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https://www.readbyqxmd.com/read/29684497/targeted-thermal-therapy-with-genetically-engineered-magnetite-magnetosomes-rgd-photothermia-is-far-more-efficient-than-magnetic-hyperthermia
#1
Anouchka Plan, Sandra Preveral, Alberto Curcio, Amanda Silva, Chistopher T Lefèvre, David Pignol, Yoann Lalatonne, Claire Wilhelm
Providing appropriate means for heat generation by low intratumoral nanoparticle concentrations is a major challenge for cancer nanotherapy. Here we propose RGD-tagged magnetosomes (magnetosomes@RGD) as a biogenic, genetically engineered, inorganic platform for multivalent thermal cancer treatment. Magnetosomes@RGD are biomagnetite nanoparticles synthesized by genetically modified magnetotactic bacteria thanks to a translational fusion of the RGD peptide with the magnetosomal protein MamC. Magnetosomes@RGD thus combine the high crystallinity of their magnetite core with efficient surface functionalization...
April 20, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29679618/is-it-time-to-perform-only-mri-targeted-cores-our-experience-in-1032-men-submitted-to-prostate-biopsy
#2
Pietro Pepe, Antonio Garufi, Gian Domenico Priolo, Antonio Galia, Filippo Fraggetta, Michele Pennisi
PURPOSE: Diagnostic accuracy of mpMRI (multiparametric magnetic resonance imaging) in the diagnosis of clinically significant prostate cancer (csPCa) has been evaluated and compared with transperineal saturation prostate biopsy (SPBx). MATERIALS AND METHODS: From January 2011 to Febraury 2018 1032 men (median age 63 years) with median PSA of 8.6 ng/ml underwent repeat SPBx (reference test) for the suspicion of cancer. All the patients underwent 3.0 Tesla pelvic mpMRI before SPBx and the lesions with PI-RADS (Prostate Imaging-Reporting and Data System) score ≥ 3 were submitted to additional targeted fusion prostate biopsy (TPBx)...
April 18, 2018: Journal of Urology
https://www.readbyqxmd.com/read/29667932/fused-data-transrectal-eit-for-prostate-cancer-imaging
#3
Ethan K Murphy, Xiaotian Wu, Ryan J Halter
OBJECTIVE: Prostate cancer is a significant problem affecting 1 in 7 men. Unfortunately, the diagnostic gold-standard of ultrasound-guided biopsy misses 10-30% of all cancers. The objective of this study was to develop an Electrical Impedance Tomography (EIT) approach that has the potential to image the entire prostate using multiple impedance measurements recorded between electrodes integrated onto an end-fired transrectal ultrasound (TRUS) device and a biopsy probe (BP). APPROACH: Simulations and sensitivity analyses were used to investigate the best combination of electrodes, and measured tank experiments were used to evaluate a fused-data transrectal EIT (fd-TREIT) and BP approach...
April 18, 2018: Physiological Measurement
https://www.readbyqxmd.com/read/29666839/the-structure-of-the-nucleus-in-normal-and-neoplastic-prostate-cells-untangling-the-role-of-type-2-dna-topoisomerases
#4
REVIEW
William G Nelson, Michael C Haffner, Srinivasan Yegnasubramanian
Donald S. Coffey, a pioneer in the study of the structural basis of mammalian genome organization, was fascinated by DNA topoisomerases, chemo-mechanical enzymes that could catalyze changes in DNA structure. Work initiated in his laboratory and carried on with his influence and inspiration has led to the elucidation of specific roles for each of the two type 2 topoisomerases in DNA replication, RNA transcription, and androgen action in prostate cells. TOP2A principally acts in DNA synthesis elongation to prevent tangling of daughter DNA molecules during genome replication and mitotic segregation; TOP2B is required for androgen-stimulation of target gene transcription...
