MAP2K2 Antibody Cat

Total Page:16

File Type:pdf, Size:1020Kb

MAP2K2 Antibody Cat MAP2K2 Antibody Cat. No.: 63-309 MAP2K2 Antibody Fluorescent image of U251 cell stained with MAP2K2 Antibody (T394). U251 cells were fixed with 4% PFA (20 min), permeabilized with Triton X-100 (0.1%, 10 min), then Formalin-fixed and paraffin-embedded human prostata incubated with MAP2K2 primary antibody (1:25). For carcinoma tissue reacted with MAP2K2 Antibody (T394) , secondary antibody, Alexa Fluor 488 conjugated donkey which was peroxidase-conjugated to the secondary anti-rabbit antibody (green) was used (1:400).Cytoplasmic antibody, followed by DAB staining. actin was counterstained with Alexa Fluor 555 (red) conjugated Phalloidin (7units/ml). MAP2K2 immunoreactivity is localized to Cytoplasm significantly. Specifications HOST SPECIES: Rabbit SPECIES REACTIVITY: Human This MAP2K2 antibody is generated from rabbits immunized with a KLH conjugated IMMUNOGEN: synthetic peptide between 372-400 amino acids from human MAP2K2. TESTED APPLICATIONS: IF, IHC-P, WB September 26, 2021 1 https://www.prosci-inc.com/map2k2-antibody-63-309.html For WB starting dilution is: 1:1000 APPLICATIONS: For IF starting dilution is: 1:10~50 For IHC-P starting dilution is: 1:10~50 PREDICTED MOLECULAR 44 kDa WEIGHT: Properties This antibody is purified through a protein A column, followed by peptide affinity PURIFICATION: purification. CLONALITY: Polyclonal ISOTYPE: Rabbit Ig CONJUGATE: Unconjugated PHYSICAL STATE: Liquid BUFFER: Supplied in PBS with 0.09% (W/V) sodium azide. CONCENTRATION: batch dependent Store at 4˚C for three months and -20˚C, stable for up to one year. As with all antibodies STORAGE CONDITIONS: care should be taken to avoid repeated freeze thaw cycles. Antibodies should not be exposed to prolonged high temperatures. Additional Info OFFICIAL SYMBOL: MAP2K2 Dual specificity mitogen-activated protein kinase kinase 2, MAP kinase kinase 2, MAPKK 2, ALTERNATE NAMES: ERK activator kinase 2, MAPK/ERK kinase 2, MEK 2, MAP2K2, MEK2, MKK2, PRKMK2 ACCESSION NO.: P36507 PROTEIN GI NO.: 547915 GENE ID: 5605 USER NOTE: Optimal dilutions for each application to be determined by the researcher. Background and References MAP2K2 is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK2/ERK3. The activation of this BACKGROUND: kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases. The inhibition or degradation of this kinase is found to be involved in the pathogenesis of Yersinia and anthrax. September 26, 2021 2 https://www.prosci-inc.com/map2k2-antibody-63-309.html REFERENCES: 1) Burroughs, K.D., et al., Mol. Cancer Res. 1(4):312-322 (2003). 2) Tran, H., et al., Mol. Cell. Biol. 23(20):7177-7188 (2003). 3) Li, S.P., et al., Cancer Res. 63(13):3473-3477 (2003). 4) Li, Y., et al., J. Biol. Chem. 278(16):13663-13671 (2003). ANTIBODIES FOR RESEARCH USE ONLY. For additional information, visit ProSci's Terms & Conditions Page. September 26, 2021 3 https://www.prosci-inc.com/map2k2-antibody-63-309.html.
