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https://www.readbyqxmd.com/read/28220817/a-simple-approach-for-preparation-of-affinity-matrices-simultaneous-purification-and-reversible-immobilization-of-a-streptavidin-mutein-to-agarose-matrix
#1
Sau-Ching Wu, Chris Wang, Dave Hansen, Sui-Lam Wong
SAVSBPM18 is an engineered streptavidin for affinity purification of both biotinylated biomolecules and recombinant proteins tagged with streptavidin binding peptide (SBP) tags. To develop a user-friendly approach for the preparation of the SAVSBPM18-based affinity matrices, a designer fusion protein containing SAVSBPM18 and a galactose binding domain was engineered. The galactose binding domain derived from the earthworm lectin EW29 was genetically modified to eliminate a proteolytic cleavage site located at the beginning of the domain...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28212572/concurrent-gene-alterations-with-egfr-mutation-and-treatment-efficacy-of-egfr-tkis-in-chinese-patients-with-non-small-cell-lung-cancer
#2
Wentao Hu, Yahui Liu, Jian Chen
PURPOSE: We investigated the frequency of concurrent genes in EGFR-mutant non-small cell lung cancer patients and determined its value in predicting the efficacy of EGFR-TKIs treatment. METHODS: Three hundred and twenty patients, who harbored EGFR activating mutations and received EGFR-TKIs treatment, were examined for another eight genes including KRAS, NRAS, PIK3CA, BRAF, and HER2 mutations and ALK, ROS1, and RET fusion genes based on reverse transcription PCR...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28204962/the-clinical-anatomy-of-the-insertion-of-the-rotator-cuff-tendons
#3
M Vosloo, N Keough, M A De Beer
The rotator cuff (RC) insertions according to most anatomical texts are described as being separate from one another. However, clear fusion of the RC tendon fibres exists with prior studies showing this interdigitation forming a common, continuous insertion onto and around the lesser and greater tubercles (LT and GT) of the humerus. Current surgical repair methods (especially arthroscopic techniques) rarely mention or consider these connections during repair and suture anchor implantation. The general principles of RC surgery remain a controversial subject, due to various available techniques, surgeon experience and preference, and the contradicting success rates...
February 16, 2017: European Journal of Orthopaedic Surgery & Traumatology: Orthopédie Traumatologie
https://www.readbyqxmd.com/read/28197355/a-case-of-crossed-left-renal-ectopia-identified-during-colostomy-reversal
#4
Rachel NeMoyer, Sumana Narayanan, Nell Maloney-Patel
Unilateral crossed renal ectopia without fusion is an uncommon anatomic anomaly, which often goes undiagnosed. We report a case of this renal variant discovered incidentally during colostomy reversal after Hartmann's procedure for diverticular stricture.
2017: Case Reports in Surgery
https://www.readbyqxmd.com/read/28194987/mass-defect-based-n-n-dimethyl-leucine-labels-for-quantitative-proteomics-and-amine-metabolomics-of-pancreatic-cancer-cells
#5
Ling Hao, Jillian Johnson, Christopher B Lietz, Amanda Buchberger, Dustin Frost, W John Kao, Lingjun Li
Mass spectrometry-based stable isotope labeling has become a key technology for protein and small-molecule analyses. We developed a multiplexed quantification method for simultaneous proteomics and amine metabolomics analyses via nano reversed-phase liquid chromatography-tandem mass spectrometry (nanoRPLC-MS/MS), called mass defect-based N,N-dimethyl leucine (mdDiLeu) labeling. The duplex mdDiLeu reagents were custom-synthesized with a mass difference of 20.5 mDa, arising from the subtle variation in nuclear binding energy between the two DiLeu isotopologues...
January 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28194887/atgl-deficiency-induces-podocyte-apoptosis-and-leads-to-glomerular-filtration-barrier-damage
#6
Wen Chen, Youzhao Jiang, Jian Han, Jiongyu Hu, Ting He, Tiantian Yan, Huang Na, Qiong Zhang, Hao Mei, Yong Liao, Yuesheng Huang, Bing Chen
Abnormal lipid metabolism, renal lipid accumulation and lipotoxicity are associated with the pathological features of glomerulopathy. However, the mechanisms by which lipid accumulation leads to the development or progression of this disease have not been fully elucidated. In this work, we have identified a role for the rate-limiting enzyme in lipolysis, adipose triglyceride lipase (ATGL; also called patatin-like phospholipase domain-containing protein 2(PNPLP2), in renal lipid metabolism and kidney disease...