2018: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/29662195/ngr-asn-gly-arg-targeted-delivery-of-coagulase-to-tumor-vasculature-arrests-cancer-cell-growth
#5
Khaled Seidi, Rana Jahanban-Esfahlan, Hassan Monhemi, Peyman Zare, Babak Minofar, Amir Daei Farshchi Adli, Davoud Farajzadeh, Ramezan Behzadi, Mehran Mesgari Abbasi, Heidi A Neubauer, Richard Moriggl, Nosratollah Zarghami, Tahereh Javaheri
Induction of selective thrombosis and infarction in tumor-feeding vessels represents an attractive strategy to combat cancer. Here we took advantage of the unique coagulation properties of staphylocoagulase and genetically engineered it to generate a new fusion protein with novel anti-cancer properties. This novel bi-functional protein consists of truncated coagulase (tCoa) and an NGR (GNGRAHA) motif that recognizes CD13 and αv β3 integrin receptors, targeting it to tumor endothelial cells. Herein, we report that tCoa coupled by its C-terminus to an NGR sequence retained its normal binding activity with prothrombin and av β3 integrins, as confirmed in silico and in vitro...
April 17, 2018: Oncogene
https://www.readbyqxmd.com/read/29662167/sequencing-of-prostate-cancers-identifies-new-cancer-genes-routes-of-progression-and-drug-targets
#6
David C Wedge, Gunes Gundem, Thomas Mitchell, Dan J Woodcock, Inigo Martincorena, Mohammed Ghori, Jorge Zamora, Adam Butler, Hayley Whitaker, Zsofia Kote-Jarai, Ludmil B Alexandrov, Peter Van Loo, Charlie E Massie, Stefan Dentro, Anne Y Warren, Clare Verrill, Dan M Berney, Nening Dennis, Sue Merson, Steve Hawkins, William Howat, Yong-Jie Lu, Adam Lambert, Jonathan Kay, Barbara Kremeyer, Katalin Karaszi, Hayley Luxton, Niedzica Camacho, Luke Marsden, Sandra Edwards, Lucy Matthews, Valeria Bo, Daniel Leongamornlert, Stuart McLaren, Anthony Ng, Yongwei Yu, Hongwei Zhang, Tokhir Dadaev, Sarah Thomas, Douglas F Easton, Mahbubl Ahmed, Elizabeth Bancroft, Cyril Fisher, Naomi Livni, David Nicol, Simon Tavaré, Pelvender Gill, Christopher Greenman, Vincent Khoo, Nicholas Van As, Pardeep Kumar, Christopher Ogden, Declan Cahill, Alan Thompson, Erik Mayer, Edward Rowe, Tim Dudderidge, Vincent Gnanapragasam, Nimish C Shah, Keiran Raine, David Jones, Andrew Menzies, Lucy Stebbings, Jon Teague, Steven Hazell, Cathy Corbishley, Johann de Bono, Gerhardt Attard, William Isaacs, Tapio Visakorpi, Michael Fraser, Paul C Boutros, Robert G Bristow, Paul Workman, Chris Sander, Freddie C Hamdy, Andrew Futreal, Ultan McDermott, Bissan Al-Lazikani, Andrew G Lynch, G Steven Bova, Christopher S Foster, Daniel S Brewer, David E Neal, Colin S Cooper, Rosalind A Eeles
Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers...
April 16, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29661508/variability-in-the-multicentre-national-registry-in-active-surveillance-a-questionnaire-for-urologists
#7
J Rubio-Briones, A Borque-Fernando, L M Esteban-Escaño, S Martínez-Breijo, R Medina-López, V Hernández
BACKGROUND: Our main objective was to report the current use of active surveillance in Spain and to identify areas for potential improvement. METHODS: A questionnaire generated by the Platform for Multicentre Studies of the Spanish Urology Association (AEU/PIEM/2014/0001, NCT02865330) was sent to all associate researchers from January to March 2016. The questionnaire included 7 domains covering various aspects of active surveillance. RESULTS: Thirty-three of the 41 associate researchers responded to the questionnaire...
April 13, 2018: Actas Urologicas Españolas
https://www.readbyqxmd.com/read/29660918/contrast-enhanced-ultrasound-ceus-with-mri-image-fusion-for-monitoring-focal-therapy-of-prostate-cancer-with-high-intensity-focused-ultrasound-hifu-1
#8
M Apfelbeck, D-A Clevert, J Ricke, C Stief, B Schlenker
INTRODUCTION: Reduced acceptance of radical prostatectomy in patients with low risk or intermediate risk prostate cancer has significantly changed treatment strategies in prostate cancer (PCa) during the last years. Focal therapy of the prostate with high intensity focused ultrasound (HIFU) is an organ-preserving treatment for prostate cancer with less impairment of health-related quality of life. Follow-up after HIFU therapy by imaging modalities remains a major problem as eg. MRI performs poorly...
