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https://www.readbyqxmd.com/read/28506695/d816v-mutation-in-the-kit-gene-activation-loop-has-a-greater-cell-proliferative-and-anti-apoptotic-ability-than-n822k-mutation-in-core-binding-factor-acute-myeloid-leukemia
#1
Ikuko Omori, Hiroki Yamaguchi, Koichi Miyake, Noriko Miyake, Tomoaki Kitano, Koiti Inokuchi
In core binding factor-acute myeloid leukemia (CBF-AML), there have been conflicting reports regarding the status as an unfavorable prognostic factor of mutation in the KIT gene, whose significance therefore remains unclear. We have reported previously that prognosis differs between the KIT D816V and N822K mutations. In the present study, we undertook an in vitro comparison of the cell-proliferative and anti-apoptotic ability of D816V and N822K. We transduced these KIT mutations into the IL-3-dependent cell line TF-1 (TF-1 KIT(D816V), TF-1 KIT(N822K))...
May 12, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28479592/a-novel-agent-sl-401-induces-anti-myeloma-activity-by-targeting-plasmacytoid-dendritic-cells-osteoclastogenesis-and-cancer-stem-like-cells
#2
A Ray, D S Das, Y Song, V Macri, P Richardson, C L Brooks, D Chauhan, K C Anderson
Novel therapies for multiple myeloma (MM) can target mechanism(s) in the host-MM bone marrow (BM) microenvironment mediating MM progression and chemoresistance. Our studies showed increased numbers of tumor-promoting, immunosuppressive, and drug-resistant plasmacytoid dendritic cells (pDCs) in the MM BM microenvironment. pDC-MM cell interactions upregulate interleukin-3 (IL-3), which stimulates both pDC survival and MM cell growth. Since IL-3R is highly expressed on pDCs in the MM BM milieu, we here targeted pDCs using a novel IL-3R-targeted therapeutic SL-401...
May 8, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28474499/inhibition-of-the-bet-family-of-epigenetic-reader-proteins-a-novel-principle-for-modulating-gene-expression-in-ige-activated-mast-cells
#3
Gianni Garcia-Faroldi, Elin Rönnberg, Mirjana Grujic, Gunnar Pejler
INTRODUCTION: The BET family of bromodomain-containing proteins constitute epigenetic readers that bind to acetylated lysine residues of core histones, thereby translating epigenetic histone marks to effects on gene expression. BET inhibitors are currently emerging as promising therapeutic agents for treatment of various pathological conditions. Here, we explored the potential of using BET inhibition to modulate IgE-mediated responses in mast cells. METHODS: We assessed the effects of BET inhibitors PFI-1, I-BET151, and I-BET762 on responses downstream of mast cell activation through IgE receptor cross-linking...
June 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28459513/effects-and-mechanisms-of-bazhen-decoction-siwu-decoction-and-sijunzi-decoction-on-5-fluorouracil-induced-anemia-in-mice
#4
Yunan Tian, Yuke Xiang, Guoran Wan, Dong Wan, Huifeng Zhu, Tao Wang, Xian Yang
OBJECTIVE: To investigate the effects of Bazhen decoction (BZD), Siwu decoction (SWD) and Sijunzi decoction (SJZD) in mice with anemia induced by 5-fluorouracil (5-FU) and discussed the possible pharmacological hematopoietic mechanism to provide experimental evidence for the clinical use of the three classical prescriptions in the treatment of anemia. METHODS: Anemia was induced by intravenous injection of 5-FU and 80 female Kunming mice were randomly, assigned to oral administration of SWD, SJZD, or BZD daily for 10 days...
August 2016: Journal of Traditional Chinese Medicine, Chung i Tsa Chih Ying Wen Pan
https://www.readbyqxmd.com/read/28445506/phenotype-function-and-differentiation-potential-of-human-monocyte-subsets
#5
Lisa B Boyette, Camila Macedo, Kevin Hadi, Beth D Elinoff, John T Walters, Bala Ramaswami, Geetha Chalasani, Juan M Taboas, Fadi G Lakkis, Diana M Metes
Human monocytes have been grouped into classical (CD14++CD16-), non-classical (CD14dimCD16++), and intermediate (CD14++CD16+) subsets. Documentation of normal function and variation in this complement of subtypes, particularly their differentiation potential to dendritic cells (DC) or macrophages, remains incomplete. We therefore phenotyped monocytes from peripheral blood of healthy subjects and performed functional studies on high-speed sorted subsets. Subset frequencies were found to be tightly controlled over time and across individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28389215/clock-gene-dysregulation-induced-by-chronic-er-stress-disrupts-%C3%AE-cell-function
#6
Yasuharu Ohta, Akihiko Taguchi, Takuro Matsumura, Hiroko Nakabayashi, Masaru Akiyama, Kaoru Yamamoto, Ruriko Fujimoto, Risa Suetomi, Akie Yanai, Koh Shinoda, Yukio Tanizawa
In Wfs1(-/-)A(y)/a islets, in association with endoplasmic reticulum (ER) stress, D-site-binding protein (Dbp) expression decreased and Nuclear Factor IL-3 (Nfil3)/E4 Promoter-binding protein 4 (E4bp4) expression increased, leading to reduced DBP transcriptional activity. Similar alterations were observed with chemically-induced ER stress. Transgenic mice expressing E4BP4 under the control of the mouse insulin I gene promoter (MIP), in which E4BP4 in β-cells is expected to compete with DBP for D-box, displayed remarkable glucose intolerance with severely impaired insulin secretion...
