu, Dali Tong, Gaolei Liu, Yuting Yi, Jing Xu, Xingxia Yang, Linang Wang, Jun Zhang, Jin Ye, Yao Zhang, Gang Yuan, Peng Wang, Rongrong Chen, Yanfang Guan, Xin Yi, Dianzheng Zhang, Jun Jiang
Genetic factors contribute to more than 40% of prostate cancer risk, and mutations in BRCA1 and BRCA2 are well-established risk factors. By using target capture-based deep sequencing to identify potential pathogenic germline mutations, followed by Sanger sequencing to determine the loci of the mutations, we identified a novel pathogenic BRCA2 mutation caused by a cytosine-to-guanine base substitution at position 4211, resulting in protein truncation (p.Ser1404Ter), which was confirmed by immunohistochemistry...
March 26, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29550200/results-of-the-flac-european-database-of-metastatic-castration-resistant-prostate-cancer-patients-treated-with-docetaxel-cabazitaxel-and-androgen-receptor-targeted-agents
#4
Antoine Angelergues, Eleni Efstathiou, Revekka Gyftaki, Piotr Jan Wysocki, Nuria Lainez, Iria Gonzalez, Daniel E Castellano, Mustafa Ozguroglu, Iciar Garcia Carbonero, Aude Flechon, Pablo Borrega, Aline Guillot, Begona Campos Balea, Sylvestre Le Moulec, Emilio Esteban, Javier Munarriz, Gustavo Rubio, Alison J Birtle, Nicolas Delanoy, Joaquim Bellmunt, Stéphane Oudard
BACKGROUND: Several agents have demonstrated an overall survival (OS) benefit in patients with metastatic castration-resistant prostate cancer (mCRPC); however, the optimal sequencing of these therapies is unknown as a result of a lack of prospective randomized controlled trials. This retrospective study aimed to identify clinical factors influencing outcomes and to determine optimal treatment sequencing in patients with mCRPC treated with cabazitaxel (CABA) and/or androgen receptor-targeted agents (ART) after androgen-deprivation therapy (ADT) and docetaxel (DOC)...
February 23, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29541409/inhibition-of-dihydrotestosterone-synthesis-in-prostate-cancer-by-combined-frontdoor-and-backdoor-pathway-blockade
#5
Michael V Fiandalo, John J Stocking, Elena A Pop, John H Wilton, Krystin M Mantione, Yun Li, Kristopher M Attwood, Gissou Azabdaftari, Yue Wu, David S Watt, Elizabeth M Wilson, James L Mohler
Androgen deprivation therapy (ADT) is palliative and prostate cancer (CaP) recurs as lethal castration-recurrent/resistant CaP (CRPC). One mechanism that provides CaP resistance to ADT is primary backdoor androgen metabolism, which uses up to four 3α-oxidoreductases to convert 5α-androstane-3α,17β-diol (DIOL) to dihydrotestosterone (DHT). The goal was to determine whether inhibition of 3α-oxidoreductase activity decreased conversion of DIOL to DHT. Protein sequence analysis showed that the four 3α-oxidoreductases have identical catalytic amino acid residues...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29493538/ab-initio-structure-determination-and-quantitative-disorder-analysis-on-nanoparticles-by-electron-diffraction-tomography
#6
Yaşar Krysiak, Bastian Barton, Bernd Marler, Reinhard B Neder, Ute Kolb
Nanoscaled porous materials such as zeolites have attracted substantial attention in industry due to their catalytic activity, and their performance in sorption and separation processes. In order to understand the properties of such materials, current research focuses increasingly on the determination of structural features beyond the averaged crystal structure. Small particle sizes, various types of disorder and intergrown structures render the description of structures at atomic level by standard crystallographic methods difficult...
