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10.1038/ncomms15090 http://scihub22266oqcxt.onion/10.1038/ncomms15090 C5436137!5436137 !28489072     free     free     free Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 249.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 249.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28489072 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Nat+Commun 2017 ; 8 (ä): 15090 Nephropedia Template TP {{tp|p=28489072 |t=2017. Antibody targeting intracellular oncogenic Ras mutants exerts anti-tumour effects after systemic administration |pdf=|usr=}}{{28489072 }} gab.com Text Antibody targeting intracellular oncogenic Ras mutants exerts anti-tumour effects after systemic administration JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=28489072 #FOAvip Oncogenic Ras mutants, frequently detected in human cancers, are high-priority anticancer drug targets. However, direct inhibition of oncogenic Ras mutants with small molecules has been extremely challenging. Here we report the development of a human IgG1 format antibody, RT11, which internalizes into the cytosol of living cells and selectively binds to the activated GTP-bound form of various oncogenic Ras mutants to block the interactions with effector proteins, thereby suppressing downstream signalling and exerting anti-proliferative effects in a variety of tumour cells harbouring oncogenic Ras mutants. When systemically administered, an RT11 variant with an additional tumour-associated integrin binding moiety for tumour tissue targeting significantly inhibits the in vivo growth of oncogenic Ras-mutated tumour xenografts in mice, but not wild-type Ras-harbouring tumours. Our results demonstrate the feasibility of developing therapeutic antibodies for direct targeting of cytosolic proteins that are inaccessible using current antibody technology. Twit Text FOAVip Antibody targeting intracellular oncogenic Ras mutants exerts anti-tumour effects after systemic administration ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=28489072 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28489072 #FOAvip English Wikipedia <ref>{{Cite pmid|28489072 }}</ref> Antibody targeting intracellular oncogenic Ras mutants exerts anti-tumour effects after systemic administration #MMPMID28489072 Shin SM ; Choi DK ; Jung K ; Bae J ; Kim JS ; Park SW ; Song KH ; Kim YS Nat Commun 2017[May]; 8 (ä): 15090 PMID28489072 show ga Oncogenic Ras mutants, frequently detected in human cancers, are high-priority anticancer drug targets. However, direct inhibition of oncogenic Ras mutants with small molecules has been extremely challenging. Here we report the development of a human IgG1 format antibody, RT11, which internalizes into the cytosol of living cells and selectively binds to the activated GTP-bound form of various oncogenic Ras mutants to block the interactions with effector proteins, thereby suppressing downstream signalling and exerting anti-proliferative effects in a variety of tumour cells harbouring oncogenic Ras mutants. When systemically administered, an RT11 variant with an additional tumour-associated integrin binding moiety for tumour tissue targeting significantly inhibits the in vivo growth of oncogenic Ras-mutated tumour xenografts in mice, but not wild-type Ras-harbouring tumours. Our results demonstrate the feasibility of developing therapeutic antibodies for direct targeting of cytosolic proteins that are inaccessible using current antibody technology. |Animals [MESH] |Antibodies, Monoclonal/*pharmacology [MESH] |Cell Line, Tumor [MESH] |Cell Proliferation/*drug effects [MESH] |Cytosol/*metabolism [MESH] |GTP Phosphohydrolases/antagonists & inhibitors/genetics/metabolism [MESH] |HL-60 Cells [MESH] |HT29 Cells [MESH] |HeLa Cells [MESH] |Humans [MESH] |Immunoglobulin G/*pharmacology [MESH] |K562 Cells [MESH] |MCF-7 Cells [MESH] |Membrane Proteins/antagonists & inhibitors/genetics/metabolism [MESH] |Mice [MESH] |Mutation [MESH] |NIH 3T3 Cells [MESH] |Neoplasm Transplantation [MESH] |Neoplasms/drug therapy/*genetics [MESH] |Protein Interaction Domains and Motifs [MESH] |Proto-Oncogene Proteins p21(ras)/antagonists & inhibitors/genetics/metabolism [MESH] |Signal Transduction/drug effects [MESH] |Xenograft Model Antitumor Assays [MESH]Antibody targeting intracellular oncogenic Ras mutants exerts anti-tum(epmc).pdf DeepDyve Pubget Overpricing