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ADT sequencing

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
Himisha Beltran, Alexander W Wyatt, Edmund Chedgy, Adam Donoghue, Matti Annala, Evan Warner, Kevin Beja, Michael Sigouros, Fan Mo, Ladan Fazli, Colin C Collins, James A Eastham, Michael J Morris, Mary-Ellen Taplin, Andrea Sboner, Susan Halabi, Martin E Gleave
BACKGROUND: 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 predictive biomarkers. METHODS: 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...
August 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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...
July 27, 2017: Journal of Steroid Biochemistry and Molecular Biology
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...
June 17, 2017: Computational Biology and Chemistry
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
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
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
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
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...
November 10, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
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...
November 25, 2015: 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
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