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https://www.readbyqxmd.com/read/29108275/functional-imaging-in-combination-with-mutation-status-aids-prediction-of-response-to-inhibiting-b-cell-receptor-signaling-in-lymphoma
#1
Laura Jacobs, Stefan Habringer, Jolanta Slawska, Katharina Huber, Elke Hauf, Zhoulei Li, Yosef Refaeli, Markus Schwaiger, Martina Rudelius, Axel Walch, Ulrich Keller
Aberrant B-cell receptor (BCR) signaling is known to contribute to malignant transformation. Two small molecule inhibitors targeting BCR pathway signaling include ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, and idelalisib, a specific Phosphatidylinositol-4,5-bisphosphate 3-kinase delta (PI3Kδ) inhibitor, both of which have been approved for use in haematological malignancies. Despite the identification of various diffuse large B-cell lymphoma (DLBCL) subtypes, mutation status alone is not sufficient to predict patient response and therapeutic resistance can arise...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28918049/silencing-vdac1-expression-by-sirna-inhibits-cancer-cell-proliferation-and-tumor-growth-in%C3%A2-vivo
#2
Tasleem Arif, Lilia Vasilkovsky, Yael Refaely, Alexander Konson, Varda Shoshan-Barmatz
No abstract text is available yet for this article.
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28905451/gene-edited-human-kidney-organoids-reveal-mechanisms-of-disease-in-podocyte-development
#3
Yong Kyun Kim, Ido Refaeli, Craig R Brooks, Peifeng Jing, Ramila E Gulieva, Michael R Hughes, Nelly M Cruz, Yannan Liu, Angela J Churchill, Yuliang Wang, Hongxia Fu, Jeffrey W Pippin, Lih Y Lin, Stuart J Shankland, A Wayne Vogl, Kelly M McNagny, Benjamin S Freedman
A critical event during kidney organogenesis is the differentiation of podocytes, specialized epithelial cells that filter blood plasma to form urine. Podocytes derived from human pluripotent stem cells (hPSC-podocytes) have recently been generated in nephron-like kidney organoids, but the developmental stage of these cells and their capacity to reveal disease mechanisms remains unclear. Here, we show that hPSC-podocytes phenocopy mammalian podocytes at the capillary loop stage (CLS), recapitulating key features of ultrastructure, gene expression, and mutant phenotype...
September 14, 2017: Stem Cells
https://www.readbyqxmd.com/read/28620883/extended-adjuvant-endocrine-therapy-in-early-breast-cancer-a-meta-analysis-of-published-randomized-trials
#4
Ezzeldin M Ibrahim, Marwan R Al-Hajeili, Ali M Bayer, Omalkhair A Abulkhair, Ahmed A Refae
Adjuvant endocrine therapy for 5 years is the standard adjuvant treatment for estrogen receptor-positive breast cancer while the benefits of extended adjuvant endocrine therapy (EAET) beyond 5 years are still controversial. That controversy prompted this meta-analysis to compare 5 years of adjuvant endocrine therapy only versus EAET. Eligible 11 randomized, controlled trials comprising 29,000 women were included. EAET showed no advantage in overall survival (OS) from all causes mortality (odds ratio [OR] = 0...
July 2017: Medical Oncology
https://www.readbyqxmd.com/read/28572509/dynamic-distinctions-in-the-na-ca-2-exchanger-adopting-the-inward-and-outward-facing-conformational-states
#5
COMPARATIVE STUDY
Moshe Giladi, Liat van Dijk, Bosmat Refaeli, Lior Almagor, Reuben Hiller, Petr Man, Eric Forest, Daniel Khananshvili
Na(+)/Ca(2+) exchanger (NCX) proteins operate through the alternating access mechanism, where the ion-binding pocket is exposed in succession either to the extracellular or the intracellular face of the membrane. The archaeal NCX_Mj (Methanococcus jannaschii NCX) system was used to resolve the backbone dynamics in the inward-facing (IF) and outward-facing (OF) states by analyzing purified preparations of apo- and ion-bound forms of NCX_Mj-WT and its mutant, NCX_Mj-5L6-8. First, the exposure of extracellular and cytosolic vestibules to the bulk phase was evaluated as the reactivity of single cysteine mutants to a fluorescent probe, verifying that NCX_Mj-WT and NCX_Mj-5L6-8 preferentially adopt the OF and IF states, respectively...