April 7, 2018: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/29653121/integration-and-diagnostic-accuracy-of-3t-non-endorectal-coil-prostate-mri-in-the-context-of-active-surveillance
#9
Nicole E Curci, Brian R Lane, Prasad R Shankar, Sabrina L Noyes, Andrew K Moriarty, Anthony Kubat, Chris Brede, Jeffrey S Montgomery, Gregory B Auffenberg, David C Miller, James E Montie, Arvin K George, Matthew S Davenport
OBJECTIVE: To evaluate the integration of 3T non-endorectal-coil multiparametric prostate MRI (mpMRI) at two high-volume practices that routinely use mpMRI in the setting of active surveillance. MATERIALS AND METHODS: This was an IRB-approved, HIPAA-compliant, dual-institution retrospective cohort study. Subjects undergoing 3T mpMRI without endorectal coil at either study institution over a 13-month period (8/1/2015-8/31/2016) were selected based on pre-defined criteria: clinical T1/T2 Gleason 6 prostate cancer, PSA<15 ng/mL, ≥40 years-old, mpMRI within 2 years of prostate biopsy, PI-RADS v2 score assigned...
April 10, 2018: Urology
https://www.readbyqxmd.com/read/29621134/dosimetric-implications-of-computerised-tomography-only-versus-magnetic-resonance-fusion-contouring-in-stereotactic-body-radiotherapy-for-prostate-cancer
#10
Daniel R Henderson, Alison C Tree, Kevin J Harrington, Nicholas J van As
Background: Magnetic resonance (MR)-fusion contouring is the standard of care in prostate stereotactic body radiotherapy (SBRT) for target volume localisation. However, the planning computerised tomography (CT) scan continues to be used for dose calculation and treatment planning and verification. Discrepancies between the planning MR and CT scans may negate the benefits of MR-fusion contouring and it adds a significant resource burden. We aimed to determine whether CT-only contouring resulted in a dosimetric detriment compared with MR-fusion contouring in prostate SBRT planning...
April 5, 2018: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/29619051/a-cold-spot-compensation-technique-using-a-combination-of-trans-rectal-ultrasonography-and-intraoperative-computed-tomography-for-interstitial-permanent-prostate-brachytherapy-a-single-arm-prospective-trial
#11
Hiromichi Ishiyama, Hideyasu Tsumura, Shogo Kawakami, Takefumi Satoh, Akane Sekiguchi, Ken-Ichi Tabata, Masatsugu Iwamura, Kazushige Hayakawa
Purpose: To evaluate the efficacy of a cold spot compensation technique using a combination of trans-rectal ultrasonography (TRUS) and computed tomography (CT) for permanent interstitial prostate brachytherapy. Material and methods: Sixty-five patients were treated with the cold spot compensation technique using TRUS-CT fusion. The prescribed dose was set at 145 Gy. The dose to 90% of prostate volume (D90 ) was planned to be within 195 Gy (134%) and 205 Gy (141%)...
February 2018: Journal of Contemporary Brachytherapy
https://www.readbyqxmd.com/read/29610475/the-long-tail-of-oncogenic-drivers-in-prostate-cancer
#12
Joshua Armenia, Stephanie A M Wankowicz, David Liu, Jianjiong Gao, Ritika Kundra, Ed Reznik, Walid K Chatila, Debyani Chakravarty, G Celine Han, Ilsa Coleman, Bruce Montgomery, Colin Pritchard, Colm Morrissey, Christopher E Barbieri, Himisha Beltran, Andrea Sboner, Zafeiris Zafeiriou, Susana Miranda, Craig M Bielski, Alexander V Penson, Charlotte Tolonen, Franklin W Huang, Dan Robinson, Yi Mi Wu, Robert Lonigro, Levi A Garraway, Francesca Demichelis, Philip W Kantoff, Mary-Ellen Taplin, Wassim Abida, Barry S Taylor, Howard I Scher, Peter S Nelson, Johann S de Bono, Mark A Rubin, Charles L Sawyers, Arul M Chinnaiyan, Nikolaus Schultz, Eliezer M Van Allen
Comprehensive genomic characterization of prostate cancer has identified recurrent alterations in genes involved in androgen signaling, DNA repair, and PI3K signaling, among others. However, larger and uniform genomic analysis may identify additional recurrently mutated genes at lower frequencies. Here we aggregate and uniformly analyze exome sequencing data from 1,013 prostate cancers. We identify and validate a new class of E26 transformation-specific (ETS)-fusion-negative tumors defined by mutations in epigenetic regulators, as well as alterations in pathways not previously implicated in prostate cancer, such as the spliceosome pathway...
