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10.2147/OTT.S161905 http://scihub22266oqcxt.onion/10.2147/OTT.S161905 C5957068!5957068!29785126     free     free     free Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Onco+Targets+Ther 2018 ; 11 (ä): 2779-96 Nephropedia Template TP {{tp|p=29785126|t=2018. Impact of targeting transforming growth factor ?-2 with antisense OT-101 on the cytokine and chemokine profile in patients with advanced pancreatic cancer |pdf=|usr=}}{{29785126}} gab.com Text Impact of targeting transforming growth factor -2 with antisense OT-101 on the cytokine and chemokine profile in patients with advanced pancreatic cancer JO: Onco Targets Ther http://www.kidney.de/pget.php?&tw=1&pmid=29785126 #FOAvip Background: Overexpression of the cytokine ? transforming growth factor-beta 2 (TGF-?2) ? has been implicated in the malignant progression of pancreatic cancer (PAC). OT-101 (trabedersen) is an antisense oligodeoxynucleotide designed to target the human TGF-?2 mRNA. In a Phase I/II study, OT-101 treatment with subsequent chemotherapy was characterized by outstanding overall survival (OS) in patients with PAC. Objective: This study sought to identify 1) co-regulated sets of cyto-/chemokines; 2) potential mechanisms that link TGF-? receptor type 2 receptor inhibition that may result in the induction of a cytokine storm; and 3) predictive biomarkers for OS outcome in OT-101-treated patients with PAC. Materials and methods: Plasma levels of 31 cyto-/chemokines were tracked over three cycles of OT-101 therapy (140 mg/m2/day) in 12 PAC patients. Samples were acquired before onset of OT-101 therapy and at eight selected time points during therapy. A mixed ANCOVA model was developed for 19 cyto-/chemokines with median expression >1 following OT-101 therapy. Regression and hierarchical clustering analyses were performed to identify correlated expressions in each patient across cyto-/chemokines or in each cyto-/chemokine across patients. Plasma cyto-/chemokine levels were compared with OS with and without subsequent chemotherapy. Results: Three highly correlated subsets of cyto-/chemokines (Cluster 1: EGF, MIP-1?, MIP-1?; Cluster 2: FGF-2, MIG, IP-10, IL-15, IFN-?, IL-12; and Cluster 3: HGF, IL-6, IL-8) were identified following OT-101 therapy. Suppression of TGF-? signaling by OT-101 led to upregulation of IL-8, IL-15, IP-10, and HGF. Protein?protein interaction networks constructed using STRING10 algorithm identified a relationship between IL-8, IL-15, and TGF-? receptor type 2 inhibition. The mixed analysis of covariance model that examined the levels of 19 cyto-/chemokines with OS as the covariate at each of the time points resulted in IL-8 and IL-15 exhibiting a significant association with OS during Cycle 1 of therapy. In the whole-blood culture model, the cytokines with the most pronounced increase after OT-101 treatment were IL-1?, IL-8, and MCP-1. Conclusion: No consistent responses in cyto-/chemokine levels were observed due to OT-101 treatment. Levels of IL-8 and IL-15 during Cycle 1 were positively associated with OS across 12 patients with PAC and served as potential biomarkers for treatment outcome following OT-101 therapy. Twit Text FOAVip Impact of targeting transforming growth factor -2 with antisense OT-101 on the cytokine and chemokine profile in patients with advanced pancreatic cancer ????Onco Targets Ther http://www.kidney.de/pget.php?&tw=1&pmid=29785126 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29785126 #FOAvip English Wikipedia <ref>{{Cite pmid|29785126}}</ref> Impact of targeting transforming growth factor ?-2 with antisense OT-101 on the cytokine and chemokine profile in patients with advanced pancreatic cancer #MMPMID29785126 D?Cruz OJ; Qazi S; Hwang L; Ng K; Trieu V Onco Targets Ther 2018[]; 11 (ä): 2779-96 PMID29785126show ga Background: Overexpression of the cytokine ? transforming growth factor-beta 2 (TGF-?2) ? has been implicated in the malignant progression of pancreatic cancer (PAC). OT-101 (trabedersen) is an antisense oligodeoxynucleotide designed to target the human TGF-?2 mRNA. In a Phase I/II study, OT-101 treatment with subsequent chemotherapy was characterized by outstanding overall survival (OS) in patients with PAC. Objective: This study sought to identify 1) co-regulated sets of cyto-/chemokines; 2) potential mechanisms that link TGF-? receptor type 2 receptor inhibition that may result in the induction of a cytokine storm; and 3) predictive biomarkers for OS outcome in OT-101-treated patients with PAC. Materials and methods: Plasma levels of 31 cyto-/chemokines were tracked over three cycles of OT-101 therapy (140 mg/m2/day) in 12 PAC patients. Samples were acquired before onset of OT-101 therapy and at eight selected time points during therapy. A mixed ANCOVA model was developed for 19 cyto-/chemokines with median expression >1 following OT-101 therapy. Regression and hierarchical clustering analyses were performed to identify correlated expressions in each patient across cyto-/chemokines or in each cyto-/chemokine across patients. Plasma cyto-/chemokine levels were compared with OS with and without subsequent chemotherapy. Results: Three highly correlated subsets of cyto-/chemokines (Cluster 1: EGF, MIP-1?, MIP-1?; Cluster 2: FGF-2, MIG, IP-10, IL-15, IFN-?, IL-12; and Cluster 3: HGF, IL-6, IL-8) were identified following OT-101 therapy. Suppression of TGF-? signaling by OT-101 led to upregulation of IL-8, IL-15, IP-10, and HGF. Protein?protein interaction networks constructed using STRING10 algorithm identified a relationship between IL-8, IL-15, and TGF-? receptor type 2 inhibition. The mixed analysis of covariance model that examined the levels of 19 cyto-/chemokines with OS as the covariate at each of the time points resulted in IL-8 and IL-15 exhibiting a significant association with OS during Cycle 1 of therapy. In the whole-blood culture model, the cytokines with the most pronounced increase after OT-101 treatment were IL-1?, IL-8, and MCP-1. Conclusion: No consistent responses in cyto-/chemokine levels were observed due to OT-101 treatment. Levels of IL-8 and IL-15 during Cycle 1 were positively associated with OS across 12 patients with PAC and served as potential biomarkers for treatment outcome following OT-101 therapy. äImpact of targeting transforming growth factor ?-2 with antisense OT-1(epmc).pdf DeepDyve Pubget Overpricing