Evaluation of combination agents in CD-DST.

<p>The in vitro sensitivity was expressed as the T/C ratio, in which T is the total volume of living cancer cells in the treated group, and C is the total volume of living cancer cells in the control group. Positive, T/C <60%; negative, T/C ≥ 60%.</p><p>5-FU, 5-fluorouracil; SN38, the active metabolite of irinotecan; OHP, the active metabolite of oxaliplatin.</p>*<p>statistically significant.</p

Comparison of chemosensitivity between primary site and lung metastasis in CD-DST.

<p>5-FU, 5-fluorouracil; SN38, the active metabolite of irinotecan; OHP, the active metabolite of oxaliplatin.</p><p>There was no significant difference in chemosensitivity when comparing the lung metastasis and the primary tumor.</p

Characteristics of patients with metastatic colorectal cancer.

<p>Characteristics of patients with metastatic colorectal cancer.</p

Effects of IL-1β on IL-36γ mRNA expression in colonic myofibroblasts.

<p>(A) Dose-dependent effects of IL-1β on IL-36γ mRNA expression. The cells were incubated for 24 h with increasing concentrations of IL-1β. IL-36γ mRNA expression was expressed relative to β-actin mRNA expression (mean ± SD from 4 different experiments). (B) Time-dependent effects of IL-1β on IL-36γ mRNA expression. The cells were stimulated with IL-1β (10 ng/ml) for the pre-determined times. IL-36γ mRNA expression was expressed relative to β-actin mRNA expression (mean ± SD from 4 different experiments). (C) Dose-dependent effects of IL-1β on IL-36γ secretion. The cells were incubated for 24 h with increasing concentrations of IL-1β. IL-36γ level in supernatant was determined by ELISA (mean ± SD from 4 different experiments). (D) Time-dependent effects of IL-1β on IL-36γ secretion. The cells were stimulated with IL-1β (10 ng/ml) for the pre-determined times. IL-36γ level was determined by ELISA (mean ± SD from 4 different experiments). *P<0.05, **P<0.01 versus medium; ANOVA followed by Bonferroni’s post hoc test.</p

Combined effects of IL-1β and other cytokines.

<p>(A) The cells were incubated for 24 h with combination of IL-1β (10 ng/ml) and other cytokines [TNF-α (100 ng/ml), IFN-γ (100 ng/ml), IL-4 (100 ng/ml), and/or IL-17A (100 ng/ml)]. IL-36γ mRNA expression was analyzed by real-time PCR. IL-36γ mRNA expression was expressed relative to the β-actin mRNA expression (mean ± SD from 4 different experiments). **P<0.01 versus IL-1β alone. (B) The cells were stimulated for 24 h with or without IL-1β (10 ng/ml), TNF-α (100 ng/ml), and/or combination of IL-1β (10 ng/ml) and TNF-α (100 ng/ml), and intracellular IL-36γ was analyzed by Western blot.</p

Involvement of activation of transcription factors, NF-κB and /AP-1, in IL-1β-induced IL-36γ expression.

<p>(A) IL-1β induced IκBα phosphorylation and degradation in colonic myofibroblasts. The cells were stimulated with IL-1β (10 ng/ml), and phosphorylated IκBα were detected by Western blotting. (B) IL-1β induced activation of NF-κB and c-Jun AP-1. The cells were stimulated with IL-1β (10 ng/ml), and NF-κB p65 and phosphorylated c-Jun were detected by immunocytochemistory. Reacted antibodies against NF-κB p65 were visualized by FITC (green fluorescence)-labeled second antibody. Reacted antibodies against phosphorylated c-Jun were detected by a DyLight^® 594 (red fluorescence)-labeled secondary antibodies. Nucleus was stained by DAPI (blue). (C) The cells were stimulated with IL-1β (10 ng/ml) or medium alone for 15 min and nuclear proteins were extracted. NF-κB p65 and phosphorylated c-Jun in nuclear extracts were detected by immunoblot. (D) Effects of silencing of NF-κB p65 and c-Jun AP-1on IL-1β-induced IL-36γ expression. The cells were transfected with control siRNA, the siRNA specific for NF-κB p65 and/or c-Jun AP-1, and incubated for 24h. IL-36γ mRNA expression was analyzed by real-time PCR. IL-36γ mRNA expression was expressed relative to the β-actin mRNA expression (mean ± SD from 4 different experiments). *P<0.05, **P < 0.01 versus IL-1β stimulation.</p

Involvement of MAPK activation in IL-1β-induced IL-36γ expression.

<p>(A) MAPK activation in colonic SEMFs. The cells were stimulated with IL-1β (10 ng/ml), and the activation of MAPKs were analyzed by Western blotting. Antibodies against phosphorylated (p)- and total- MAPKs were used. *P < 0.05, **P<0.01. (B) The cells were stimulated for 24 h with IL-1β (10ng/ml) in the presence or absence of MEK inhibitors [U0216 (10 μM) and PD98059 (10 μM)] and a p38 inhibitor [SB203580 (10 μM)]. IL-36γ mRNA expression was analyzed by real-time PCR. IL-36γ mRNA expression was expressed relative to the β-actin mRNA expression (mean ± SD from 4 different experiments).</p

Patient Characteristics.

<p>p: Difference in means or rates were tested using Student's t-test or Chi-square test.</p><p>HT, height; BW, body weight; BMI, body mass index; ASA, American Society of Anesthesiologists; CRP, C reactive protein; Hb, hemoglobin; AND, adiponectin.</p

The receiver operating curves (ROCs) of postoperative infection for four potential predictors.

<p>The AUC values for preoperative ADN levels, ADN ratio, blood loss, operating time, and CRP levels were 0.616, 0.848, 0.757, 0.675, and 0.617, respectively. The useful cut-off values (sensitivity/specificity) for predicting preoperative ADN levels, ADN ratio, blood loss, operating time, and CRP levels were 8.81 µg/dL (0.567/0.568), 0.76 (0.767/0.761), 405 g (0.717/0.693), 342 min (0.617/0.614), and 8.94 mg/dL (0·583/0·591), respectively.</p

The multivariate adjusted odds ratios for postoperative infection.

*<p><i>p</i><0.05,</p>**<p><i>p</i><0.01.</p><p>Model 1: Basic potential risk factors [gender, patient age, BMI, log (blood loss), ASA, T2DM, and the surgical procedure]; Model 2: Basic factors plus CRP levels; Model 3: Basic factors plus ADN ratio; Model 4: Basic factors plus preoperative ADN levels; Model 5: Basic factors plus CRP and preoperative ADN levels and ADN ratio. Blood loss was included in the models as log (blood loss), which was normally distributed, whereas CRP levels were mostly normally distributed. The odds ratio for each continuous variable was expressed for one standard deviation increase [11.61 for age; 3.82 for BMI; 616.17 for log (blood loss); 114.12 for time; 3.47 for CRP levels (POD 1); 5.09 for preoperative ADN levels; and 0.21 for ADN ratio]. The odds ratio was calculated for one standard deviation decrease only for the ADN ratio. CI: confidence interval.</p