Array to Receive $1,000,000 Milestone Payment From AstraZeneca -. BOULDER, Colo., April 10 /PRNewswire-FirstCall/ -- Array BioPharma Inc. (Nasdaq: ARRY) and AstraZeneca AB selected a third compound for their small molecule MEK anti-cancer program, triggering a $1 million milestone payment from AstraZeneca to Array. The second compound was selected in January 2006, which also paid a $1 million milestone to Array. In December 2003, Array partnered the oncology portion of its MEK program, including its lead compound, ARRY-142886 (AZD6244), for co-development and commercialization with AstraZeneca. At that time, Array and AstraZeneca established a collaboration for research and development of additional clinical candidates.. About MEK Inhibition. MEK is a critical enzyme at the intersection of several biological pathways, which regulates cell proliferation and survival as part of the Ras/Raf/MEK/ERK pathway. Constitutive activation of the Ras/Raf/MEK/ERK pathway has been implicated in many cancers, ...
Sigma-Aldrich offers abstracts and full-text articles by [Qi Zhang, Liang Wei, Hongchuan Yang, Wanqi Yang, Qingyu Yang, Zhuofan Zhang, Kailang Wu, Jianguo Wu].
RAF activation and inhibition. A promising approach is to target the RAF protein, a crucial intermediary in cell signal transmission. Because of its preponderant role in tumor formation, pharmaceutical companies have invested considerable effort to identify molecules that inhibit RAF enzymatic activity. Although there has been some clinical success, it turns out that on the whole these inhibitors have the unfortunate habit of stimulating the growth of cancer cells instead of reducing it; a paradox that has puzzled an entire community of investigators and clinicians.. IRIC investigators recently discovered new elements to explain this paradox by showing how RAF activation requires three interconnected events involving RAF and RAS and how the drugs currently available unexpectedly stimulate some of those interactions. This new understanding at the molecular level results in being able to propose characteristics that the new generation of RAF inhibitors must possess to constitute effective cancer ...
Inhibition of the Raf/MEK/ERK pathway is sufficient to partially restore CD24 mRNA but not protein expression in RasV12 cells. (A-C) RasV12 cells were treated
Melanomas are well known to be "addicted" to signaling through the Ras/Raf/MEK/ERK MAPK pathway, with the majority of melanoma driver oncogenes reported thus far known to activate this signal transduction cascade. Even among those melanomas lacking the obvious MAPK pathway activators such as oncogenic BRAF and NRAS, constitutive levels of MEK/ERK signaling are still required. It therefore comes as little surprise that melanomas possess multiple means to reactivate MAPK signaling and that many of the acquired BRAF inhibitor resistance mechanisms reported so far, including most of those that have been convincingly validated in clinical specimens, are MAPK dependent. The fact that near total MAPK pathway blockade is required for BRAF inhibitor efficacy in patients with melanoma suggests that even modest increases in the level of signaling through the Ras/Raf/MEK/ERK pathway are sufficient to convey drug resistance, and there is now experimental evidence to support this contention (3).. In this ...
PROTOCOL SUMMARY:. Phase 1: Patients with non-hematologic malignancies that are recurrent, progressive, or refractory after standard up-front therapy receiving MEK162 will define the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and toxicity profile.. Phase 2: Patients with recurrent or progressive tumors signaling through the ras/raf pathway after standard up-front therapy will be treated in three strata to define the activity of MEK162.. Stratum 1: Pediatric patients with recurrent or progressive low-grade glioma (LGG) characterized by a BRAF truncated fusion (KIAA1549 and similar translocations).. Stratum 2: Pediatric patients with neurofibromatosis type 1 (NF1) and recurrent or progressive LGG.. Stratum 3: Pediatric patients with recurrent or progressive tumors thought to involve the ras/raf/MAP pathway but not included in strata 1 or 2. This includes any LGG not included in strata 1 or 2 (i.e., any LGG without a BRAF truncated fusion in a patient without NF1), any tumor ...
