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https://www.readbyqxmd.com/read/29151104/clinical-efficacy-and-safety-of-first-line-dasatinib-therapy-and-the-relevance-of-velocity-of-bcr-abl1-transcript-decline-for-achievement-of-molecular-responses-in-newly-diagnosed-chronic-phase-chronic-myeloid-leukemia-report-from-the-juntendo-yamanashi-cooperative
#1
Tomoiku Takaku, Noriyoshi Iriyama, Toru Mitsumori, Eriko Sato, Akihiko Gotoh, Keita Kirito, Masaaki Noguchi, Michiaki Koike, Junichi Sakamoto, Koji Oba, Norio Komatsu
OBJECTIVE: The use of tyrosine kinase inhibitors led to an improvement in the prognoses of patients with chronic myeloid leukemia (CML). The aims of this study were to investigate the efficacy and safety of dasatinib in Japanese patients and to explore the factors that affect the achievement of molecular responses. METHODS: The primary endpoint was a major molecular response (MMR) by 12 months. The halving time for BCR-ABL1 transcripts was calculated using transcript levels...
November 18, 2017: Oncology
https://www.readbyqxmd.com/read/29150831/the-extracellular-membrane-proximal-domain-of-membrane-bound-ige-restricts-b-cell-activation-by-limiting-b-cell-antigen-receptor-surface-expression
#2
Kanika Vanshylla, Felipe Opazo, Konrad Gronke, Jürgen Wienands, Niklas Engels
Immunoglobulin E (IgE) antibodies are key mediators of allergic reactions. Due to their potentially harmful anaphylactic properties their production is tightly regulated. The membrane-bound isoform of IgE (mIgE), which is an integral component of the B cell antigen receptor, has been shown to be critical for the regulation of IgE responses in mice. In primate species including humans, mIgE can be expressed in two isoforms that are produced by alternative splicing of the primary ε Ig heavy chain transcript, and differ in the absence or presence of an extracellular membrane-proximal domain (EMPD) consisting of 52 amino acids...
November 17, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29150438/a-pip2-derived-amplification-loop-fuels-the-sustained-initiation-of-b-cell-activation
#3
Chenguang Xu, Hengyi Xie, Xingdong Guo, Haipeng Gong, Lei Liu, Hai Qi, Chenqi Xu, Wanli Liu
Lymphocytes have evolved sophisticated signaling amplification mechanisms to efficiently activate downstream signaling after detection of rare ligands in their microenvironment. B cell receptor microscopic clusters (BCR microclusters) are assembled on the plasma membrane and recruit signaling molecules for the initiation of lymphocyte signaling after antigen binding. We identified a signaling amplification loop derived from phosphatidylinositol 4,5-biphosphate (PIP2) for the sustained B cell activation. Upon antigen recognition, PIP2 was depleted by phospholipase C-γ2 (PLC-γ2) within the BCR microclusters and was regenerated by phosphatidic acid-dependent type I phosphatidylinositol 4-phosphate 5-kinase outside the BCR microclusters...
November 17, 2017: Science Immunology
https://www.readbyqxmd.com/read/29150116/acute-myeloid-leukemia-with-e1a2-bcr-abl1-fusion-gene-two-cases-with-peculiar-molecular-and-clinical-presentations
#4
Fernanda Borges da Silva, João Agostinho Machado-Neto, Luisa Corrêa de Araujo Koury, Virginia Helena Leira Lipoli Bertini, Cristina Alonso Ratis, Maria de Lourdes Lopes Ferrari Chauffaille, Elvira Deolinda Rodrigues Pereira Velloso, Belinda Pinto Simões, Eduardo Magalhães Rego, Fabiola Traina
No abstract text is available yet for this article.
October 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/29149682/signalling-for-b-cell-survival
#5
REVIEW
Edina Schweighoffer, Victor Lj Tybulewicz
The number of mature B cells is carefully controlled by signalling from receptors that support B cell survival. The best studied of these are the B cell antigen receptor (BCR) and BAFFR. Recent work has shown that signalling from these receptors is closely linked, involves the CD19 co-receptor, and leads to activation of canonical and non-canonical NF-κB pathways, ERK1, ERK2 and ERK5 MAP kinases, and PI-3 kinases. Importantly, studies show that investigation of the importance of signalling molecules in cell survival requires the use of inducible gene deletions within mature B cells...
