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https://www.readbyqxmd.com/read/28821013/rictor-positively-regulates-b-cell-receptor-signaling-by-modulating-actin-reorganization-via-ezrin
#1
Lu Huang, Yongjie Zhang, Chenguang Xu, Xiaomei Gu, Linlin Niu, Jinzhi Wang, Xiaoyu Sun, Xiaoming Bai, Xingtian Xuan, Qubei Li, Chunwei Shi, Bing Yu, Heather Miller, Gangyi Yang, Lisa S Westerberg, Wanli Liu, Wenxia Song, Xiaodong Zhao, Chaohong Liu
As the central hub of the metabolism machinery, the mammalian target of rapamycin complex 2 (mTORC2) has been well studied in lymphocytes. As an obligatory component of mTORC2, the role of Rictor in T cells is well established. However, the role of Rictor in B cells still remains elusive. Rictor is involved in B cell development, especially the peripheral development. However, the role of Rictor on B cell receptor (BCR) signaling as well as the underlying cellular and molecular mechanism is still unknown. This study used B cell-specfic Rictor knockout (KO) mice to investigate how Rictor regulates BCR signaling...
August 2017: PLoS Biology
https://www.readbyqxmd.com/read/28819864/molecular-processes-involved-in-b-cell-acute-lymphoblastic-leukaemia
#2
REVIEW
Camille Malouf, Katrin Ottersbach
B cell leukaemia is one of the most frequent malignancies in the paediatric population, but also affects a significant proportion of adults in developed countries. The majority of infant and paediatric cases initiate the process of leukaemogenesis during foetal development (in utero) through the formation of a chromosomal translocation or the acquisition/deletion of genetic material (hyperdiploidy or hypodiploidy, respectively). This first genetic insult is the major determinant for the prognosis and therapeutic outcome of patients...
August 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28819731/erratum-to-a-novel-tubulin-polymerization-inhibitor-mpt0b206-downregulates-bcr-abl-expression-and-induces-apoptosis-in-imatinib-sensitive-and-imatinib-resistant-cml-cells
#3
Chih-Wei Chen, Yueh-Lun Lee, Jing-Ping Liou, Yu-Hsiu Liu, Chin-Wei Liu, Tsai-Yun Chen, Huei-Mei Huan
No abstract text is available yet for this article.
August 18, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28819285/phosphorylation-of-sos1-on-tyrosine-1196-promotes-its-rac-gef-activity-and-contributes-to-bcr-abl-leukemogenesis
#4
S Gerboth, E Frittoli, A Palamidessi, F C Baltanas, S Mogjiborahman, J Rappsilber, C Giuliani, F Troglio, Y Rolland, G Pruneri, S Kreutmair, I Pallavicini, M Zobel, M Cinquanta, S Minucci, C Gomez, E Santos, A L Illert, G Scita
Son of Sevenless 1 (SOS1) is a dual guanine nucleotide exchange factor (GEF) that activates the small GTPases RAC and RAS. While the molecular mechanisms of RAS GEF catalysis have been unveiled, how SOS1 acquires RAC GEF activity and what is the physio-pathological relevance of this activity is much less understood. Here, we show that SOS1 is tyrosine phosphorylated on Y1196 by ABL. Phosphorylation of Y1196 controls SOS1 inter-molecular interaction, is required to promote the exchange of nucleotides on RAC in vitro, and for PDGF activation of RAC and RAC-dependent actin remodeling and cell migration...
August 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28819281/mechanisms-of-resistance-to-the-bcr-abl1-allosteric-inhibitor-asciminib
#5
W Qiang, O Antelope, M S Zabriskie, A D Pomicter, N A Vellore, P Szankasi, D Rea, J M Cayuela, T W Kelley, M W Deininger, T O'Hare
Leukemia accepted article preview online, 18 August 2017. doi:10.1038/leu.2017.264.
August 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28818808/potent-induction-of-apoptosis-by-givinostat-in-bcr-abl1-positive-and-bcr-abl1-negative-precursor-b-cell-acute-lymphoblastic-leukemia-cell-lines
#6
Chenjiao Yao, Guojuan Zhang, Alison Walker, Kevin Y Zhao, Ying Li, Lei Lyu, Yan Tang, Peng Ru, Dan Jones, Weiqiang Zhao
We have previously shown that givinostat can induce potent apoptosis in the BCR-ABL1-positive, TP53-wild type B-cell acute lymphoblastic leukemia (B-ALL) cell line SUP-B15. We extend our studies here to two additional B-ALL cell lines, BCR-ABL1-negative CCRF-SB and p210 BCR-ABL1-positive NAML1. Givinostat induced significant cell growth inhibition in both cell lines, with an IC50 of 0.65±0.052μM and 0.25±0.028μM in CCRF-SB and NAML1, respectively. The key signal protein of the BCR-ABL1, Crk-L1, was significantly reduced by givinostat treatment in NAML1...
