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https://www.readbyqxmd.com/read/29782975/roles-of-germline-jak2-activation-mutation-jak2-v625f-in-the-pathology-of-myeloproliferative-neoplasms
#1
Qing-Yun Wu, Meng-Meng Ma, Lin Fu, Yuan-Yuan Zhu, Yang Liu, Jiang Cao, Ping Zhou, Zhen-Yu Li, Ling-Yu Zeng, Feng Li, Xiao-Yun Wang, Kai-Lin Xu
Janus tyrosine kinase 2 (JAK2) mediates downstream signaling of cytokine receptors in all hematological lineages, constitutively active somatic JAK2 mutations play key roles in the pathology of myeloproliferative neoplasms (MPNs). Recently, germline JAK2 mutations are also associated with triple-negative MPNs. A novel germline mutation JAK2 V625F is reported to be involved in a subset of MPNs patients. However, the pathogenesis of this mutation caused MPN is still unclear. In this study, the homology models of JAK2 V625F showed that the newly formed interaction between F625 and Y613 disrupted the JAK2 JH1-JH2 domain interactions was responsible for its activation, when F625 and Y613 interaction was disrupted, its activity significantly decreased...
May 18, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29779334/-effect-of-iron-chelation-therapy-on-epo-stat5-signaling-pathway-and-treg-expression-in-ipss-low-risk-medium-risk-1-group-myelodysplastic-syndrome-patients
#2
Y Zhang, S Han, C Guo, Q X Zhang, C K Chang
No abstract text is available yet for this article.
April 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29778097/hyperprolactinemia-inducing-antipsychotics-increase-breast-cancer-risk-by-activating-jak-stat5-in-precancerous-lesions
#3
A N Johnston, W Bu, S Hein, S Garcia, L Camacho, L Xue, L Qin, C Nagi, S G Hilsenbeck, J Kapali, K Podsypanina, J Nangia, Y Li
BACKGROUND: Psychiatric medications are widely prescribed in the USA. Many antipsychotics cause serum hyperprolactinemia as an adverse side effect; prolactin-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) signaling both induces cell differentiation and suppresses apoptosis. It is controversial whether these antipsychotics increase breast cancer risk. METHODS: We investigated the impact of several antipsychotics on mammary tumorigenesis initiated by retrovirus-mediated delivery of either ErbB2 or HRas or by transgenic expression of Wnt-1...
May 19, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29777794/regulatory-t-cell-targeted-hybrid-nanoparticles-combined-with-immuno-checkpoint-blockage-for-cancer-immunotherapy
#4
Wenquan Ou, Raj Kumar Thapa, Liyuan Jiang, Soe Zar Chi, Milan Gautam, Jae-Hoon Chang, Jee-Heon Jeong, Sae Kwang Ku, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Immunosuppression in tumor microenvironments induced by regulatory T (Treg) cells is regarded a critical mechanism of tumor immune escape and poses a major impediment to cancer immunotherapy. In this study, we developed tLyp1 peptide-conjugated hybrid nanoparticles for targeting Treg cells in the tumor microenvironment. The tLyp1 peptide-modified hybrid nanoparticles presented good stability and effective targeting to Treg cells, and they enhanced the effect of imatinib in downregulating Treg cell suppression through inhibition of STAT3 and STAT5 phosphorylation...
May 16, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29776611/nasal-delivery-of-chitosan-alginate-nanoparticle-encapsulated-bee-apis-mellifera-venom-promotes-antibody-production-and-viral-clearance-during-porcine-reproductive-and-respiratory-syndrome-virus-infection-by-modulating-t-cell-related-responses
#5
Jina Lee, Yun-Mi Kim, Ju-Heon Kim, Cheong-Weon Cho, Jong-Woon Jeon, Jin-Kyu Park, Sang-Ho Lee, Bock-Gie Jung, Bong-Joo Lee
In this study, we administered specially developed chitosan/alginate nanoparticle encapsulated BV (CH/AL-BV) which has slow-releasing properties and mucosal adhesiveness to pig via nasal route and evaluate whether it can facilitate systemic immune response and improve clearance of porcine reproductive and respiratory syndrome virus (PRRSV). The CH/AL-BV-administered group with PRRSV vaccination showed significantly enhanced Th1-related responses including a high population of CD4+ T lymphocyte and cytokine mRNA levels including interferon-gamma (IFN-γ) and interleukin (IL)-12 and increased PRRSV-specific IgG levels...