Recommended publications
  • Gene Symbol Gene Description ACVR1B Activin a Receptor, Type IB
    Table S1. Kinase clones included in human kinase cDNA library for yeast two-hybrid screening Gene Symbol Gene Description ACVR1B activin A receptor, type IB ADCK2 aarF domain containing kinase 2 ADCK4 aarF domain containing kinase 4 AGK multiple substrate lipid kinase;MULK AK1 adenylate kinase 1 AK3 adenylate kinase 3 like 1 AK3L1 adenylate kinase 3 ALDH18A1 aldehyde dehydrogenase 18 family, member A1;ALDH18A1 ALK anaplastic lymphoma kinase (Ki-1) ALPK1 alpha-kinase 1 ALPK2 alpha-kinase 2 AMHR2 anti-Mullerian hormone receptor, type II ARAF v-raf murine sarcoma 3611 viral oncogene homolog 1 ARSG arylsulfatase G;ARSG AURKB aurora kinase B AURKC aurora kinase C BCKDK branched chain alpha-ketoacid dehydrogenase kinase BMPR1A bone morphogenetic protein receptor, type IA BMPR2 bone morphogenetic protein receptor, type II (serine/threonine kinase) BRAF v-raf murine sarcoma viral oncogene homolog B1 BRD3 bromodomain containing 3 BRD4 bromodomain containing 4 BTK Bruton agammaglobulinemia tyrosine kinase BUB1 BUB1 budding uninhibited by benzimidazoles 1 homolog (yeast) BUB1B BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast) C9orf98 chromosome 9 open reading frame 98;C9orf98 CABC1 chaperone, ABC1 activity of bc1 complex like (S. pombe) CALM1 calmodulin 1 (phosphorylase kinase, delta) CALM2 calmodulin 2 (phosphorylase kinase, delta) CALM3 calmodulin 3 (phosphorylase kinase, delta) CAMK1 calcium/calmodulin-dependent protein kinase I CAMK2A calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha CAMK2B calcium/calmodulin-dependent
    [Show full text]
  • Recombinant MAP2K2 Protein
    Recombinant MAP2K2 protein Catalog No: 81332, 81632 Quantity: 20, 1000 µg Expressed In: Baculovirus Concentration: 0.3 µg/µl Source: Human Buffer Contents: Recombinant MAP2K2 protein is supplied in 25 mM HEPES-NaOH pH 7.5, 300 mM NaCl, 10% glycerol, 0.04% Triton X-100, and 0.5 mM TCEP. Background: MAP2K2 (Mitogen-Activated Protein Kinase Kinase Kinase 2) is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase plays a critical role in mitogen growth factor signal transduction. It phosphorylates and activates MAPK1/ERK2 and MAPK2/ERK3. The activation of this kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases. Mutations in this gene cause cardiofaciocutaneous syndrome (CFC syndrome), a disease characterized by heart defects, cognitive disability, and distinctive facial features similar to those found in Noonan syndrome. Protein Details: Recombinant MAP2K2 protein was expressed in baculovirus expression system as the full length protein (accession number NP_109587.1) with a N-terminal FLAG Tag. The molecular weight of the protein is 45.7 kDa. Application Notes: This product was manufactured as described in Protein Details. Where possible, Active Motif has developed functional or activity assays for Recombinant MAP2K2 protein gel recombinant proteins. Additional characterization such as enzyme kinetic activity 10% SDS-PAGE with Coomassie blue assays, inhibitor screening or other biological activity assays may not have been staining MW: 45.7 kDa performed for every product. All available data for a given product is shown on the lot- Purity: >90% specific Technical Data Sheet. Storage and Guarantee: Recombinant proteins in solution are temperature sensitive and must be stored at -80°C to prevent degradation.