April 2017: EBioMedicine
https://www.readbyqxmd.com/read/28386107/constitutively-active-abl-family-kinases-tel-abl-and-tel-arg-harbor-distinct-leukemogenic-activities-in-vivo
#7
A Yokota, H Hirai, T Shoji, T Maekawa, K Okuda
ABL (ABL1) and ARG (ABL2) are highly homologous to each other in overall domain structure and amino-acid sequence, with the exception of their C termini. As with ABL, translocations that fuse ARG to ETV6/TEL have been identified in patients with leukemia. To assess the in vivo leukemogenic activity of constitutively active ABL and ARG, we generated a bone marrow (BM) transplantation model using the chimeric forms TEL/ABL and TEL/ARG, which have comparable kinase activities. TEL/ABL rapidly induced fatal myeloid leukemia in recipient mice, whereas recipients of TEL/ARG-transduced cells did not develop myeloid leukemia, instead, they succumbed to a long-latency infiltrative mastocytosis that could be adoptively transferred to secondary recipients...
May 5, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28382822/a-chemically-inducible-helper-module-for-detecting-protein-protein-interactions-with-tunable-sensitivity-based-on-kippis
#8
Daiki Kashima, Raiji Kawade, Teruyuki Nagamune, Masahiro Kawahara
As protein-protein interactions (PPIs) play essential roles in regulating their functional consequences in cells, methods to detect PPIs in living cells are desired for correct understanding of intracellular PPIs and pharmaceutical development therefrom. Here we demonstrate a c-kit-based PPI screening (KIPPIS) system in combination with a chemically inducible helper module for detecting PPIs in living mammalian cells. In this system, a mutant of FK506-binding protein 12 (FKBPF36 V) is fused with a protein of interest and the intracellular domain of a receptor tyrosine kinase c-kit...
April 13, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28377320/do-il-3-gm-csf-effect-on-the-myofibroblastic-differentiation-of-human-adipose-derived-stromal-cells
#9
Jae-Sun Lee, Son-Seung Tae, Deok-Yeol Kim, Seung-Kyu Han, Woo-Kyung Kim, Eun-Sang Dhong
BACKGROUND: Capsular contracture is an incurable complication after silicone-based implant surgery. Myofibroblast is the predominant cell in the contracted capsule. We hypothesized that human adipose derive stromal cells (hASCs) together with fibroblast may show a similar phenotypic characteristics of myofibroblast after the treatment of inflammatory cytokines in vitro. MATERIALS AND METHODS: Interleukin 3 (IL-3) and granulocyte macrophage colony stimulating factor (GM-CSF) were treated in the culture of hASCs and HDFs...
April 2, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28344320/dpp4-truncated-gm-csf-il-3-manifest-distinct-receptor-binding-regulatory-functions-compared-to-their-full-length-forms
#10
H A O'Leary, M Capitano, S Cooper, C Mantel, H S Boswell, R Kapur, B Ramdas, R Chan, L Deng, C-K Qu, H E Broxmeyer
Dipeptidylpeptidase 4 (DPP4/CD26) enzymatically cleaves select penultimate amino acids of proteins, including colony stimulating factors (CSFs), and has been implicated in cellular regulation. To better understand the role of DPP4 regulation of hematopoiesis, we analyzed the activity of DPP4 on the surface of immature blood cells and then comparatively assessed the interactions and functional effects of full-length (FL) and DPP4 truncated factors [(T)-GM-CSF and- IL-3] on both in vitro and in vivo models of normal and leukemic cells...