There is a significant unmet medical need for the development of effective therapies that can stabilize or slow the progression of solid tumors. In this article, we identify BAY 43-9006 as a novel, orally active, dual action RAF kinase and VEGFR inhibitor that targets tumor cell proliferation and tumor angiogenesis. Biochemical assays described here demonstrated that BAY 43-9006 inhibits Raf-1 (IC50, 6 nmol/L), wt BRAF (IC50, 22 nmol/L), and V599E mutant BRAF (IC50, 38 nmol/L), as well as the split kinase family: VEGFR-2 (IC50, 90 nmol/L), VEGFR-3 (IC50, 20 nmol/L), PDGFR-β (IC50, 57 nmol/L), c-KIT (IC50, 68 nmol/L), and Flt3 (IC50, 58 nmol/L). Furthermore, BAY 43-9006 is not active against ERK-1, MEK-1, EGFR, HER-2, IGFR-1, c-met, c-yes, PKB, PKA, cdk1/cyclinB, PKCα, PKCγ, and pim-1. The bi-aryl urea BAY 43-9006 was recently co-crystallized in complex with both wt and oncogenic V599E BRAF kinase (33) . The structure revealed that the distal pyridyl ring of BAY 43-9006 directly interacts with ...
Cancer and CIB. Cancerous tumor cells often proliferate rapidly. Some cancer cell types appear to be addicted to CIB1 for survival. We find that when we knockdown CIB1 in breast and neuroblastoma cancer cells, the cells die by an unusual mechanism that involves GAPDH translocation to the nucleus. We also find that this cell death appears to be so potent because loss of CIB1 causes two oncogenic pathways to fail: the PI3K/AKT pathway and the RAS/RAF/MEK/ERK pathway. However, normal cells do not appear to be addicted to CIB1 for survival. Moreover, once tumors grow beyond a few mm in size, they require blood vessels to provide nourishment in order to grow further. Endothelial cells are essential for blood vessel formation. CIB1 is expressed in multiple cell types, including endothelial cells. We found that efficient tumor-induced blood vessel growth depends upon CIB1. If endothelial cells do not express CIB1, the cells grow more slowly and tumor-induced blood vessel formation is impaired. We have ...
Another purpose of this study is to measure the concentration of drug in the blood to help understand how much drug gets into the body and how quickly the drug is removed from the body. Another purpose of this study is to determine whether MEK162 turns off the Ras/Raf/MAP pathway as expected by measuring this pathway in blood cells. Finally, in this study, the investigators hope to start finding out whether or not MEK162 causes different types of tumors in children to shrink or stop growing ...
Phosphorylation of the activation loop in RAF kinases has been suggested to be critical for changes in activity. The extent to which the activation segment is phosphorylated, the specific structural consequences, and the in vivo relevance have however remained elusive. In this issue of the The EMBO Journal, Köhler et al (2015) addressed these questions by generating a knock‐in mouse expressing a B‐Raf mutant with a non‐phosphorylatable activation loop. The mutant causes a range of developmental phenotypes; intriguingly, it also impairs the tumorigenic potential of a subset of BRAF mutants, suggesting potential new strategies for RAF inhibition.. See also: M Köhler et al (January 2016) ...
Mutations in RAS oncogenes are frequently observed in human cancers, and the mutations result in activation of the RAS-RAF-MEK-ERK pathway, leading to cell proliferation and survival. The pathway is, therefore, a potent therapeutic target in the RAS-mutant cancers. MEK inhibitors can specifically block the pathway and are one of the key types of drugs for the treatment of the RAS-mutant cancers. As RAS proteins activate other downstream signaling proteins in addition to the RAS-RAF-MEK-ERK pathway, combination therapeutic approaches with MEK inhibitors are also being evaluated. Moreover, MEK inhibitors can arrest cancer cells in G1 phase and repress prosurvival Bcl2 family proteins such as MCL1 and BCL2/BCLXL, and increase expression of Bim, a proapoptotic BH3-only family protein. This mechanism may explain the efficacy of the combination of MEK inhibitors with cytotoxic agents or other targeted inhibitors. A better understanding of the pathway will help us with development of rational ...
The development of combination therapies is important to cancer treatment due to the potential to target multiple oncogenic pathways together, which may lead to enhanced anti-tumor activity and decreased chance for resistance. The RAS/RAF/MEK/ERK (MAP kinase) and PI3K/AKT/mTOR pathways are well-known pathways driving the oncogenic process in many cancer types; therefore, the simultaneous inhibition of these pathways may produce increased anti-tumor activity. It is important to find ideal cancer indications and molecular subtypes that may be most sensitive to drug combination inhibiting these pathways; this requires understanding of the molecular and genetic underpinnings. In this study, an in-vitro cell viability assay on 240 cancer cell lines was used to reveal the synergy mechanisms of the combination of investigational agents MLN0128 (mTORC1/2 inhibitor) with TAK733 (MEK1/2 inhibitor). Cells were administered with MLN0128 and TAK733 in DMSO in ten 2-fold serial dilutions and cell viability ...