    [Show full text]
  • Map2k1 and Map2k2 Genes Contribute to the Normal Development of Syncytiotrophoblasts During Placentation
    RESEARCH ARTICLE 1363 Development 136, 1363-1374 (2009) doi:10.1242/dev.031872 Map2k1 and Map2k2 genes contribute to the normal development of syncytiotrophoblasts during placentation Valérie Nadeau*, Stéphanie Guillemette*, Louis-François Bélanger, Olivier Jacob, Sophie Roy and Jean Charron† The mammalian genome contains two ERK/MAP kinase kinase genes, Map2k1 and Map2k2, which encode dual-specificity kinases responsible for ERK/MAP kinase activation. In the mouse, loss of Map2k1 function causes embryonic lethality, whereas Map2k2 mutants survive with a normal lifespan, suggesting that Map2k1 masks the phenotype due to the Map2k2 mutation. To uncover the specific function of MAP2K2 and the threshold requirement of MAP2K proteins during embryo formation, we have successively ablated the Map2k gene functions. We report here that Map2k2 haploinsufficiency affects the normal development of placenta in the absence of one Map2k1 allele. Most Map2k1+/–Map2k2+/– embryos die during gestation because of placenta defects restricted to extra-embryonic tissues. The impaired viability of Map2k1+/–Map2k2+/– embryos can be rescued when the Map2k1 deletion is restricted to the embryonic tissues. The severity of the placenta phenotype is dependent on the number of Map2k mutant alleles, the deletion of the Map2k1 allele being more deleterious. Moreover, the deletion of one or both Map2k2 alleles in the context of one null Map2k1 allele leads to the formation of multinucleated trophoblast giant (MTG) cells. Genetic experiments indicate that these structures are derived from Gcm1-expressing syncytiotrophoblasts (SynT), which are affected in their ability to form the uniform SynT layer II lining the maternal sinuses. Thus, even though Map2k1 plays a predominant role, these results enlighten the function of Map2k2 in placenta development.
    [Show full text]
  • Type of the Paper (Article
    Supplementary Materials: Identification of Linkages between EDCs in Personal Care Products and Breast Cancer through Data Integration Combined with Gene Network Analysis Hyeri Jeong 1,2, Jongwoon Kim 1,2,* and Youngjun Kim 1,2 Table S1. Interacting genes and their network types of the 27 common related genes between four selected EDCs and ER positive breast cancer based on GeneMANIA network analysis. Degree Centrality Gene Symbol Official Full Name Interacting Gene Networks * AKT1 2 AR 2, 3, 5, 6 BRCA1 2, 3 CASP8 7 EP300 2, 3 ERBB2 2 13 ESR1 Estrogen receptor 1 HDAC5 2 NCOA1 2, 3 NCOA7 2, 3 PIK3CA 2, 3 SLC10A1 1 SMO 1 TP53 2 AKT1 1 AR 2, 7 BCL6 2, 3 BRCA1 2, 3 CASP8 2 EP300 2, 7 12 TP53 Tumor protein p53 ERBB2 1 ESR1 2 HDAC5 2 MTOR 2 NCOA1 2 SMO 1 AKT1 1, 3 AR 2, 3 BRCA1 2 CYP1A1 1 DUSP10 1, 7 Nuclear receptor EP300 1, 2, 3, 6 12 NCOA1 coactivator 1 ESR1 2, 3 HDAC5 7 KLHL24 1 NCOA7 7 PTCH1 7 TP53 2 AR 2 BRCA1 2 EP300 2 ERBB2 1 ESR1 2 AKT serine/threonine 11 AKT1 MAP2K2 1 kinase 1 MTOR 2, 3, 5, 4 NCOA1 1, 3 PIK3CA 2, 3 SMO 3 TP53 1 Int. J. Environ. Res. Public Health 2017, 14 S2 of S7 Table S1. Cont. Degree Centrality Gene Symbol Official Full Name Interacting Gene Networks * ABCG1 7 APOB 1, 7 EP300 2, 7 GABRR1 7 HDAC5 2, 3 11 BCL6 B-cell CLL/lymphoma 6 KLHL24 1 PIK3CA 1 PTCH1 7 SLC10A1 1 SMO 2 TP53 2, 3 AKT1 2 BRCA1 2, 3 CASP8 1, 3, 4 EP300 2 ESR1 2, 3, 5, 6 10 AR Androgen receptor NCOA1 2, 3 PIK3CA 3 SLC10A1 1 SMO 1 TP53 2, 4 AKT1 2 AR 2 BCL6 2, 7 BRCA1 2, 7 E1A binding protein 9 EP300 ESR1 2, 3 p300 KLHL24 1 NCOA1 1, 2, 3, 6 PIK3CA 1 TP53 2, 7 ABCG1 1 AKT1 2, 3 AR 3 Phosphatidylinositol- BCL6 1 4,5-bisphosphate 9 PIK3CA EP300 1 3-kinase catalytic ERBB2 3 subunit alpha ESR1 2, 3 KLHL24 1 MTOR 3, 6 AR 1 AKT1 3 BCL6 2 Smoothened, frizzled CYP1A1 1 8 SMO class receptor ESR1 1 ERBB2 1 PTCH1 2, 3 TP53 1 AKT1 2 AR 2, 3 EP300 2, 7 BRCA1, DNA 7 BRCA1 ESR1 2, 3 repair associated MTOR 2 NCOA1 2 TP53 2, 3 AR 2, 3, 4 CYP1A1 1 ESR1 7 7 CASP8 Caspase 8 GABRA6 7 KLHL24 7 MTOR 7 TP53 2 Int.