June 2018: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29774100/differential-proteomic-profile-of-leukemic-cd34-progenitor-cells-from-chronic-myeloid-leukemia-patients
#6
Maria Rosaria Ricciardi, Valentina Salvestrini, Roberto Licchetta, Simone Mirabilii, Mattia Forcato, Gabriele Gugliotta, Simona Salati, Fausto Castagnetti, Gianantonio Rosti, Massimo Breccia, Giuliana Alimena, Rossella Manfredini, Silvio Bicciato, Roberto Massimo Lemoli, Agostino Tafuri
Chronic Myeloid Leukemia (CML) is a stem cell disease sustained by a rare population of quiescent cells which are to some extent resistant to tyrosine kinase inhibitors (TKIs). BCR-ABL oncogene activates multiple cross-talking signal transduction pathways (STP), such as RAS/MEK/ERK, PI3K/Akt, Wnt and STAT5, contributing to abnormal proliferation of clonal cells. From this perspective, the aim of this study was to analyze the expression and activation profile of STP involved in the mechanisms of cell proliferation/quiescence and survival of the progenitor CD34+ cells from chronic phase (CP) CML...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773601/combinatorial-targeting-of-xpo1-and-flt3-exerts-synergistic-anti-leukemia-effects-through-induction-of-differentiation-and-apoptosis-in-flt3-mutated-acute-myeloid-leukemias-from-concept-to-clinical-trial
#7
Weiguo Zhang, Charlie Ly, Jo Ishizawa, Hong Mu, Vivian Ruvolo, Sharon Shacham, Naval Daver, Michael Andreeff
Targeted therapies against FLT3-mutated acute myeloid leukemia have shown limited clinical efficacy primarily because of the acquisition of secondary mutations in FLT3 and persistent activation of downstream pro-survival pathways such as MEK/ERK, PI3K/AKT, and STAT5. Activation of these additional kinases may also result in phosphorylation of tumor suppressor proteins promoting their nuclear export. Thus, co-targeting nuclear export proteins (i.e., XPO1) and FLT3 concomitantly may be therapeutically effective...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29765322/therapeutic-potential-of-ginsenosides-as-an-adjuvant-treatment-for-diabetes
#8
REVIEW
Litao Bai, Jialiang Gao, Fan Wei, Jing Zhao, Danwei Wang, Junping Wei
Ginseng, one of the oldest traditional Chinese medicinal herbs, has been used widely in China and Asia for thousands of years. Ginsenosides extracted from ginseng, which is derived from the roots and rhizomes of Panax ginseng C. A. Meyer, have been used in China as an adjuvant in the treatment of diabetes mellitus. Owing to the technical complexity of ginsenoside production, the total ginsenosides are generally extracted. Accumulating evidence has shown that ginsenosides exert antidiabetic effects. In vivo and in vitro tests revealed the potential of ginsenoside Rg1, Rg3, Rg5, Rb1, Rb2, Rb3, compound K, Rk1, Re, ginseng total saponins, malonyl ginsenosides, Rd, Rh2, F2, protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins to treat diabetes and its complications, including type 1 diabetes mellitus, type 2 diabetes mellitus, diabetic nephropathy, diabetic cognitive dysfunction, type 2 diabetes mellitus with fatty liver disease, diabetic cerebral infarction, diabetic cardiomyopathy, and diabetic erectile dysfunction...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29763380/angiogenin-and-the-mmp9-timp2-axis-are-up-regulated-in-proangiogenic-decidual-nk-like-cells-from-patients-with-colorectal-cancer
#9
Antonino Bruno, Barbara Bassani, Davide Giuseppe D'Urso, Ilvana Pitaku, Elisa Cassinotti, Giuseppe Pelosi, Luigi Boni, Lorenzo Dominioni, Douglas M Noonan, Lorenzo Mortara, Adriana Albini
NK cells are effector lymphocytes involved in tumor immunosurveillance; however, in patients with solid malignancies, NK cells have compromised functions. We have previously reported that lung tumor-associated NK cells (TANKs; peripheral blood) and tumor-infiltrating NK cells (TINKs) show proangiogenic, decidual NK-like (dNK) phenotype. In this study, we functionally and molecularly investigated TINKs and TANKs from blood and tissue samples of patients with colorectal cancer (CRC), a neoplasm in which inflammation and angiogenesis have clinical relevance, and compared them to NK cells from controls and patients with nononcologic inflammatory bowel disease...
