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https://www.readbyqxmd.com/read/29665227/microenvironment-induced-pim-kinases-promote-cxcr4-triggered-mtor-pathway-required-for-chronic-lymphocytic-leukaemia-cell-migration
#1
Emilia Białopiotrowicz, Patryk Górniak, Monika Noyszewska-Kania, Bartosz Puła, Hanna Makuch-Łasica, Grażyna Nowak, Aleksandra Bluszcz, Maciej Szydłowski, Ewa Jabłonska, Karolina Piechna, Tomasz Sewastianik, Anna Polak, Ewa Lech-Marańda, Bożena K Budziszewska, Maja Wasylecka-Juszczyńska, Katarzyna Borg, Krzysztof Warzocha, Wojciech Czardybon, Michał Gałęzowski, Renata Windak, Krzysztof Brzózka, Przemysław Juszczyński
Lymph node microenvironment provides chronic lymphocytic leukaemia (CLL) cells with signals promoting their survival and granting resistance to chemotherapeutics. CLL cells overexpress PIM kinases, which regulate apoptosis, cell cycle and migration. We demonstrate that BCR crosslinking, CD40 stimulation, and coculture with stromal cells increases PIMs expression in CLL cells, indicating microenvironment-dependent PIMs regulation. PIM1 and PIM2 expression at diagnosis was higher in patients with advanced disease (Binet C vs...
April 17, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29570932/pim2-interacts-with-tristetraprolin-and-promotes-breast-cancer-tumorigenesis
#2
Chune Ren, Tingting Yang, Pengyun Qiao, Li Wang, Xue Han, Shijun Lv, Yonghong Sun, Zhijun Liu, Yu Du, Zhenhai Yu
Tristetraprolin (TTP) is an AU-rich element-binding protein that regulates mRNA stability and plays important roles in cancer. The mechanisms by which TTP is regulated in breast cancer are poorly understood. Using multiple biochemical approaches, we found that Proviral Insertion in Murine Lymphomas 2 (PIM2) is a novel binding partner of TTP. Interestingly, PIM2 decreased TTP protein levels independent of its kinase activity. PIM2 instead targeted TTP protein for degradation via the ubiquitin-proteasome pathway...
March 23, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29472550/pim1-mediates-epithelial-mesenchymal-transition-by-targeting-smads-and-c-myc-in-the-nucleus-and-potentiates-clear-cell-renal-cell-carcinoma-oncogenesis
#3
Bin Zhao, Lei Liu, Jun Mao, Zhiwei Zhang, Qifei Wang, Quanlin Li
Emerging evidence has shown that the PIM serine/threonine kinase family, including PIM1, PIM2 and PIM3, is associated with tumour progression towards metastasis. PIM1, an attractive molecular target, has been identified as a potential prognostic biomarker for haematological and epithelial malignancies. However, to date, the potential regulatory roles and molecular mechanisms by which PIM1 affects the development and progression of cancers, including clear-cell renal-cell carcinoma (ccRCC), remain largely unknown...
February 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29327347/unique-anti-myeloma-activity-by-thiazolidine-2-4-dione-compounds-with-pim-inhibiting-activity
#4
Shiro Fujii, Shingen Nakamura, Asuka Oda, Hirokazu Miki, Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Ariunzaya Bat-Erdene, Yusaku Maeda, Masahiro Oura, Mamiko Takahashi, Masami Iwasa, Itsuro Endo, Sumiko Yoshida, Ken-Ichi Aihara, Kiyoe Kurahashi, Takeshi Harada, Kumiko Kagawa, Michiyasu Nakao, Shigeki Sano, Masahiro Abe
Proviral Integrations of Moloney virus 2 (PIM2) is overexpressed in multiple myeloma (MM) cells, and regarded as an important therapeutic target. Here, we aimed to validate the therapeutic efficacy of different types of PIM inhibitors against MM cells for their possible clinical application. Intriguingly, the thiazolidine-2,4-dione-family compounds SMI-16a and SMI-4a reduced PIM2 protein levels and impaired MM cell survival preferentially in acidic conditions, in contrast to other types of PIM inhibitors, including AZD1208, CX-6258 and PIM447...
January 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29185694/the-molecular-mechanism-of-substrate-recognition-and-catalysis-of-the-membrane-acyltransferase-pata-from-mycobacteria
#5
Montse Tersa, Lluís Raich, David Albesa-Jové, Beatriz Trastoy, Jacques Prandi, Martine Gilleron, Carme Rovira, Marcelo E Guerin
Glycolipids play a central role in a variety of important biological processes in all living organisms. PatA is a membrane acyltransferase involved in the biosynthesis of phosphatidyl-myo-inositol mannosides (PIMs), key structural elements, and virulence factors of Mycobacterium tuberculosis. PatA catalyzes the transfer of a palmitoyl moiety from palmitoyl-CoA to the 6-position of the mannose ring linked to the 2-position of inositol in PIM1 /PIM2 . We report here the crystal structure of PatA in the presence of 6-O-palmitoyl-α-d-mannopyranoside, unraveling the acceptor binding mechanism...
