Anti-proliferation effect of sorafenib in combination with 5-FU for hepatocellular carcinoma in vitro: antagonistic performance and mechanism / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the anti-cancer efficacy and mechanism of sorafenib and 5-fluorouracil (5-FU) therapy in vitro using the HCC cell line MHCCLM3.</p><p><b>METHODS</b>The effects of sorafenib and 5-FU, alone or in combination, on the proliferation of MHCCLM3 cells were evaluated by cell viability assays. Combined-effects analyses were conducted according to the median-effect principle established by Chou and Talalay. Effects on cell cycle distributions were tested by flow cytometry and expression of proteins related to the RAF/MEK/ERK and STAT3 signaling pathways and cyclinD1 were tested by western blotting.</p><p><b>RESULTS</b>Sorafenib and 5-FU alone or in combination displayed significant efficacy in inhibiting proliferation of the MHCCLM3 cells, with the following inhibition rates: sorafenib: 46.16% +/- 2.52%, 5-FU: 28.67% +/- 6.16%, and sorafenib + 5-FU: 22.59% +/- 6.89%. The sorafenib + 5-FU combination did not provide better results than treatment with either drug alone. The combination index values of the sorafenib and 5-FU treatments were mainly greater than 1, indicating that the two agents induced antagonistic, instead of synergistic, effects on the MHCCLM3 cells. In addition, the MHCCLM3 cells were less sensitive to 5-FU when administrated in combination with sorafenib, as evidenced by the half inhibitory concentration (IC50) significantly increasing from (102.86 +/- 27.84) mg/L to (178.61 +/- 20.73) mg/L (P = 0.003). Sorafenib alone induced G1 phase arrest (increasing from 44.73% +/- 1.63% to 65.80% +/- 0.56%; P less than 0.001) and significantly decreased the proportion of cells in S phase (decreasing from 46.63% +/- 0.65% to 22.83% +/- 1.75%; P less than 0.01), as well as down-regulated cyclinD1 expression (0.57 +/- 0.03-fold change vs. untreated control group; P less than 0.01). 5-FU alone up-regulated cyclinD1 expression (1.45 +/- 0.12-fold change vs. untreated control group; P less than 0.01). Moreover, sorafenib alone significantly inhibited the RAF/MEK/ERK and STAT3 pathways, with the fold-changes of p-C-RAF, p-ERK1/2 and p-STAT3 being 0.56 +/- 0.05, 0.54 +/- 0.02 and 0.36 +/- 0.02, respectively (all P less than 0.01); 5-FU alone produced no significant effects on these pathways.</p><p><b>CONCLUSION</b>Administered alone, both sorafenib and 5-FU exert anti-tumoral activity on in vitro cultured HCC cells. The sorafenib + 5-FU combination treatment produces antagonistic, rather than synergistic, effects. Sorafenib-inhibited RAF/MEK/ERK and STAT3 signaling and cyclinD1 expression may have induced the observed G1phase arrest and S phase reduction, thereby reducing the cells' sensitivity to 5-FU.</p>

Influence of reducing buccolingual width of artificial crown of implant prosthesis on distribution of biting force and masticatory efficiency / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To discuss the influence of reducing buccolingual width of artificial crown on distribution of biting force and masticatory efficiency in unilateral distal-extension implant denture and provide valuable information for the design of buccolingual width. To find a design that the biting force of implant prothesis was less evident than those on the contralateral natural teeth without compromising masticatory efficiency.</p><p><b>METHODS</b>T-Scan II occlusal analyzer and 722 grating spectrophotometer were used to analyze the distribution of biting force and masticatory efficiency in unilateral distal-extension implant denture. Heat-cured resin crowns with three different buccolingual width (group A: standard buccolingual width; group B: the buccolingual width was reduced by 1/4; group C: the buccolingual width was reduced by 1/3) were designed as follow, one was contoured with standard buccolingual width, the other two were made with reducd buccolingual width by 1/4 and 1/3.</p><p><b>RESULTS</b>The ratio of biting force (ROF) of group C was 16.25%, which was significantly lower than group A (27.38%) and B (22.60%) (P < 0.0083). The X axis displacement of center of occlusal force (COF) of group C was 2.0 mm, which was significantly difference with group A (1.5 mm, P = 0.004). The masticatory efficiency absorbance A value (MEA) of group C was 0.217, which was significantly lower than group A (0.345, P = 0.005) and B (0.289, P = 0.004).</p><p><b>CONCLUSIONS</b>According to the study, the buccolingual width of the crown reduced by 1/4 was a more ideal design for unilateral distal-extension implant denture.</p>