April 2, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29610121/response-to-erbb3-directed-targeted-therapy-in-nrg1-rearranged-cancers
#13
Alexander Drilon, Romel Somwar, Biju P Mangatt, Henrik Edgren, Patrice Desmeules, Anja Ruusulehto, Roger S Smith, Lukas Delasos, Morana Vojnic, Andrew J Plodkowski, Joshua Sabari, Kenneth Ng, Joseph Montecalvo, Jason Chang, Huichun Tai, William W Lockwood, Victor Martinez, Gregory J Riely, Charles M Rudin, Mark G Kris, Maria E Arcila, Christopher Matheny, Ryma Benayed, Natasha Rekhtman, Marc Ladanyi, Gopinath Ganji
NRG1 rearrangements are oncogenic drivers that are enriched in invasive mucinous adenocarcinomas (IMAs) of the lung. The oncoprotein binds ERBB3-ERBB2 heterodimers and activates downstream signaling, supporting a therapeutic paradigm of ERBB3/ERBB2 inhibition. As proof of concept, a durable response was achieved with anti-ERBB3 monoclonal antibody therapy (GSK2849330) in an exceptional responder with an NRG1-rearranged IMA on a phase 1 trial (NCT01966445). In contrast, response was not achieved with anti-ERBB2 therapy (afatinib) in four NRG1-rearranged IMA patients (including the index patient post-GSK2849330)...
April 2, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29604086/em-enhanced-us-based-seed-detection-for-prostate-brachytherapy
#14
Ehsan Dehghan, Shyam Bharat, Cynthia Kung, Antonio Bonillas, Luc Beaulieu, Jean Pouliot, Jochen Kruecker
PURPOSE: Intraoperative dosimetry in low-dose-rate (LDR) permanent prostate brachytherapy requires accurate localization of the implanted seeds with respect to the prostate anatomy. Transrectal Ultrasound (TRUS) imaging, which is the main imaging modality used during the procedure, is not sufficiently robust for accurate seed localization. We present a method for integration of electromagnetic (EM) track-ing into LDR prostate brachytherapy procedure by fusing it with TRUS imaging for seed localization...
March 31, 2018: Medical Physics
https://www.readbyqxmd.com/read/29603833/prospective-comparison-of-pi-rads-version-2-and-qualitative-in-house-categorization-system-in-detection-of-prostate-cancer
#15
Sonia Gaur, Stephanie Harmon, Sherif Mehralivand, Sandra Bednarova, Brian P Calio, Dordaneh Sugano, Abhinav Sidana, Maria J Merino, Peter A Pinto, Bradford J Wood, Joanna H Shih, Peter L Choyke, Baris Turkbey
BACKGROUND: Prostate Imaging-Reporting and Data System v. 2 (PI-RADSv2) provides standardized nomenclature for interpretation of prostate multiparametric MRI (mpMRI). Inclusion of additional features for categorization may provide benefit to stratification of disease. PURPOSE: To prospectively compare PI-RADSv2 to a qualitative in-house system for detecting prostate cancer on mpMRI. STUDY TYPE: Prospective. POPULATION: In all, 338 patients who underwent mpMRI May 2015-May 2016, with subsequent MRI/transrectal ultrasound fusion-guided biopsy...