August 9, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28811021/quantitative-analysis-of-major-and-trace-elements-in-nh4hf2-modified-silicate-rock-powders-by-laser-ablation-inductively-coupled-plasma-mass-spectrometry
#7
Wen Zhang, Zhaochu Hu, Yongsheng Liu, Wenwu Yang, Haihong Chen, Shenghong Hu, Hongyan Xiao
In this paper, we described a NH4HF2 digestion method as sample preparation for the rapid determination of major and trace elements in silicate rocks using laser ablation-inductively coupled plasma mass spectrometry (LA-ICP-MS). Sample powders digested by NH4HF2 at 230 °C for 3 h form ultrafine powders with a typical grain size d80 < 8.5 μm, and various silicate rocks have a consistent grain morphology and size, allowing us to produce pressed powder pellets that have excellent cohesion and homogeneity suitable for laser ablation micro-analysis without the addition of binder...
August 29, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28810255/ponatinib-induced-graft-versus-host-disease-graft-versus-leukemia-effect-in-a-patient-with-philadelphia-positive-acute-lymphoblastic-leukemia-without-the-t315i-mutation-relapsing-after-allogeneic-transplant
#8
Annamaria Petrungaro, Massimo Gentile, Carla Mazzone, Rosa Greco, Giuseppina Uccello, Anna Grazia Recchia, Laura De Stefano, Sabrina Bossio, Angela Palummo, Rosellina Morelli, Caterina Musolino, Fortunato Morabito, Ernesto Vigna
We describe the case of a patient with Philadelphia-positive acute lymphoblastic leukemia treated with dasatinib plus steroids as first-line therapy, who achieved a major molecular response (MMR) before undergoing matched, unrelated donor allogeneic stem cell transplant. Eleven months after the transplant, she experienced molecular relapse. Mutational screening showed negativity for the T315I mutation, The patient underwent a salvage chemotherapy regimen with clofarabine + cyclophosphamide + steroids and ponatinib (clofarabine 70 mg i...
August 16, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28810039/distinguishing-white-dot-syndromes-with-patterns-of-choroidal-hypoperfusion-on-optical-coherence-tomography-angiography
#9
Jay C Wang, Inês Laíns, Lucia Sobrin, John B Miller
BACKGROUND AND OBJECTIVE: To compare patterns of choroidal hypoperfusion in white dot syndromes (WDS) using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: Consecutive patients with WDS were imaged with either the Zeiss AngioPlex OCT Angiography (Carl Zeiss AG, Oberkochen, Germany) or the AngioVue OCT Angiography (Optovue, Fremont, CA) from February to November 2016. Four patients with acute posterior multifocal placoid pigment epitheliopathy (APMPPE), birdshot chorioretinopathy (BCR), presumed ocular histoplasmosis syndrome (POHS), and multiple evanescent white dot syndrome (MEWDS) were selected...
August 1, 2017: Ophthalmic Surgery, Lasers & Imaging Retina
https://www.readbyqxmd.com/read/28808717/the-opening-closure-of-the-p-loop-and-hinge-of-bcr-abl1-decodes-the-low-high-bioactivities-of-dasatinib-and-axitinib
#10
Jianyi Wang, Qing Chen, Mian Wang, Cheng Zhong
To obtain new insights into the resistance caused by T315I and the differential selectivities of dasatinib and axitinib against BCR-ABL1(WT) and BCR-ABL1(T315), molecular dynamics simulations and free energy calculations were performed. A rule is summarized that the opening/closure of the P-loop and hinge of BCR-ABL1 could reflect the low/high bioactivities of dasatinib and axitinib. This may be because strong interactions of the ligands with key residues induce the P-loop and hinge of BCR-ABL1 to close, being favorable for the retention of the ligand in the binding site...
