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https://www.readbyqxmd.com/read/28432356/a-role-of-human-rnase-p-subunits-rpp29-and-rpp21-in-homology-directed-repair-of-double-strand-breaks
#1
Enas R Abu-Zhayia, Hanan Khoury-Haddad, Noga Guttmann-Raviv, Raphael Serruya, Nayef Jarrous, Nabieh Ayoub
DNA damage response (DDR) is needed to repair damaged DNA for genomic integrity preservation. Defective DDR causes accumulation of deleterious mutations and DNA lesions that can lead to genomic instabilities and carcinogenesis. Identifying new players in the DDR, therefore, is essential to advance the understanding of the molecular mechanisms by which cells keep their genetic material intact. Here, we show that the core protein subunits Rpp29 and Rpp21 of human RNase P complex are implicated in DDR. We demonstrate that Rpp29 and Rpp21 depletion impairs double-strand break (DSB) repair by homology-directed repair (HDR), but has no deleterious effect on the integrity of non-homologous end joining...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28417998/marker-free-coselection-for-crispr-driven-genome-editing-in-human-cells
#2
Daniel Agudelo, Alexis Duringer, Lusiné Bozoyan, Caroline C Huard, Sophie Carter, Jeremy Loehr, Dafni Synodinou, Mathieu Drouin, Jayme Salsman, Graham Dellaire, Josée Laganière, Yannick Doyon
Targeted genome editing enables the creation of bona fide cellular models for biological research and may be applied to human cell-based therapies. Therefore, broadly applicable and versatile methods for increasing its efficacy in cell populations are highly desirable. We designed a simple and robust coselection strategy for enrichment of cells with either nuclease-driven nonhomologous end joining (NHEJ) or homology-directed repair (HDR) events by harnessing the multiplexing capabilities of CRISPR-Cas9 and Cpf1 systems...
April 17, 2017: Nature Methods
https://www.readbyqxmd.com/read/28398198/functional-and-mutational-landscapes-of-brca1-for-homology-directed-repair-and-therapy-resistance
#3
Rachel W Anantha, Srilatha Simhadri, Tzeh Keong Foo, Susanna Miao, Jingmei Liu, Zhiyuan Shen, Shridar Ganesan, Bing Xia
BRCA1 plays a critical role in homology-directed repair (HDR) of DNA double strand breaks, and the repair defect of BRCA1-mutant cancer cells is being targeted with platinum drugs and poly (ADP-ribose) polymerase (PARP) inhibitors. We have employed relatively simple and sensitive assays to determine the function of BRCA1 variants or mutants in two HDR mechanisms, homologous recombination (HR) and single strand annealing (SSA), and in conferring resistance to cisplatin and olaparib in human cancer cells. Our results define the functionality of the top 22 patient-derived BRCA1 missense variants and the contribution of different domains of BRCA1 and its E3 ubiquitin ligase activity to HDR and drug resistance...
April 11, 2017: ELife
https://www.readbyqxmd.com/read/28392144/iridium-knife-another-knife-in-radiation-oncology
#4
Natasa Milickovic, Nikolaos Tselis, Efstratios Karagiannis, Konstantinos Ferentinos, Nikolaos Zamboglou
PURPOSE: Intratarget dose escalation with superior conformity is a defining feature of three-dimensional (3D) iridium-192 ((192)Ir) high-dose-rate (HDR) brachytherapy (BRT). In this study, we analyzed the dosimetric characteristics of interstitial (192)Ir HDR BRT for intrathoracic and cerebral malignancies. We examined the dose gradient sharpness of HDR BRT compared with that of linear accelerator-based stereotactic radiosurgery and stereotactic body radiation therapy, usually called X-Knife, to demonstrate that it may as well be called a Knife...
April 6, 2017: Brachytherapy
https://www.readbyqxmd.com/read/28388623/fzuimagereg-a-toolbox-for-medical-image-registration-and-dose-fusion-in-cervical-cancer-radiotherapy
#5
Qinquan Gao, Shaohui Lin, Penggang Bai, Min Du, Xiaolei Ni, Dongzhong Ke, Tong Tong
The combination external-beam radiotherapy and high-dose-rate brachytherapy is a standard form of treatment for patients with locally advanced uterine cervical cancer. Personalized radiotherapy in cervical cancer requires efficient and accurate dose planning and assessment across these types of treatment. To achieve radiation dose assessment, accurate mapping of the dose distribution from HDR-BT onto EBRT is extremely important. However, few systems can achieve robust dose fusion and determine the accumulated dose distribution during the entire course of treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28374058/control-of-gene-editing-by-manipulation-of-dna-repair-mechanisms
#6
Eric Danner, Sanum Bashir, Saniye Yumlu, Wolfgang Wurst, Benedikt Wefers, Ralf Kühn
DNA double-strand breaks (DSBs) are produced intentionally by RNA-guided nucleases to achieve genome editing through DSB repair. These breaks are repaired by one of two main repair pathways, classic non-homologous end joining (c-NHEJ) and homology-directed repair (HDR), the latter being restricted to the S/G2 phases of the cell cycle and notably less frequent. Precise genome editing applications rely on HDR, with the abundant c-NHEJ formed mutations presenting a barrier to achieving high rates of precise sequence modifications...