Inactivating somatic mutation of LKB1 is found in approximately 30% of NSCLC and is often coincident with activating K‐RAS mutation. In a mutant K‐RAS‐driven model of mouse lung cancer, strong cooperation and aggressive phenotype was seen with hemizygous inactivation of LKB1. Loss of LKB1 results in activation of mTOR pathway while somatic activating mutation in K‐RAS results in activation of PI3K/AKT and RAS/RAF/ERK. Therefore therapeutic stratagies which target these pathways may have significant affect on the outcome of these cancers. NVP‐BEZ235 is a dual PI3K and mTOR inhibitor and panobinostat (PS) (Novartis Pharmaceuticals Inc) is a pan‐histone deacetylase (HDAC) inhibitor, which has been shown to induce proteasomal degradation and depletion of the levels of hsp90 client proteins, including AKT and c‐RAF. Here, we determined the effects of BEZ235 and/or PS or AUY922 (an hsp90 inhibitor) on NSCLC A549 and H460 cells with LKB1 and K‐RAS mutations (A549 and H460). Treatment ...
Although extracellular signal-regulated kinase (ERK) ? has been shown for its necessity for a variety of the Raf/MEK/ERK pathway signaling its sufficiency in mediating the pathway signaling has not been firmly established. promote ERK autophosphorylation is sufficient to induce growth arrest and differentiation whereas ERK2-I84A and ERK2-R65S/D319N are not as effective. When compared to the […]. ...
RAF1 - RAF1 (untagged)-Kinase deficient mutant (K375M) of Human v-raf-1 murine leukemia viral oncogene homolog 1 (RAF1) available for purchase from OriGene - Your Gene Company.
1.0 Introduction RAF Cosford is the home to a number of RAF, Defence and several civilian organisations (as discussed above). Several training schools are at the site and between them they are responsible for the provision of all Phase 2 and some Phase 3 training for the RAF trade specialisations of Aeronautical Engineering, Information and…
Polyclonal antibody for RAF B/BRAF detection. Host: Rabbit.Size: 100μg/vial. Tested applications: WB. Reactive species: Human. RAF B/BRAF information: Molecular Weight: 84437 MW; Subcellular Localization: Nucleus . Cytoplasm. Cell membrane . Colocalizes w
If youre looking for a RAF (Recruit A Friend) partner, or just a leveling partner, please post your request in here. Do not create your own thread as that will be removed as soon as we spot it. This thread is the only way to post your LF RAF or leveling partners. Please limit yourself to one bump a day for Recruit a Friend requests only. Please do not edit the size of the font in your posts. Larger font will be edited out. Do not post your IM nick or phonenumber.
Tumor-associated antigens such as NY-ESO-1 are expressed in a variety of solid tumors but absent in mature healthy tissues with the exception of germline cells. expanded with IL-2 IL-7 and IL-15. Large numbers of NY-ESO-1-specific CD4+ T cells with a TH1 cytokine profile and lower numbers of cytokine-secreting CD8+ T cells could be generated from […]. ...
GW 5074 is a potent, cell-permeable, reversible, and ATP-competitive cRAF1 kinase inhibitor (IC50 = 9 nM). It shows ≥100-fold selectivity for Raf kinase versus Cdk1, Cdk2, c-Src, ERK2, MEK, p38, Tie2, VEGFR2, and c-Fms.[
Bacterial cell division occurs by a highly conserved process predominantly, termed binary fission, that requires the microbial homologue of tubulin, FtsZ. of VX-765 manufacture the unipolar development and FtsZ-independent fission of this coccoid patient. This system of cell department offers not really been recorded in additional human being microbial pathogens recommending the potential for developing […]. ...
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The Center for the Environment (C4E) serves to better connect faculty and students across departments and disciplines, strengthen support for innovative projects, and increase the impact of Purdues work on important environmental issues.
