Cbl-b and PI3K/Akt pathway are differently involved in oxygen-glucose deprivation preconditioning in PC12 cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Transient sublethal ischemia is known as ischemic preconditioning, which enables cells and tissues to survive subsequent prolonged lethal ischemic injury. Ischemic preconditioning exerts neuroprotection through phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Cbl-b belongs to the Casitas B-lineage lymphoma (Cbl) family, and it can regulate the cell signal transduction.The roles of ubiquitin ligase Cbl-b and PI3K/Akt pathway and the relationship between them in oxygen-glucose deprivation preconditioning (OGDPC) in PC12 cells were investigated in the present study.</p><p><b>METHODS</b>Oxygen and glucose deprivation (OGD) model in PC12 cells was used in the present study. The 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, nuclear staining with Hoechst 33258, and Western blotting were applied to explore the roles of Cbl-b and PI3K/Akt pathway and the relationship between them in OGDPC in PC12 cells.</p><p><b>RESULTS</b>Cell viability was significantly changed by OGD and OGDPC. OGD significantly decreased cell viability compared with the control group (P < 0.05), and preconditioning could rescue this damage was demonstrated by the increase of cell viability (P < 0.05). The expression of Cbl-b was significantly increased after OGD treatment. However, the activation of Akt and GSK3β was greatly inhibited. Preconditioning could inhibit the increase of Cbl-b caused by OGD and increase the activation of Akt and GSK3β. LY294002, a specific inhibitor of PI3K, could effectively inhibit the increase of Akt and GSK3β after preconditioning treatment. It partly inhibited the decrease of Cbl-b expression after preconditioning treatment.</p><p><b>CONCLUSION</b>Ubiquitin ligase Cbl-b and PI3K/Akt pathway are differently involved in OGDPC in PC12 cells.</p>

Prognostic role of apoptosis-related gene Fas-1377 and -670 polymorphisms in breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the correlations between Fas-1377 and -670 polymorphisms and survival in Chinese women with breast cancer.</p><p><b>METHODS</b>Polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP) was used to detect the polymorphism of Fas gene in 310 breast cancer patients with a long-term follow-up (median 10.5 years, range 0.2 - 16.1 years). Survival curves were analyzed by Kaplan-Meier method.</p><p><b>RESULTS</b>The polymorphism of neither Fas-1377 nor Fas-670 was significantly correlated with the overall survival in this series of 310 cases (P > 0.05). However, among 146 patients without lymph node metastasis, the 5-year overall survival (OS) rate was significantly lower in the patients with Fas-1377 AA genotype than that in the patients with Fas-1377 GA or GG genotype (OS: 66.7% vs. 95.4%, P = 0.03). Among 117 patients with lymph node metastasis, both the Fas-1377 and Fas-670 polymorphisms were not significantly correlated with OS (P = 0.42).</p><p><b>CONCLUSION</b>Among breast cancer patients without lymph node metastasis, patients with Fas-1377 AA genotype may have a worse survival, while patients with Fas-1377 GA or GG genotype may not be so.</p>