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ADT sequencing

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...
August 22, 2016: Prostate
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
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
Martin G Dalin, Alexis Desrichard, Nora Katabi, Vladimir Makarov, Logan A Walsh, Ken-Wing Lee, Qingguo Wang, Joshua Armenia, Lyndsay West, Snjezana Dogan, Lu Wang, Deepa Ramaswami, Alan L Ho, Ian Ganly, David B Solit, Michael F Berger, Nikolaus D Schultz, Jorge S Reis-Filho, Timothy A Chan, Luc G T Morris
PURPOSE: Salivary duct carcinoma (SDC) is an aggressive salivary malignancy, which is resistant to chemotherapy and has high mortality rates. We investigated the molecular landscape of SDC, focusing on genetic alterations and gene expression profiles. EXPERIMENTAL DESIGN: We performed whole-exome sequencing, RNA sequencing, and immunohistochemical analyses in 16 SDC tumors and examined selected alterations via targeted sequencing of 410 genes in a second cohort of 15 SDCs...
September 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Liisa Sjöblom, Outi Saramäki, Matti Annala, Katri Leinonen, Janika Nättinen, Teemu Tolonen, Tiina Wahlfors, Matti Nykter, G Steven Bova, Johanna Schleutker, Teuvo L J Tammela, Hans Lilja, Tapio Visakorpi
Microseminoprotein-beta (MSMB, MSMB) is an abundant secretory protein contributed by the prostate, and is implicated as a prostate cancer (PC) biomarker based on observations of its lower expression in cancerous cells compared with benign prostate epithelium. However, as the current literature on MSMB is inconsistent, we assessed the expression of MSMB at the protein and mRNA levels in a comprehensive set of different clinical stages of PC. Immunohistochemistry using monoclonal and polyclonal antibodies against MSMB was used to study protein expression in tissue specimens representing prostatectomies (n = 261) and in diagnostic needle biopsies from patients treated with androgen deprivation therapy (ADT) (n = 100), and in locally recurrent castration-resistant PC (CRPC) (n = 105) and CRPC metastases (n = 113)...
2016: PloS One
Paula Arielle M R Valdisser, Georgios J Pappas, Ivandilson P P de Menezes, Bárbara S F Müller, Wendell J Pereira, Marcelo G Narciso, Claudio Brondani, Thiago L P O Souza, Tereza C O Borba, Rosana P Vianello
Researchers have made great advances into the development and application of genomic approaches for common beans, creating opportunities to driving more real and applicable strategies for sustainable management of the genetic resource towards plant breeding. This work provides useful polymorphic single-nucleotide polymorphisms (SNPs) for high-throughput common bean genotyping developed by RAD (restriction site-associated DNA) sequencing. The RAD tags were generated from DNA pooled from 12 common bean genotypes, including breeding lines of different gene pools and market classes...
June 2016: Molecular Genetics and Genomics: MGG
John Thomas Helgstrand, Kasper Drimer Berg, Solvej Lippert, Klaus Brasso, Martin Andreas Røder
Objective Primary androgen deprivation therapy (ADT) remains the gold standard in the management of patients with advanced prostate cancer (PCa). ADT relieves symptoms and reduces tumor burden, but it has never been demonstrated to increase either PCa-specific or overall survival per se. Several trials have challenged this dogma. The aim of this study was to evaluate how endocrine therapy (ET) affects survival in different clinical settings of PCa. Materials and methods A review of published phase II, III and IV studies evaluating the effect of ET on survival was performed...
June 2016: Scandinavian Journal of Urology
Gisselle N Medina, Nestor Montiel, Fayna Diaz-San Segundo, Diego Sturza, Elizabeth Ramirez-Medina, Marvin J Grubman, Teresa de los Santos
Novel vaccination approaches against foot-and-mouth disease (FMD) include the use of replication-defective human adenovirus type 5 (Ad5) vectors that contain the capsid-encoding regions of FMD virus (FMDV). Ad5 containing serotype A24 capsid sequences (Ad5.A24) has proved to be effective as a vaccine against FMD in livestock species. However, Ad5-vectored FMDV serotype O1 Campos vaccine (Ad5.O1C.2B) provides only partial protection of cattle against homologous challenge. It has been reported that a fiber-modified Ad5 vector expressing Arg-Gly-Asp (RGD) enhances transduction of antigen-presenting cells (APC) in mice...
