ABSTRACT
ß-Amyloid protein (Aß) is thought to cause neuronal loss in Alzheimer's disease (AD). Aß treatment promotes the re-activation of a mitotic cycle and induces rapid apoptotic death of neurons. However, the signaling pathways mediating cell-cycle activation during neuron apoptosis have not been determined. We find that Wnt5a acts as a mediator of cortical neuron survival, and Aß42 promotes cortical neuron apoptosis by downregulating the expression of Wnt5a. Cell-cycle activation is mediated by the reduced inhibitory effect of Wnt5a in Aß42 treated cortical neurons. Furthermore, Wnt5a signals through the non-canonical Wnt/Ca2+ pathway to suppress cyclin D1 expression and negatively regulate neuronal cell-cycle activation in a cell-autonomous manner. Together, aberrant downregulation of Wnt5a signaling is a crucial step during Aß42 induced cortical neuron apoptosis and might contribute to AD-related neurodegeneration.
ABSTRACT
BACKGROUND & OBJECTIVE: Liver metastasis is the major cause of treatment failure of colorectal cancer. The median survival time of patients with untreated liver metastases is only about 6 months. Surgical resection is the major treatment to prolong survival time of the patients. This study was to assess surgical treatment efficacy on these patients and their prognosis. METHODS: Records of 59 colorectal cancer patients with liver metastases, treated with hepatectomy (including 14 cases of anatomical segmentectomy and 45 cases of wedge resection) from Jan. 1987 to Dec. 1998 in Cancer Hospital of Chinese Academy of Medical Sciences were reviewed. Postoperative complications occurred in 4 (6.8%) patients, without surgical death. Survival rate was estimated by Kaplan-Meier method, and compared by log-rank test. Prognostic factors were analyzed by multivariate Cox regression model. RESULTS: The overall 1-, 3-, and 5-year survival rates were 91.4%, 34.8%, and 21.9%. Survival rate was significantly lower in patients with heterochronia metastasis than in patients with synchronal metastasis (P < 0.05), and lower in patients with metastasis size of > 5 cm than in patients with metastasis size of < or = 5 cm. Univariate analysis showed that time of liver metastasis and metastasis size of > 5 cm were prognostic factors (P < 0.05); while node status of primary tumor, number of liver tumors, and carcinoembryonic antigen level had no significant relations with prognosis (P < 0.05). CONCLUSIONS: Hepatectomy may prolong survival time of colorectal cancer patients with liver metastases. Early diagnosis with intensive follow-up is crucial to increase the resectability of liver metastasis.