0004] BRAF is a member of the Raf kinase family of serine/threonine-specific protein kinases. BRAF plays an important role in regulating the MAPK/ERK signaling pathway, which affects cell division, proliferation, differentiation, and secretion. The RAS/RAF/MEK/ERK pathway acts as a signal transducer to send extracellular signals such as hormones, cytokines, and various growth factors into cell nucleus, directing a range of biochemical and physiological processes including cell differentiation, proliferation, growth, and apoptosis (McCubrey, J. A., et al., Biochim. Biophys. Acta, 2007, 1773 (8): 1263-84). The RAS/RAF/MEK/ERK pathway is frequently mutated in many human cancers (Downward, J., Nat. Rev. Cancer, 2003, 3 (1): 11-22). The finding that mutations in BRAF caused a wide range of human cancers and many of these tumors are dependent on the constitutive activation of BRAF/MEK/ERK pathway fueled drug discovery efforts in searching for small molecule inhibitors targeting BRAF mutants ...
A genome wide association study has previously found a variant, rs889312, at 5q11.2 to be associated with breast cancer risk. To identify the causal variant(s) underlying this association, we analysed 909 genetic variants across 5q11.2 in 103,991 breast cancer cases and controls from 52 studies. Three sets of independent, correlated, highly trait-associated variants (iCHAVs), spanning a 183 kb region at 5q11.2, were identified in Europeans (46,451 cases and 42,599 controls). This region encompasses MAP3K1, a frequently mutated gene in breast cancer, encoding a stress-induced serine/threonine kinase which regulates apoptosis and induces cell proliferation through a RAS/RAF/MEK/ERK pathway. Using ENCODE data and chromatin conformation studies, we found that variants from the three iCHAVs coincide with five putative regulatory elements (PREs). We show that all five PREs physically interact with the MAP3K1 promoter through chromatin looping and have effects on MAP3K1 promoter activity in reporter ...
Mus musculus ATCC ® 63340™ Designation: CMV-p57 TypeStrain=False Application: in another host, produces protein cyclin-dependent kinase inhibitor 1C (p57, Kip2) P57, kinase inhibitory protein 2 of cyclins (p57)
Buy our Recombinant Human A RAF protein. Ab127659 is a protein fragment produced in Baculovirus infected Sf9 cells and has been validated in WB, SDS-PAGE…
GDC-0623, also known as G-868, is an orally active, selective MEK inhibitor with potential antineoplastic activity. MEK inhibitor GDC-0623 specifically inhibits mitogen-activated protein kinase kinase (MEK or MAP/ERK kinase), resulting in inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK is a key component of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth; constitutive activation of this pathway has been implicated in many cancers.
Evaluation of the in vivo biological activity of protocol therapy will be explored by a within patient comparison of EGFR activation (measured by pEGFR), PI3K/AKT/mTOR/S6K signaling (measured by pS6K and pAKT and related molecules), RAS/RAF/MEK/ERK signaling (measured by pERK and related molecules) and cell proliferation (measured by Ki-67 immunostaining to estimate the proliferation index as the % of tumor cells staining per high power field) in pre-treatment archived tissue versus the tissue acquired during treatment for patients in cohort B. Slides analyzed by immunohistochemistry will be scored for staining on a 4 point scale (0-3 ...
Aronov A.M., Baker C., Bemis G.W., Cao J., Chen G., Ford P.J., Germann U.A., Green J., Hale M.R., Jacobs M., Janetka J.W., Maltais F., Martinez-Botella G., Namchuk M.N., Straub J., Tang Q., Xie X.. The Ras/Raf/MEK/ERK signal transduction is a key oncogenic pathway implicated in a variety of human cancers. We have identified a novel series of pyrazolylpyrroles as inhibitors of ERK. Aided by the discovery of two distinct binding modes for the pyrazolylpyrrole scaffold, structure-guided optimization culminated in the discovery of 6p, a potent and selective inhibitor of ERK.. J. Med. Chem. 50:1280-1287(2007) [PubMed] [Europe PMC] ...
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Buy L779450 (CAS 303727-31-3), a potent Raf kinase inhibitor. Join researchers using high quality L779450 from Abcam and achieve your mission, faster.