July 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28492345/the-focinator-v2-0-graphical-interface-four-channels-colocalization-analysis-and-cell-phase-identification
#6
Sebastian Oeck, Nathalie M Malewicz, Sebastian Hurst, Klaudia Al-Refae, Adam Krysztofiak, Verena Jendrossek
The quantitative analysis of foci plays an important role in various cell biological methods. In the fields of radiation biology and experimental oncology, the effect of ionizing radiation, chemotherapy or molecularly targeted drugs on DNA damage induction and repair is frequently performed by the analysis of protein clusters or phosphorylated proteins recruited to so called repair foci at DNA damage sites, involving for example γ-H2A.X, 53BP1 or RAD51. We recently developed "The Focinator" as a reliable and fast tool for automated quantitative and qualitative analysis of nuclei and DNA damage foci...
July 2017: Radiation Research
https://www.readbyqxmd.com/read/28294312/the-mediating-role-of-cultural-coping-behaviours-on-the-relationships-between-academic-stress-and-positive-psychosocial-well-being-outcomes
#7
Ben C H Kuo, Kendall M Soucie, Siqi Huang, Refa Laith
While culture's effect on the coping process has long been acknowledged in the stress-coping literature conceptually, empirical evidence and attempts to discern the specific relationship between culture and coping remain very scarce. Against this backdrop, the present study applied the Cultural Transactional Theory (Chun, Moos, & Cronkite, 2006) to examine the mediating role of cultural coping behaviours (Collective, Engagement and Avoidance Coping) on the relationship between academic stress (AS) and two positive psychosocial well-being outcome measures: Collective Self-esteem (CSE) and Subjective Well-being (SWB)...
March 10, 2017: International Journal of Psychology: Journal International de Psychologie
https://www.readbyqxmd.com/read/28273117/activation-of-odorant-receptor-in-colorectal-cancer-cells-leads-to-inhibition-of-cell-proliferation-and-apoptosis
#8
Lea Weber, Klaudia Al-Refae, Juliane Ebbert, Peter Jägers, Janine Altmüller, Christian Becker, Stephan Hahn, Günter Gisselmann, Hanns Hatt
The analysis and functional characterization of ectopically expressed human olfactory receptors (ORs) is becoming increasingly important, as many ORs have been identified in several healthy and cancerous tissues. OR activation has been demonstrated to have influence on cancer cell growth and progression. Here, ORs were identified using RNA-Seq analyses and RT-PCR. We demonstrated the OR protein localization in HCT116 cells using immunocytochemistry (IHC). In order to analyze the physiological role of OR51B4, we deorphanized the receptor by the use of CRE-Luciferase assays, conducted calcium imaging experiments as well as scratch- and proliferation assays...
2017: PloS One
https://www.readbyqxmd.com/read/28209968/activating-akt1-mutations-alter-dna-double-strand-break-repair-and-radiosensitivity
#9
S Oeck, K Al-Refae, H Riffkin, G Wiel, R Handrick, D Klein, G Iliakis, V Jendrossek
The survival kinase Akt has clinical relevance to radioresistance. However, its contributions to the DNA damage response, DNA double strand break (DSB) repair and apoptosis remain poorly defined and often contradictory. We used a genetic approach to explore the consequences of genetic alterations of Akt1 for the cellular radiation response. While two activation-associated mutants with prominent nuclear access, the phospho-mimicking Akt1-TDSD and the clinically relevant PH-domain mutation Akt1-E17K, accelerated DSB repair and improved survival of irradiated Tramp-C1 murine prostate cancer cells and Akt1-knockout murine embryonic fibroblasts in vitro, the classical constitutively active membrane-targeted myrAkt1 mutant had the opposite effects...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193536/blood-brain-barrier-disruption-after-cardiopulmonary-bypass-diagnosis-and-correlation-to-cognition
#10
Dan Abrahamov, Oren Levran, Sharon Naparstek, Yael Refaeli, Shani Kaptson, Mahmud Abu Salah, Yaron Ishai, Gideon Sahar
BACKGROUND: Cardiopulmonary bypass (CPB) elicits a systemic inflammatory response that may impair blood-brain barrier (BBB) integrity. BBB disruption can currently be detected by dynamic contrast enhancement magnetic resonance imaging (MRI), reflected by an increase in the permeability constant (K(trans)). We aimed to determine (1) whether CPB induces BBB disruption, (2) duration until BBB disruption resolution, and (3) the obtainable correlation between BBB injury (location and intensity) and neurocognitive dysfunction...