February 2016: Clinical and Vaccine Immunology: CVI
Edoardo Longo, Karen Wright, Mario Caruso, Emanuela Gatto, Antonio Palleschi, Manuela Scarselli, Maurizio De Crescenzi, Marco Crisma, Fernando Formaggio, Claudio Toniolo, Mariano Venanzi
A helical hexapeptide was designed to link in a rigid parallel orientation to a gold surface. The peptide sequence of the newly synthesized compound is characterized by the presence of two 4-amino-1,2-dithiolane-4-carboxylic acid (Adt) residues (positions 1 and 4) to promote a bidentate interaction with the gold surface, two L-Ala residues (positions 2 and 5) and two-aminoisobutyric acid (Aib) residues (positions 3 and 6) to favor a high population of the 310-helix conformation. Furthermore, a ferrocenoyl (Fc) probe was inserted at the N-terminus to investigate the electronic conduction properties of the peptide...
October 7, 2015: Nanoscale
Chen-Lin Hsieh, Ginevra Botta, Shuai Gao, Tiantian Li, Eliezer M Van Allen, Daniel J Treacy, Changmeng Cai, Housheng Hansen He, Christopher J Sweeney, Myles Brown, Steven P Balk, Peter S Nelson, Levi A Garraway, Philip W Kantoff
Whole-exome sequencing of metastatic castration-resistant prostate cancer (mCRPC) reveals that 5% to 7% of tumors harbor promyelocytic leukemia zinc finger (PLZF) protein homozygous deletions. PLZF is a canonical androgen-regulated putative tumor suppressor gene whose expression is inhibited by androgen deprivation therapy (ADT). Here, we demonstrate that knockdown of PLZF expression promotes a CRPC and enzalutamide-resistant phenotype in prostate cancer cells. Reintroduction of PLZF expression is sufficient to reverse androgen-independent growth mediated by PLZF depletion...
May 15, 2015: Cancer Research
Seth R Blacksburg, Matthew R Witten, Jonathan A Haas
Metastatic castrate-resistant prostate cancer (CRPC) refers to the disease state in which metastatic prostate cancer fails to respond to androgen deprivation therapy (ADT). This can be manifest as a rising PSA, increase in radiographically measurable disease, or progression of clinical disease. Roughly 90 % of men with metastatic prostate cancer have bone metastases, which is a predictor of both morbidity and mortality. Historically, treatment has been palliative, consisting of external beam radiation therapy (EBRT) and pharmacological analgesics for pain control and osteoclast inhibitors, such as bisphosphonates and denosumab to mitigate skeletal-related events...
March 2015: Current Treatment Options in Oncology
Gang Wu, Shengsong Huang, Kent L Nastiuk, Jinliang Li, Jun Gu, Ming Wu, Qimin Zhang, Hanqing Lin, Denglong Wu
BACKGROUND: 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1), which is a rate-limiting enzyme that catalyzes the conversion of adrenal-derived steroid dehydroepiandrosterone to dihydrotestosterone (DHT), may be a promising target for treating castration-resistant prostate cancer (CRPC). METHODS: From 2004 to 2011, a total of 103 consecutive patients presenting with advanced prostate cancer were included in this study. All patients were treated with surgical castration as androgen-deprivation therapy (ADT)...
May 2015: Prostate
Michael A Weller, Patrick A Kupelian, Chandana A Reddy, Kevin L Stephans, Rahul D Tendulkar
INTRODUCTION/BACKGROUND: Androgen deprivation therapy (ADT) is typically provided neoadjuvantly and concurrently with radiotherapy (RT) in the management of intermediate and high-risk prostate cancer. Our objective was to compare outcomes between patients who received adjuvant ADT (ADJ), ie, immediately after the completion of RT, to those who received a neoadjuvant and concurrent regimen (NEO). MATERIALS AND METHODS: From 1995 to 2002, 515 patients with prostate cancer were definitively treated with RT and ADT...
June 2015: Clinical Genitourinary Cancer
Prabhakar Rajan, Jacqueline Stockley, Ian M Sudbery, Janis T Fleming, Ann Hedley, Gabriela Kalna, David Sims, Chris P Ponting, Andreas Heger, Craig N Robson, Rhona M McMenemin, Ian D Pedley, Hing Y Leung
BACKGROUND: Although chemotherapy for prostate cancer (PCa) can improve patient survival, some tumours are chemo-resistant. Tumour molecular profiles may help identify the mechanisms of drug action and identify potential prognostic biomarkers. We performed in vivo transcriptome profiling of pre- and post-treatment prostatic biopsies from patients with advanced hormone-naive prostate cancer treated with docetaxel chemotherapy and androgen deprivation therapy (ADT) with an aim to identify the mechanisms of drug action and identify prognostic biomarkers...