1795 yılından sonra Nicephore Niepce fotoğraf alanında yeni deneyler geliştirdi. Litografi ile ilgilenerek taşın üzerine çizilen herhangi bir resmin görünmesini sağlayacak derecede şeffaf maddeleri taş üzerine uyguladı. Bu yöntemle 1822 yılında asfalt tabaka ile kaplanmış bir cam plaka üzerine Papa VII. Plusu gösteren resmi çizmiştir. Niepce, deneylerine devam ederek 1826 yılında evinin penceresinden çatısını dünyanın kalıcı ilk fotoğrafik görüntüsünü çekti. Bu işleme "Heliografi" yani "güneş yazısı" adını verdi. Niepce bu yıllarda Fransız mucit Daguerre ile birlikte çalışmaya başladı. Birlikte geliştirdikleri aygıt ile ışık kaynağı bol olan hareketsiz ve yakın objelerin fotoğraflarını 4 dakika gibi kısa sürede çekebiliyorlardı. Niepce 1833 yılında ölünce Daguerre, çalışmalarına yalnız devam etti ve 1837 yılında kamerada film yerine iyot buharına tutulmuş parlak yüzeyli bir gümüş levha kullandı. Pozlanan bu ...
1795 yılından sonra Nicephore Niepce fotoğraf alanında yeni deneyler geliştirdi. Litografi ile ilgilenerek taşın üzerine çizilen herhangi bir resmin görünmesini sağlayacak derecede şeffaf maddeleri taş üzerine uyguladı. Bu yöntemle 1822 yılında asfalt tabaka ile kaplanmış bir cam plaka üzerine Papa VII. Plusu gösteren resmi çizmiştir. Niepce, deneylerine devam ederek 1826 yılında evinin penceresinden çatısını dünyanın kalıcı ilk fotoğrafik görüntüsünü çekti. Bu işleme "Heliografi" yani "güneş yazısı" adını verdi. Niepce bu yıllarda Fransız mucit Daguerre ile birlikte çalışmaya başladı. Birlikte geliştirdikleri aygıt ile ışık kaynağı bol olan hareketsiz ve yakın objelerin fotoğraflarını 4 dakika gibi kısa sürede çekebiliyorlardı. Niepce 1833 yılında ölünce Daguerre, çalışmalarına yalnız devam etti ve 1837 yılında kamerada film yerine iyot buharına tutulmuş parlak yüzeyli bir gümüş levha kullandı. Pozlanan bu ...
RAF Church Fenton is currently the home of 3 Squadron of No. 1 Elementary Flying Training School and Yorkshire Universities Air Squadron, flying Tutor T1s, and serves as a relief landing ground for Tucano T1s from RAF Linton-on-Ouse.
Mouse polyclonal antibody raised against a full-length human RAF1 protein. RAF1 (NP_002871.1, 1 a.a. ~ 648 a.a) full-length human protein. (H00005894-B01P) - Products - Abnova
Looking for the definition of RAF? Find out what is the full meaning of RAF on Abbreviations.com! Rapid Action Force is one option -- get in to view more @ The Webs largest and most authoritative acronyms and abbreviations resource.
20 years after its inception in 1995, the Raf Simons label had become an oracle for a pre-Internet notion of beauty and freedom. Its a brand rooted in the site specificity of IRL subculture, the iconoclasm of 20th century design, and the melodramatic land-scape of suburban isolation. Yet, after 40 collections and counting, the man behind RAF SIMONS remains an enigma. Published for the first time online, 032cs dossier on Simons from our instantly sold out 27th issue includes an essay and interview, an archival shoot by Willy Vanderperre, and a poem by Peter De Potter.
Families at RAF High Wycombe enjoyed a range of special activities on 18 November to celebrate the opening of new Airplay Parks - state-of-the-art play areas for children and young people living on or around the station.
