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PIM2

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https://www.readbyqxmd.com/read/27901106/the-role-of-pim1-pim2-kinases-in-tumors-of-the-male-reproductive-system
#1
Manuel Pedro Jiménez-García, Antonio Lucena-Cacace, María José Robles-Frías, Maja Narlik-Grassow, Carmen Blanco-Aparicio, Amancio Carnero
The PIM family of serine/threonine kinases has three highly conserved isoforms (PIM1, PIM2 and PIM3). PIM proteins are regulated through transcription and stability by JAK/STAT pathways and are overexpressed in hematological malignancies and solid tumors. The PIM kinases possess weak oncogenic abilities, but enhance other genes or chemical carcinogens to induce tumors. We generated conditional transgenic mice that overexpress PIM1 or PIM2 in male reproductive organs and analyzed their contribution to tumorigenesis...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27826617/expression-and-function-of-pim-kinases-in-osteosarcoma
#2
Shuai Mou, Guangbin Wang, Ding Ding, Dongdong Yu, Yi Pei, Songling Teng, Qin Fu
The provirus integrating site Moloney murine leukemia virus (PIM) family of serine/threonine protein kinases is composed of three members, PIM1, PIM2 and PIM3, which have been identified as oncoproteins in various malignancies. However, their role in osteosarcoma (OS) remains largely unknown. This study aimed to examine the expression patterns and the clinical significance of PIM kinases in human OS and their biological effects in human OS cell lines. Immunohistochemical staining was used to detect PIM kinases in archived pathologic material from 43 patients with primary OS; in addition, the effects of PIM knockdown and overexpression on the proliferation, migration and invasion of OS cell lines were determined...
November 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27664710/nras-nras-which-mutation-is-fairest-of-them-all
#3
Christine Grill, Lionel Larue
In 28% of melanomas, NRAS is mutated in one of two hotspots: G12 or Q61. Phosphoproteomic analysis of primary human melanocytes transduced with G12 and Q61 showed different phosphorylation events in the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Surprisingly, NRAS(G12) modulates the PI3K pathway and overexpresses the kinase PIM2, whereas NRAS(Q61) is associated with the MAPK pathway and overexpression of CK2α.
October 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27564460/pim2-is-important-for-regulating-dna-damage-response-in-multiple-myeloma-cells
#4
J Ramachandran, L Santo, K T Siu, C Panaroni, N Raje
Pan proviral integrations of Moloney virus (PIM) inhibition in multiple myeloma (MM) results in reduced cell viability in tested human-derived MM cell lines and reduces tumor burden in xenograft mouse models, making PIMs important therapeutic targets for the disease. PIM kinase inhibitors are currently being tested clinically in MM. We sought to elucidate the role of the various PIMs in MM. Our data demonstrate that Pim2 has a significant role in MM cell cytotoxicity. Our data provide evidence for a novel role for Pim2 in the regulation of the DNA damage response (DDR)...
2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27448973/pim-kinases-as-therapeutic-targets-against-advanced-melanoma
#5
Batool Shannan, Andrea Watters, Quan Chen, Stefan Mollin, Markus Dörr, Eric Meggers, Xiaowei Xu, Phyllis A Gimotty, Michela Perego, Ling Li, Joseph Benci, Clemens Krepler, Patricia Brafford, Jie Zhang, Zhi Wei, Gao Zhang, Qin Liu, Xiangfan Yin, Katherine L Nathanson, Meenhard Herlyn, Adina Vultur
Therapeutic strategies for the treatment of metastatic melanoma show encouraging results in the clinic; however, not all patients respond equally and tumor resistance still poses a challenge. To identify novel therapeutic targets for melanoma, we screened a panel of structurally diverse organometallic inhibitors against human-derived normal and melanoma cells. We observed that a compound that targets PIM kinases (a family of Ser/Thr kinases) preferentially inhibited melanoma cell proliferation, invasion, and viability in adherent and three-dimensional (3D) melanoma models...
July 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27107179/sequence-based-analysis-of-5-utr-and-coding-regions-of-casp3-in-terms-of-mirsnps-and-snps-in-targetting-mirnas
#6
Sercan Ergun, Serdar Oztuzcu
Apoptosis is described as a mechanism of cell death occurring after adequate cellular harm. Deregulation of apoptosis occurs in many human conditions such as autoimmune disorders, ischemic damage, neurodegenerative diseases and different cancer types. Information relating miRNAs to cancer is increasing. miRNAs can affect development of cancer via many different pathways, including apoptosis. Polymorphisms in miRNA genes or miRNA target sites (miRSNPs) can change miRNA activity. Although polymorphisms in miRNA genes are very uncommon, SNPs in miRNA-binding sites of target genes are quite common...