March 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28342988/an-anti-inflammatory-dietary-intervention-to-reduce-breast-cancer-recurrence-risk-study-design-and-baseline-data
#11
Amelie G Ramirez, Dorothy Long Parma, Edgar Muñoz, Kristin D Mendoza, Crystel Harb, Alan E C Holden, Michael Wargovich
U.S. breast cancer survivors (BCSs) are expected to increase to 4 million in the next 5-10years. Cancer recurrence risk is highest among obese survivors. Inflammatory (Pro-I) biomarkers including C-reactive protein (CRP), Interleukins -3, -6, and -8 (IL-3, IL-6, IL-8), and Tumor Necrosis Factor (TNF)-α have been associated with cancer recurrence risk. Nutritional interventions aimed at reducing inflammation (INF) may contribute to reduced cancer recurrence risk, but studies have been limited to animal models...
March 22, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28342911/basophils-high-affinity-ige-receptors-and-ccl2-in-human-anaphylaxis
#12
Peter Korosec, Paul J Turner, Mira Silar, Peter Kopac, Mitja Kosnik, Bernhard F Gibbs, Mohamed H Shamji, Adnan Custovic, Matija Rijavec
BACKGROUND: The role of basophils in anaphylaxis is unclear. OBJECTIVE: We sought to investigate whether basophils have an important role in human anaphylaxis. METHODS: In an emergency department study we recruited 31 patients with acute anaphylaxis, predominantly to Hymenoptera venom. We measured expression of basophil activation markers (CD63 and CD203c); the absolute number of circulating basophils; whole-blood FCER1A, carboxypeptidase A3 (CPA3), and L-histidine decarboxylase (HDC) gene expression; and serum markers (CCL2, CCL5, CCL11, IL-3, and thymic stromal lymphopoietin) at 3 time points (ie, during the anaphylactic episode and in convalescent samples 7 and 30 days later)...
March 22, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28330111/effect-of-stat3-inhibitor-in-chronic-myeloid-leukemia-associated-signaling-pathway-a-mathematical-modeling-simulation-and-systems-biology-study
#13
Himansu Kumar, Swapnil Tichkule, Utkarsh Raj, Saurabh Gupta, Swati Srivastava, Pritish Kumar Varadwaj
Chronic myeloid leukemia (CML) is a hematopoietic stem-cell disorder which proliferates due to abnormal growth of basophil cells. Several proangiogenic molecules have been reported to be associated in CML progression, including the hepatocyte growth factor (HGF). However, detail mechanism about the cellular distribution and function of HGF in CML is yet to be revealed. The proliferation of hematopoietic cells are regulated by some of the growth factors like interleukin 3 (IL-3), IL-6, erythropoietin, thrombopoietin, etc...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28320377/application-of-an-e-coli-signal-sequence-as-a-versatile-inclusion-body-tag
#14
Wouter S P Jong, David Vikström, Diane Houben, H Bart van den Berg van Saparoea, Jan-Willem de Gier, Joen Luirink
BACKGROUND: Heterologous protein production in Escherichia coli often suffers from bottlenecks such as proteolytic degradation, complex purification procedures and toxicity towards the expression host. Production of proteins in an insoluble form in inclusion bodies (IBs) can alleviate these problems. Unfortunately, the propensity of heterologous proteins to form IBs is variable and difficult to predict. Hence, fusing the target protein to an aggregation prone polypeptide or IB-tag is a useful strategy to produce difficult-to-express proteins in an insoluble form...