November 14, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29149649/chk1-inhibitors-overcome-imatinib-resistance-in-chronic-myeloid-leukemia-cells
#6
Hu Lei, Jin Jin, Meng Liu, Xiangyun Li, Hao Luo, Li Yang, Hanzhang Xu, Yingli Wu
Drug resistance to tyrosine kinase inhibitors (TKIs) is currently a clinical problem of chronic myelogenous leukemia (CML). Bcr-Abl protein depletion is considered as a way to overcome drug resistance to TKIs. In our study, Chk1 inhibitors, AZD7762 and MK-8776, had strong antitumor effects on CML cell line KBM5 and imatinib-resistant form KBM5(T315I). Moreover, Chk1 inhibitors showed a strong cytotoxic effect on leukemia cells from primary CML and imatinib-resistance CML patients, but low cytotoxic effect on normal human mononuclear cells...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29149380/psa-kinetics-following-primary-focal-cryotherapy-hemiablation-in-organ-confined-prostate-cancer-patients
#7
Michael Kongnyuy, Shahidul Islam, Alfred K Mbah, Daniel M Halpern, Glenn T Werneburg, Kaitlin E Kosinski, Connie Chen, David J Habibian, Jeffrey T Schiff, Anthony T Corcoran, Aaron E Katz
PURPOSE: We aim to evaluate prostate-specific antigen (PSA) trends in post-primary focal cryotherapy (PFC) patients. MATERIALS AND METHODS: This was an institutional review board-approved retrospective study of PFC patients from 2010 to 2015. Patients with at least one post-PFC PSA were included in the study. Biochemical recurrence (BCR) was determined using the Phoenix criteria. PSA bounce was also assessed. We analyzed rates of change of PSA over time of post-PFC between BCR and no BCR groups...
November 17, 2017: World Journal of Urology
https://www.readbyqxmd.com/read/29145092/ionic-liquid-solvent-bar-micro-extraction-of-cdcln-n-2-species-for-ultra-trace-cd-determination-in-seawater
#8
Belén Herce-Sesa, José A López-López, Carlos Moreno
Water analysis of trace metals has been benefited by recent studies on sample preparation by liquid micro-extraction. However, there are still limitations for its application to seawater, such as the need of additives to preserve the sample or the availability of chemical extractants for the selective extraction from highly saline samples. In this work, a three phase solvent bar micro-extraction (3SBME) system containing the ionic liquid trioctylmethylammonium chloride (Aliquat(®) 336) has been used for isolation and pre-concentration of Cd from seawater samples, due to its ability for ionic exchange of CdCln((n-2)-)...
November 1, 2017: Chemosphere
https://www.readbyqxmd.com/read/29140551/b-cell-receptor-repertoire-sequencing-in-patients-with-primary-immunodeficiency-a-review
#9
REVIEW
Marie Ghraichy, Jacob D Galson, Dominic F Kelly, Johannes Trück
The advent of next-generation sequencing now allows a detailed assessment of the adaptive immune system in health and disease. In particular, high-throughput B-cell receptor (BCR) repertoire sequencing provides detailed information about the functionality and abnormalities of the B-cell system. However, it is mostly unknown how the BCR repertoire is altered in the context of primary immunodeficiencies (PID) and whether findings are consistent across phenotypes and genotypes. We have performed an extensive literature search of the published work on BCR repertoire sequencing in PID patients, including several forms of predominantly antibody disorders and combined immunodeficiencies...
November 15, 2017: Immunology
https://www.readbyqxmd.com/read/29138846/itr%C3%A2-284-modulates-cell-differentiation-in-human-chronic-myelogenous-leukemia-k562-cells
#10
Jai-Sing Yang, Chao-Ying Lee, Hsin-Chung Cho, Chi-Cheng Lu, Sheng-Chu Kuo, Yen-Fang Wen, Fuu-Jen Tsai, Miau-Rong Lee, Shih-Chang Tsai
ITR‑284 is a carboxamide analog that can inhibit proliferation in human promyelocytic leukemia HL-60 cells. To understand the effects and molecular mechanisms of ITR‑284 in human erythromyeloblastoid leukemia, we treated K562 cells with different concentrations of ITR‑284 (0, 2, 4, 6, 8 and 10 nM) and all-trans retinoic acid (ATRA) (0, 0.1, 0.5, 1, 5 and 10 µM) for 24 h. The IC50 of ITR‑284 was ~10 nM in K562 cells treated for 24 h as determined by MTT assay. May-Grünwald-Giemsa staining and nitro blue tetrazolium (NBT) assays were used to determine cell morphology changes and differentiation after ITR‑284 and ATRA treatment...
