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https://www.readbyqxmd.com/read/29677469/multidomain-control-over-tec-kinase-activation-state-tunes-the-t-cell-response
#1
Amy H Andreotti, Raji E Joseph, James M Conley, Janet Iwasa, Leslie J Berg
Signaling through the T cell antigen receptor (TCR) activates a series of tyrosine kinases. Directly associated with the TCR, the SRC family kinase LCK and the SYK family kinase ZAP-70 are essential for all downstream responses to TCR stimulation. In contrast, the TEC family kinase ITK is not an obligate component of the TCR cascade. Instead, ITK functions as a tuning dial, to translate variations in TCR signal strength into differential programs of gene expression. Recent insights into TEC kinase structure have provided a view into the molecular mechanisms that generate different states of kinase activation...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29669753/pilot-trial-of-ibrutinib-in-patients-with-relapsed-or-refractory-t-cell-lymphoma
#2
Anita Kumar, Santosha Vardhana, Alison J Moskowitz, Pierluigi Porcu, Ahmet Dogan, Jason A Dubovsky, Matthew J Matasar, Zhigang Zhang, Anas Younes, Steven M Horwitz
Ibrutinib has previously been shown to inhibit Bruton's tyrosine kinase (BTK) and interleukin-2-inducible T-cell kinase (ITK), which mediate B-cell and T-cell receptor signaling, respectively. BTK inhibition with ibrutinib has demonstrated impressive clinical responses in a variety of B-cell malignancies. Whether ibrutinib inhibition of ITK can lead to clinical response in T-cell malignancies is unknown. We hypothesized that ibrutinib-mediated ITK inhibition in T-cell lymphoma would result in decreased signaling through the T-cell receptor pathway and promote antitumor immune response by driving selective cytotoxic Th1 CD4 effector T-cell differentiation...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29613842/rapid-contour-based-segmentation-for-18-f-fdg-pet-imaging-of-lung-tumors-by-using-itk-snap-comparison-to-expert-based-segmentation
#3
Florent L Besson, Théophraste Henry, Céline Meyer, Virgile Chevance, Victoire Roblot, Elise Blanchet, Victor Arnould, Gilles Grimon, Malika Chekroun, Laurence Mabille, Florence Parent, Andrei Seferian, Sophie Bulifon, David Montani, Marc Humbert, Philippe Chaumet-Riffaud, Vincent Lebon, Emmanuel Durand
Purpose To assess the performance of the ITK-SNAP software for fluorodeoxyglucose (FDG) positron emission tomography (PET) segmentation of complex-shaped lung tumors compared with an optimized, expert-based manual reference standard. Materials and Methods Seventy-six FDG PET images of thoracic lesions were retrospectively segmented by using ITK-SNAP software. Each tumor was manually segmented by six raters to generate an optimized reference standard by using the simultaneous truth and performance level estimate algorithm...
April 3, 2018: Radiology
https://www.readbyqxmd.com/read/29599589/direct-linear-measurement-of-root-dentin-thickness-and-dentin-volume-changes-with-post-space-preparation-a-cone-beam-computed-tomography-study
#4
Shoeb Yakub Shaikh, Safia Shoeb Shaikh
Aim: The purpose of the present study was direct linear measurement of dentin thickness and dentin volume changes for post space preparation with cone-beam computed tomography (CBCT). Materials and Methods: Ten maxillary central incisors were scanned, before and after root canal and post space preparation, with Orthophos XG three-dimensional hybrid unit. Thirteen axial section scans of each tooth from orifice to apex and dentin thickness for buccal, lingual, mesial, and distal were measured using proprietary measuring tool and thereafter subjected to statistical analysis...