    [Show full text]
  • Personalized Prediction of Acquired Resistance to EGFR-Targeted Inhibitors Using a Pathway-Based Machine Learning Approach
    Cancers 2019, 11, x S1 of S9 Supplementary Materials: Personalized Prediction of Acquired Resistance to EGFR-Targeted Inhibitors Using a Pathway-Based Machine Learning Approach Young Rae Kim, Yong Wan Kim, Suh Eun Lee, Hye Won Yang and Sung Young Kim Table S1. Characteristics of individual studies. Sample Size Origin of Cancer Drug Dataset Platform S AR (Cell Lines) Lung cancer Agilent-014850 Whole Human GSE34228 26 26 (PC9) Genome Microarray 4x44K Gefitinib Epidermoid carcinoma Affymetrix Human Genome U133 GSE10696 3 3 (A431) Plus 2.0 Head and neck cancer Illumina HumanHT-12 V4.0 GSE62061 12 12 (Cal-27, SSC-25, FaDu, expression beadchip SQ20B) Erlotinib Head and neck cancer Illumina HumanHT-12 V4.0 GSE49135 3 3 (HN5) expression beadchip Lung cancer (HCC827, Illumina HumanHT-12 V3.0 GSE38310 3 6 ER3, T15-2) expression beadchip Lung cancer Illumina HumanHT-12 V3.0 GSE62504 1 2 (HCC827) expression beadchip Afatinib Lung cancer * Illumina HumanHT-12 V4.0 GSE75468 1 3 (HCC827) expression beadchip Head and neck cancer Affymetrix Human Genome U133 Cetuximab GSE21483 3 3 (SCC1) Plus 2.0 Array GEO, gene expression omnibus; GSE, gene expression series; S, sensitive; AR, acquired EGFR-TKI resistant; * Lung Cancer Cells Derived from Tumor Xenograft Model. Table S2. The performances of four penalized regression models. Model ACC precision recall F1 MCC AUROC BRIER Ridge 0.889 0.852 0.958 0.902 0.782 0.964 0.129 Lasso 0.944 0.957 0.938 0.947 0.889 0.991 0.042 Elastic Net 0.978 0.979 0.979 0.979 0.955 0.999 0.023 EPSGO Elastic Net 0.989 1.000 0.979 0.989 0.978 1.000 0.018 AUROC, area under curve of receiver operating characteristic; ACC, accuracy; MCC, Matthews correlation coefficient; EPSGO, Efficient Parameter Selection via Global Optimization algorithm.
    [Show full text]
  • Phosphorylation Sites in Protein Kinases and Phosphatases Regulated by Formyl Peptide Receptor 2 Signaling
    International Journal of Molecular Sciences Review Phosphorylation Sites in Protein Kinases and Phosphatases Regulated by Formyl Peptide Receptor 2 Signaling Maria Carmela Annunziata 1, Melania Parisi 1, Gabriella Esposito 2 , Gabriella Fabbrocini 1, Rosario Ammendola 2 and Fabio Cattaneo 2,* 1 Department of Clinical Medicine and Surgery, School of Medicine, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy; [email protected] (M.C.A.); [email protected] (M.P.); [email protected] (G.F.) 2 Department of Molecular Medicine and Medical Biotechnology, School of Medicine,, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy; [email protected] (G.E.); [email protected] (R.A.) * Correspondence: [email protected]; Fax: +39-081-7464-359 Received: 5 May 2020; Accepted: 25 May 2020; Published: 27 May 2020 Abstract: FPR1, FPR2, and FPR3 are members of Formyl Peptides Receptors (FPRs) family belonging to the GPCR superfamily. FPR2 is a low affinity receptor for formyl peptides and it is considered the most promiscuous member of this family. Intracellular signaling cascades triggered by FPRs include the activation of different protein kinases and phosphatase, as well as tyrosine kinase receptors transactivation. Protein kinases and phosphatases act coordinately and any impairment of their activation or regulation represents one of the most common causes of several human diseases. Several phospho-sites has been identified in protein kinases and phosphatases, whose role may be to expand the repertoire of molecular mechanisms of regulation or may be necessary for fine-tuning of switch properties. We previously performed a phospho-proteomic analysis in FPR2-stimulated cells that revealed, among other things, not yet identified phospho-sites on six protein kinases and one protein phosphatase.