2014: BMC Cancer
Hannelore V Heemers, James L Mohler
Ever since the Noble prize-winning findings of Huggins and Hodges, the androgen receptor (AR) has been the main target for treatment of advanced prostate cancer (CaP). Today, second- and even third-line androgen deprivation strategies, which have been designed rationally to interfere with the AR signaling that re-emerges under conditions of androgen deprivation and is at least in part responsible for disease recurrence, are effective in impeding progression of advanced CaP. The therapeutic success of these novel agents in CaP that has failed initial androgen deprivation therapy (ADT) and subsequent chemotherapy is prompting studies to explore their use earlier in the course of CaP progression...
2014: American Journal of Clinical and Experimental Urology
G von Amsberg, P Stroelin, C Bokemeyer, T Steuber
Metastasized castration-resistant prostate cancer (mCRPC) is defined by disease progression despite androgen depletion therapy (ADT). While until recently a life-prolonging effect could only be demonstrated for the taxane docetaxel, various alternative therapeutic options based on different mechanisms of action are available today: CYP17-inhibitor abiraterone and antiandrogen enzalutamide target the androgen receptor-signaling pathway, which maintains a crucial role in mCRPC. Cabazitxel - a semisynthetic taxane derivate - is the only second line chemotherapy, which results in a prolongation of overall survival to date...
October 2014: Deutsche Medizinische Wochenschrift
Tin Oo Khor, Francisco Fuentes, Limin Shu, Ximena Paredes-Gonzalez, Anne Yuqing Yang, Yue Liu, Dominic J Smiraglia, Srinivasan Yegnasubramanian, William G Nelson, Ah-Ng Tony Kong
Epigenetic control of NRF2, a master regulator of many critical antioxidative stress defense genes in human prostate cancer (CaP), is unknown. Our previous animal study found decreased Nrf2 expression through promoter CpG methylation/histone modifications during prostate cancer progression in TRAMP mice. In this study, we evaluated CpG methylation of human NRF2 promoter in 27 clinical prostate cancer samples and in LNCaP cells using MAQMA analysis and bisulfite genomic DNA sequencing. Prostate cancer tissue microarray (TMA) containing normal and prostate cancer tissues was studied by immunohistochemistry...
December 2014: Cancer Prevention Research
Adam G Sowalsky, Zheng Xia, Liguo Wang, Hao Zhao, Shaoyong Chen, Glenn J Bubley, Steven P Balk, Wei Li
UNLABELLED: Men with metastatic prostate cancer who are treated with androgen deprivation therapies (ADT) usually relapse within 2 to 3 years with disease that is termed castration-resistant prostate cancer (CRPC). To identify the mechanism that drives these advanced tumors, paired-end RNA-sequencing (RNA-seq) was performed on a panel of CRPC bone marrow biopsy specimens. From this genome-wide approach, mutations were found in a series of genes with prostate cancer relevance, including AR, NCOR1, KDM3A, KDM4A, CHD1, SETD5, SETD7, INPP4B, RASGRP3, RASA1, TP53BP1, and CDH1, and a novel SND1:BRAF gene fusion...
January 2015: Molecular Cancer Research: MCR
Jakob Voelkl, Tatsiana Pakladok, Yun Lin, Robert Viereck, Aleksandra Lebedeva, Damaris Kukuk, Bernd J Pichler, Ioana Alesutan, Florian Lang
BACKGROUND/AIMS: Fetuin-A (alpha-2-HS-glycoprotein, AHSG), a liver borne plasma protein, contributes to the prevention of soft tissue calcification, modulates inflammation, reduces insulin sensitivity and fosters weight gain following high fat diet or ageing. In polycystic ovary syndrome, fetuin-A levels correlate with free androgen levels, an observation pointing to androgen sensitivity of fetuin-A expression. The present study thus explored whether the expression of hepatic fetuin-A is modified by testosterone...
2014: Cellular Physiology and Biochemistry
A Irelli, G Bruera, K Cannita, E Palluzzi, G L Gravina, C Festuccia, C Ficorella, E Ricevuto
Different options are available as second-line treatment of metastatic castrate-resistant prostate cancer: cabazitaxel, abiraterone, and enzalutamide. Phase III studies evaluating cabazitaxel and the two hormonal agents have been shown to significantly prolong overall survival compared to mitoxantrone and placebo, respectively. Several studies have also demonstrated feasibility and activity of docetaxel rechallenge in case of a sufficient progression-free interval (3-6 months), good performance status, and previous acceptable safety profile, thus providing an additional treatment option in clinical practice...
2014: BioMed Research International
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