March 21, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28303135/a-human-lin-cd123-cd127-low-population-endowed-with-ilc-features-and-migratory-capabilities-contributes-to-immunopathological-hallmarks-of-psoriasis
#15
Luz María Mora-Velandia, Octavio Castro-Escamilla, Andrés González Méndez, Cristina Aguilar-Flores, Martha Velázquez-Avila, María Isabel Tussié-Luna, Juan Téllez-Sosa, César Maldonado-García, Fermín Jurado-Santacruz, Eduardo Ferat-Osorio, Jesus Martínez-Barnetche, Rosana Pelayo, Laura C Bonifaz
Innate lymphoid cells (ILC) are members of a heterogeneous family with a lymphoid origin that mimics the T helper (Th) cytokine profile. ILC are involved in early effector cytokine-mediated responses during infections in peripheral tissues. ILC also play an important role in chronic skin inflammatory diseases, including psoriasis. Although classical ILC express CD127, it has been recently reported that the presence of non-classical CD127(-) ILC populations and an early ILC precursor (EILP) CD127(low). ILC development has predominately been investigated in mouse models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28289333/influence-of-vaginal-lactoferrin-administration-on-amniotic-fluid-cytokines-and-its-role-against-inflammatory-complications-of-pregnancy
#16
Martina Maritati, Manola Comar, Nunzia Zanotta, Silva Seraceni, Alessandro Trentini, Fabrizio Corazza, Fortunato Vesce, Carlo Contini
BACKGROUND: An altered amniotic cytokine profile has been reported in inflammatory pregnancy complications with a leading role for IL-6, a marker of the foetal systemic inflammatory response. Up to this date there is no exhaustive information neither on the foetal cytokine balance nor on the best method for its modulation. We aimed to evaluate the influence of vaginal lactoferrin administration on amniotic fluid concentration of 47 cytokines, chemokines and growth factors. METHODS: Sixty women undergoing genetic amniocentesis were enrolled in an open-label clinical trial...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28284718/novel-jak3-activating-mutations-in-extranodal-nk-t-cell-lymphoma-nasal-type
#17
Sung H Sim, Soyeon Kim, Tae M Kim, Yoon K Jeon, Soo J Nam, Yong-Oon Ahn, Bhumsuk Keam, Hyun H Park, Dong-Wan Kim, Chul W Kim, Dae S Heo
Inhibition of the Janus kinase (JAK)-STAT pathway has been implicated as a treatment option for extranodal natural killer/T-cell lymphoma, nasal type (NTCL). However, JAK-STAT pathway alterations in NTCL are variable, and the efficacy of JAK-STAT pathway inhibition has been poorly evaluated. JAK3 mutation and STAT3 genetic alterations were investigated by direct sequencing and immunohistochemistry in 84 patients with newly diagnosed NTCL. Five of 71 patients with NTCL (7.0%) had JAK3 mutations in the pseudokinase domain: two JAK3(A573V), two JAK3(H583Y), and one JAK3(G589D) mutation...
March 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28235674/thrombopoietin-contributes-to-the-formation-and-the-maintenance-of-hematopoietic-progenitor-containing-cell-clusters-in-the-aorta-gonad-mesonephros-region
#18
Kaho Harada, Ikuo Nobuhisa, Maha Anani, Kiyoka Saito, Tetsuya Taga
In the midgestation mouse embryo, hematopoietic cell clusters containing hematopoietic stem/progenitor cells arise in the aorta-gonad-mesonephros (AGM) region. We have previously reported that forced expression of the Sox17 transcription factor in CD45(low)c-Kit(high) AGM cells, which are the hematopoietic cellular component of the cell clusters, and subsequent coculture with OP9 stromal cells in the presence of three cytokines, stem cell factor (SCF), interleukin-3 (IL-3), and thrombopoietin (TPO), led to the formation and the maintenance of cell clusters with cells at an undifferentiated state in vitro...
February 21, 2017: Cytokine
https://www.readbyqxmd.com/read/28212655/elderly-onset-hereditary-pulmonary-alveolar-proteinosis-and-its-cytokine-profile
#19
Masayuki Ito, Kazuyuki Nakagome, Hiromitsu Ohta, Keiichi Akasaka, Yoshitaka Uchida, Atsushi Hashimoto, Ayako Shiono, Toshinori Takada, Makoto Nagata, Jun Tohyama, Koichi Hagiwara, Minoru Kanazawa, Koh Nakata, Ryushi Tazawa
BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by surfactant accumulation, and is caused by disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. Abnormalities in CSF2 receptor alpha (CSF2RA) were reported to cause pediatric hereditary PAP. We report here the first case of CSF2RA-mutated, elderly-onset hereditary (h) PAP. CASE PRESENTATION: The patient developed dyspnea on exertion, and was diagnosed with PAP at the age of 77 years, based on findings from chest computed tomography scan and bronchoalveolar lavage...
February 17, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28212528/the-crispr-cas9-system-efficiently-reverts-the-tumorigenic-ability-of-bcr-abl-in-vitro-and-in-a-xenograft-model-of-chronic-myeloid-leukemia
#20
Ignacio García-Tuñón, María Hernández-Sánchez, José Luis Ordoñez, Veronica Alonso-Pérez, Miguel Álamo-Quijada, Rocio Benito, Carmen Guerrero, Jesús María Hernández-Rivas, Manuel Sánchez-Martín
CRISPR/Cas9 technology was used to abrogate p210 oncoprotein expression in the Boff-p210 cell line, a pro-B line derived from interlukin-3-dependent Baf/3, that shows IL-3-independence arising from the constitutive expression of BCR-ABL p210. Using this approach, pools of Boff-p210-edited cells and single edited cell-derived clones were obtained and functionally studied in vitro. The loss of p210 expression in Boff-p210 cells resulted in the loss of ability to grow in the absence of IL-3, as the Baf/3 parental line, showing significantly increased apoptosis levels...
April 18, 2017: Oncotarget
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