January 2018: Contemporary Clinical Dentistry
https://www.readbyqxmd.com/read/29541057/small-lesion-size-is-associated-with-sleep-related-epilepsy-in-focal-cortical-dysplasia-type-ii
#5
Bo Jin, Wenhan Hu, Linmei Ye, Balu Krishnan, Thandar Aung, Stephen E Jones, Imad M Najm, Andreas V Alexopoulos, Kai Zhang, Junming Zhu, Jianguo Zhang, Meiping Ding, Zhong Chen, Shuang Wang, Zhong Irene Wang
Objective: To investigate the neuroimaging and clinical features associated with sleep-related epilepsy (SRE) in patients with focal cortical dysplasia (FCD) type II. Methods: Patients with histopathologically proven FCD type II were included from three epilepsy centers. SRE was defined according to the video EEG findings and seizure history. Cortical surface reconstruction and volume calculation were performed using FreeSurfer. The lesions were manually delineated on T1 volumetric MRI using the ITK-SNAP software...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29532266/ibrutinib-exacerbates-bleomycin-induced-pulmonary-fibrosis-via-promoting-inflammation
#6
Yangyang Gu, Bo Huang, Yanfei Yang, Mengdie Qi, Guohua Lu, Dajing Xia, Hequan Li
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease with high mortality rate. The etiology is unknown and treatment choices are limited. Thus, there is great interest to investigate novel agents for IPF therapy. Ibrutinib, BTK, and ITK irreversible inhibitor is a FDA-approved small molecule for the clinical therapy of B cell lymphoma. Its role in pulmonary fibrosis remains unknown. In this study, we investigated the anti-fibrotic activity of ibrutinib. Strikingly, ibrutinib did not inhibit but exacerbated bleomycin-induced pulmonary fibrosis by increased epithelial cell apoptosis, and inflammation in the lung...
March 13, 2018: Inflammation
https://www.readbyqxmd.com/read/29453458/il-2-inducible-kinase-itk-is-critical-for-hiv-1-infection-of-jurkat-t-cells
#7
Anika Hain, Melanie Krämer, René M Linka, Saeideh Nakhaei-Rad, Mohammad Reza Ahmadian, Dieter Häussinger, Arndt Borkhardt, Carsten Münk
Successful replication of Human immunodeficiency virus (HIV)-1 depends on the expression of various cellular host factors, such as the interleukin-2 inducible T-cell kinase (ITK), a member of the protein family of TEC-tyrosine kinases. ITK is selectively expressed in T-cells and coordinates signaling pathways downstream of the T-cell receptor and chemokine receptors, including PLC-1 activation, Ca2+ -release, transcription factor mobilization, and actin rearrangements. The exact role of ITK during HIV-1 infection is still unknown...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29442273/a-comparative-study-of-segmentation-techniques-for-the-quantification-of-brain-subcortical-volume
#8
Theophilus N Akudjedu, Leila Nabulsi, Migle Makelyte, Cathy Scanlon, Sarah Hehir, Helen Casey, Srinath Ambati, Joanne Kenney, Stefani O'Donoghue, Emma McDermott, Liam Kilmartin, Peter Dockery, Colm McDonald, Brian Hallahan, Dara M Cannon
Manual tracing of magnetic resonance imaging (MRI) represents the gold standard for segmentation in clinical neuropsychiatric research studies, however automated approaches are increasingly used due to its time limitations. The accuracy of segmentation techniques for subcortical structures has not been systematically investigated in large samples. We compared the accuracy of fully automated [(i) model-based: FSL-FIRST; (ii) patch-based: volBrain], semi-automated (FreeSurfer) and stereological (Measure®) segmentation techniques with manual tracing (ITK-SNAP) for delineating volumes of the caudate (easy-to-segment) and the hippocampus (difficult-to-segment)...
February 13, 2018: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/29437271/novel-radiomic-signature-as-a-prognostic-biomarker-for-locally-advanced-rectal-cancer
#9
Yankai Meng, Yuchen Zhang, Di Dong, Chunming Li, Xiao Liang, Chongda Zhang, Lijuan Wan, Xinming Zhao, Kai Xu, Chunwu Zhou, Jie Tian, Hongmei Zhang
BACKGROUND: Locally advanced rectal cancer (LARC) patient stratification by clinicoradiologic factors may yield variable results. Therefore, more efficient prognostic biomarkers are needed for improved risk stratification of LARC patients, personalized treatment, and prognostication. PURPOSE/HYPOTHESIS: To compare the ability of a radiomic signature to predict disease-free survival (DFS) with that of a clinicoradiologic risk model in individual patients with LARC...