February 14, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28193277/anti-tumor-effects-of-a-recombinant-anti-prostate-specific-membrane-antigen-immunotoxin-against-prostate-cancer-cells
#7
Ping Meng, Qing-Chuan Dong, Guang-Guo Tan, Wei-Hong Wen, He Wang, Geng Zhang, Yan-Zhu Wang, Yu-Ming Jing, Chen Wang, Wei-Jun Qin, Jian-Lin Yuan
BACKGROUND: To evaluate anti-prostate cancer effects of a chimeric tumor-targeted killer protein. METHODS: We established a novel fusion gene, immunocasp-3, composed of NH2-terminal leader sequence fused with an anti-prostate-specific membrane antigen (PSMA) antibody (J591), the furin cleavage sequences of diphtheria toxin (Fdt), and the reverse coding sequences of the large and small subunits of caspase-3 (revcaspase-3). The expressing level of the immunocasp-3 gene was evaluated by using the reverse transcription-PCR (RT-PCR) and western blot analysis...
February 13, 2017: BMC Urology
https://www.readbyqxmd.com/read/28183697/safety-and-antitumor-activity-of-the-multi-targeted-pan-trk-ros1-and-alk-inhibitor-entrectinib-rxdx-101-combined-results-from-two-phase-1-trials-alka-372-001-and-startrk-1
#8
Alexander Drilon, Salvatore Siena, Sai-Hong Ignatius Ou, Manish Patel, Myung Ju Ahn, Jeeyun Lee, Todd M Bauer, Anna F Farago, Jennifer J Wheler, Stephen V Liu, Robert Doebele, Laura Giannetta, Giulio Cerea, Giovanna Marrapese, Michele Schirru, Alessio Amatu, Katia Bencardino, Laura Palmeri, Andrea Sartore-Bianchi, Angelo Vanzulli, Sara Cresta, Silvia Damian, Matteo Duca, Elena Ardini, Gang Li, Jason Christiansen, Karey Kowalski, Ann Johnson, Rupal Patel, David Luo, Edna Chow-Maneval, Zachary Hornby, Pratik S Multani, Alice T Shaw, Filippo G De Braud
Entrectinib, a potent oral inhibitor of the tyrosine kinases TRKA/B/C, ROS1, and ALK, was evaluated in two Phase 1 studies in patients with advanced or metastatic solid tumors, including patients with active CNS disease. Here we summarize the overall safety and report the antitumor activity of entrectinib in a cohort of patients with tumors harboring NTRK1/2/3, ROS1, or ALK gene fusions, naïve to prior TKI treatment targeting the specific gene, and who were treated at doses that achieved therapeutic exposures consistent with the RP2D...
February 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28183680/diagnosis-of-variant-rara-translocation-using-standard-dual-color-dual-fusion-pml-rara-fish-probes-an-illustrative-report
#9
Manish K Singh, Mayur Parihar, Neeraj Arora, D K Mishra, Saurabh J Bhave, Mammen Chandy
Acute promyelocytic leukemia (APML) with variant RARa translocations comprises 1-2% of APML cases. However, the diagnosis of these cases is challenging as the routine practice includes fluorescence in situ hybridization (FISH) reverse transcription polymerase chain reaction targeting the PML and RARA genes to detect PML/RARA fusions. Here, we report a case highlighting the importance of atypical FISH signal patterns in standard dual-color dual-fusion PML/RARa FISH analysis complimented by karyotyping to detect these variant RARA translocations...
February 1, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28173821/identification-of-influenza-a-nucleoprotein-body-domain-residues-essential-for-viral-rna-expression-expose-antiviral-target
#10
Alicia M Davis, Jose Ramirez, Laura L Newcomb
BACKGROUND: Influenza A virus is controlled with yearly vaccination while emerging global pandemics are kept at bay with antiviral medications. Unfortunately, influenza A viruses have emerged resistance to approved influenza antivirals. Accordingly, there is an urgent need for novel antivirals to combat emerging influenza A viruses resistant to current treatments. Conserved viral proteins are ideal targets because conserved protein domains are present in most, if not all, influenza subtypes, and are presumed less prone to evolve viable resistant versions...