July 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28008282/expression-and-functionality-of-trpv1-in-breast-cancer-cells
#11
Lea V Weber, Klaudia Al-Refae, Gerhard Wölk, Gabriele Bonatz, Janine Altmüller, Christian Becker, Günter Gisselmann, Hanns Hatt
Transient receptor potential (TRP) channels contribute to the regulation of intracellular calcium, which can promote cancer hallmarks in cases of dysregulation of gene transcription and calcium-dependent pro-proliferative or anti-apoptotic mechanisms. Several studies have begun to elucidate the roles of TRPV1, TRPV6, TRPM8, and TRPC1 in cancer progression; however, no study has examined the expression profiles of human TRP channels in breast cancer on a large scale. This study focused on the expression and functionality of TRPV1, a nonselective cation channel that was found to be expressed in different carcinoma tissues...
2016: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/27621456/tuning-electronic-transport-via-hepta-alanine-peptides-junction-by-tryptophan-doping
#12
Cunlan Guo, Xi Yu, Sivan Refaely-Abramson, Lior Sepunaru, Tatyana Bendikov, Israel Pecht, Leeor Kronik, Ayelet Vilan, Mordechai Sheves, David Cahen
Charge migration for electron transfer via the polypeptide matrix of proteins is a key process in biological energy conversion and signaling systems. It is sensitive to the sequence of amino acids composing the protein and, therefore, offers a tool for chemical control of charge transport across biomaterial-based devices. We designed a series of linear oligoalanine peptides with a single tryptophan substitution that acts as a "dopant," introducing an energy level closer to the electrodes' Fermi level than that of the alanine homopeptide...
September 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27606697/extended-anti-her2-therapy-in-early-breast-cancer-longer-beats-shorter
#13
REVIEW
Sadal Refae, Barbara Pistilli, Suzette Delaloge
PURPOSE OF REVIEW: One-year duration of adjuvant trastuzumab is the gold standard since 2005. During the last decade many attempts have been made to both increase and reduce the treatment duration. The purpose of this article is to review the current available evidence regarding alternative anti-HER2 therapy durations in the (neo)adjuvant treatment of HER2-positive localized breast cancer patients. RECENT FINDINGS: According to the majority of published data, shorter trastuzumab schedule has shown a decreased benefit in the overall HER2 population, whereas extending adjuvant trastuzumab, beyond 1 year, does not improve the outcome and is associated with increased cardiac toxicity...
November 2016: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27602795/therapists-recognition-of-alliance-ruptures-as-a-moderator-of-change-in-alliance-and-symptoms
#14
Roei Chen, Dana Atzil-Slonim, Eran Bar-Kalifa, Ilanit Hasson-Ohayon, Eshkol Refaeli
Therapists' awareness of ruptures in the alliance may determine whether such ruptures will prove beneficial or obstructive to the therapy process. OBJECTIVE: This study investigated the associations between therapists' recognition of these ruptures, and changes in clients' alliance ratings and symptom reports, using time-series data in a naturalistic treatment setting. METHOD: Eighty-four clients treated by 56 therapists completed alliance measures after each session, and the clients also completed symptom measures at the beginning of each session...
September 7, 2016: Psychotherapy Research: Journal of the Society for Psychotherapy Research
https://www.readbyqxmd.com/read/27587540/humanized-mouse-xenograft-models-narrowing-the-tumor-microenvironment-gap
#15
REVIEW
J Jason Morton, Gregory Bird, Yosef Refaeli, Antonio Jimeno
Cancer research has long been hampered by the limitations of the current model systems. Both cultured cells and mouse xenografts grow in an environment highly dissimilar to that of their originating tumor, frequently resulting in promising treatments that are ultimately clinically ineffective. The development of highly immunodeficient mouse strains into which human immune systems can be engrafted can help bridge this gap. Humanized mice (HM) allow researchers to examine xenograft growth in the context of a human immune system and resultant tumor microenvironment, and recent studies have highlighted the increased similarities in attendant tumor structure, metastasis, and signaling to those features in cancer patients...