April 3, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28356322/mechanisms-of-precise-genome-editing-using-oligonucleotide-donors
#7
Yinan Kan, Brian Ruis, Taylor Takasugi, Eric Abner Hendrickson
The use of programmable meganucleases is transforming genome editing and functional genomics. CRISPR/Cas9 was developed such that targeted genomic lesions could be introduced in vivo with unprecedented ease. In the presence of homology donors, these lesions facilitate high-efficiency precise genome editing (PGE) via homology-directed repair (HDR) pathways. However, the identity and hierarchy of the HDR (sub)pathways leading to the formation of PGE products remain elusive. Here we established a green to blue fluorescent protein conversion system to systematically characterize oligodeoxynucleotide (ODN)-mediated PGE using Cas9 and its nickase variants in human cells...
March 29, 2017: Genome Research
https://www.readbyqxmd.com/read/28353447/on-the-experimental-validation-of-model-based-dose-calculation-algorithms-for-sup-192-sup-ir-hdr-brachytherapy-treatment-planning
#8
Eleftherios Pappas, Emmanouil Zoros, Argyris Moutsatsos, Vassiliki Peppa, Kyveli Zourari, Pantelis Karaiskos, Panagiotis Papagiannis
There is an acknowledged need for the design and implementation of physical phantoms appropriate for the experimental validation of model-based dose calculation algorithms (MBDCA) introduced recently in <sup>192</sup>Ir brachytherapy treatment planning systems (TPSs), and this work investigates whether it can be met. A PMMA phantom was prepared to accommodate material inhomogeneities (air and Teflon), 4 plastic brachytherapy catheters, as well as 84 LiF TLD dosimeters (MTS-100M 1x1x1 mm<sup>3</sup> microcubes), 2 radiochromic films (Gafchromic EBT3) and a plastic 3D dosimeter (PRESAGE)...
March 29, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28351759/simplified-crispr-tools-for-efficient-genome-editing-and-streamlined-protocols-for-their-delivery-into-mammalian-cells-and-mouse-zygotes
#9
Ashley M Jacobi, Garrett R Rettig, Rolf Turk, Michael A Collingwood, Sarah A Zeiner, Rolen M Quadros, Donald W Harms, Paul J Bonthuis, Christopher Gregg, Masato Ohtsuka, Channabasavaiah B Gurumurthy, Mark A Behlke
Genome editing using the CRISPR/Cas9 system requires the presence of guide RNAs bound to the Cas9 endonuclease as a ribonucleoprotein (RNP) complex in cells, which cleaves the host cell genome at sites specified by the guide RNAs. New genetic material may be introduced during repair of the double-stranded break via homology dependent repair (HDR) if suitable DNA templates are delivered with the CRISPR components. Early methods used plasmid or viral vectors to make these components in the host cell, however newer approaches using recombinant Cas9 protein with synthetic guide RNAs introduced directly as an RNP complex into cells shows faster onset of action with fewer off-target effects...
March 25, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28346805/brachytherapy-for-patients-with-prostate-cancer-american-society-of-clinical-oncology-cancer-care-ontario-joint-guideline-update
#10
Joseph Chin, R Bryan Rumble, Marisa Kollmeier, Elisabeth Heath, Jason Efstathiou, Tanya Dorff, Barry Berman, Andrew Feifer, Arthur Jacques, D Andrew Loblaw
Purpose To jointly update the Cancer Care Ontario guideline on brachytherapy for patients with prostate cancer to account for new evidence. Methods An Update Panel conducted a targeted systematic literature review and identified more recent randomized controlled trials comparing dose-escalated external beam radiation therapy (EBRT) with brachytherapy in men with prostate cancer. Results Five randomized controlled trials provided the evidence for this update. Recommendations For patients with low-risk prostate cancer who require or choose active treatment, low-dose rate brachytherapy (LDR) alone, EBRT alone, and/or radical prostatectomy (RP) should be offered to eligible patients...
