Treatment with ML-7, as well as with MP6-XT22, may reduce CAC development in AOM/DSS model.

<p>(A) Numbers of microscopically indicated tumors per colon in AOM/DSS-administered mice with either vehicle control (Ctrl), anti-TNF Ab (MP6-XT22), ML-7 treatment during the entire protocol (ML-7 entire), or ML-7 treatment at the final phase of protocol (ML-7 final) (n = 10) are shown. Tumors were determined under the microscope. Data are expressed as means ± SEM. *; p<0.01, **; p<0.05. (B) Macroscopic overview of representative colonic samples from each group is shown. (C) Histological assessment of colitis in mice treated with either control, MP6-XT22 or ML-7 (at the final phase) (n = 10). Data are expressed as means ± SEM. *; p<0.05. (D) Relative mRNA expressions for IL-1β, IL-6 MIP-2 and TNFR2 in inflamed mucosa from non-tumor or tumor tissues in mice treated with either control, MP6-XT22 or ML-7 (final phase) were analyzed. Each mRNA level was quantified by RT-PCR and normalized to the level of G3PDH (n = 3). *; p<0.01, **; p<0.05. (E) Protein lysates of the isolated epithelial cells from non-tumor or tumor tissues in mice administered with either control, MP6-XT22 or ML-7 (final phase) treatment were subjected to Western blotting with either anti-TNFR1, anti-TNFR2, anti-p-p65, anti-pIκBα, anti-MLCK, anti-p-MLC, or anti-β-actin Abs, respectively. (F) Electron microscopic images of representative non-tumor and tumor samples from either control, MP6-XT22 or ML-7 (final phase) treated group are shown (n = 10). Arrows indicate fine tight junction, and arrow heads indicate disrupted intercellular junctional complexes.