February 7, 2017: Virology Journal
https://www.readbyqxmd.com/read/28161752/reversibility-of-nerve-root-sedimentation-sign-in-lumbar-spinal-stenosis-patients-after-decompression-surgery
#11
Christian Barz, Markus Melloh, Lukas P Staub, Sarah J Lord, Harry R Merk, Thomas Barz
PURPOSE: The nerve root sedimentation sign (SedSign) is a magnetic resonance imaging (MRI) sign for the diagnosis of lumbar spinal stenosis (LSS). It is included in the assessment of LSS to help determine whether decompression surgery is indicated. Assessment of the reversibility of the SedSign after surgery may also have clinical implications for the decision about whether or not a secondary operation or revision is needed. This study investigated if lumbar decompression leads to a reversal of the SedSign in patients with LSS and a positive SedSign pre-operatively; and if a reversal is associated with more favourable clinical outcomes...
February 4, 2017: European Spine Journal
https://www.readbyqxmd.com/read/28151467/augmented-trophoblast-cell-death-in-preeclampsia-can-proceed-via-ceramide-mediated-necroptosis
#12
Liane Jennifer Bailey, Sruthi Alahari, Andrea Tagliaferro, Martin Post, Isabella Caniggia
Preeclampsia, a serious hypertensive disorder of pregnancy, is characterized by elevated ceramide (CER) content that is responsible for heightened trophoblast cell death rates via apoptosis and autophagy. Whether trophoblast cells undergo necroptosis, a newly characterized form of regulated necrosis, and the potential role of CER in this process remain to be established. Herein, we report that exposure of both JEG3 cells and primary isolated cytotrophoblasts to C16:0 CER in conjunction with a caspase-8 inhibitor (Q-VD-OPh) promoted necroptotic cell death, as evidenced by increased expression and association of receptor-interacting protein kinases RIP1 and RIP3, as well as phosphorylation of mixed lineage kinase domain-like (MLKL) protein...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28147314/the-antiangiogenic-role-of-the-pro-inflammatory-cytokine-interleukin-31
#13
Shiri Davidi, Ella Fremder, Tal Kan, Ziv Raviv, Michael Timaner, Nathan Karin, Dov Hershkovitz, Ami Arohneim, Yuval Shaked
Pro-inflammatory cytokines in the tumor microenvironment are known for their ability to either inhibit or promote cancer progression. Here we evaluated the role of Interleukin-31 (IL31), a protein belonging to the pro-inflammatory IL-6 cytokine family which has been characterized in autoimmune disease, in tumorigenesis. We show that IL31 and its receptor, IL31RA, are highly expressed in various human and mouse cancer cell lines, as well as in tumor specimens from cancer patients. MC38 murine colon carcinoma cells depleted of IL31 exhibit an increase in invasive and migratory properties in vitro, effects that are reversed by supplementing the cells with exogenous IL31...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28141799/the-spectrum-of-ewsr1-rearranged-neoplasms-at-a-tertiary-sarcoma-centre-assessing-772-tumour-specimens-and-the-value-of-current-ancillary-molecular-diagnostic-modalities
#14
Jonathan Noujaim, Robin L Jones, John Swansbury, David Gonzalez, Charlotte Benson, Ian Judson, Cyril Fisher, Khin Thway
BACKGROUND: EWSR1 rearrangements were first identified in Ewing sarcoma, but the spectrum of EWSR1-rearranged neoplasms now includes many soft tissue tumour subtypes including desmoplastic small round cell tumour (DSRCT), myxoid liposarcoma (MLPS), extraskeletal myxoid chondrosarcoma (EMC), angiomatoid fibrous histiocytoma (AFH), clear cell sarcoma (CCS) and myoepithelial neoplasms. We analysed the spectrum of EWSR1-rearranged soft tissue neoplasms at our tertiary sarcoma centre, by assessing ancillary molecular diagnostic modalities identifying EWSR1-rearranged tumours and reviewing the results in light of our current knowledge of these and other Ewing sarcoma-like neoplasms...
