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10.1158/1078-0432.CCR-12-1708 http://scihub22266oqcxt.onion/10.1158/1078-0432.CCR-12-1708 C4453928!4453928 !23035210     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 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\23035210 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Clin+Cancer+Res 2012 ; 18 (22 ): 6260-70 Nephropedia Template TP {{tp|p=23035210 |t=2012. Synthetic miR-34a mimics as a novel therapeutic agent for multiple myeloma: in vitro and in vivo evidence |pdf=|usr=}}{{23035210 }} gab.com Text Synthetic miR-34a mimics as a novel therapeutic agent for multiple myeloma: in vitro and in vivo evidence JO: Clin Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=23035210 #FOAvip PURPOSE: Deregulated expression of miRNAs has been shown in multiple myeloma (MM). A promising strategy to achieve a therapeutic effect by targeting the miRNA regulatory network is to enforce the expression of miRNAs that act as tumor suppressor genes, such as miR-34a. EXPERIMENTAL DESIGN: Here, we investigated the therapeutic potential of synthetic miR-34a against human MM cells in vitro and in vivo. RESULTS: Either transient expression of miR-34a synthetic mimics or lentivirus-based miR-34a-stable enforced expression triggered growth inhibition and apoptosis in MM cells in vitro. Synthetic miR-34a downregulated canonic targets BCL2, CDK6, and NOTCH1 at both the mRNA and protein level. Lentiviral vector-transduced MM xenografts with constitutive miR-34a expression showed high growth inhibition in severe combined immunodeficient (SCID) mice. The anti-MM activity of lipidic-formulated miR-34a was further shown in vivo in two different experimental settings: (i) SCID mice bearing nontransduced MM xenografts; and (ii) SCID-synth-hu mice implanted with synthetic 3-dimensional scaffolds reconstituted with human bone marrow stromal cells and then engrafted with human MM cells. Relevant tumor growth inhibition and survival improvement were observed in mice bearing TP53-mutated MM xenografts treated with miR-34a mimics in the absence of systemic toxicity. CONCLUSIONS: Our findings provide a proof-of-principle that formulated synthetic miR-34a has therapeutic activity in preclinical models and support a framework for development of miR-34a-based treatment strategies in MM patients. Twit Text FOAVip Synthetic miR-34a mimics as a novel therapeutic agent for multiple myeloma: in vitro and in vivo evidence ????Clin Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=23035210 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=23035210 #FOAvip English Wikipedia <ref>{{Cite pmid|23035210 }}</ref> Synthetic miR-34a mimics as a novel therapeutic agent for multiple myeloma: in vitro and in vivo evidence #MMPMID23035210 Di Martino MT ; Leone E ; Amodio N ; Foresta U ; Lionetti M ; Pitari MR ; Cantafio ME ; Gullà A ; Conforti F ; Morelli E ; Tomaino V ; Rossi M ; Negrini M ; Ferrarini M ; Caraglia M ; Shammas MA ; Munshi NC ; Anderson KC ; Neri A ; Tagliaferri P ; Tassone P Clin Cancer Res 2012[Nov]; 18 (22 ): 6260-70 PMID23035210 show ga PURPOSE: Deregulated expression of miRNAs has been shown in multiple myeloma (MM). A promising strategy to achieve a therapeutic effect by targeting the miRNA regulatory network is to enforce the expression of miRNAs that act as tumor suppressor genes, such as miR-34a. EXPERIMENTAL DESIGN: Here, we investigated the therapeutic potential of synthetic miR-34a against human MM cells in vitro and in vivo. RESULTS: Either transient expression of miR-34a synthetic mimics or lentivirus-based miR-34a-stable enforced expression triggered growth inhibition and apoptosis in MM cells in vitro. Synthetic miR-34a downregulated canonic targets BCL2, CDK6, and NOTCH1 at both the mRNA and protein level. Lentiviral vector-transduced MM xenografts with constitutive miR-34a expression showed high growth inhibition in severe combined immunodeficient (SCID) mice. The anti-MM activity of lipidic-formulated miR-34a was further shown in vivo in two different experimental settings: (i) SCID mice bearing nontransduced MM xenografts; and (ii) SCID-synth-hu mice implanted with synthetic 3-dimensional scaffolds reconstituted with human bone marrow stromal cells and then engrafted with human MM cells. Relevant tumor growth inhibition and survival improvement were observed in mice bearing TP53-mutated MM xenografts treated with miR-34a mimics in the absence of systemic toxicity. CONCLUSIONS: Our findings provide a proof-of-principle that formulated synthetic miR-34a has therapeutic activity in preclinical models and support a framework for development of miR-34a-based treatment strategies in MM patients. |Animals [MESH] |Apoptosis [MESH] |Cell Line [MESH] |Cell Proliferation [MESH] |Genes, Tumor Suppressor [MESH] |Genetic Therapy [MESH] |Humans [MESH] |Lentivirus/genetics [MESH] |Male [MESH] |Mice [MESH] |Mice, SCID [MESH] |MicroRNAs/biosynthesis/*genetics [MESH] |Multiple Myeloma/genetics/pathology/*therapy [MESH] |Neoplasm Transplantation [MESH] |RNA Interference [MESH] |Transduction, Genetic [MESH] |Transfection [MESH] |Tumor Burden [MESH]Synthetic miR-34a mimics as a novel therapeutic agent for multiple mye(epmc).pdf DeepDyve Pubget Overpricing