June 2016: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/27045080/pkm2-thr454-phosphorylation-increases-its-nuclear-translocation-and-promotes-xenograft-tumor-growth-in-a549-human-lung-cancer-cells
#7
Zhenhai Yu, Liangqian Huang, Pengyun Qiao, Aifang Jiang, Li Wang, Tingting Yang, Shengjian Tang, Wei Zhang, Chune Ren
Pyruvate kinase M2 (PKM2) is a key enzyme of glycolysis which is highly expressed in many tumor cells, and plays an important role in the Warburg effect. In previous study, we found PIM2 phosphorylates PKM2 at Thr454 residue (Yu, etl 2013). However, the functions of PKM2 Thr454 modification in cancer cells still remain unclear. Here we find PKM2 translocates into the nucleus after Thr454 phosphorylation. Replacement of wild type PKM2 with a mutant (T454A) enhances mitochondrial respiration, decreases pentose phosphate pathway, and enhances chemosensitivity in A549 cells...
May 13, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26965057/structural-basis-for-selective-recognition-of-acyl-chains-by-the-membrane-associated-acyltransferase-pata
#8
David Albesa-Jové, Zuzana Svetlíková, Montse Tersa, Enea Sancho-Vaello, Ana Carreras-González, Pascal Bonnet, Pedro Arrasate, Ander Eguskiza, Shiva K Angala, Javier O Cifuente, Jana Korduláková, Mary Jackson, Katarína Mikušová, Marcelo E Guerin
The biosynthesis of phospholipids and glycolipids are critical pathways for virtually all cell membranes. PatA is an essential membrane associated acyltransferase involved in the biosynthesis of mycobacterial phosphatidyl-myo-inositol mannosides (PIMs). The enzyme transfers a palmitoyl moiety from palmitoyl-CoA to the 6-position of the mannose ring linked to 2-position of inositol in PIM1/PIM2. We report here the crystal structures of PatA from Mycobacterium smegmatis in the presence of its naturally occurring acyl donor palmitate and a nonhydrolyzable palmitoyl-CoA analog...
2016: Nature Communications
https://www.readbyqxmd.com/read/26960717/soluble-urokinase-plasminogen-activator-receptor-a-new-biomarker-in-the-pediatric-intensive-care-unit
#9
Muhammad S El-Mekkawy, Nagwan Y Saleh, Ahmed A Sonbol
OBJECTIVE: To evaluate the value of soluble urokinase plasminogen activator receptor (suPAR) in diagnosing sepsis and predicting mortality in critically ill children. METHODS: In a prospective cohort study, 69 critically ill children admitted into the pediatric intensive care unit (PICU) were randomly enrolled in addition to 15 healthy children as a control group. Clinical examination was performed, including calculation of the Pediatric Risk of Mortality (PRISM) and Pediatric Index of Mortality2 (PIM2)...
July 2016: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/26874332/combining-chemical-and-genetic-approaches-for-development-of-responsive-fret-based-sensor-systems-for-protein-kinases
#10
Ganesh Babu Manoharan, Erki Enkvist, Asko Uri
Chemical and genetic approaches were combined for the development of responsive FRET-based sensor systems for protein kinases, using PIM2 as the model kinase. Fusions of PIM2 and a red fluorescent protein, TagRFP were expressed in mammalian cells and small-molecule ARC-Lum photoluminescent probes possessing different phosphorescent and fluorescent properties were constructed. Based on a variety of Förster-type resonant energy transfer (FRET) mechanisms (including intermolecular or intramolecular energy transfer and transfer between singlet-singlet or triplet-singlet electronic states of interacting luminophores) of the probe and that of the fluorescently tagged PIM2, FRET-based sensor systems were constructed...
April 2016: Biophysical Chemistry
https://www.readbyqxmd.com/read/26837956/infectious-etiologies-and-patient-outcomes-in-pediatric-septic-shock
#11
Stefanie G Ames, Jennifer K Workman, Jared A Olson, E Kent Korgenski, Susan Masotti, Elizabeth D Knackstedt, Susan L Bratton, Gitte Y Larsen
BACKGROUND: Septic shock remains an important cause of death and disability in children. Optimal care requires early recognition and treatment. METHODS: We evaluated a retrospective cohort of children (age <19) treated in our emergency department (ED) for septic shock during 2008-2012 to investigate the association between timing of antibiotic therapy and outcomes. The exposures were (1) receipt of empiric antibiotics in ≤1 hour and (2) receipt of appropriate antibiotics in ≤1 hour...