May 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29755466/controlling-mast-cell-activation-and-homeostasis-work-influenced-by-bill-paul-that-continues-today
#10
REVIEW
Heather L Caslin, Kasalina N Kiwanuka, Tamara T Haque, Marcela T Taruselli, H Patrick MacKnight, Anuya Paranjape, John J Ryan
Mast cells are tissue resident, innate immune cells with heterogenous phenotypes tuned by cytokines and other microenvironmental stimuli. Playing a protective role in parasitic, bacterial, and viral infections, mast cells are also known for their role in the pathogenesis of allergy, asthma, and autoimmune diseases. Here, we review factors controlling mast cell activation, with a focus on receptor signaling and potential therapies for allergic disease. Specifically, we will discuss our work with FcεRI and FγR signaling, IL-4, IL-10, and TGF-β1 treatment, and Stat5...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29752311/myeloid-derived-suppressor-cells-impair-b-cell-responses-in-lung-cancer-through-il-7-and-stat5
#11
Yong Wang, Cara C Schafer, Kenneth P Hough, Sultan Tousif, Steven R Duncan, John F Kearney, Selvarangan Ponnazhagan, Hui-Chen Hsu, Jessy S Deshane
Myeloid-derived suppressor cells (MDSCs) are known suppressors of antitumor immunity, affecting amino acid metabolism and T cell function in the tumor microenvironment. However, it is unknown whether MDSCs regulate B cell responses during tumor progression. Using a syngeneic mouse model of lung cancer, we show reduction in percentages and absolute numbers of B cell subsets including pro-, pre-, and mature B cells in the bone marrow (BM) of tumor-bearing mice. The kinetics of this impaired B cell response correlated with the progressive infiltration of MDSCs...
May 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29751003/special-at-rich-binding1-protein-satb1-in-malignant-t-cells
#12
Simon Fredholm, Andreas Willerslev-Olsen, Özcan Met, Linda Kubat, Maria Gluud, Sarah L Mathiasen, Christina Friese, Edda Blümel, David L Petersen, Tengpeng Hu, Claudia Nastasi, Lise M Lindahl, Terkild B Buus, Thorbjørn Krejsgaard, Mariusz A Wasik, Katharina L Kopp, Sergei B Koralov, Jenny L Persson, Charlotte M Bonefeld, Carsten Geisler, Anders Woetmann, Lars Iversen, Jurgen C Becker, Niels Odum
Deficient expression of Suppressor Special AT-rich Binding-1 (SATB1) hampers thymocyte development and results in inept T cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides (MF), the most frequent variant of cutaneous T cell lymphoma (CTCL). Here we report on a disease-stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. Importantly, STAT5 inhibited SATB1 expression through induction of miR-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32) whereas increased SATB1 expression had the opposite effect indicating that the mir-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells...