March 1, 2018: Acta Crystallographica. Section A, Foundations and Advances
https://www.readbyqxmd.com/read/29044613/effect-of-androgen-deprivation-therapy-on-the-contractile-properties-of-type-i-and-type-ii-skeletal-muscle-fibres-in-men-with-non-metastatic-prostate-cancer
#7
Cedric R Lamboley, Hongyang Xu, Travis L Dutka, Erik D Hanson, Alan Hayes, John A Violet, Robyn M Murphy, Graham D Lamb
The contractile properties of vastus lateralis muscle fibres were examined in prostate cancer (PrCa) patients undergoing androgen deprivation therapy (ADT) and in age- and activity-matched healthy male subjects (Control). Mechanically-skinned muscle fibres were exposed to a sequence of heavily Ca2+ -buffered solutions at progressively higher free [Ca2+ ] to determine their force-Ca2+ relationship. Ca2+ -sensitivity was decreased in both type I and type II muscle fibres of ADT subjects relative to Controls (by -0...
February 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28980150/comparison-of-circulating-mirnas-expression-alterations-in-matched-tissue-and-plasma-samples-during-colorectal-cancer-progression
#8
Zsófia Brigitta Nagy, Barbara Kinga Barták, Alexandra Kalmár, Orsolya Galamb, Barnabás Wichmann, Magdolna Dank, Péter Igaz, Zsolt Tulassay, Béla Molnár
MicroRNAs (miRNAs) have been found to play a critical role in colorectal adenoma-carcinoma sequence. MiRNA-specific high-throughput arrays became available to detect promising miRNA expression alterations even in biological fluids, such as plasma samples, where miRNAs are stable. The purpose of this study was to identify circulating miRNAs showing altered expression between normal colonic (N), tubular adenoma (ADT), tubulovillous adenoma (ADTV) and colorectal cancer (CRC) matched plasma and tissue samples. Sixteen peripheral plasma and matched tissue biopsy samples (N n = 4; ADT n = 4; ADTV n = 4; CRC n = 4) were selected, and total RNA including miRNA fraction was isolated...
October 4, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28886115/androgen-receptor-mediated-downregulation-of-microrna-221-and-222-in-castration-resistant-prostate-cancer
#9
Bin Gui, Chen-Lin Hsieh, Philip W Kantoff, Adam S Kibel, Li Jia
MicroRNAs (miRNAs) play important roles in cancer formation and progression by suppressing the production of key functional proteins at the post-transcriptional level in a sequence-specific manner. While differential expression of miRNAs is widely observed in cancers including prostate cancer (PCa), how these miRNAs are transcriptionally regulated is largely unknown. MiRNA-221 and miRNA-222 (miR-221/-222) are well-established oncogenes and overexpressed in breast, liver, pancreas, and lung cancer, but their expression and biological functions in PCa remain controversial...
2017: PloS One
https://www.readbyqxmd.com/read/28842510/impact-of-therapy-on-genomics-and-transcriptomics-in-high-risk-prostate-cancer-treated-with-neoadjuvant-docetaxel-and-androgen-deprivation-therapy
#10
Himisha Beltran, Alexander W Wyatt, Edmund C Chedgy, Adam Donoghue, Matti Annala, Evan W Warner, Kevin Beja, Michael Sigouros, Fan Mo, Ladan Fazli, Colin C Collins, James Eastham, Michael Morris, Mary-Ellen Taplin, Andrea Sboner, Susan Halabi, Martin E Gleave
Purpose: The combination of docetaxel chemotherapy and androgen deprivation therapy (ADT) has become a standard treatment for patients with metastatic prostate cancer. The recently accrued phase III CALGB 90203 trial was designed to investigate the clinical effectiveness of this treatment approach earlier in the disease. Specimens from this trial offer a unique opportunity to interrogate the acute molecular response to docetaxel and ADT and identify potential biomarkers. Experimental Design: We evaluated baseline clinical data, needle biopsies, and radical prostatectomy (RP) specimens from 52 (of 788) patients enrolled on CALGB 90203 at one high volume center...
November 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28756295/actin-alpha-cardiac-muscle-1-gene-expression-is-upregulated-in-the-skeletal-muscle-of-men-undergoing-androgen-deprivation-therapy-for-prostate-cancer
#11
Ada S Cheung, Casey de Rooy, Itamar Levinger, Kesha Rana, Michele V Clarke, Jackie M How, Andrew Garnham, Catriona McLean, Jeffrey D Zajac, Rachel A Davey, Mathis Grossmann
Androgen deprivation therapy (ADT) decreases muscle mass and function but no human studies have investigated the underlying genetic or cellular effects. We tested the hypothesis that ADT will lead to changes in skeletal muscle gene expression, which may explain the adverse muscle phenotype seen clinically. We conducted a prospective cohort study of 9 men with localised prostate cancer who underwent a vastus lateralis biopsy before and after 4 weeks of ADT. Next-generation RNA sequencing was performed and genes differentially expressed following ADT underwent gene ontology mining using Ingenuity Pathway Analysis...
