Journal: Toxicological Sciences

Article Title: Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques

doi: 10.1093/toxsci/kfac128

Figure Lengend Snippet: Inhibition of αvβ6 integrin or TGFβR1 induce proliferation in primary human bladder epithelial cells in culture. All proliferation measurements were assessed following 3 days of exposure to treatments. Selective αvβ6 integrin inhibitor, MORF-627 (A). Structurally distinct tool αvβ6 integrin inhibitor (B). TGFβR1 multikinase inhibitor (C). Proliferative changes induced by MORF-627 were reversed by concomitant incubation of test agent with exogenous TGF-β (D). Graphs represent 3 independent experiments, with each concentration run in triplicate per study. All data are plotted as raw luminescence mean ± SEM; * p < .05, ** p < .01, *** p < .001, and **** p < .0001 indicate statistical significance compared with bleomycin IgG isotype group, using 2-tailed unpaired t -test with Welsh’s correction.

Article Snippet: An anti-αvβ6 antibody ( Weinreb et al. , 2004 ) without effector function was generated by Morphic Therapeutic at ATUM Bio, based on the sequence of the variable fragment (Fab) of 3G9 (US patent 8,153,126 B2) fused with the constant fragment (Fc) of mouse IgG1 backbone.

Techniques: Inhibition, Incubation, Concentration Assay

Journal: Toxicological Sciences

Article Title: Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques

doi: 10.1093/toxsci/kfac128

Figure Lengend Snippet: Inhibition of αvβ6 integrin or TGFβR1 induce proliferation in primary human alveolar epithelial cells in culture. All proliferation measurements were assessed following 3 days of exposure to treatments. Selective αvβ6 integrin inhibitor, MORF-627 (A). Structurally distinct tool αvβ6 integrin inhibitor (B). TGFβR1 multikinase inhibitor (C). Proliferative changes induced by MORF-627 were reversed by concomitant incubation of test agent with exogenous TGF-β (D). Graphs represent 3 independent experiments, with each concentration run in triplicate per study. All data are plotted as raw luminescence mean ± SEM; * p < .05, ** p < .01, *** p < .001, and **** p < .0001 indicate statistical significance compared with bleomycin IgG isotype group, using 2-tailed unpaired t -test with Welsh’s correction.

Article Snippet: An anti-αvβ6 antibody ( Weinreb et al. , 2004 ) without effector function was generated by Morphic Therapeutic at ATUM Bio, based on the sequence of the variable fragment (Fab) of 3G9 (US patent 8,153,126 B2) fused with the constant fragment (Fc) of mouse IgG1 backbone.

Techniques: Inhibition, Incubation, Concentration Assay

Journal: Toxicological Sciences

Article Title: Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques

doi: 10.1093/toxsci/kfac128

Figure Lengend Snippet: Tool αvβ6 inhibitor and TGFβR1 selective inhibitor increased biliary epithelial cell proliferation in DDC-induced biliary fibrosis model. A, Representative images of IHC staining for CK19 expressing epithelial cells in healthy mice ( n = 5) and mice fed with DDC diet with or without treatment ( n = 9–15/group). Scale bar = 200 µm. B, IHC quantification of CK19 expressing biliary epithelial cells. (**** p < .0001 indicate statistical significance compared with DDC vehicle group, using 1-way ANOVA with Dunnett’s post hoc test.) C, IHC quantification of Ki67 positive proliferating cells (* p < .05, ** p < .01 indicate statistical significance compared with DDC vehicle group using 2-tailed Student’s T test). All data are shown as means ± SEM.

Article Snippet: An anti-αvβ6 antibody ( Weinreb et al. , 2004 ) without effector function was generated by Morphic Therapeutic at ATUM Bio, based on the sequence of the variable fragment (Fab) of 3G9 (US patent 8,153,126 B2) fused with the constant fragment (Fc) of mouse IgG1 backbone.

Techniques: Immunohistochemistry, Expressing

Journal: Toxicological Sciences

Article Title: Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques

doi: 10.1093/toxsci/kfac128

Figure Lengend Snippet: Anti-αvβ6 antibody (3G9) increased biliary epithelial cell proliferation in DDC-induced biliary fibrosis model. A, IHC quantification of CK19 expressing epithelial cells in healthy mice and mice fed with DDC diet with or without treatment ( n = 10/group). B, IHC quantification of Ki67 positive proliferating cells. C, KEGG pathway analysis of bulk RNA sequencing data from liver tissues. All data are shown as means ± SEM. * p < .05, ** p < .01, *** p < .001, and **** p < .0001 indicate statistical significance compared with DDC vehicle group, using 1-way ANOVA with Dunnett’s post hoc test.

Article Snippet: An anti-αvβ6 antibody ( Weinreb et al. , 2004 ) without effector function was generated by Morphic Therapeutic at ATUM Bio, based on the sequence of the variable fragment (Fab) of 3G9 (US patent 8,153,126 B2) fused with the constant fragment (Fc) of mouse IgG1 backbone.

Techniques: Expressing, RNA Sequencing

Journal: Toxicological Sciences

Article Title: Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques

doi: 10.1093/toxsci/kfac128

Figure Lengend Snippet: Anti-αvβ6 antibody (3G9) promoted cell proliferation in bleomycin-induced lung fibrosis model. A, KEGG pathway analysis of bulk RNA sequencing data from lung tissues. mRNA levels of cell cycle genes, (B) Mki67 and (C) Pcna, in lung tissues. All data are shown as means ± SEM. * p < .05, ** p < .01, *** p < .001, and **** p < .0001 indicate statistical significance compared with bleomycin IgG isotype group, using 1-way ANOVA with Dunnett’s post hoc test.

Article Snippet: An anti-αvβ6 antibody ( Weinreb et al. , 2004 ) without effector function was generated by Morphic Therapeutic at ATUM Bio, based on the sequence of the variable fragment (Fab) of 3G9 (US patent 8,153,126 B2) fused with the constant fragment (Fc) of mouse IgG1 backbone.

Techniques: RNA Sequencing