Identification of differential PI3K pathway target dependencies in T-cell
Recommend Documents
Mar 10, 2016 - Combining AZD8931, a novel. EGFR/HER2/HER3 signalling inhibitor, with AZD5363 limits AKT inhibitor induced feedback and enhances.
Feb 11, 2016 - Abstract. This review is focused in PI3K's involvement in two widespread mental disorders: Autism and Schizophrenia. A large body of evidence ...
Methods: Gene Expression Omnibus database (GEO) datasets of pancreatic ... Results: Three GEO datasets, including 74 pancreatic cancer samples and 55 ...
Sep 15, 2013 - Like functional dependencies and matching dependencies [5], differential ..... If X → B holds, then the following DDs are not minimal:.
Dec 2, 2011 - Pennsylvania, John Morgan Building,. Room 195 ..... ski, C., Maisonpierre, P. C., and Yan- copoulos ... Dimmeler, S., Dernbach, E., and Zeiher,.
Patrick S. Ward and Craig B. Thompson. Calcium Signaling. Martin D. Bootman. Signaling Pathways in Cell Polarity. Luke Martin McCaffrey and Ian G. Macara.
Dec 2, 2011 - 2 Abramson Cancer Center, Perelman School of Medicine at the University ... College of Medicine, USA .... PTEN loss is also seen in advanced.
Aug 5, 2015 - rsp-4, and hog-1) (Ferguson and Horvitz 1985; Longman et al. 2001; ...... protein, POP-1, converts from repressor to activator as a result of Wnt-.
ABSTRACT The evolutionarily conserved Wnt/b-catenin signaling pathway plays a ... of target genes activated and inhibited by Wnt signaling, providing.
Aug 31, 2012 - **Temsirolimus: approved for the treatment of advanced renal cell carcinoma; Everolimus: approved for the treatment of progressive ...
causes tumour-susceptibility diseases such as Cowden disease. We used the Cre-loxP system to generate an endothelial cell-specific mutation of PTEN in mice.
distinct group of 20 cancer types. These proteins are AKTIP,. ARP1, BAD, GSK3A, GSK3B, MERTK-1, PIK3CA, PRR5,. PSTPIP2, PTEN, FOX1, RHEB, RPS6KB1, ...
Phosphoinositide 3-kinases (PI3Ks) are an evolutionarily conserved family of ... malignancy (7), and inhibitors associated with this pathway have been shown to ...
described in a group of autosomal dominant syndromes collectively referred to ..... Swisher E. Cowden Syndrome and the PTEN Hamartoma. Tumor Syndrome: ...
Oct 14, 2018 - leptinâdeficient ob/ob mice, indicating that leptin is required for .... ther dorsomorphin (5 mg kgâ1 dayâ1) or LY294002 (PI3K inhibitor;.
Jun 20, 2014 - Carlson GA, Lanier LM, Yuan LL, Ashe KH, Liao D: Tau ... Howes AL, Arthur JF, Zhang T, Miyamoto S, Adams JW, Dorn GW 2nd,. Woodcock EA ...
targets v-akt murine thymoma viral oncogene homolog (Akt) and mechanistic target of rapamycin .... controls cell growth
Jun 30, 2017 - of Adenosine A2B Receptor Inhibits. Endothelin-1-Induced Cardiac. Fibroblast Proliferation and α-Smooth. Muscle Actin Synthesis Through.
Sep 11, 2014 - The phosphoinositide 3-kinase. (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway plays an important ...
Mar 16, 2011 - HER2-related target drugs trastuzumab and lapatinib ... HER2-positive metastatic breast cancer patients were recruited into a global lapatinib.
*Departamento de Microbiologıa II, Facultad de Farmacia, Universidad Complutense de Madrid, Pza. de ... The mammalian signalling pathway involving class I PI3K (phos- ... Key words: c-Akt, phosphorylation, phosphoinositide 3-kinase.
Dec 8, 2014 - Medicine, Richmond, Virginia, United States of America, 5. Department of Internal Medicine, ... status of the urinary bladder in normal and diseased states following cyclophosphamide ..... Bar 5200 mm. n53. *, p,0.05 vs vehicle ...