August 15, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28805811/caveolin-1-dependent-nanoscale-organization-of-the-bcr-regulates-b-cell-tolerance
#11
Susana Minguet, Kathrin Kläsener, Anna-Maria Schaffer, Gina J Fiala, Teresa Osteso-Ibánez, Katrin Raute, Inmaculada Navarro-Lérida, Frederike A Hartl, Maximilian Seidl, Michael Reth, Miguel A Del Pozo
Caveolin-1 (Cav1) regulates the nanoscale organization and compartmentalization of the plasma membrane. Here we found that Cav1 controlled the distribution of nanoclusters of isotype-specific B cell antigen receptors (BCRs) on the surface of B cells. In mature B cells stimulated with antigen, the immunoglobulin M BCR (IgM-BCR) gained access to lipid domains enriched for GM1 glycolipids, by a process that was dependent on the phosphorylation of Cav1 by the Src family of kinases. Antigen-induced reorganization of nanoclusters of IgM-BCRs and IgD-BCRs regulated BCR signaling in vivo...
August 14, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28805806/lung-tumor-exome-files-with-t-cell-receptor-recombinations-a-mouse-model-of-t-cell-infiltrates-reflecting-mutation-burdens
#12
Yaping N Tu, Wei Lue Tong, Timothy J Fawcett, George Blanck
Tumor exomes and RNASeq data were originally intended for obtaining tumor mutations and gene expression profiles, respectively. However, recent work has determined that tumor exome and RNAseq read files contain reads representing T-cell and B-cell receptor (TcR and BcR) recombinations, presumably due to infiltrating lymphocytes. Furthermore, the recovery of immune receptor recombination reads has demonstrated correlations with specific, previously appreciated aspects of tumor immunology. To further understand the usefulness of recovering TcR and BcR recombinations from tumor exome files, we developed a scripted algorithm for recovery of reads representing these recombinations from a previously described mouse model of lung tumorigenesis...
August 14, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28805047/outcomes-of-post-prostatectomy-radiotherapy-at-a-regional-cancer-centre
#13
Luke Nicholls, Amber Winter, Ashley Harwood, Ashley Plank, Preeti Bagga, Winnie Wong, Eric Khoo
INTRODUCTION: To investigate the efficacy and toxicity of radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer at Radiation Oncology Centres, Toowoomba. METHODS: The electronic medical records of 130 consecutive patients with histologically proven prostate adenocarcinoma who underwent post-prostatectomy RT between January 2008 and December 2014 were analysed. Primary endpoint was Biochemical Recurrence (BCR) after RT. BCR was defined by PSA > 0...
August 14, 2017: Journal of Medical Radiation Sciences
https://www.readbyqxmd.com/read/28801986/persistent-detection-of-alternatively-spliced-bcr-abl-variant-results-in-a-failure-to-achieve-deep-molecular-response
#14
Junichiro Yuda, Toshihiro Miyamoto, Jun Odawara, Yasuyuki Ohkawa, Yuichiro Semba, Masayasu Hayashi, Koichi Miyamura, Mitsune Tanimoto, Kazuhito Yamamoto, Masafumi Taniwaki, Koichi Akashi
Treatment with tyrosine kinase inhibitors (TKIs) may sequentially induce TKI-resistant BCR-ABL mutants in chronic myeloid leukemia (CML). Conventional polymerase chain reaction (PCR) monitoring of BCR-ABL is an important indicator to determine therapeutic intervention for preventing disease progression. However, PCR cannot quantify separately amounts of BCR-ABL and its mutants, including alternatively spliced BCR-ABL with an insertion of 35 intronic nucleotides (BCR-ABL(I)(ns35bp) ) between ABL exons 8 and 9 which introduces the premature termination and loss of kinase activity...
August 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28801832/simultaneous-measurement-of-total-estradiol-and-testosterone-in-human-serum-by-isotope-dilution-liquid-chromatography-tandem-mass-spectrometry
#15
Hui Zhou, Yuesong Wang, Matthew Gatcombe, Jacob Farris, Julianne C Botelho, Samuel P Caudill, Hubert W Vesper
Reliable measurement of total testosterone and estradiol is critical for their use as biomarkers of hormone-related disorders in patient care and translational research. We developed and validated a mass spectrometry method to simultaneously quantify these analytes in human serum without chemical derivatization. Serum is equilibrated with isotopic internal standards and treated with acidic buffer to release hormones from their binding proteins. Lipids are isolated and polar impurities are removed by two serial liquid-liquid extraction steps...