This synthetic peptide is phosphorlated on S339 of human RAF1 and is used as the immunogen for PAB1669. (P1644) - Products - Abnova
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Gastric cancer (GC) is a threat to human health with increasing incidence and mortality worldwide. Down-regulation or absence of RAF kinase inhibitor protein (RKIP) was associated with the occurrence, differentiation, invasion, and metastasis of GC. This study aims to investigate the molecular mechanisms and biological functions of RKIP in the GC biology. The fusion expression plasmid pcDNA3.1-RKIP-3xFLAG was transfected into SGC7901 cells, the RKIP fusion proteins were purified with anti-flag M2 magnetic beads, and the RKIP-interacting proteins were identified with tandem mass spectrometry (MS/MS), and were analyzed with bioinformatics tools. Western blot and co-immunoprecipitation were used to confirm the interaction complex. A total of 72 RKIP-interacting proteins were identified by MS/MS. Those proteins play roles in enzyme metabolism, molecular chaperoning, biological oxidation, cytoskeleton organization, signal transduction, and enzymolysis. Three RKIP-interaction protein network diagrams were
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
NRAS and its effector BRAF are frequently mutated in melanoma. Paradoxically, CRAF but not BRAF was shown to be critical for various RAS-driven cancers, raising the question of the role of RAF proteins in NRAS-induced melanoma. Here, using conditional ablation of Raf genes in NRAS-induced mouse melanoma models, we investigate their contribution in tumour progression, from the onset of benign tumours to malignant tumour maintenance. We show that BRAF expression is required for ERK activation and nevi development, demonstrating a critical role in the early stages of NRAS-driven melanoma. After melanoma formation, single Braf or Craf ablation is not sufficient to block tumour growth, showing redundant functions for RAF kinases. Finally, proliferation of resistant cells emerging in the absence of BRAF and CRAF remains dependent on ARAF-mediated ERK activation. These results reveal specific and compensatory functions for BRAF and CRAF and highlight an addiction to RAF signalling in NRAS-driven ...
This patent search tool allows you not only to search the PCT database of about 2 million International Applications but also the worldwide patent collections. This search facility features: flexible search syntax; automatic word stemming and relevance ranking; as well as graphical results.
PubMed journal article: SNHG1 promotes MPP+-induced cytotoxicity by regulating PTEN/AKT/mTOR signaling pathway in SH-SY5Y cells via sponging miR-153-3p. Download Prime PubMed App to iPhone, iPad, or Android
Antigen Background p27 protein, also known as kinase inhibitory protein 1 (Kip1), binds to cyclin E/cdk2 complexes, but not to cdk2 alone, and is detected in purified extracts of growth-arrested cells. p27 protein constrains cell proliferation by setting the threshold level of cyclin E necessary to activate cdk2. The p27 protein is also present in proliferating cells, but only in a sequestered form when it is unavailable to interact with cyclin E/cdk2 complexes. It is likely that cyclin D complexed with catalytically inactive cdk4 is sufficient to sequester p27 protein and titrate its function. The presence of bound p27 protein in proliferating cells suggests that its role may not be restricted to inducing cell cycle arrest but to also set the cyclin E threshold for execution of the G1 to S phase transition during each mitotic cycle.. ...
Abstract: : Purpose: To investigate the activation of the Ras/Raf/MEK/ERK cascade by serum, epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) stimulation. Methods: Rat corneal endothelial cells in primary culture were serum starved for 48 hrs. The serum starved cells, were then stimulated with either 10% serum, EGF (50 ng/ml) or bFGF (50 ng/ml) for 0, 5, 10, 30 min and 1, 2, 4, and 6 hr. The cells were then harvested in ice-cold homogenization buffer and sonicated on ice. The cell lysates were then prepared for western blotting. The samples were blotted phospho ERK (pERK) to determine activation and total ERK to determine protein loading. pERK was quantified by using Scion Image (Scion Corp.) software. Results: Serum stimulation of rat corneal endothelium cells induced phosphorylation of ERK at 5 min which was 10 fold above basal, this phosphorylation was sustained above basal levels throughout the 6 hr (5 fold) time coarse. In comparison, EGF induced a 17 fold increase of ...
Purpose: The chromosomal deletion 11q affects biology and clinical outcome in CLL but del11q-deregulated genes remain incompletely characterized. Experimental Design: We have employed integrated genomic profiling approaches upon CLL cases with and without del11q to identify 11q-relevant genes. Results: We have identified differential expression of the insulin receptor (INSR) in CLL, including high-level INSR expression in the majority of CLL with del11q. High INSR mRNA expression in 11q CLL (~10-fold higher mean levels than other genomic categories) was confirmed by Q-PCR in 247 CLL cases. INSR protein measurements in 257 CLL cases through FACS, compared with measurements in normal CD19+ B-cells and monocytes, confirmed that a subset of CLL aberrantly expresses high INSR levels. INSR stimulation by insulin in CLL cells ex vivo resulted in the activation of canonical INSR signaling pathways, including the AKT-mTOR and Ras/Raf/Erk pathways, and INSR activation partially abrogated spontaneous CLL ...