May 8, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29743313/ivig-promote-cross-tolerance-against-inflammatory-stimuli-in-vitro-and-in-vivo
#13
Ángeles Domínguez-Soto, Miriam Simón-Fuentes, Mateo de Las Casas-Engel, Víctor D Cuevas, María López-Bravo, Jorge Domínguez-Andrés, Paula Saz-Leal, David Sancho, Carlos Ardavín, Juliana Ochoa-Grullón, Silvia Sánchez-Ramón, Miguel A Vega, Angel L Corbí
IVIg is an approved therapy for immunodeficiency and for several autoimmune and inflammatory diseases. However, the molecular basis for the IVIg anti-inflammatory activity remains to be fully explained and cannot be extrapolated from studies on animal models of disease. We now report that IVIg impairs the generation of human monocyte-derived anti-inflammatory macrophages by inducing JNK activation and activin A production and limits proinflammatory macrophage differentiation by inhibiting GM-CSF-driven STAT5 activation...
May 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29739850/small-molecule-targeting-of-the-stat5-6-src-homology-2-sh2-domains-to-inhibit-allergic-airway-disease
#14
J Morgan Knight, Pijus Mandal, Pietro Morlacchi, Garbo Mak, Evan Li, Matthew Madison, Cameron Landers, Brandon Saxton, Ed Felix, Brian Gilbert, Joel Sederstrom, Atul Varadhachary, Melissa M Singh, Dev Chatterjee, David B Corry, John S McMurray
Asthma is a chronic inflammatory disease of the lungs and airways and one of the most burdensome of all chronic maladies. Previous studies have established that expression of experimental and human asthma requires the IL-4/IL-13/IL-4 receptor alpha (IL-4Rα) signaling pathway, which activates the transcription factor STAT6. However, no small molecules targeting this important pathway are currently in clinical development. To this end, using a preclinical asthma model, we sought to develop and test a small-molecule inhibitor of the Src homology 2 domains in mouse and human STAT6...
May 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29738538/the-hypoxia-inducible-factor-erythropoietin-epo-epo-receptor-pathway-is-disturbed-in-a-rat-model-of-chronic-kidney-disease-related-anemia
#15
Daniel Landau, Lital London, Inbar Bandach, Yael Segev
OBJECTIVES: Anemia is a known driver for hypoxia inducible factor (HIF) which leads to increased renal erythropoietin (EPO) synthesis. Bone marrow (BM) EPO receptor (EPOR) signals are transduced through a JAK2-STAT5 pathway. The origins of anemia of chronic kidney disease (CKD) are multifactorial, including impairment of both renal EPO synthesis as well as intestinal iron absorption. We investigated the HIF- EPO- EPOR axis in kidney, BM and proximal tibia in anemic juvenile CKD rats. METHODS: CKD was induced by 5/6 nephrectomy in young (20 days old) male Sprague-Dawley rats while C group was sham operated...
2018: PloS One
https://www.readbyqxmd.com/read/29728695/implications-of-stat3-and-stat5-signaling-on-gene-regulation-and-chromatin-remodeling-in-hematopoietic-cancer
#16
REVIEW
Bettina Wingelhofer, Heidi A Neubauer, Peter Valent, Xiaonan Han, Stefan N Constantinescu, Patrick T Gunning, Mathias Müller, Richard Moriggl
STAT3 and STAT5 proteins are oncogenic downstream mediators of the JAK-STAT pathway. Deregulated STAT3 and STAT5 signaling promotes cancer cell proliferation and survival in conjunction with other core cancer pathways. Nuclear phosphorylated STAT3 and STAT5 regulate cell-type-specific transcription profiles via binding to promoter elements and exert more complex functions involving interaction with various transcriptional coactivators or corepressors and chromatin remodeling proteins. The JAK-STAT pathway can rapidly reshape the chromatin landscape upon cytokine, hormone, or growth factor stimulation and unphosphorylated STAT proteins also appear to be functional with respect to regulating chromatin accessibility...