    [Show full text]
  • Characterization of the Small Molecule Kinase Inhibitor SU11248 (Sunitinib/ SUTENT in Vitro and in Vivo
    TECHNISCHE UNIVERSITÄT MÜNCHEN Lehrstuhl für Genetik Characterization of the Small Molecule Kinase Inhibitor SU11248 (Sunitinib/ SUTENT in vitro and in vivo - Towards Response Prediction in Cancer Therapy with Kinase Inhibitors Michaela Bairlein Vollständiger Abdruck der von der Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigten Dissertation. Vorsitzender: Univ. -Prof. Dr. K. Schneitz Prüfer der Dissertation: 1. Univ.-Prof. Dr. A. Gierl 2. Hon.-Prof. Dr. h.c. A. Ullrich (Eberhard-Karls-Universität Tübingen) 3. Univ.-Prof. A. Schnieke, Ph.D. Die Dissertation wurde am 07.01.2010 bei der Technischen Universität München eingereicht und durch die Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt am 19.04.2010 angenommen. FOR MY PARENTS 1 Contents 2 Summary ................................................................................................................................................................... 5 3 Zusammenfassung .................................................................................................................................................... 6 4 Introduction .............................................................................................................................................................. 8 4.1 Cancer ..............................................................................................................................................................
    [Show full text]
  • Activation of Diverse Signalling Pathways by Oncogenic PIK3CA Mutations
    ARTICLE Received 14 Feb 2014 | Accepted 12 Aug 2014 | Published 23 Sep 2014 DOI: 10.1038/ncomms5961 Activation of diverse signalling pathways by oncogenic PIK3CA mutations Xinyan Wu1, Santosh Renuse2,3, Nandini A. Sahasrabuddhe2,4, Muhammad Saddiq Zahari1, Raghothama Chaerkady1, Min-Sik Kim1, Raja S. Nirujogi2, Morassa Mohseni1, Praveen Kumar2,4, Rajesh Raju2, Jun Zhong1, Jian Yang5, Johnathan Neiswinger6, Jun-Seop Jeong6, Robert Newman6, Maureen A. Powers7, Babu Lal Somani2, Edward Gabrielson8, Saraswati Sukumar9, Vered Stearns9, Jiang Qian10, Heng Zhu6, Bert Vogelstein5, Ben Ho Park9 & Akhilesh Pandey1,8,9 The PIK3CA gene is frequently mutated in human cancers. Here we carry out a SILAC-based quantitative phosphoproteomic analysis using isogenic knockin cell lines containing ‘driver’ oncogenic mutations of PIK3CA to dissect the signalling mechanisms responsible for oncogenic phenotypes induced by mutant PIK3CA. From 8,075 unique phosphopeptides identified, we observe that aberrant activation of PI3K pathway leads to increased phosphorylation of a surprisingly wide variety of kinases and downstream signalling networks. Here, by integrating phosphoproteomic data with human protein microarray-based AKT1 kinase assays, we discover and validate six novel AKT1 substrates, including cortactin. Through mutagenesis studies, we demonstrate that phosphorylation of cortactin by AKT1 is important for mutant PI3K-enhanced cell migration and invasion. Our study describes a quantitative and global approach for identifying mutation-specific signalling events and for discovering novel signalling molecules as readouts of pathway activation or potential therapeutic targets. 1 McKusick-Nathans Institute of Genetic Medicine and Department of Biological Chemistry, Johns Hopkins University School of Medicine, 733 North Broadway, BRB 527, Baltimore, Maryland 21205, USA.
