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10.1158/1078-0432.CCR-14-1404 http://scihub22266oqcxt.onion/10.1158/1078-0432.CCR-14-1404 C4253985!4253985!25294913     free     free     free Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Clin+Cancer+Res 2014 ; 20 (23): 5946-55 Nephropedia Template TP {{tp|p=25294913|t=2014. A Phase 1 Trial of Single Agent Reolysin in Patients with Relapsed Multiple Myeloma |pdf=|usr=}}{{25294913}} gab.com Text A Phase 1 Trial of Single Agent Reolysin in Patients with Relapsed Multiple Myeloma JO: Clin Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=25294913 #FOAvip Introduction: Reolysin®, a proprietary isolate of reovirus Type 3 Dearing, enters and preferentially induces apoptosis of malignant cells. RAS pathway activation has been associated with more efficient reoviral infectivity and enhanced oncolysis. Reovirus is currently in advanced solid tumor phase 1 ? 2 trials; no clinical trials have been conducted in patients with hematologic malignancies. Methodologies: A phase 1 trial treated 12 relapsed myeloma patients at two dose levels. Reolysin was infused daily for 5 days every 28 days. Bone marrow specimens were examined by In situ based hybridization (ISH) for CD138, p38, caspase-3, reoviral RNA and capsid protein at screening and cycle 1 day 8. Junctional adhesion molecule 1 (JAM-1) and cancer up regulated gene 2 (CUG2) were evaluated in patient samples and MM cell lines. Neutralizing Anti-Reovirus Antibody (NARA) assay was performed weekly during cycle 1. Results: There were no dose limiting toxicities (DLTs), patients reached the 3 x 1010 TCID50 daily on days 1-5 dose level, and grade 3 laboratory toxicities included neutropenia, thrombocytopenia, and hypophosphatemia. In situ hybridization demonstrated reoviral genome confined in MM cells. Reoviral capsid protein and caspase-3 were rarely identified within reoviral RNA positive cells. The longest durations of stable disease were 4, 5 and 8 months. Conclusions: Treatment with single-agent Reolysin was well tolerated and associated with avid reoviral RNA myeloma cell entry but only minimal intracellular reoviral protein production within MM cells. Our data support that in MM cells, Reolysin-induced oncolysis requires combination therapy, similar to other cancers. Twit Text FOAVip A Phase 1 Trial of Single Agent Reolysin in Patients with Relapsed Multiple Myeloma ????Clin Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=25294913 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25294913 #FOAvip English Wikipedia <ref>{{Cite pmid|25294913}}</ref> A Phase 1 Trial of Single Agent Reolysin in Patients with Relapsed Multiple Myeloma #MMPMID25294913 Sborov DW; Nuovo GJ; Stiff A; Mace T; Lesinski GB; Benson DM; Efebera YA; Rosko AE; Pichiorri F; Grever MR; Hofmeister CC Clin Cancer Res 2014[Dec]; 20 (23): 5946-55 PMID25294913show ga Introduction: Reolysin®, a proprietary isolate of reovirus Type 3 Dearing, enters and preferentially induces apoptosis of malignant cells. RAS pathway activation has been associated with more efficient reoviral infectivity and enhanced oncolysis. Reovirus is currently in advanced solid tumor phase 1 ? 2 trials; no clinical trials have been conducted in patients with hematologic malignancies. Methodologies: A phase 1 trial treated 12 relapsed myeloma patients at two dose levels. Reolysin was infused daily for 5 days every 28 days. Bone marrow specimens were examined by In situ based hybridization (ISH) for CD138, p38, caspase-3, reoviral RNA and capsid protein at screening and cycle 1 day 8. Junctional adhesion molecule 1 (JAM-1) and cancer up regulated gene 2 (CUG2) were evaluated in patient samples and MM cell lines. Neutralizing Anti-Reovirus Antibody (NARA) assay was performed weekly during cycle 1. Results: There were no dose limiting toxicities (DLTs), patients reached the 3 x 1010 TCID50 daily on days 1-5 dose level, and grade 3 laboratory toxicities included neutropenia, thrombocytopenia, and hypophosphatemia. In situ hybridization demonstrated reoviral genome confined in MM cells. Reoviral capsid protein and caspase-3 were rarely identified within reoviral RNA positive cells. The longest durations of stable disease were 4, 5 and 8 months. Conclusions: Treatment with single-agent Reolysin was well tolerated and associated with avid reoviral RNA myeloma cell entry but only minimal intracellular reoviral protein production within MM cells. Our data support that in MM cells, Reolysin-induced oncolysis requires combination therapy, similar to other cancers. äA Phase 1 Trial of Single Agent Reolysin in Patients with Relapsed Mul(epmc).pdf DeepDyve Pubget Overpricing