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10.1038/bcj.2014.74 http://scihub22266oqcxt.onion/10.1038/bcj.2014.74 C5424099!5424099 !25382610     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 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\25382610 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Blood+Cancer+J 2014 ; 4 (11 ): e260 Nephropedia Template TP {{tp|p=25382610 |t=2014. Nimbolide targets BCL2 and induces apoptosis in preclinical models of Waldenströms macroglobulinemia |pdf=|usr=}}{{25382610 }} gab.com Text Nimbolide targets BCL2 and induces apoptosis in preclinical models of Waldenströms macroglobulinemia JO: Blood Cancer J http://www.kidney.de/pget.php?&tw=1&pmid=25382610 #FOAvip Neem leaf extract (NLE) has medicinal properties, which have been attributed to its limonoid content. We identified the NLE tetranorterpenoid, nimbolide, as being the key limonoid responsible for the cytotoxicity of NLE in various preclinical models of human B-lymphocyte cancer. Of the models tested, Waldenströms macroglobulinemia (WM) cells were most sensitive to nimbolide, undergoing significant mitochondrial mediated apoptosis. Notably, nimbolide toxicity was also observed in drug-resistant (bortezomib or ibrutinib) WM cells. To identify putative targets of nimbolide, relevant in WM, we used chemoinformatics-based approaches comprised of virtual in silico screening, molecular modeling and target-ligand reverse docking. In silico analysis revealed the antiapoptotic protein BCL2 was the preferential binding partner of nimbolide. The significance of this finding was further tested in vitro in RS4;11 (BCL2-dependent) tumor cells, in which nimbolide induced significantly more apoptosis compared with BCL2 mutated (Jurkat BCL2(Ser70-Ala)) cells. Lastly, intraperitoneal administration of nimbolide in WM tumor xenografted mice, significantly reduced tumor growth and IgM secretion in vivo, while modulating the expression of several proteins as seen on immunohistochemistry. Overall, our data demonstrate that nimbolide is highly active in WM cells, as well as other B-cell cancers, and engages BCL2 to exert its cytotoxic activity. Twit Text FOAVip Nimbolide targets BCL2 and induces apoptosis in preclinical models of Waldenströms macroglobulinemia ????Blood Cancer J http://www.kidney.de/pget.php?&tw=1&pmid=25382610 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25382610 #FOAvip English Wikipedia <ref>{{Cite pmid|25382610 }}</ref> Nimbolide targets BCL2 and induces apoptosis in preclinical models of Waldenströms macroglobulinemia #MMPMID25382610 Chitta K ; Paulus A ; Caulfield TR ; Akhtar S ; Blake MK ; Ailawadhi S ; Knight J ; Heckman MG ; Pinkerton A ; Chanan-Khan A Blood Cancer J 2014[Nov]; 4 (11 ): e260 PMID25382610 show ga Neem leaf extract (NLE) has medicinal properties, which have been attributed to its limonoid content. We identified the NLE tetranorterpenoid, nimbolide, as being the key limonoid responsible for the cytotoxicity of NLE in various preclinical models of human B-lymphocyte cancer. Of the models tested, Waldenströms macroglobulinemia (WM) cells were most sensitive to nimbolide, undergoing significant mitochondrial mediated apoptosis. Notably, nimbolide toxicity was also observed in drug-resistant (bortezomib or ibrutinib) WM cells. To identify putative targets of nimbolide, relevant in WM, we used chemoinformatics-based approaches comprised of virtual in silico screening, molecular modeling and target-ligand reverse docking. In silico analysis revealed the antiapoptotic protein BCL2 was the preferential binding partner of nimbolide. The significance of this finding was further tested in vitro in RS4;11 (BCL2-dependent) tumor cells, in which nimbolide induced significantly more apoptosis compared with BCL2 mutated (Jurkat BCL2(Ser70-Ala)) cells. Lastly, intraperitoneal administration of nimbolide in WM tumor xenografted mice, significantly reduced tumor growth and IgM secretion in vivo, while modulating the expression of several proteins as seen on immunohistochemistry. Overall, our data demonstrate that nimbolide is highly active in WM cells, as well as other B-cell cancers, and engages BCL2 to exert its cytotoxic activity. |*Xenograft Model Antitumor Assays [MESH] |Animals [MESH] |Apoptosis/*drug effects/genetics [MESH] |Cell Line, Tumor [MESH] |Female [MESH] |Humans [MESH] |Jurkat Cells [MESH] |Limonins/*pharmacology [MESH] |Male [MESH] |Mice [MESH] |Mice, SCID [MESH] |Neoplasms, Experimental/*drug therapy/genetics/metabolism/pathology [MESH] |Proto-Oncogene Proteins c-bcl-2/*antagonists & inhibitors/genetics/metabolism [MESH]Nimbolide targets BCL2 and induces apoptosis in preclinical models of (epmc).pdf DeepDyve Pubget Overpricing