November 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28666141/computational-design-of-peptide-ligands-to-target-the-intermolecular-interaction-between-viral-envelope-protein-and-pediatric-receptor
#12
Darong Xu, Hongliang Bian, Jinlan Cai, Daocheng Bao, Qing Jin, Min Zhu, Cuifeng Zhang, Tingting Tao
The recognition and binding of viral envelope protein to pediatric receptor subverts the membrane-trafficking apparatus to mediate virion export in young children. Here, we described a successful computational design of peptide ligands to target the intermolecular interaction between the virus large envelope protein (LHB) and adaptin receptor (ADT). Based on the crystal structure of ADT in complex with an oligopeptide segment corresponding to the core binding site of LHB, a sequence-specific amino acid preference profile was determined systematically for the ADT-binding peptides using structural bioinformatics approach...
August 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28275218/epigenomic-regulation-of-androgen-receptor-signaling-potential-role-in-prostate-cancer-therapy
#13
REVIEW
Vito Cucchiara, Joy C Yang, Vincenzo Mirone, Allen C Gao, Michael G Rosenfeld, Christopher P Evans
Androgen receptor (AR) signaling remains the major oncogenic pathway in prostate cancer (PCa). Androgen-deprivation therapy (ADT) is the principle treatment for locally advanced and metastatic disease. However, a significant number of patients acquire treatment resistance leading to castration resistant prostate cancer (CRPC). Epigenetics, the study of heritable and reversible changes in gene expression without alterations in DNA sequences, is a crucial regulatory step in AR signaling. We and others, recently described the technological advance Chem-seq, a method to identify the interaction between a drug and the genome...
January 16, 2017: Cancers
https://www.readbyqxmd.com/read/28259476/treatment-outcomes-and-tumor-loss-of-heterozygosity-in-germline-dna-repair-deficient-prostate-cancer
#14
Matti Annala, Werner J Struss, Evan W Warner, Kevin Beja, Gillian Vandekerkhove, Amanda Wong, Daniel Khalaf, Irma-Liisa Seppälä, Alan So, Gregory Lo, Rahul Aggarwal, Eric J Small, Matti Nykter, Martin E Gleave, Kim N Chi, Alexander W Wyatt
BACKGROUND: Germline mutations in DNA repair genes were recently reported in 8-12% of patients with metastatic castration-resistant prostate cancer (mCRPC). It is unknown whether these mutations associate with differential response to androgen receptor (AR)-directed therapy. OBJECTIVE: To determine the clinical response of mCRPC patients with germline DNA repair defects to AR-directed therapies and to establish whether biallelic DNA repair gene loss is detectable in matched circulating tumor DNA (ctDNA)...
July 2017: European Urology
https://www.readbyqxmd.com/read/28185462/-options-of-chemotherapy-in-the-treatment-of-prostate-cancer
#15
REVIEW
I Richter, J Dvořák, J Bartoš
BACKGROUND: Prostate cancer is one of the most common malignancies in men. Chemotherapy has an important role in the management of prostate cancer, especially for the treatment of castrate resistant prostate cancer (mCRPC). According to recently published studies, chemotherapy can also be used to treat advanced hormone sensitive disease. AIM: The aim of this report is to review the currently available options for chemotherapy of prostate cancer. RESULTS: Docetaxel is a chemotherapeutic agent used for standard treatment of mCRPC as 1st line therapy...
December 0: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28134791/a-tale-of-two-signals-ar-and-wnt-in-development-and-tumorigenesis-of-prostate-and-mammary-gland
#16
REVIEW
Hubert Pakula, Dongxi Xiang, Zhe Li
Prostate cancer (PCa) is one of the most common cancers and among the leading causes of cancer deaths for men in industrialized countries. It has long been recognized that the prostate is an androgen-dependent organ and PCa is an androgen-dependent disease. Androgen action is mediated by the androgen receptor (AR). Androgen deprivation therapy (ADT) is the standard treatment for metastatic PCa. However, almost all advanced PCa cases progress to castration-resistant prostate cancer (CRPC) after a period of ADT...