    [Show full text]
  • Protein-Protein Interactions Among Signaling Pathways May Become New Therapeutic Targets in Liver Cancer (Review)
    ONCOLOGY REPORTS 35: 625-638, 2016 Protein-protein interactions among signaling pathways may become new therapeutic targets in liver cancer (Review) XIAO ZHANG1*, YULAN WANG1*, Jiayi WANG1,2 and FENYONG SUN1 1Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072; 2Translation Medicine of High Institute, Tongji University, Shanghai 200092, P.R. China Received May 29, 2015; Accepted July 6, 2015 DOI: 10.3892/or.2015.4464 Abstract. Numerous signaling pathways have been shown to be 1. Introduction dysregulated in liver cancer. In addition, some protein-protein interactions are prerequisite for the uncontrolled activation Liver cancer is the sixth most common cancer and the second or inhibition of these signaling pathways. For instance, in most common cause of cancer-associated mortality world- the PI3K/AKT signaling pathway, protein AKT binds with wide (1). Approximately 75% of all primary liver cancer types a number of proteins such as mTOR, FOXO1 and MDM2 to are hepatocellular carcinoma (HCC) that formed from liver play an oncogenic role in liver cancer. The aim of the present cells. Liver cancer can be formed from other structures in review was to focus on a series of important protein-protein the liver such as bile duct, blood vessels and immune cells. interactions that can serve as potential therapeutic targets Secondary liver cancer is a result of metastasis of cancer from in liver cancer among certain important pro-carcinogenic other body sites into the liver. The major cause of primary liver signaling pathways. The strategies of how to investigate and cancer is viral infection with either hepatitis C virus (HCV) analyze the protein-protein interactions are also included in or hepatitis B virus (HBV), which leads to massive inflamma- this review.
    [Show full text]
  • Inhibition of ERK 1/2 Kinases Prevents Tendon Matrix Breakdown Ulrich Blache1,2,3, Stefania L
    www.nature.com/scientificreports OPEN Inhibition of ERK 1/2 kinases prevents tendon matrix breakdown Ulrich Blache1,2,3, Stefania L. Wunderli1,2,3, Amro A. Hussien1,2, Tino Stauber1,2, Gabriel Flückiger1,2, Maja Bollhalder1,2, Barbara Niederöst1,2, Sandro F. Fucentese1 & Jess G. Snedeker1,2* Tendon extracellular matrix (ECM) mechanical unloading results in tissue degradation and breakdown, with niche-dependent cellular stress directing proteolytic degradation of tendon. Here, we show that the extracellular-signal regulated kinase (ERK) pathway is central in tendon degradation of load-deprived tissue explants. We show that ERK 1/2 are highly phosphorylated in mechanically unloaded tendon fascicles in a vascular niche-dependent manner. Pharmacological inhibition of ERK 1/2 abolishes the induction of ECM catabolic gene expression (MMPs) and fully prevents loss of mechanical properties. Moreover, ERK 1/2 inhibition in unloaded tendon fascicles suppresses features of pathological tissue remodeling such as collagen type 3 matrix switch and the induction of the pro-fbrotic cytokine interleukin 11. This work demonstrates ERK signaling as a central checkpoint to trigger tendon matrix degradation and remodeling using load-deprived tissue explants. Tendon is a musculoskeletal tissue that transmits muscle force to bone. To accomplish its biomechanical function, tendon tissues adopt a specialized extracellular matrix (ECM) structure1. Te load-bearing tendon compart- ment consists of highly aligned collagen-rich fascicles that are interspersed with tendon stromal cells. Tendon is a mechanosensitive tissue whereby physiological mechanical loading is vital for maintaining tendon archi- tecture and homeostasis2. Mechanical unloading of the tissue, for instance following tendon rupture or more localized micro trauma, leads to proteolytic breakdown of the tissue with severe deterioration of both structural and mechanical properties3–5.