January 19, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29174722/functional-progression-of-patients-with-neurological-diseases-in-a-tertiary-paediatric-intensive-care-unit-our-experience
#6
P Madurga Revilla, J López Pisón, P Samper Villagrasa, J P García Íñiguez, R Garcés Gómez, M Domínguez Cajal, I Gil Hernández
INTRODUCTION: Neurological diseases explain a considerable proportion of admissions to paediatric intensive care units (PICU), and are a significant cause of morbidity and mortality. This study aims to analyse the functional progression of children with critical neurological conditions. MATERIAL AND METHODS: Retrospective descriptive study of children admitted to PICU with neurological diseases over a period of 3 years (2012-2014), assessing vital and functional prognosis at PICU discharge and at one year according to the Pediatric Cerebral and Overall Performance Category scales (PCPC-POPC) and the Functional Status Scale (FSS)...
November 23, 2017: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/29042609/structural-analysis-of-pim1-kinase-complexes-with-atp-competitive-inhibitors
#7
Jozefina Bogusz, Karol Zrubek, Krzysztof P Rembacz, Przemyslaw Grudnik, Przemyslaw Golik, Malgorzata Romanowska, Benedykt Wladyka, Grzegorz Dubin
PIM1 is an oncogenic kinase overexpressed in a number of cancers where it correlates with poor prognosis. Several studies demonstrated that inhibition of PIM1 activity is an attractive strategy in fighting overexpressing cancers, while distinct structural features of ATP binding pocket make PIM1 an inviting target for the design of selective inhibitors. To facilitate development of specific PIM1 inhibitors, in this study we report three crystal structures of ATP-competitive inhibitors at the ATP binding pocket of PIM1...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28944837/role-of-pim2-in-allergic-asthma
#8
Wei Du, Tiantian Chen, Yingmeng Ni, Xiaoxia Hou, Youchao Yu, Qi Zhou, Fang Wu, Wei Tang, Guochao Shi
T cell‑associated inflammation, particularly type 2 inflammation, has an important role in asthma pathogenesis, which is suppressed by regulatory T cells (Tregs). Proviral integration site for Moloney murine leukemia virus 2 (PIM2), a member off the serine/threonine kinase family, promotes the growth and survival of T cells and influences the function of Treg cells. However, whether PIM2 affects asthma pathogenesis remains unclear. Peripheral blood mononuclear cells and Treg cells from asthmatic and healthy subjects were obtained, and the expression level of PIM2 was measured by reverse transcription‑quantitative polymerase chain reaction and immunocytochemistry...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28938604/inflammation-and-stem-markers-association-to-pim1-pim2-kinase-induced-tumors-in-breast-and-uterus
#9
Manuel-Pedro Jiménez-García, Antonio Lucena-Cacace, María-José Robles-Frías, Irene Ferrer, Maja Narlik-Grassow, Carmen Blanco-Aparicio, Amancio Carnero
The PIM family of Ser/Thr kinase proteins has been implicated in tumorigenesis at different levels. PIM proteins are overexpressed in several tumor types and have been associated with chemoresistance. However, their role in hormone-dependent female tissues has not been explored, especially in the uterus, breast and ovary. We generated conditional transgenic mice with confined expression of human PIM1 or PIM2 genes in these tissues. We characterized the tumoral response to these genetic alterations corroborating their role as oncogenes since they induce hyperproliferation in all tissues and tumors in mammary gland and uterus...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914261/rsk2-is-a-new-pim2-target-with-pro-survival-functions-in-flt3-itd-positive-acute-myeloid-leukemia
#10
M-A Hospital, A Jacquel, F Mazed, E Saland, C Larrue, J Mondesir, R Birsen, A S Green, M Lambert, P Sujobert, E-F Gautier, V Salnot, M Le Gall, J Decroocq, L Poulain, N Jacque, M Fontenay, O Kosmider, C Récher, P Auberger, P Mayeux, D Bouscary, J-E Sarry, J Tamburini
Acute myeloid leukemia (AML) with the FLT3 internal tandem duplication (FLT3-ITD AML) accounts for 20-30% of AML cases. This subtype usually responds poorly to conventional therapies, and might become resistant to FLT3 tyrosine kinase inhibitors (TKIs) due to molecular bypass mechanisms. New therapeutic strategies focusing on resistance mechanisms are therefore urgently needed. Pim kinases are FLT3-ITD oncogenic targets that have been implicated in FLT3 TKI resistance. However, their precise biological function downstream of FLT3-ITD requires further investigation...