November 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29138221/immature-cml-cells-implement-a-bmp-autocrine-loop-to-escape-tki-treatment
#11
Elodie Grockowiak, Bastien Laperrousaz, Sandrine Jeanpierre, Thibault Voeltzel, Boris Guyot, Stéphanie Gobert, Franck E Nicolini, Véronique Maguer-Satta
The BCR-ABL specific Tyrosine Kinase Inhibitors (TKI) changed the outcome of Chronic Myeloid Leukemia (CML), turning a life-threatening disease into a chronic illness. However, TKI are not yet curative, since most patients retain leukemic stem cells (LSC) and their progenitors in bone marrow and relapse following treatment cessation. At diagnosis, deregulations of the Bone Morphogenetic Proteins (BMP) pathway are involved in LSC and progenitors expansion. Here, we report that BMP pathway alterations persist in TKI-resistant patients...
November 14, 2017: Blood
https://www.readbyqxmd.com/read/29137414/salvage-lymph-node-dissection-after-68-ga-psma-or-18-f-fec-pet-ct-for-nodal-recurrence-in-prostate-cancer-patients
#12
Annika Herlemann, Alexander Kretschmer, Alexander Buchner, Alexander Karl, Stefan Tritschler, Lina El-Malazi, Wolfgang P Fendler, Vera Wenter, Harun Ilhan, Peter Bartenstein, Christian G Stief, Christian Gratzke
The management of patients with biochemical recurrence (BCR) after definitive treatment for prostate cancer remains controversial. Our aim was to determine survival rates and complications of salvage lymph node dissection (sLND) in patients with recurrent prostate cancer after radical prostatectomy, while evaluating biochemical response (BR) with two different positron emission tomography/computed tomography (PET/CT) tracers used for preoperative imaging. sLND was performed in 104 patients diagnosed with isolated nodal recurrence on either (18)F-fluoroethylcholine ((18)F-FEC) or (68)Ga-PSMA-HBED-CC ((68)Ga-PSMA) PET/CT...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137222/pi3k%C3%AE-inhibition-causes-feedback-activation-of-pi3k%C3%AE-in-the-abc-subtype-of-diffuse-large-b-cell-lymphoma
#13
Georgios N Pongas, Christina M Annunziata, Louis M Staudt
Cell line models of the activated B cell-like (ABC) subtype of diffuse large B cell (DLBCL) depend on both NF-κB and phosphatidylinositol 3-kinase (PI3K) signaling pathways for survival, especially those with gain-of-function B cell receptor (BCR) mutations. Here we show that these cells depend specifically on the PI3Kδ isoform, but that PI3K pathway interruption by PI3Kδ inhibitors is short-lived due to feedback activation of the PI3Kα isoform. PI3Kδ and PI3Kα inhibition cooperated in killing ABC DLBCL lines, and genetic knockdown of PI3Kα sensitized cells to PI3Kδ inhibition and prolonged the interruption of PI3K signaling...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136733/-exploratory-study-of-circulating-tumor-dna-detection-in-early-breast-cancer-an-analysis-of-75-next-generation-sequencing-results
#14
B Zhou, L Xin, L Xu, Y H Liu, M M Zhang, R L Jing, X Y Liang, S B Cao
Objective: To explore the utility of circulating tumor DNA detection in early breast cancer by using next-generation sequencing. Methods: This exploratory study of circulating tumor DNA detection is for early invasive breast cancer patients treated in Breast Disease Center, Peking University First Hospital from December 2015 to July 2016. Plasma samples were collected and were used to isolate plasma cell-free DNA.Exons or hotspots of 247 cancer related genes were sequenced by next-generation sequencing. Mutations and their correlation with clinic-pathological factors were analyzed...
November 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/29134817/the-bcr-abl1-negative-myeloproliferative-neoplasms-a-review-of-jak-inhibitors-in-the-therapeutic-armamentarium
#15
Martin Griesshammer, Parvis Sadjadian
The classical BCR-ABL1-negative myeloproliferative neoplasms (MPN) include primary myelofibrosis (PMF), polycythaemia vera (PV) and essential thrombocythaemia (ET). They are characterized by stem cell-derived clonal proliferation, harbour Janus kinase 2 (JAK2), or calreticulin (CALR), or myeloproliferative leukaemia virus oncogene (MPL) driver mutations and exert an over activated JAK-signal transducer and activator of transcription (STAT) pathway. Therefore JAK inhibiting strategies have been successfully investigated in MPN clinical trials...
November 14, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29130130/heavy-metal-distribution-in-tiaoxi-river-s-sediment
#16
Binghui Zheng, Shaoyong Lu, Jinan Wu, Xiaochun Guo, Fengchang Wu, Xiangling Li, Qi He, Zhiyou Fu, Libin Xu
According to current study, seven surface sediments and three sediment cores were collected from three typical areas of Tiaoxi River, which were living area, agricultural area, and industrial area. The water quantity into the Lake Taihu from the Tiaoxi River accounted for almost one third of the total water quantity by all rivers into the Lake Taihu. To study geochemical features and pollution history of heavy metals in three typical areas of Tiaoxi River, total content and chemical fractionations of Cu, Pb, Cd, Cr, Mn, Zn, Fe, As, and Hg were analyzed for surface and core sediments using the speciation extraction procedure, proposed by the Commission of the European Communities Bureau of Reference (BCR), together with grain size and organic carbon measurements...