March 27, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28345004/homology-directed-recombination-for-enhanced-engineering-of-chimeric-antigen-receptor-t-cells
#11
Malika Hale, Baeckseung Lee, Yuchi Honaker, Wai-Hang Leung, Alexandra E Grier, Holly M Jacobs, Karen Sommer, Jaya Sahni, Shaun W Jackson, Andrew M Scharenberg, Alexander Astrakhan, David J Rawlings
Gene editing by homology-directed recombination (HDR) can be used to couple delivery of a therapeutic gene cassette with targeted genomic modifications to generate engineered human T cells with clinically useful profiles. Here, we explore the functionality of therapeutic cassettes delivered by these means and test the flexibility of this approach to clinically relevant alleles. Because CCR5-negative T cells are resistant to HIV-1 infection, CCR5-negative anti-CD19 chimeric antigen receptor (CAR) T cells could be used to treat patients with HIV-associated B cell malignancies...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344606/edema-worsens-target-coverage-in-high-dose-rate-interstitial-brachytherapy-of-mobile-tongue-cancer-a-report-of-two-cases
#12
Ken Yoshida, Hideya Yamazaki, Tadayuki Kotsuma, Hironori Akiyama, Tadashi Takenaka, Koji Masui, Yasuo Yoshioka, Yasuo Uesugi, Taiju Shimbo, Nobuhiko Yoshikawa, Hiroto Yoshioka, Takumi Arika, Eiichi Tanaka, Yoshifumi Narumi
PURPOSE: We report our study on two patients to highlight the risk of underdosage of the clinical target volume (CTV) due to edema during high-dose-rate interstitial brachytherapy (HDR-ISBT) of mobile tongue cancer. MATERIAL AND METHODS: To treat the lateral side of the CTV, flexible applicator tubes were implanted on the mouth floor. Two-dimensional planning was performed using X-ray images for Case 1, and three-dimensional (3D) planning was performed using computed tomography (CT) for Case 2...
February 2017: Journal of Contemporary Brachytherapy
https://www.readbyqxmd.com/read/28344601/high-dose-rate-intraluminal-brachytherapy-prior-to-external-radiochemotherapy-in-locally-advanced-esophageal-cancer-preliminary-results
#13
Afsaneh Maddah Safaei, Reza Ghalehtaki, Nezhat Khanjani, Borna Farazmand, Mohammad Babaei, Ebrahim Esmati
PURPOSE: Dysphagia is a common initial presentation in locally advanced esophageal cancer and negatively impacts patient quality of life and treatment compliance. To induce fast relief of dysphagia in patients with potentially operable esophageal cancer high-dose-rate (HDR) brachytherapy was applied prior to definitive radiochemotherapy. MATERIAL AND METHODS: In this single arm phase II clinical trial between 2013 to 2014 twenty patients with locally advanced esophageal cancer (17 squamous cell and 3 adenocarcinoma) were treated with upfront 10 Gy HDR brachytherapy, followed by 50...
February 2017: Journal of Contemporary Brachytherapy
https://www.readbyqxmd.com/read/28342026/high-dose-rate-brachytherapy-source-measurement-intercomparison
#14
Joel Poder, Ryan L Smith, Nikki Shelton, May Whitaker, Duncan Butler, Annette Haworth
This work presents a comparison of air kerma rate (AKR) measurements performed by multiple radiotherapy centres for a single HDR (192)Ir source. Two separate groups (consisting of 15 centres) performed AKR measurements at one of two host centres in Australia. Each group travelled to one of the host centres and measured the AKR of a single (192)Ir source using their own equipment and local protocols. Results were compared to the (192)Ir source calibration certificate provided by the manufacturer by means of a ratio of measured to certified AKR...
March 24, 2017: Australasian Physical & Engineering Sciences in Medicine
https://www.readbyqxmd.com/read/28341865/radioablation-of-adrenal-gland-malignomas-with-interstitial-high-dose-rate-brachytherapy-efficacy-and-outcome
#15
K Mohnike, K Neumann, P Hass, M Seidensticker, R Seidensticker, M Pech, S Klose, T Streitparth, B Garlipp, C Benckert, J J Wendler, U B Liehr, M Schostak, D Göppner, G Gademann, J Ricke
PURPOSE: To assess the efficacy, safety, and outcome of image-guided high-dose-rate (HDR) brachytherapy in patients with adrenal gland metastases (AGM). MATERIALS AND METHODS: From January 2007 to April 2014, 37 patients (7 female, 30 male; mean age 66.8 years, range 41.5-82.5 years) with AGM from different primary tumors were treated with CT-guided HDR interstitial brachytherapy (iBT). Primary endpoint was local tumor control (LTC). Secondary endpoints were time to untreatable progression (TTUP), time to progression (TTP), overall survival (OS), and safety...
