The role of Skp2 in extranodal NK/T-cell lymphoma / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Expression of Skp2 was related with the prognosis of several tumors. However, there was no intensive study on the relationship between Skp2 and extranodal NK/T cell lymphoma. This study was to explore the role of Skp2 in extranodal NK/T cell lymphoma.</p><p><b>METHODS</b>The clinicopathological data of 39 patients with extranodal NK/T cell lymphoma were analyzed. The expression of Skp2 was examined by immunohistochemistry on formalin fixed, paraffin embedded tissue sections.</p><p><b>RESULTS</b>Among the patients with high expression of Skp2, complete remission (CR) rate was only 14.3% (2/14). However, CR rate among the patients with low expression of Skp2 was 68.0% (17/25). Significant difference was shown between these two groups (P < 0.001). In the group of low expression, the median overall survival (OS) was 85.59 months (95% CI: 35.83 135.34 months), the 1 and 2 year OS rates were 81% and 71%, respectively. However, in the group of high expression, the median OS was only 9.73 months (95% CI: 2.05-17.40 months), the 1 and 2 year OS rates were 42% and 14%, respectively. There was statistical difference between these two groups (P < 0.001). Multivariate analysis showed that Skp2 expression (P <0.001), LDH (P = 0.026) and ECOG PS (P = 0.003) were dependent prognostic factors of extranodal NK/T cell lymphoma.</p><p><b>CONCLUSION</b>High expression of Skp2 is an independent unfavorite adverse prognostic factor of extranodal NK/T cell lymphoma.</p>

5-Fluorouracil upregulates the activity of Wnt signaling pathway in CD133-positive colon cancer stem-like cells / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>CD133-positive colon cancer stem like cells (CSLCs) are resistant to the conventional cytotoxic drug 5-fluorouracil (5-FU). Wnt signaling pathway plays important roles in colon cancer carcinogenesis and metastasis, and regulates the self-renewal capacity of CSLCs. In the present study, we explored the impact of 5-FU on Wnt signaling pathway of CD133-positive colon CSLCs, and the relation between Wnt signaling pathway and drug resistance of CD133-positive colon CSLCs.</p><p><b>METHODS</b>Magnetic activation cell separation was used to collect CD133-positive cells from colon cancer cell line DLD1, which was transfected with luciferase reporter for Wnt signaling activity. The activity of Wnt signaling pathway was compared between CD133-positive and CD133-negative cells. After the treatment with 1 μg/mL of 5-FU, the cell proliferation rates of DLD1 cells, CD133-positive cells, and CD133-negative cells were compared. After the treatment with 1 μg/mL and 10 μg/mL of 5-FU for 48 h, Wnt activity was compared between CD133-positive and CD133-negative cells. The expression of CD133 and cell apoptosis of CD133-positive cells was detected after exposure to 50 ng/mL of dickkopf (DKK)-1, a Wnt pathway inhibitor.</p><p><b>RESULTS</b>After the treatment with 5-FU, the cell proliferation rate of CD133-positive cells was higher than that of CD133-negative cells and the sensitivity of CD133-positive cells to 5-FU decreased. Wnt activity was higher in CD133-positive cells than in CD133-negative cells [(46.3 ± 0.3)% vs. (33.9 ± 2.7)%, P = 0.009]. After the treatment with 1 μg/mL and 10 μg/mL of 5-FU, Wnt activity of CD133-positive cells was (90.1 ± 10.0)% (P = 0.012) and (52.9 ± 2.5)% (P = 0.047), respectively, whereas that of CD133-negative cells was (35.5 ± 3.3)% (P = 0.434) and (26.5 ± 0.4)% (P = 0.046), respectively. CD133 expression in CD133-positive cells decreased from (87.2 ± 5.3)% to (60.6 ± 3.1)% (P = 0.022) after treatment with DKK-1, whereas the cell apoptosis rate increased from (11.8 ± 0.2)% to (28.3 ± 0.6)% (P = 0.013).</p><p><b>CONCLUSIONS</b>Wnt activity is higher in CD133-positive DLD1 cells than in CD133-negative DLD1 cells. 5-FU can upregulate Wnt activity of CD133-positive colon CSLCs. Blocking Wnt activity may reverse drug sensitivity of CD133-positive cells to 5-FU.</p>

Effect of KRAS mutation on efficacy of Cetuximab combined with chemotherapy in advanced colorectal cancer patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the relationship between KRAS gene status and efficacy of Cetuximab (C225) combined with chemotherapy on advanced colorectal cancer in Chinese patients, and to evaluate the safety of C225.</p><p><b>METHODS</b>From May 2006 to March 2009, 81 patients with advanced colorectal cancer received Cetuximab combined with chemotherapy were enrolled in this study. The rate of KRAS mutation and the relationship of KRAS with response rate (RR), progression-free survivor (PFS), overall survival (OS) and adverse reaction of C225 were analyzed retrospectively.</p><p><b>RESULTS</b>All the 81 patients received C225 therapy, and the overall RR was 33.3%. The RR of initiate therapy was 57.1%; of the second line and over the third line therapy was 38.5% and 22.0% respectively. KRAS gene phenotype examination was performed in 44 patients whose tumor samples were available. KRAS mutation was found in 20 cases (45%). Out of 44 patients, 43 were evaluable for response. RR was 5% and 43.48% in KRAS mutation and wild KRAS patients respectively (P =0.002). The median PFS was 7.0 weeks and 18.6 weeks in mutational KRAS patients and wild KRAS patients, reaching statistical significance (P =0.003). The median OS was 15.2 months and 17.3 months in mutational KRAS patients and wild KRAS patients respectively without statistical significance (P =0.463). The common adverse reactions were leucopenia, nausea, vomiting and rash. All the adverse reactions were tolerated. The incidence of skin rash in patients with mutational KRAS and patients without KRAS mutation was 40% and 42% respectively, without statistical significance (P =0.91).</p><p><b>CONCLUSION</b>C225 combined with chemotherapy is well-tolerated in Chinese patients with advanced colorectal cancer, and it can significantly prolong PFS of patients with wild KRAS as compared to patients with KRAS mutation.</p>