November 12, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29129756/assessment-of-oncological-outcomes-after-radical-prostatectomy-according-to-preoperative-and-postoperative-cancer-of-the-prostate-risk-assessment-scores-results-from-a-large-two-center-experience
#17
Sami-Ramzi Leyh-Bannurah, Paolo Dell'Oglio, Emanuele Zaffuto, Alberto Briganti, Jonas Schiffmann, Raisa S Pompe, Derya Tilki, Hans Heinzer, Markus Graefen, Pierre I Karakiewicz, Lars Budäus
BACKGROUND: Among prostate cancer (PCa) patients undergoing radical prostatectomy (RP) and with virtually identical unfavorable pathological characteristics, those deemed at low risk (LR) preoperatively had better oncological outcomes than those with intermediate (IR) or high risk (HR) preoperatively. OBJECTIVE: To examine if this phenomenon still applies when preoperative Cancer of the Prostate Risk Assessment (CAPRA) scores are compared to postoperative scores (CAPRA-S) in RP patients...
November 9, 2017: European Urology Focus
https://www.readbyqxmd.com/read/29128577/pathological-and-3-tesla-volumetric-mr-predictors-of-biochemical-recurrence-after-robotic-assisted-radical-prostatectomy-correlation-with-whole-mount-histopathology
#18
Nelly Tan, Luyao Shen, Pooria Khoshnoodi, Héctor E Alcalá, Weixia Yu, William Hsu, Robert E Reiter, David Y Lu, Steven S Raman
OBJECTIVE: To identify the clinical and MRI variables predictive of biochemical recurrence (BCR) after robotic assisted radical prostatectomy (RALP) in patients who underwent multi-parametric 3 Tesla prostate MR Imaging. METHODS: An IRB approved, HIPAA compliant, a single arm observational study with 3T mpMRI prior to RALP from December 2009 until March 2016 was performed. Clinical, MRI, pathological information and clinical outcome were compiled. Biochemical recurrence was defined as PSA greater > 0...
November 8, 2017: Journal of Urology
https://www.readbyqxmd.com/read/29127384/targeting-c-kit-cd117-by-dasatinib-and-radotinib-promotes-acute-myeloid-leukemia-cell-death
#19
Sook-Kyoung Heo, Eui-Kyu Noh, Jeong Yi Kim, Yoo Kyung Jeong, Jae-Cheol Jo, Yunsuk Choi, SuJin Koh, Jin Ho Baek, Young Joo Min, Hawk Kim
Dasatinib and radotinib are oral BCR-ABL tyrosine kinase inhibitors that were developed as drugs for the treatment of chronic myeloid leukemia. We report here that the c-KIT (CD117) targeting with dasatinib and radotinib promotes acute myeloid leukemia (AML) cell death, and c-KIT endocytosis is essential for triggering c-KIT-positive AML cell death by dasatinib and radotinib during the early stages. In addition, dasatinib and radotinib reduce heat shock protein 90β (HSP90β) expression and release Apaf-1 in c-KIT-positive AML cells...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29125235/comparison-of-the-mrna-expression-profile-of-b-cell-receptor-components-in-normal-cd5-high-b-lymphocytes-and-chronic-lymphocytic-leukemia-a-key-role-of-zap70
#20
Aleena A Gladkikh, Daria M Potashnikova, Victor Tatarskiy, Margarita Yastrebova, Alvina Khamidullina, Natasha Barteneva, Ivan Vorobjev
The B-cell receptor (BCR) signaling pathway is of great importance for B-cell survival and proliferation. The BCR expressed on malignant B-CLL cells contributes to the disease pathogenesis, and its signaling pathway is currently the target of several therapeutic strategies. Although various BCR alterations have been described in B-CLL at the protein level, the mRNA expression levels of tyrosine kinases in B-CLL compared to that in normal CD5-high and CD5-low B-lymphocytes remain unknown. In the current study, we measured the mRNA expression levels of CD79A, CD79B, LYN, SYK, SHP1, and ZAP70 in purified populations of CD5-high B-CLL cells, CD5-low B-cells from the peripheral blood of healthy donors, and CD5-high B-cells from human tonsils...
November 10, 2017: Cancer Medicine
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