November 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27271983/personal-and-environmental-predictors-of-depression-among-victims-of-intimate-partner-violence-comparison-of-immigrant-and-israeli-born-women
#16
Tehila Refaeli, Drorit Levy, Anat Ben-Porat, Rachel Dekel, Haya Itzhaky
In the present study, ecological theory was used as a basis for predicting depression among women who survive intimate partner violence (IPV). The predictors examined in the study derived from three ecological systems: the microsystem (background variables and frequency of the violence), the ontogenic system (personal resources), and the mesosystem (support resources). One hundred twenty-five women who immigrated from the Former Soviet Union and 149 Israeli-born Jewish women filled in questionnaires when they entered shelters for victims of IPV...
June 5, 2016: Journal of Interpersonal Violence
https://www.readbyqxmd.com/read/27046831/setd7-controls-intestinal-regeneration-and-tumorigenesis-by-regulating-wnt-%C3%AE-catenin-and-hippo-yap-signaling
#17
Menno J Oudhoff, Mitchell J S Braam, Spencer A Freeman, Denise Wong, David G Rattray, Jia Wang, Frann Antignano, Kimberly Snyder, Ido Refaeli, Michael R Hughes, Kelly M McNagny, Michael R Gold, Cheryl H Arrowsmith, Toshiro Sato, Fabio M V Rossi, John H Tatlock, Dafydd R Owen, Peter J Brown, Colby Zaph
Intestinal tumorigenesis is a result of mutations in signaling pathways that control cellular proliferation, differentiation, and survival. Mutations in the Wnt/β-catenin pathway are associated with the majority of intestinal cancers, while dysregulation of the Hippo/Yes-Associated Protein (YAP) pathway is an emerging regulator of intestinal tumorigenesis. In addition, these closely related pathways play a central role during intestinal regeneration. We have previously shown that methylation of the Hippo transducer YAP by the lysine methyltransferase SETD7 controls its subcellular localization and function...
April 4, 2016: Developmental Cell
https://www.readbyqxmd.com/read/26988554/anterior-versus-posterior-debridement-fusion-for-single-level-dorsal-tuberculosis-the-role-of-graft-type-and-level-of-fixation-on-determining-the-outcome
#18
Yasser M Assaghir, Hesham Hamed Refae, Mohamed Alam-Eddin
PURPOSE: This study compared the clinical, radiological and functional outcome of anterior versus posterior approaches for single-level dorsal tuberculosis with analysis of effect of graft type and fixation level on the outcome. METHODS: Anterior group (AG): 43 cases (mean age: 49.5 years) fixed with Z-plate by anterior transthoracic-transpleural approach. Posterior group (PG): 49 cases (47.0 years) fixed with transpedicular-screws with unilateral facetectomy ± pediculectomy...
December 2016: European Spine Journal
https://www.readbyqxmd.com/read/26958982/structure-based-engineering-of-lithium-transport-capacity-in-an-archaeal-sodium-calcium-exchanger
#19
Bosmat Refaeli, Moshe Giladi, Reuben Hiller, Daniel Khananshvili
Members of the Ca(2+)/cation exchanger superfamily (Ca(2+)/CA) share structural similarities (including highly conserved ion-coordinating residues) while exhibiting differential selectivity for Ca(2+), Na(+), H(+), K(+), and Li(+). The archaeal Na(+)/Ca(2+) exchanger (NCX_Mj) and its mammalian orthologs are highly selective for Na(+), whereas the mitochondrial ortholog (NCLX) can transport either Li(+) or Na(+) in exchange with Ca(2+). Here, structure-based replacement of ion-coordinating residues in NCX_Mj resulted in a capacity for transporting either Na(+) or Li(+), similar to the case for NCLX...
March 29, 2016: Biochemistry
https://www.readbyqxmd.com/read/26916536/cold-denaturation-induces-inversion-of-dipole-and-spin-transfer-in-chiral-peptide-monolayers
#20
Meital Eckshtain-Levi, Eyal Capua, Sivan Refaely-Abramson, Soumyajit Sarkar, Yulian Gavrilov, Shinto P Mathew, Yossi Paltiel, Yaakov Levy, Leeor Kronik, Ron Naaman
Chirality-induced spin selectivity is a recently-discovered effect, which results in spin selectivity for electrons transmitted through chiral peptide monolayers. Here, we use this spin selectivity to probe the organization of self-assembled α-helix peptide monolayers and examine the relation between structural and spin transfer phenomena. We show that the α-helix structure of oligopeptides based on alanine and aminoisobutyric acid is transformed to a more linear one upon cooling. This process is similar to the known cold denaturation in peptides, but here the self-assembled monolayer plays the role of the solvent...
2016: Nature Communications
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