March 24, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28341241/high-dose-rate-brachytherapy-as-monotherapy-for-localised-prostate-cancer-review-of-the-current-status
#16
N Tselis, P Hoskin, D Baltas, V Strnad, N Zamboglou, C Rödel, G Chatzikonstantinou
The aim of this article is to review and present the published data on high dose rate (HDR) brachytherapy as monotherapy in the treatment of localised prostate cancer. A search and review of the literature was carried out on PubMed and MedLine using the medical subject headings 'high-dose-rate, brachytherapy, prostate cancer, monotherapy' as search terms. The search yielded more than 100 articles and abstracts published between 2000 and 2016. Only original clinical data on HDR monotherapy reporting oncological outcomes were included...
March 22, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28341011/interstitial-high-dose-rate-brachytherapy-as-salvage-treatment-for-locally-recurrent-prostate-cancer-after-definitive-radiation-therapy-toxicity-and-5-year-outcome
#17
Ping Jiang, Christof van der Horst, Bernhard Kimmig, Fabian Zinsser, Bjoern Poppe, Ulf Luetzen, Klaus-Peter Juenemann, Juergen Dunst, Frank-André Siebert
PURPOSE: We report our results with interstitial high-dose-rate brachytherapy (HDR-BT) as a salvage therapy option after external beam therapy with or without BT. Emphasis was put on toxicity and 5-year outcome. METHODS AND MATERIALS: From 2003 to 2011, 29 patients with local failure after previous radiotherapy for prostate cancer were treated with salvage interstitial HDR-BT. The diagnosis of local recurrence was made on the basis of choline positron emission tomography...
January 2017: Brachytherapy
https://www.readbyqxmd.com/read/28334931/rgf1p-rho1p-gef-is-required-for-double-strand-break-repair-in-fission-yeast
#18
Elvira Manjón, Tomás Edreira, Sofía Muñoz, Yolanda Sánchez
Rho GTPases are conserved molecules that control cytoskeletal dynamics. These functions are expedited by Rho GEFs that stimulate the release of GDP to enable GTP binding, thereby allowing Rho proteins to initiate intracellular signaling. How Rho GEFs and Rho GTPases protect cells from DNA damage is unknown. Here, we explore the extreme sensitivity of a deletion mutation in the Rho1p exchange factor Rgf1p to the DNA break/inducing antibiotic phleomycin (Phl). The Rgf1p mutant cells are defective in reentry into the cell cycle following the induction of severe DNA damage...
March 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334779/targeted-gene-knock-in-by-homology-directed-genome-editing-using-cas9-ribonucleoprotein-and-aav-donor-delivery
#19
Thomas Gaj, Brett T Staahl, Gonçalo M C Rodrigues, Prajit Limsirichai, Freja K Ekman, Jennifer A Doudna, David V Schaffer
Realizing the full potential of genome editing requires the development of efficient and broadly applicable methods for delivering programmable nucleases and donor templates for homology-directed repair (HDR). The RNA-guided Cas9 endonuclease can be introduced into cells as a purified protein in complex with a single guide RNA (sgRNA). Such ribonucleoproteins (RNPs) can facilitate the high-fidelity introduction of single-base substitutions via HDR following co-delivery with a single-stranded DNA oligonucleotide...
March 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28333633/no-reference-quality-assessment-of-tone-mapped-hdr-pictures
#20
Debarati Kundu, Deepti Ghadiyaram, Alan Bovik, Brian Evans
Being able to automatically predict digital picture quality, as perceived by human observers, has become important in many applications where humans are the ultimate consumers of displayed visual information. Standard dynamic range (SDR) images provide 8 bits/color/pixel. High dynamic range (HDR) images which are usually created from multiple exposures of the same scene, can provide 16 or 32 bits/color/pixel, but must be tonemapped to SDR for display on standard monitors. Multi-exposure fusion (MEF) techniques bypass HDR creation, by fusing the exposure stack directly to SDR format while aiming for aesthetically pleasing luminance and color distributions...
March 22, 2017: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
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