Suppression of the PI3K Pathway In Vivo ... - CiteSeerX › publication › fulltext › publication › fulltextby Z Qiao · 2014 · Cited by 13 · Related articlesDec 8, 2014 — erythematous swelling and hemorrhage of the bladder [1, 2, 3, 4, 5]. Dysfunctio
Identification of differential PI3K pathway target dependencies in T-cell
Identification of differential PI3K pathway target dependencies in T-cell acute lymphoblastic leukemia through a large cancer cell panel screen Supplementary Materials
Supplementary Figure S1: A screen targeting multiple nodes of the PI3K pathway identify their differential requirements in T-ALL. A panel of T-ALL cell lines were treated with a dose response of different PI3K pathway inhibitors. Live cell
number was assessed after five days using a sytox green endpoint. (A–G) Exemplar mean ± S.E.M. dose response curves for the inhibitors across the T-ALL cell line panel. Zero activity represents the initial seeding density on the day of dosing (Day 0) (n = 2). (h) mean ± S.E.M. growth inhibition following rapamycin treatment across the cell line panel (n = 2). S.E.M = standard error of the mean.
Supplementary Figure S2: PI3K intra-pathway combinations induce additive but not synergistic effects in T-ALL.
A panel of T-ALL cell lines were treated with a dose response of different PI3K pathway inhibitors in a 8 × 8 dose response matrix. Live cell number was assessed after five days using a sytox green endpoint and synergy scores were generated using the Loewe model of additivity. Representative dose matrices and synergy scores from one experiment from the SUPT1 cell line. Fitted data: dose matrix representing percent growth inhibition values. Model Loewe: Loewe model of additivity calculated from the monotherapy dose response curves. Excess Loewe: Excess heatmap (synergy) calculated by subtracting the Loewe model of additivity data from the fitted data. Calculated synergy scores for each cell line are shown in the far right column.
Supplementary Figure S3: PI3K intra-pathway combinations induce additive but not synergistic effects in T-ALL.
A panel of T-ALL cell lines were treated with a dose response of different PI3K pathway inhibitors in a 8 × 8 dose response matrix. Live cell number was assessed after 5 days using a sytox green endpoint and synergy scores were generated using the Loewe model of additivity. (A) Exemplar mean dose response curves for the inhibitor combinations in the SUPT1 cell line. 100% activity represents the initial seeding density on the day of dosing (Day 0) (n = 2). (B) Comparison of mean synergy scores for the PI3K intra-pathway combinations across the T-ALL cell lines (n = 2). S.E.M = standard error of the mean.
Supplementary Table 1: Sanger cancer cell line pharmacology results Cell Line
blood/lymph blood/lymph blood/lymph bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone bone brain brain brain brain brain brain brain
brain brain breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast breast
nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) nervous system (PNS) oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus oesophagus
Supplementary Table 3: Synergy scores from the T-ALL PI3K intra-pathway combination screen AZD2014_AZD5363 AZD8186_AZD2014 AZD8186_AZD5363 AZD8186_AZD8835 AZD8835_AZD2014 AZD8835_AZD5363
CCRFCEM −2.3 −0.93 0.82 0.09 1.69 −0.64
JRT3T35 1.46 0.13 0.12 0 −0.32 −0.19
JURKAT 1.89 2.1 −0.26 0.54 −0.89 −1.28
MOLT4 −4.38 −0.04 −2.04 1.19 −1.01 −3.36
PF382 −0.55 −0.16 −0.29 0.3 0.03 −0.11
RPMI8402 −0.44 0.84 −0.85 −0.62 −0.42 −1.54
SUPT1 1.24 −0.7 −3.17 −3.61 −0.18 −3.32
A panel of T-ALL cell lines were treated with a dose response of different PI3K pathway inhibitors in a 8 × 8 dose response matrix. Live cell number was assessed after 5 days using a sytox green endpoint and synergy scores were generated using the Loewe model of additivity. Values represent the mean synergy score for each combination indicated (n = 2).
Supplementary Table 4: PI3K enzyme and cell IC50 (μM) data for PI3K compounds Enzyme Assay
