The canonical Wnt signalling pathway is activated in most sporadic colorectal cancers (CRCs). We previously reported that FZD7 functions as a receptor for the canonical Wnt signalling pathway in ...colon cancer cells.
In this study, we examined the function of FZD7 in survival, invasion and metastatic capabilities of colon cancer cells. FZD7_siRNA transfection decreased cell viability of HT-29 and HCT-116 colon cancer cells. Expression of c-Jun, phosphorylation of JNK and c-Jun, and activation of RhoA were suppressed after FZD7_siRNA transfection into HCT-116 cells. In vitro invasion activity and Wnt target gene expression were also reduced in HCT-116 cells transfected with FZD7_siRNA. Liver metastasis of stable FZD7_siRNA HCT-116 cell transfectants in scid mice was decreased to 40-50% compared to controls. The mRNA levels of FZD7 in 135 primary CRC tissues were examined by real-time PCR. FZD7 mRNA levels were significantly higher in stage II, III or IV tumours than in non-tumour tissues (P<0.005), and overall survival was shorter in those patients with higher FZD7 expression (P<0.001).
These data suggest that FZD7 may be involved in enhancement of survival, invasion and metastatic capabilities of colon cancer cells through non-canonical Wnt signalling pathways as well as the canonical pathway.
Ras association domain family 1A (RASSF1A) is a tumor suppressor that regulates the cell cycle, apoptosis, and microtubule stability. The association between the methylation levels of RASSF1A and the ...prognosis of clear-cell renal cell carcinoma (CCRCC) remains unclear. Therefore, we investigated this relationship to determine the prognostic value of RASSF1A methylation levels for CCRCC.
The study comprised 179 Japanese patients who underwent radical or partial nephrectomy for CCRCC. The methylation level of 5′ CpG islands in the RASSF1A was evaluated using combined bisulfite restriction analysis and bisulfite sequencing.
High levels of methylation in the RASSF1A promoter were significantly more frequent in grade 3 compared with grade 1 or 2 tumors (P = 0.028) and in patients with stage III or IV compared with patients with stage I or II (P = 0.043). Patients with high methylation levels had a significantly less favorable prognosis compared with those with low methylation levels (P = 0.040). Higher methylation levels were independently associated with a poor prognosis following multivariate analysis (P = 0.0053).
These results indicate that quantitative promoter methylation levels of the RASSF1A gene may be a useful marker to predict the prognosis of CCRCC.
Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) represent severe late effects in patients receiving hematopoietic cell transplantation (HCT) for lymphoma. The choice ...between high-dose therapy with autologous HCT and allogeneic HCT with reduced-intensity conditioning remains controversial in patients with relapsed lymphoma. We retrospectively analyzed incidence and risk factors for the development of t-AML/MDS in lymphoma patients treated with autologous or allogeneic HCT. A total of 13 810 lymphoma patients who received autologous (n=9963) or allogeneic (n=3847) HCT between 1985 and 2012 were considered. At a median overall survival (OS) of 52 and 46 months in autologous and allogeneic HCT groups, respectively, lymphoma patients receiving autologous HCT (1.38% at 3 years after autologous HCT) had a significant risk for developing t-AML/MDS compared to allogeneic HCT (0.37% at 3 years after allogeneic HCT, P<0.001). Significant risk factors for the development of t-AML/MDS after autologous and allogeneic HCT were high-stage risk at HCT (P=0.04) or secondary malignancies (P<0.001) and receiving cord blood stem cell (P=0.03) or involved field radiotherapy (P=0.002), respectively. Strategies that carefully select lymphoma patients for autologous HCT, by excluding lymphoma patients with high-stage risk at HCT, may allow the identification of individual lymphoma patients at particular high risk for t-AML/MDS.
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