February 1, 2016: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/26824321/differential-regulation-of-mtor-signaling-determines-sensitivity-to-akt-inhibition-in-diffuse-large-b-cell-lymphoma
#12
Scott A Ezell, Suping Wang, Teeru Bihani, Zhongwu Lai, Shaun E Grosskurth, Suprawee Tepsuporn, Barry R Davies, Dennis Huszar, Kate F Byth
Agents that target components of the PI3K/AKT/mTOR pathway are under investigation for the treatment of diffuse large B cell lymphoma (DLBCL). Given the highly heterogeneous nature of DLBCL, it is not clear whether all subtypes of DLBCL will be susceptible to PI3K pathway inhibition, or which kinase within this pathway is the most favorable target. Pharmacological profiling of a panel of DLBCL cell lines revealed a subset of DLBCL that was resistant to AKT inhibition. Strikingly, sensitivity to AKT inhibitors correlated with the ability of these inhibitors to block phosphorylation of S6K1 and ribosomal protein S6...
February 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/26796541/inflammation-and-organ-failure-severely-affect-midazolam-clearance-in-critically-ill-children
#13
Nienke J Vet, Janneke M Brussee, Matthijs de Hoog, Miriam G Mooij, Carin W M Verlaat, Isabel S Jerchel, Ron H N van Schaik, Birgit C P Koch, Dick Tibboel, Catherijne A J Knibbe, Saskia N de Wildt
RATIONALE: Various in vitro, animal, and limited human adult studies suggest a profound inhibitory effect of inflammation and disease on cytochrome P-450 3A (CYP3A)-mediated drug metabolism. Studies showing this relationship in critically ill patients are lacking, whereas clearance of many CYP3A drug substrates may be decreased, potentially leading to toxicity. OBJECTIVES: To prospectively study the relationship between inflammation, organ failure, and midazolam clearance as a validated marker of CYP3A-mediated drug metabolism in critically ill children...
July 1, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/26764044/elevated-pim2-gene-expression-is-associated-with-poor-survival-of-patients-with-acute-myeloid-leukemia
#14
Katarzyna Kapelko-Slowik, Tomasz B Owczarek, Krzysztof Grzymajlo, Donata Urbaniak-Kujda, Bozena Jazwiec, Miroslaw Slowik, Kazimierz Kuliczkowski, Maciej Ugorski
The PIM2 gene encodes the serine/threonine kinase involved in cell survival and apoptosis. The aim of the study was to evaluate the expression of the PIM2 gene in acute myeloid leukemia (AML) and to examine its role in apoptosis of the blastic cells. We analyzed the PIM2 expression in 148 patients: 91 with AML, 57 with acute lymphoblastic leukemia and 24 healthy controls by Real-Time PCR and Western blot. Inhibition of the PIM2 gene in human leukemic HL60 cell line was performed with RNAi and apoptosis rate was analyzed...
September 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/26744626/red-cell-transfusions-as-an-independent-risk-for-mortality-in-critically-ill-children
#15
Surender Rajasekaran, Eric Kort, Richard Hackbarth, Alan T Davis, Dominic Sanfilippo, Robert Fitzgerald, Sandra Zuiderveen, Akunne N Ndika, Hilary Beauchamp, Anthony Olivero, Nabil Hassan
BACKGROUND: Severity of illness is an important consideration in making the decision to transfuse as it is the sicker patient that often needs a red cell transfusion. Red blood cell (RBC) transfusions could potentially have direct effects and interact with presenting illness by contributing to pathologies such as multi-organ dysfunction and acute lung injury thus exerting a considerable impact on overall morbidity and mortality. In this study, we examine if transfusion is an independent predictor of mortality, or if outcomes are merely a result of the initial severity as predicted by Pediatric Risk of Mortality (PRISM) III, Pediatric Index of Mortality (PIM2), and day 1 Pediatric Logistic Organ Dysfunction (PELOD) scores...
2016: Journal of Intensive Care
https://www.readbyqxmd.com/read/26643319/loss-of-pim2-enhances-the-anti-proliferative-effect-of-the-pan-pim-kinase-inhibitor-azd1208-in-non-hodgkin-lymphomas
#16
S Kreuz, K B Holmes, R M Tooze, P F Lefevre
BACKGROUND: A promising therapeutic approach for aggressive B-cell Non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma (BL) is to target kinases involved in signal transduction and gene regulation. PIM1/2 serine/threonine kinases are highly expressed in activated B-cell-like DLBCL (ABC-DLBCL) with poor prognosis. In addition, both PIM kinases have a reported synergistic effect with c-MYC in mediating tumour development in several cancers, c-MYC gene being translocated to one of the immunoglobulin loci in nearly all BLs...