September 15, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28881451/validation-of-a-pediatric-early-warning-system-for-hospitalized-pediatric-oncology-patients-in-a-resource-limited-setting
#11
Asya Agulnik, Alejandra Méndez Aceituno, Lupe Nataly Mora Robles, Peter W Forbes, Dora Judith Soberanis Vasquez, Ricardo Mack, Federico Antillon-Klussmann, Monica Kleinman, Carlos Rodriguez-Galindo
BACKGROUND: Pediatric oncology patients are at high risk of clinical deterioration, particularly in hospitals with resource limitations. The performance of pediatric early warning systems (PEWS) to identify deterioration has not been assessed in these settings. This study evaluates the validity of PEWS to predict the need for unplanned transfer to the pediatric intensive care unit (PICU) among pediatric oncology patients in a resource-limited hospital. METHODS: A retrospective case-control study comparing the highest documented and corrected PEWS score before unplanned PICU transfer in pediatric oncology patients (129 cases) with matched controls (those not requiring PICU care) was performed...
December 15, 2017: Cancer
https://www.readbyqxmd.com/read/28845671/polyamide-polyamine-cryptand-as-dicarboxylate-receptor-dianion-binding-studies-in-the-solid-state-in-solution-and-in-the-gas-phase
#12
Sourav Chakraborty, Subrata Saha, Luís M P Lima, Ulrike Warzok, Sayan Sarkar, Bidyut Akhuli, Mandira Nandi, Somnath Bej, Nayarassery N Adarsh, Christoph A Schalley, Rita Delgado, Pradyut Ghosh
Polyamide-polyamine hybrid macrobicycle L is explored with respect to its ability to bind α,ω-dicarboxylate anions. Potentiometric studies of protonated L with the series of dianions from succinate (suc(2-)) through glutarate (glu(2-)), α-ketoglutarate (kglu(2-)), adipate (adi(2-)), pimelate (pim(2-)), suberate (sub(2-)), to azelate (aze(2-)) have shown adipate preference with association constant value of K = 4900 M(-1) in a H2O/DMSO (50:50 v/v) binary solvent mixture. The binding constant increases from glu(2-) to adi(2-) and then continuously decreases with the length of the anion chain...
September 12, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28753556/inflammation-and-stem-markers-association-to-pim1-pim2-kinase-induced-tumors-in-breast-and-uterus
#13
Manuel-Pedro Jiménez-García, Antonio Lucena-Cacace, María-José Robles-Frías, Irene Ferrer, Maja Narlik-Grassow, Carmen Blanco-Aparicio, Amancio Carnero
The PIM family of Ser/Thr kinase proteins has been implicated in tumorigenesis at different levels. PIM proteins are overexpressed in several tumor types and have been associated with chemoresistance. However, their role in hormone-dependent female tissues has not been explored, especially in the uterus, breast and ovary. We generated conditional transgenic mice with confined expression of human PIM1 or PIM2 genes in these tissues. We characterized the tumoral response to these genetic alterations corroborating their role as oncogenes since they induce hyperproliferation in all tissues and tumors in mammary gland and uterus...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28729093/pim-kinases-1-2-and-3-in-intracellular-lif-signaling-proliferation-and-apoptosis-in-trophoblastic-cells
#14
Stella Mary Photini, Wittaya Chaiwangyen, Maja Weber, Boodor Al-Kawlani, Rodolfo R Favaro, Udo Jeschke, Ekkehard Schleussner, Diana M Morales-Prieto, Udo R Markert
Proviral insertion in murine (PIM) lymphoma proteins are mainly regulated by the Janus Kinase/Signal Transducer Activator of Transcription (JAK/STAT) signaling pathway, which can be activated by members of the Interleukin-6 (IL-6) family, including Leukemia Inhibitory Factor (LIF). Aim of the study was to compare PIM1, PIM2 and PIM3 expression and potential cellular functions in human first and third trimester trophoblast cells, the immortalized first trimester extravillous trophoblast cell line HTR8/SVneo and the choriocarcinoma cell line JEG-3...
October 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28671859/being-underweight-is-an-independent-risk-factor-for-poor-outcomes-among-acutely-critically-ill-children
#15
Ming-Yin Chen, Yao-Jong Yang
BACKGROUND: Malnutrition is associated with impaired immune function; thus, nutrition status assessment is crucial in critical care medicine. We aimed to investigate the impact of being underweight or overweight on major sequelae and mortality among healthy children with an intensive care unit admission. METHODS: In this retrospective study, 282 patients aged 1 month to 18 years were enrolled on intensive care unit admission between 2011 and 2012. Children were excluded if they had underlying chronic diseases and were transferred to other hospitals or discharged against medical advice...