January 27, 2017: Cancers
https://www.readbyqxmd.com/read/27836866/sequencing-of-sipuleucel-t-and-androgen-deprivation-therapy-in-men-with-hormone-sensitive-biochemically-recurrent-prostate-cancer-a-phase-ii-randomized-trial
#17
RANDOMIZED CONTROLLED TRIAL
Emmanuel S Antonarakis, Adam S Kibel, Evan Y Yu, Lawrence I Karsh, Aymen Elfiky, Neal D Shore, Nicholas J Vogelzang, John M Corman, Frederick E Millard, Johnathan C Maher, Nancy N Chang, Todd DeVries, Nadeem A Sheikh, Charles G Drake
Purpose: STAND, a randomized, phase II, open-label trial (NCT01431391), assessed sequencing of sipuleucel-T (an autologous cellular immunotherapy) with androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BRPC) patients at high risk for metastasis. Experimental Design: Men with BRPC following prostatectomy and/or radiotherapy, a PSA doubling time ≤12 months, and no metastasis were enrolled. Patients were randomized (34/arm) to sipuleucel-T followed by ADT (started 2 weeks after sipuleucel-T completion), or ADT followed by sipuleucel-T (started 12 weeks after ADT initiation); ADT continued for 12 months in both arms...
May 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27550197/transcript-levels-of-androgen-receptor-variant-7-and-ubiquitin-conjugating-enzyme-2c-in-hormone-sensitive-prostate-cancer-and-castration-resistant-prostate-cancer
#18
Chan Ho Lee, Ja Yoon Ku, Jung Min Ha, Sun Sik Bae, Jeong Zoo Lee, Choung-Soo Kim, Hong Koo Ha
PURPOSE: This study is designed to identify the androgen receptor variant 7 (AR-V7) status, clinical significance of AR-V7 in hormone sensitive prostate cancer (HSPC). Then, we evaluated AR-V7 and changes of its target gene, ubiquitin-conjugating enzyme E2C (UBE2C) which is an anaphase-promoting complex/cyclosome (APC/C)-specific ubiquitin-conjugating enzyme, in castration-resistant prostate cancer (CRPC) in serial tumor biopsies from patients receiving androgen deprivation therapy. METHODS: We used RT-PCR and Q-PCR assay to evaluate AR-V7, androgen receptor full length (AR-FL), and UBE2C in tumor biopsies from patients with HSPC and CRPC...
January 2017: Prostate
https://www.readbyqxmd.com/read/27182208/characterizing-magnetic-resonance-signal-decay-due-to-gaussian-diffusion-the-path-integral-approach-and-a-convenient-computational-method
#19
Evren Özarslan, Carl-Fredrik Westin, Thomas H Mareci
The influence of Gaussian diffusion on the magnetic resonance signal is determined by the apparent diffusion coefficient (ADC) and tensor (ADT) of the diffusing fluid as well as the gradient waveform applied to sensitize the signal to diffusion. Estimations of ADC and ADT from diffusion-weighted acquisitions necessitate computations of, respectively, the b-value and b-matrix associated with the employed pulse sequence. We establish the relationship between these quantities and the gradient waveform by expressing the problem as a path integral and explicitly evaluating it...
July 2015: Concepts in Magnetic Resonance. Part A, Bridging Education and Research
https://www.readbyqxmd.com/read/27125254/identification-of-a-small-protein-domain-present-in-all-plant-lineages-that-confers-high-prephenate-dehydratase-activity
#20
Jorge El-Azaz, Fernando de la Torre, Concepción Ávila, Francisco M Cánovas
l-Phenylalanine serves as a building block for the biosynthesis of proteins, but also as a precursor for a wide range of plant-derived compounds essential for plants and animals. Plants can synthesize Phe within the plastids using arogenate as a precursor; however, an alternative pathway using phenylpyruvate as an intermediate, described for most microorganisms, has recently been proposed. The functionality of this pathway requires the existence of enzymes with prephenate dehydratase (PDT) activity (EC 4.2...
July 2016: Plant Journal: for Cell and Molecular Biology
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