January 31, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28137864/entirely-plasmid-based-reverse-genetics-system-for-rotaviruses
#15
Yuta Kanai, Satoshi Komoto, Takahiro Kawagishi, Ryotaro Nouda, Naoko Nagasawa, Misa Onishi, Yoshiharu Matsuura, Koki Taniguchi, Takeshi Kobayashi
Rotaviruses (RVs) are highly important pathogens that cause severe diarrhea among infants and young children worldwide. The understanding of the molecular mechanisms underlying RV replication and pathogenesis has been hampered by the lack of an entirely plasmid-based reverse genetics system. In this study, we describe the recovery of recombinant RVs entirely from cloned cDNAs. The strategy requires coexpression of a small transmembrane protein that accelerates cell-to-cell fusion and vaccinia virus capping enzyme...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28135248/systematic-analysis-of-telomere-length-and-somatic-alterations-in-31-cancer-types
#16
Floris P Barthel, Wei Wei, Ming Tang, Emmanuel Martinez-Ledesma, Xin Hu, Samirkumar B Amin, Kadir C Akdemir, Sahil Seth, Xingzhi Song, Qianghu Wang, Tara Lichtenberg, Jian Hu, Jianhua Zhang, Siyuan Zheng, Roel G W Verhaak
Cancer cells survive cellular crisis through telomere maintenance mechanisms. We report telomere lengths in 18,430 samples, including tumors and non-neoplastic samples, across 31 cancer types. Telomeres were shorter in tumors than in normal tissues and longer in sarcomas and gliomas than in other cancers. Among 6,835 cancers, 73% expressed telomerase reverse transcriptase (TERT), which was associated with TERT point mutations, rearrangements, DNA amplifications and transcript fusions and predictive of telomerase activity...
January 30, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28134577/primary-intraprostatic-synovial-sarcoma
#17
Andrea M Olofson, Konstantinos Linos
Primary intraprostatic synovial sarcoma is a rare presentation of an otherwise well-studied disease, and it is one of the few primary sarcomas to occur in the prostate. Ancillary diagnostic techniques including immunohistochemistry and molecular genetics are useful to establish a definitive diagnosis. Despite its unorthodox location, it shares histologic and molecular genetic characteristics with tumors found elsewhere in the body. Most notably, the chromosomal translocation t(X;18)(p11;q11) encodes a chimeric transcription-activating protein, SS18-SSX, which has been identified as the primary driver mutation...
February 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28133905/simultaneous-detection-of-45-fusion-genes-in-leukemia-by-dual-color-fluorescence-real-time-pcr
#18
Z Zheng, P Zhang, G He, K Liao, Z Wang, J Pan, K Du, J Du, B-A Li
INTRODUCTION: Detection of recurrent genetic abnormalities is of great significance for a refined diagnosis and assessment of prognosis in leukemia. Conventional nested reverse transcription PCR is labor intensive and time-consuming. METHODS: We have developed a novel dual-color TaqMan probe-based real-time PCR method for the simultaneous screening of 45 fusion transcripts in 12 parallel reactions. The method was tested and validated with cell lines carrying known fusion transcripts and patient samples...
January 30, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28129120/targeting-of-aberrant-%C3%AE-v%C3%AE-6-integrin-expression-in-solid-tumors-using-chimeric-antigen-receptor-engineered-t-cells
#19
Lynsey M Whilding, Ana C Parente-Pereira, Tomasz Zabinski, David M Davies, Roseanna M G Petrovic, Y Vincent Kao, Shobhit A Saxena, Alex Romain, Jose A Costa-Guerra, Shelia Violette, Hiroaki Itamochi, Sadaf Ghaem-Maghami, Sabari Vallath, John F Marshall, John Maher
Expression of the αvβ6 integrin is upregulated in several solid tumors. In contrast, physiologic expression of this epithelial-specific integrin is restricted to development and epithelial re-modeling. Here, we describe, for the first time, the development of a chimeric antigen receptor (CAR) that couples the recognition of this integrin to the delivery of potent therapeutic activity in a diverse repertoire of solid tumor models. Highly selective targeting αvβ6 was achieved using a foot and mouth disease virus-derived A20 peptide, coupled to a fused CD28(+)CD3 endodomain...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28123608/the-novel-pim1-inhibitor-nms-p645-reverses-pim1-dependent-effects-on-tmprss2-erg-positive-prostate-cancer-cells-and-shows-anti-proliferative-activity-in-combination-with-pi3k-inhibition
#20
Luca Mologni, Vera Magistroni, Francesco Casuscelli, Marisa Montemartini, Carlo Gambacorti-Passerini
PIM1 is over-expressed in multiple tumors, including prostate cancer (PCa). PIM1 upregulation is mediated by direct binding of the ERG transcription factor to its promoter. About 50% of PCa cases are characterized by the presence of the TMPRSS2/ERG fusion, leading to ERG over-expression and thus to PIM1 transcriptional activation. PIM kinases are considered as weak oncogenes, but when combined with additional genetic alterations can induce strong transforming effects. Here we show anti-proliferative activity of the newly described PIM1 inhibitor NMS-P645 in combination with the PI3K inhibitor GDC-0941 in TMPRSS2/ERG positive and negative PCa cells...
2017: Journal of Cancer
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