    [Show full text]
  • Hypoxia Transcriptomic Modifications Induced by Proton Irradiation In
    Journal of Personalized Medicine Article Hypoxia Transcriptomic Modifications Induced by Proton Irradiation in U87 Glioblastoma Multiforme Cell Line Valentina Bravatà 1,2,† , Walter Tinganelli 3,†, Francesco P. Cammarata 1,2,* , Luigi Minafra 1,2,* , Marco Calvaruso 1,2 , Olga Sokol 3 , Giada Petringa 2, Giuseppe A.P. Cirrone 2, Emanuele Scifoni 4 , Giusi I. Forte 1,2,‡ and Giorgio Russo 1,2,‡ 1 Institute of Molecular Bioimaging and Physiology–National Research Council (IBFM-CNR), 90015 Cefalù, Italy; [email protected] (V.B.); [email protected] (M.C.); [email protected] (G.I.F.); [email protected] (G.R.) 2 Laboratori Nazionali del SUD, Istituto Nazionale di Fisica Nucleare (LNS-INFN), 95100 Catania, Italy; [email protected] (G.P.); [email protected] (G.A.P.C.) 3 Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung GmbH, 64291 Darmstadt, Germany; [email protected] (W.T.); [email protected] (O.S.) 4 Trento Institute for Fundamental Physics and Applications (TIFPA), Istituto Nazionale Fisica Nucleare (INFN), 38123 Trento, Italy; [email protected] * Correspondence: [email protected] (F.P.C.); [email protected] (L.M.) † These authors contributed equally to this work. ‡ These authors contributed equally to this work. Abstract: In Glioblastoma Multiforme (GBM), hypoxia is associated with radioresistance and poor prognosis. Since standard GBM treatments are not always effective, new strategies are needed Citation: Bravatà, V.; Tinganelli, W.; to overcome resistance to therapeutic treatments, including radiotherapy (RT). Our study aims Cammarata, F.P.; Minafra, L.; to shed light on the biomarker network involved in a hypoxic (0.2% oxygen) GBM cell line that Calvaruso, M.; Sokol, O.; Petringa, G.; is radioresistant after proton therapy (PT).
    [Show full text]
  • The Curing AI for Precision Medicine
    The Curing AI for Precision Medicine Hoifung Poon 1 Medicine Today Is Imprecise Top 20 drugs 80% non-responders Wasted 1/3 health spending $750 billion / year 2 Disruption 1: Big Data 2009 2013: 40% 93% 3 Disruption 2: Pay-for-Performance Goal: 75% by 2020 4 Vemurafenib on BRAF-V600 Melanoma Before Treatment 15 Weeks 5 Vemurafenib on BRAF-V600 Melanoma Before Treatment 15 Weeks 23 Weeks 6 Why We Haven’t Solved Precision Medicine? … ATTCGGATATTTAAGGC … … ATTCGGGTATTTAAGCC … … ATTCGGATATTTAAGGC … … ATTCGGGTATTTAAGCC … … ATTCGGATATTTAAGGC … … ATTCGGGTATTTAAGCC … High-Throughput Data Discovery Bottleneck #1: Knowledge Bottleneck #2: Reasoning AI is the key to overcome these bottlenecks 7 Use Case: Molecular Tumor Board 8 www.ucsf.edu/news/2014/11/120451/bridging-gap-precision-medicine Use Case: Molecular Tumor Board Problem: Hard to scale U.S. 2015: 1.6 million new cases, 600K deaths 902 cancer hospitals Memorial Sloan Kettering 2016: Sequence: Tens of thousand Board can review: A few hundred Wanted: Decision support for cancer precision medicine 9 First-Generation Molecular Tumor Board Knowledge bottleneck E.g., given a tumor sequence, determine: What genes and mutations are important What drugs might be applicable Can do manually but hard to scale 10 Next-Generation Molecular Tumor Board Reasoning bottleneck E.g., personalize drug combinations Can’t do manually, ever 11 Big Medical Data Decision Support Precision Medicine Machine Predict Reading Drug Combo 12 13 PubMed 26 millions abstracts Two new abstracts every minute Adds over one million every year 14 Machine Reading PMID: 123 … VDR+ binds to SMAD3 to form … PMID: 456 Knowledge … JUN expression Base is induced by SMAD3/4 … …… 15 Machine Reading Involvement of p70(S6)-kinase activation in IL-10 up-regulation in human monocytes by gp41 envelope protein of human immunodeficiency virus type 1 ..
    [Show full text]