2015: Molecular Cancer
https://www.readbyqxmd.com/read/26500282/control-of-pim2-kinase-stability-and-expression-in-transformed-human-haematopoietic-cells
#17
Kévin Adam, Mireille Lambert, Elsa Lestang, Gabriel Champenois, Isabelle Dusanter-Fourt, Jérôme Tamburini, Didier Bouscary, Catherine Lacombe, Yael Zermati, Patrick Mayeux
The oncogenic Pim2 kinase is overexpressed in several haematological malignancies, such as multiple myeloma and acute myeloid leukaemia (AML), and constitutes a strong therapeutic target candidate. Like other Pim kinases, Pim2 is constitutively active and is believed to be essentially regulated through its accumulation. We show that in leukaemic cells, the three Pim2 isoforms have dramatically short half-lives although the longer isoform is significantly more stable than the shorter isoforms. All isoforms present a cytoplasmic localization and their degradation was neither modified by broad-spectrum kinase or phosphatase inhibitors such as staurosporine or okadaic acid nor by specific inhibition of several intracellular signalling pathways including Erk, Akt and mTORC1...
2015: Bioscience Reports
https://www.readbyqxmd.com/read/26365288/effects-of-low-doses-of-tat-pim2-protein-against-hippocampal-neuronal-cell-survival
#18
Su Jung Woo, Min Jea Shin, Dae Won Kim, Hyo Sang Jo, Ji In Yong, Eun Ji Ryu, Hyun Ju Cha, Sang Jin Kim, Hyeon Ji Yeo, Su Bin Cho, Jung Hwan Park, Chi Hern Lee, Eun Ji Yeo, Yeon Joo Choi, Sungyeon Park, Seung Kwon Im, Duk-Soo Kim, Oh-Shin Kwon, Jinseu Park, Won Sik Eum, Soo Young Choi
Oxidative stress is considered a major factor in various neuronal diseases including ischemia-reperfusion injury. Proviral Integration Moloney 2 (PIM2) proteins, one of the families of PIM kinases, play crucial roles in cell survival. However, the functions of PIM2 protein against ischemia are not understood. Therefore, the protective effects of PIM2 against oxidative stress-induced hippocampal HT22 cell death and brain ischemic injury were evaluated using Tat-PIM2, a cell permeable fusion protein. Tat-PIM2 protein transduced into hippocampal HT22 cells...
November 15, 2015: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/26340096/ribosomal-biogenesis-and-translational-flux-inhibition-by-the-selective-inhibitor-of-nuclear-export-sine-xpo1-antagonist-kpt-185
#19
Yoko Tabe, Kensuke Kojima, Shinichi Yamamoto, Kazumasa Sekihara, Hiromichi Matsushita, Richard Eric Davis, Zhiqiang Wang, Wencai Ma, Jo Ishizawa, Saiko Kazuno, Michael Kauffman, Sharon Shacham, Tsutomu Fujimura, Takashi Ueno, Takashi Miida, Michael Andreeff
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by the aberrant expression of several growth-regulating, oncogenic effectors. Exportin 1 (XPO1) mediates the nucleocytoplasmic transport of numerous molecules including oncogenic growth-regulating factors, RNAs, and ribosomal subunits. In MCL cells, the small molecule KPT-185 blocks XPO1 function and exerts anti-proliferative effects. In this study, we investigated the molecular mechanisms of this putative anti-tumor effect on MCL cells using cell growth/viability assays, immunoblotting, gene expression analysis, and absolute quantification proteomics...
2015: PloS One
https://www.readbyqxmd.com/read/26337557/pediatric-index-of-mortality-2-as-a-predictor-of-death-risk-in-children-admitted-to-pediatric-intensive-care-units-in-latin-america-a-prospective-multicenter-study
#20
MULTICENTER STUDY
Maria Pilar Arias Lopez, Ariel L Fernández, María E Ratto, Liliana Saligari, Alejandro Siaba Serrate, In Ja Ko, Eduardo Troster, Eduardo Schnitzler
PURPOSE: The purpose of this study is to asses the performance of the Pediatric Index of Mortality 2 (PIM2) score in pediatric intensive care units (PICUs) in Latin America. MATERIALS AND METHODS: This is a prospective, observational, multicenter study. We included patients aged 1 month to 16 years old admitted consecutively during 1 year to 34 PICUs in 9 Latin American countries. Discrimination and calibration tests were performed to validate the performance of PIM2 in the entire sample and in different subgroups...
December 2015: Journal of Critical Care
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