August 11, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28801451/adult-high-grade-b-cell-lymphoma-with-burkitt-lymphoma-signature-genomic-features-and-potential-therapeutic-targets
#16
Alyssa Bouska, Chengfeng Bi, Waseem Lone, Weiwei Zhang, Ambreen Kedwaii, Tayla Heavican, Cynthia M Lachel, Jiayu Yu, Roberto Ferro, Nanees Eldorghamy, Timothy C Greiner, Julie Vose, Dennis D Weisenburger, Randy D Gascoyne, Andreas Rosenwald, German Ott, Elias Campo, Lisa M Rimsza, Elaine S Jaffe, Rita M Braziel, Reiner Siebert, Rodney R Miles, Sandeep Dave, Anupama Reddy, Jan Delabie, Louis M Staudt, Joo Y Song, Timothy W McKeithan, Kai Fu, Michael Green, Wing C Chan, Javeed Iqbal
The adult high-grade B-cell lymphomas sharing molecular features with Burkitt lymphoma (BL) are highly aggressive lymphomas with poor clinical outcome. High-resolution structural and functional genomic analysis of adult Burkitt lymphoma (BL) and high-grade B-cell lymphoma with BL gene-signature (adult-mBL), revealed the MYC-ARF-p53 axis as the primary deregulated pathway. Adult-mBL had either unique or more frequent genomic aberrations (del13q14, del17p, gain8q24 and gain18q21) compared with pediatric-mBL, but shared commonly mutated genes...
August 11, 2017: Blood
https://www.readbyqxmd.com/read/28801357/the-autoimmune-risk-variant-ptpn22-c1858t-alters-b-cell-tolerance-at-discrete-checkpoints-and-differentially-shapes-the-naive-repertoire
#17
Genita Metzler, Xuezhi Dai, Christopher D Thouvenel, Socheath Khim, Tania Habib, Jane H Buckner, David J Rawlings
A common genetic variant in the gene encoding the protein tyrosine phosphatase nonreceptor type 22 (PTPN22 C1858T) has been linked to a wide range of autoimmune disorders. Although a B cell-intrinsic role in promoting disease has been reported, the mechanism(s) through which this variant functions to alter the preimmune B cell repertoire remains unknown. Using a series of polyclonal and transgenic self-reactive models harboring the analogous mutation in murine Ptpn22, we show evidence for enhanced BCR, B cell-activating factor receptor, and CD40 coreceptor programs, leading to broadly enhanced positive selection of B cells at two discrete checkpoints in the bone marrow and spleen...
August 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28801299/-effect-of-bortezomib-in-inducing-apoptosis-of-imatinib-resistant-k562-cells-and-the-mechanism
#18
Jia-Ye Hua, Xu-Hong Zhou, Shu-Ting Ouyang, Yong-Bin Wu
OBJECTIVE: To investigate the effect of bortezomib in inducing apoptosis in imatinib-resistant K562 (K562R) cells and its possible mechanism. METHODS: K562 cells were cultured in gradient concentrations of imatinib for several months to generate imatinib-resistant K562 cells. The viability of K562R cells treated with bortezomib was measured using CCK-8 cell proliferation assay, and the cell apoptosis was analyzed by flow cytometry with annexin V/PI dual staining...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28799121/3-t-multiparametric-mri-characteristics-of-prostate-cancer-patients-suspicious-for-biochemical-recurrence-after-primary-focal-cryosurgery-hemiablation
#19
Michael Kongnyuy, Daniel M Halpern, Corinne C Liu, Kaitlin E Kosinski, David J Habibian, Anthony T Corcoran, Aaron E Katz
INTRODUCTION: We aimed to report on multiparametric MRI (mpMRI) characteristics of post-primary focal cryosurgery (PFC) patients suspected of biochemical recurrence (BCR) by the Phoenix criteria. METHODS: We retrospectively reviewed all patients at our institution who had undergone PFC. Prostate-specific antigen nadir was determined using 2 or more post-PFC values. Suspicion of BCR was determined using the Phoenix criteria (nadir + 2 ng/ml). At the discretion of the physician, pre-and post-PFC 3-T mpMRIs were obtained and in a few cases biopsies were performed...
August 10, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28793393/diverse-immunoprofile-of-ductal-adenocarcinoma-of-the-prostate-with-an-emphasis-on-the-prognostic-factors
#20
Se Un Jeong, Anuja Kashikar Kekatpure, Ja-Min Park, Minkyu Han, Hee Sang Hwang, Hui Jeong Jeong, Heounjeong Go, Yong Mee Cho
Background: Ductal adenocarcinoma (DAC) of the prostate is an uncommon histologic subtype whose prognostic factors and immunoprofile have not been fully defined. Materials and Methods: To define its prognostic factors and immunoprofile, the clinicopathological features, including biochemical recurrence (BCR), of 61 cases of DAC were analyzed. Immunohistochemistry was performed on tissue microarray constructs to assess the expression of prostate cancer-related and mammalian target of rapamycin (mTOR) signaling-related proteins...
August 9, 2017: Journal of Pathology and Translational Medicine
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