March 31, 2018: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/29599367/cost-effectiveness-of-multiparametric-mri-in-800-men-submitted-to-repeat-prostate-biopsy-results-of-a-public-health-model
#16
Pietro Pepe, Gabriele Pepe, Ludovica Pepe, Antonio Garufi, Gian Domenico Priolo, Michele Pennisi
BACKGROUND/AIM: To evaluate the cost-effectiveness of multiparametric magnetic imaging resonance (mpMRI) in men submitted to repeat saturation prostate biopsy (SPBx). MATERIALS AND METHODS: From January 2011 to June 2017, 800 men underwent repeat SPBx; the cost-effectiveness of mpMRI if used as a 'triage test' to avoid unnecessary repeat prostate biopsy was retrospectively calculated using the Italian Public National Health System Day Service. RESULTS: SPBx vs...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29595039/an-update-on-prostate-biopsy-in-the-era-of-magnetic-resonance-imaging
#17
Antonio Cicione, Cosimo DE Nunzio, Stefano Manno, Rocco Damiano, Alessandro Posti, Estevao Lima, Andrea Tubaro, Filippo Balloni
INTRODUCTION: Prostate cancer (PCa) is a singular disease owing to absence of imaging technique able to detect suspicious glandular area at higher risk of disease. Nowadays, Magnetic Resonance Imaging (MRI) has been used as a way to detect PCa and simplify targeting prostate biopsy (PB). The aim of this study is to review the most recent data regarding prostate biopsy and MRI guided PB. EVIDENCE ACQUISITION: A comprehensive systematic MEDLINE search was performed in December 2017 for English language reports by using the following terms: prostate biopsy, multiparametric magnetic resonance imaging, prostate cancer, transrectal and transperineal ultrasound, target biopsy...
March 28, 2018: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
https://www.readbyqxmd.com/read/29594027/reduction-of-mri-targeted-biopsies-in-men-with-low-risk-prostate-cancer-on-active-surveillance-by-stratifying-to-pi-rads-and-psa-density-with-different-thresholds-for-significant-disease
#18
Ivo G Schoots, Daniel F Osses, Frank-Jan H Drost, Jan F M Verbeek, Sebastiaan Remmers, Geert J L H van Leenders, Chris H Bangma, Monique J Roobol
Background: The fear of undergrading prostate cancer (PCa) in men on active surveillance (AS) have led to strict criteria for monitoring, which have resulted in good long-term cancer-specific survival, proving the safety of this approach. Reducing undergrading, MRI-targeted biopsies are increasingly used in men with low-risk disease despite their undefined role yet. The objective of this study is to investigate the rate of upgrading using MRI-targeted biopsies in men with low-risk disease on AS, stratified on the basis of PI-RADS and PSA-density, with the aim to reduce potential unnecessary repeat biopsy procedures...
February 2018: Translational Andrology and Urology
https://www.readbyqxmd.com/read/29581856/fibroblast-growth-factor-receptor-signaling-plays-a-key-role-in-transformation-induced-by-the-tmprss2-erg-fusion-gene-and-decreased-pten
#19
Longjiang Shao, Jianghua Wang, Omer Faruk Karatas, Shu Feng, Yiqun Zhang, Chad J Creighton, Michael Ittmann
Prostate cancer is the most common visceral malignancy and the second leading cause of cancer deaths in US men. Correlative studies in human prostate cancers reveal a frequent association of the TMPRSS2/ERG (TE) fusion gene with loss of PTEN and studies in mouse models reveal that ERG expression and PTEN loss synergistically promote prostate cancer progression. To determine the mechanism by which ERG overexpression and PTEN loss leads to transformation, we overexpressed the TE fusion gene and knocked down PTEN in an immortalized but non-transformed prostate epithelial cell line...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29569320/primary-mri-us-fusion-guided-biopsy-of-the-prostate
#20
Andreas Maxeiner, Beatrice Kittner, Carsten Stephan, Thomas Fischer, Patrick Asbach, Matthias Haas, Tobias Penzkofer, Florian Fuller, Kurt Miller, Hannes Cash
OBJECTIVE: To examine the performance of a primary MRI/ultrasound fusion guided targeted biopsy (TB) and in combination with an added systematic biopsy (SB). PATIENTS AND METHODS: Analysis of 318 consecutive biopsy naïve men with suspicious mpMRI (PI-RADS score ≥3) undergoing transrectal TB and 10-core systematic biopsy (SB) between January 2012 and December 2016. The indication for performing a mpMRI was based on clinical parameters and decided by the treating urologist prior to admittance...
March 22, 2018: BJU International
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