March 27, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29728440/peripheral-pdgfr%C3%AE-gp38-mesenchymal-cells-support-the-differentiation-of-fetal-liver-derived-ilc2
#17
Satoshi Koga, Katsuto Hozumi, Ken-Ichi Hirano, Masaki Yazawa, Tommy Terooatea, Aki Minoda, Takashi Nagasawa, Shigeo Koyasu, Kazuyo Moro
Group 2 innate lymphoid cells (ILC2s) are derived from common lymphoid progenitors (CLPs) via several specific precursors, and the transcription factors essential for ILC2 differentiation have been extensively studied. However, the external factors regulating commitment to the ILC lineage as well as the sites and stromal cells that constitute the optimal microenvironment for ILC2-specific differentiation are not fully defined. In this study, we demonstrate that three key external factors, the concentration of interleukin 7 (IL-7) and strength and duration of Notch signaling, coordinately determine the fate of CLP toward the T, B, or ILC lineage...
May 4, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29728128/the-ovarian-estrogen-synthesis-function-was-impaired-in-y123f-mouse-and-partly-restored-by-exogenous-fsh-supplement
#18
Xiaoyu Tu, Miao Liu, Jianan Tang, Yu Zhang, Yan Shi, Lin Yu, Zhaogui Sun
BACKGROUND: LepR tyrosine site mutation mice (Y123F) exhibit decreased serum E2 levels, immature reproductive organs, infertility as well as metabolic abnormalities. Although the actions of leptin and lepR in the control of reproductive function are thought to be exerted mainly via the hypothalamic-pituitary-gonadal axis, relatively less is known regarding their local effects on the peripheral ovary, especially on steroid hormone synthesis. Meanwhile, whether the decreased fertility of Y123F mouse could be restored by gonadotropin has not been clear yet...
May 4, 2018: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/29725593/phosphorylated-forms-of-stat1-stat3-and-stat5-are-expressed-in-proliferating-but-not-involuted-infantile-hemangioma
#19
Lucy Sulzberger, Elysia M S Tan, Paul F Davis, Helen D Brasch, Swee T Tan, Tinte Itinteang
We have recently demonstrated the expression of embryonic stem cell markers on the endothelium of infantile hemangioma, a functional hemogenic endothelium with the capacity for primitive erythropoiesis in vitro . Despite recent work characterizing stem cells within proliferating infantile hemangioma, the expression of STAT proteins, well documented for their roles in stem cell signaling, has not been investigated. 3,3-Diaminobenzidine and immunofluorescence immunohistochemical staining revealed expression of pSTAT1, pSTAT3 and pSTAT5 in proliferating infantile hemangioma samples with the strongest expression of pSTAT3...
2018: Frontiers in Surgery
https://www.readbyqxmd.com/read/29724813/egfrviii-stat5-signaling-enhances-glioblastoma-cell-migration-and-survival
#20
Alison Roos, Harshil D Dhruv, Sen Peng, Landon J Inge, Serdar Tuncali, Michael Pineda, Nghia Millard, Zachary Mayo, Jennifer M Eschbacher, Joseph C Loftus, Jeffrey A Winkles, Nhan L Tran
Glioblastoma multiforme (GBM) is the most common brain malignancies in adults. Most GBM patients succumb to the disease less than one year post-diagnosis due to the highly invasive nature of the tumor, which prevents complete surgical resection and gives rise to tumor recurrence. The invasive phenotype also confers radio- and chemo-resistant properties to the tumor cells; therefore, there is a critical need to develop new therapeutics that target drivers of GBM invasion. Amplification of EGFR is observed in over 50% of GBM tumors, of which half concurrently overexpress the variant EGFRvIII, and expression of both receptors confers a worse prognosis...
May 3, 2018: Molecular Cancer Research: MCR
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