February 13, 2018: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/29429648/the-usefulness-of-fibrin-glue-as-a-support-in-the-dissection-of-malignant-cystic-brain-tumors
#10
J Todeschi, Y Pin, F Lersy, F Séverac, I Ollivier, S Kremer, F Proust, H Cebula
BACKGROUND: If the complete microsurgical resection of a brain tumor is a logical oncologic goal, the surgical strategy for the cystic component remains controversial secondary to the risk of morbidity. The objective of this study was to analyze the interest of using fibrin glue in the resection of malignant cystic brain tumors (MCBT). METHODS: Seven patients (median: 60-years-old (range [52-72]/sex ratio M/F: 2.5) were analyzed prospectively in the Neurosurgery Department at Strasbourg University Hospital, from October 2014 to November 2016...
February 8, 2018: Neuro-Chirurgie
https://www.readbyqxmd.com/read/29285806/systematic-review-of-infectious-events-with-the-bruton-tyrosine-kinase-inhibitor-ibrutinib-in-the-treatment-of-hematologic-malignancies
#11
REVIEW
Benjamin F Tillman, James M Pauff, Gowri Satyanarayana, Mahsa Talbott, Jeremy L Warner
OBJECTIVE: Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase (BTK) in B lymphocytes as well as other kinases including interleukin-2-inducible T-cell kinase (ITK) in CD4+ Th2 regulatory T cells. Increased infections have been observed in patients taking ibrutinib. The overall incidence has not been systematically evaluated. METHODS: The published literature and conference abstracts of prospective clinical trials using ibrutinib in hematologic malignancies were identified and reviewed using PubMed, Google Scholar, and HemOnc...
April 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29279549/recent-progress-in-the-understanding-of-angioimmunoblastic-t-cell-lymphoma
#12
Manabu Fujisawa, Shigeru Chiba, Mamiko Sakata-Yanagimoto
Angioimmunoblastic T-cell lymphoma (AITL) has been classified as a subtype of mature T-cell neoplasms. The recent revision of the WHO classification proposed a new category of nodal T-cell lymphoma with follicular helper T (TFH)-cell phenotype, which was classified into three diseases: AITL, follicular T-cell lymphoma, and nodal peripheral T-cell lymphoma with TFH phenotype. These lymphomas are defined by the expression of TFH-related antigens, CD279/PD-1, CD10, BCL6, CXCL13, ICOS, SAP, and CXCR5. Although recurrent mutations in TET2, IDH2, DNMT3A, RHOA, and CD28, as well as gene fusions, such as ITK-SYK and CTLA4-CD28, were not diagnostic criteria, they may be considered as novel criteria in the near future...
2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/29276997/cancer-immunotherapy-in-a-neglected-population-the-current-use-and-future-of-t-cell-mediated-checkpoint-inhibitors-in-organ-transplant-patients
#13
REVIEW
Young Kwang Chae, Carlos Galvez, Jonathan F Anker, Wade T Iams, Manali Bhave
Although the indications for immune checkpoint inhibitors continue to grow, organ transplant recipients with advanced malignancies have been largely excluded from clinical trials testing the safety and efficacy of these therapies given their need for chronic immunosuppression and the risk of allograft rejection. With the rapid growth of transplant medicine and the increased risk of malignancy associated with chronic immunosuppression, it is critical that we systematically analyze the available data describing immune checkpoint blockade in the organ transplant population...
February 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29237091/epidermodysplasia-verruciformis-in-an-adult-patient-with-a-germline-interleukin-2-inducible-t-cell-kinase-mutation-and-lymphoma-the-case-of-inherited-versus-acquired
#14
LETTER
S Fouéré, F Aubin, H Péré, L Galicier, T Gheit, M Tommasino, C Ram Wolff, D Boutboul, M Bagot
No abstract text is available yet for this article.
December 13, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29234112/a-switch-in-nucleotide-affinity-governs-activation-of-the-src-and-tec-family-kinases
#15
Freia von Raußendorf, Anita de Ruiter, Thomas A Leonard
The Tec kinases, closely related to Src family kinases, are essential for lymphocyte function in the adaptive immune system. Whilst the Src and Abl kinases are regulated by tail phosphorylation and N-terminal myristoylation respectively, the Tec kinases are notable for the absence of either regulatory element. We have found that the inactive conformations of the Tec kinase Itk and Src preferentially bind ADP over ATP, stabilising both proteins. We demonstrate that Itk adopts the same conformation as Src and that the autoinhibited conformation of Src is independent of its C-terminal tail...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233700/volumetric-analysis-of-keratocystic-odontogenic-tumors-and-non-neoplastic-jaw-cysts-comparison-and-its-clinical-relevance
#16
Martin Kauke, Ali-Farid Safi, Andrea Grandoch, Hans-Joachim Nickenig, Joachim Zöller, Matthias Kreppel
The keratocystic odontogenic tumor (KCOT) is capable of causing vast osseous destruction. Histopathological examination is pivotal for diagnosis. The diagnostic process can sometimes be hindered by tissue inflammation of KCOTs with loss of defining criteria, resulting in misdiagnosis as an odontogenic jaw cyst. We discuss the possible merits of volumetric analysis when facing this particular diagnostic dilemma and for pathophysiological characterization of KCOTs. We included 114 patients, of whom 27 were histopathologically diagnosed with a KCOT and 87 with dentigerous (n = 41) and periapical cyst (n = 46)...
