The aberrant activation of Wnt pathway caused by ß-catenin mutation and its prognostic significance in NK/T-cell lymphoma.

The aberrant activation of the Wnt/ß-catenin signal has an important role in the progression of cancers. Herein, we investigated ß-catenin mutation and the activation of the Wnt pathway in association with the clinical-pathological characteristics, chemo-resistance and prognosis of NK/T-cell lymphoma (NKTCL). Real-time quantitative PCR, immunocytochemistry and immunohistochemistry SP methods detected the levels of ß-catenin, c-myc and cyclin D1 in human NKTCL cell lines (SNK-6 and YTS) and NKTCL tissues. Mutation analysis was detected in exon 3 of ß-catenin gene; and we analyzed cell viability after histone deacetylase inhibitor (HDACi) treatment. As a result, 19 (38%) of NK/T-cell lymphoma displayed nuclear ß-catenin and 16 (32%) contained mutations in exon 3; while no mutations were detected in lymphomas negative for ß-catenin nuclear staining (p<0.05). Most mutations affecting ß-catenin were adjacent to regulatory phosphorylation sites. ß-catenin, c-myc and cyclin D1 were significantly elevated in SNK-6 and YTS cell lines compared to normal NK/T cells (p<0.05). Furthermore, the high expression of ß-catenin, c-myc and cyclin D1 significantly correlated with the III/IV Ann Arbor stage. Additionally, the expression of ß-catenin in the SNK-6 cell line decreased significantly after treatment with HDACi, and Kaplan-Meier survival analysis revealed that the elevated expression of ß-catenin correlated with poor prognosis in NKTCL patients (23.66±2.77 months vs 31.65±1.78 months, p=0.023). In conclusion: mutations in exon 3 of ß-catenin and the activated Wnt pathway are common in NK/T-cell lymphoma that has nuclear ß-catenin, and it is closely correlated with the Ann Arbor stage and prognosis in NKTCL patients.

Interaction between synchronous bilateral prophylactic oophorectomy and adjuvant chemotherapy in female patients with locally advanced colorectal cancer.

AIM: In this study we explored the prognostic impact of synchronous bilateral prophylactic oophorectomy in female patients with primary colorectal cancer undergoing radical surgery. METHOD: From 1991 to 2000, 267 female patients with stage II or stage III colorectal cancer, who had undergone curative resection, were retrospectively reviewed. In 224 patients, the ovaries were preserved. The other 43 patients underwent synchronous bilateral prophylactic oophorectomy. Univariate and multivariate analyses (Kaplan-Meier and Cox regression, respectively) were used to evaluate the effect of prophylactic oophorectomy and other clinical factors on the prognosis of patients. RESULTS: Both univariate and multivariate analyses showed that tumor stage and adjuvant chemotherapy were the only two significant clinical factors that affected the 5-year overall survival of patients (P < 0.01). There was no significant difference in the 5-year overall survival between patients who had, or had not, undergone prophylactic oophorectomy (75%vs 73%, P > 0.05). In the subgroup analysis by adjuvant chemotherapy, the 5-year overall survival in patients receiving adjuvant chemotherapy was similar between nonoophorectomy and oophorectomy groups. However, in patients without adjuvant chemotherapy, the oophorectomy group was shown to have a significantly better 5-year overall survival than the nonoophorectomy group (76%vs 51%, P = 0.047). CONCLUSION: Prophylactic oophorectomy may improve the overall survival of female patients with locally advanced colorectal cancer without adjuvant chemotherapy, but its survival benefit vanished in patients receiving adjuvant chemotherapy. The role of prophylactic oophorectomy may be substituted by adjuvant chemotherapy, which makes prophylactic oophorectomy unnecessary during surgery for locally advanced colorectal cancer.

Growth performance, rumen fermentation, bacteria composition, and gene expressions involved in intracellular pH regulation of rumen epithelium in finishing Hu lambs differing in residual feed intake phenotype.

The objective of this study was to evaluate the effect of residual feed intake (RFI) on rumen function in finishing lambs. A total of 60 male Hu lambs (average initial BW = 25.2 ± 2.5kg) were used and were offered a pelleted high-concentrate diet, of which the forage to concentrate ratio was 25:75. Individual feed intake was recorded over a period of 42 d, then 10 lambs with the lowest RFI and the highest RFI were selected, respectively. The rumen fluid used for fermentation variables and relative abundance of bacteria measurement was obtained on d 10 and 20 after RFI measurement. At the end of this experiment, the selected lambs were slaughtered and rumen epithelium and liver tissues were collected for RNA extraction. Low-RFI lambs had lower ( < 0.01) DMI and greater ( < 0.05) G:F than the high-RFI ones, while the RFI groups did not differ in ADG and BW ( > 0.05). Additionally, RFI was positively ( = 0.57; < 0.01) correlated with DMI and negatively ( = -0.53; < 0.05) correlated with G:F. Total VFA and individual VFA decreased ( < 0.05) over time. The concentrations of total VFA, acetate, valerate, isobutyrate, isovalerate, and rumen pH ( > 0.05) were not affected by RFI classification. Nonetheless, low-RFI group lambs had a greater ( < 0.05) concentration of propionate, a lower ( < 0.05) concentration of butyrate, and a lower ( < 0.05) acetate to propionate ratio compared with the high-RFI group. There was a significant ( < 0.05) effect of RFI on the relative abundance of and . The relative abundance of , , and decreased ( < 0.05) over time in high-RFI group. And the relative abundance of in high-RFI group was greater ( < 0.05) than its low-RFI counterpart. Furthermore, RFI had no effect ( > 0.05) on gene expression associated with intracellular pH regulation (, , , , , , , and ) in rumen epithelium and ß-hydroxybutyrate metabolism () in both rumen epithelium and liver tissues. In conclusion, even though low-RFI lambs had lower DMI, however, the number of was lower. Additionally, there was no difference in gene expressions level associated with intracellular pH regulation in rumen epithelium between RFI groups.