July 1, 2017: Nutrition in Clinical Practice
https://www.readbyqxmd.com/read/28561737/synergistic-interactions-with-pi3k-inhibition-that-induce-apoptosis
#16
Yaara Zwang, Oliver Jonas, Casandra Chen, Mikael L Rinne, John G Doench, Federica Piccioni, Li Tan, Hai-Tsang Huang, Jinhua Wang, Young Jin Ham, Joyce O'Connell, Patrick Bhola, Mihir Doshi, Matthew Whitman, Michael Cima, Anthony Letai, David E Root, Robert S Langer, Nathanael Gray, William C Hahn
Activating mutations involving the PI3K pathway occur frequently in human cancers. However, PI3K inhibitors primarily induce cell cycle arrest, leaving a significant reservoir of tumor cells that may acquire or exhibit resistance. We searched for genes that are required for the survival of PI3K mutant cancer cells in the presence of PI3K inhibition by conducting a genome scale shRNA-based apoptosis screen in a PIK3CA mutant human breast cancer cell. We identified 5 genes (PIM2, ZAK, TACC1, ZFR, ZNF565) whose suppression induced cell death upon PI3K inhibition...
May 31, 2017: ELife
https://www.readbyqxmd.com/read/28469150/serum-anion-gap-at-admission-as-a-predictor-of-mortality-in-the-pediatric-intensive-care-unit
#17
Min Jung Kim, Yoon Hee Kim, In Suk Sol, Soo Yeon Kim, Jong Deok Kim, Ha Yan Kim, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim
An accurate method to predict the mortality in the intensive care unit (ICU) patients has been required, especially in children. The aim of this study is to evaluate the value of serum anion gap (AG) for predicting mortality in pediatric ICU (PICU). We reviewed a data of 461 pediatric patients were collected on PICU admission. Corrected anion gap (cAG), the AG compensated for abnormal albumin levels, was significantly lower in survivors compared with nonsurvivors (p < 0.001). Multivariable logistic regression analysis identified the following variables as independent predictors of mortality; cAG (OR 1...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28383407/comparison-of-the-pediatric-risk-of-mortality-pediatric-index-of-mortality-and-pediatric-index-of-mortality-2-models-in-a-pediatric-intensive-care-unit-in-china-a-validation-study
#18
COMPARATIVE STUDY
Jun Qiu, Xiulan Lu, Kewei Wang, Yimin Zhu, Chao Zuo, Zhenghui Xiao
This study was designed with the aim of comparing the performances of the pediatric risk of mortality (PRISM), pediatric index of mortality (PIM), and revised version pediatric index of mortality 2 (PIM2) models in a pediatric intensive care unit (PICU) in China.A total of 852 critically ill pediatric patients were recruited in the study between January 1 and December 31, 2014. The variables required to calculate PRISM, PIM, and PIM2 were collected. Mode l performance was evaluated by assessing the calibration and discrimination...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28306719/chromosome-19q13-disruption-alters-expressions-of-cyp2a7-mia-and-mia-rab4b-lncrna-and-contributes-to-fap-like-phenotype-in-apc-mutation-negative-familial-colorectal-cancer-patients
#19
Lai Fun Thean, Yu Hui Wong, Michelle Lo, Carol Loi, Min Hoe Chew, Choong Leong Tang, Peh Yean Cheah
Familial adenomatous polyposis (FAP) is an autosomal-dominantly inherited form of colorectal cancer (CRC) caused by mutation in the adenomatous polyposis coli (APC) gene. Our ability to exhaustively screen for APC mutations identify microsatellite-stable and APC-mutation negative familial CRC patients, enabling us to search for novel genes. We performed genome-wide scan on two affected siblings of one family and 88 ethnicity- and gender-matched healthy controls to identify deletions shared by the siblings. Combined loss of heterozygosity, copy number and allelic-specific copy number analysis uncovered 5 shared deletions...
2017: PloS One
https://www.readbyqxmd.com/read/28190740/protective-efficacy-of-a-lipid-antigen-vaccine-in-a-guinea-pig-model-of-tuberculosis
#20
Gérald Larrouy-Maumus, Emilie Layre, Simon Clark, Jacques Prandi, Emma Rayner, Marco Lepore, Gennaro de Libero, Ann Williams, Germain Puzo, Martine Gilleron
The bacillus Calmette Guérin (BCG) vaccine, the only licensed vaccine against TB, displays partial and variable efficacy, thus making the exploitation of novel vaccination strategies a major priority. Most of the current vaccines in pre-clinical or clinical development are based on the induction of T cells recognizing protein antigens. However, a large number of T cells specific for mycobacterial lipids are induced during infection, suggesting that lipid-based vaccines might represent an important component of novel sub-unit vaccines...
March 7, 2017: Vaccine
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