February 2018: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/29215439/age-related-volumetric-changes-in-mandibular-condyles
#17
Ali-Farid Safi, Martin Kauke, Andrea Grandoch, Hans-Joachim Nickenig, Joachim E Zöller, Matthias Kreppel
A precise knowledge of the condylar changes with advancing age may improve understanding of pathophysiological alterations of the mandibular condyles. However, the majority of studies focusses on morphological changes, although volumetric analysis based upon cone beam computerized tomography may provide important additional data to characterize mandibular condyles. Therefore, we aimed to provide and compare volumetric data of mandibular condyles of a young and old patient group. This is a retrospective chart review of 195 patients with cone beam computerized tomography between 2007 and 2016...
March 2018: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/29215437/volumetric-analysis-of-700-mandibular-condyles-based-upon-cone-beam-computed-tomography
#18
Ali-Farid Safi, Martin Kauke, Andrea Grandoch, Hans-Joachim Nickenig, Joachim E Zöller, Matthias Kreppel
The authors' aim was to provide volumetric data of mandibular condyles based upon cone beam computed tomography with the means of semiautomatic segmentation.Retrospective chart review of 350 patients (700 mandibular condyles) with cone beam computerized tomography between February 2007 and December 2016. Univariate analysis was performed to analyze associations between variables. P values <0.05 were considered significant. Volume measurement was performed in a semiautomatic segmentation method with the program "ITK-Snap...
March 2018: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/29199677/effect-of-tyrosine-kinase-inhibitors-on-the-glucose-levels-in-diabetic-and-nondiabetic-patients
#19
E Y Romero-Ventosa, L Otero-Millán, S González-Costas, P Vilasoa-Boo, A Silva-López, C Arroyo-Conde, G Piñeiro-Corrales
CONTEXT: Tyrosine kinase inhibitors (TKIs) are used in different types of cancers due to their good profile of adverse reactions and their convenience in the oral administration. Some studies describe that certain TKIs are associated with changes in the glycemic profile of the patients. AIMS: This study aims to determine if treatment with ITK affects to serum glucose levels in clinical practice. SETTINGS AND DESIGN: A retrospective study was carried out in 136 episodes (112 patients treated with sorafenib, sunitinib, imatinib, dasatinib, or nilotinib)...
January 2017: Indian Journal of Cancer
https://www.readbyqxmd.com/read/29129717/a-chemoproteomic-approach-to-query-the-degradable-kinome-using-a-multi-kinase-degrader
#20
Hai-Tsang Huang, Dennis Dobrovolsky, Joshiawa Paulk, Guang Yang, Ellen L Weisberg, Zainab M Doctor, Dennis L Buckley, Joong-Heui Cho, Eunhwa Ko, Jaebong Jang, Kun Shi, Hwan Geun Choi, James D Griffin, Ying Li, Steven P Treon, Eric S Fischer, James E Bradner, Li Tan, Nathanael S Gray
Heterobifunctional molecules that recruit E3 ubiquitin ligases, such as cereblon, for targeted protein degradation represent an emerging pharmacological strategy. A major unanswered question is how generally applicable this strategy is to all protein targets. In this study, we designed a multi-kinase degrader by conjugating a highly promiscuous kinase inhibitor with a cereblon-binding ligand, and used quantitative proteomics to discover 28 kinases, including BTK, PTK2, PTK2B, FLT3, AURKA, AURKB, TEC, ULK1, ITK, and nine members of the CDK family, as degradable...
January 18, 2018: Cell Chemical Biology
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