RESUMO
Accumulating evidence suggests that a history of diabetes may be involved in the occurrence of various types of cancer. However, the association of diabetes with the risk of brain tumors remains unclear. We identified relevant studies by performing a literature search of PubMed and EMBASE (through to 24 May 2012) and by searching the reference lists of pertinent articles. All data were extracted independently by two investigators using a standardized data abstraction tool. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Inter-study heterogeneity was assessed using the Cochran's Q and I(2) statistical tests. A total of 13 studies were included in this meta-analysis, including the entire Danish population, 5,107,506 other participants and more than 2,206 cases of brain tumors. In the analysis of these 13 studies, we observed that diabetic individuals had a similar risk of brain tumors as non-diabetic individuals (SRR, 1.12; 95% CI, 0.89-1.42). There was significant evidence of heterogeneity among these studies (P<0.001; I(2), 93.5%). Sub-group analysis revealed that diabetic females had a 24.2% increased risk of brain tumors (SRR, 1.242; 95% CI, 1.026-1.502), which was not observed in diabetic males. No significant publication bias was found in this study. The findings of this meta-analysis indicate that diabetic individuals have a similar risk of brain tumors as non-diabetic individuals. However, a significant positive correlation between the risk of brain tumors and diabetes mellitus was revealed in females, but not in males.
RESUMO
The purpose of this study was to investigate the mechanism of glioma cell invasion in hypoxic conditions. We demonstrated that hypoxia increased cell invasion, matrix metalloproteinase-2 (MMP2) activity and time-dependent expression of hypoxia inducible factor-1α (HIF-1α) in human glioma cells. These data suggest that MMP2 may play a significant role in tumor invasion in hypoxic conditions. We investigated the mechanisms involved in the increased MMP2 activity and cell invasion in hypoxic conditions. Increased expression of phospho-Jun NH2-terminal kinase (p-JNK) and phospho-c-Jun (p-c-Jun) in glioma cells induced by hypoxia was detected. Furthermore, this effect may be reduced by inhibiting the JNK signaling pathway. We found that inhibition of RhoA geranylgeranylation by geranylgeranyltransferase inhibitor-2147 (GGTI-2147) or knockdown of RhoA by siRNA against RhoA reduced the expression of p-JNK and p-c-Jun, and decreased MMP2 activity and glioma cell invasion in hypoxic conditions. These data suggest a link among RhoA, JNK, c-Jun and MMP2 activity that is functionally involved in the increased glioma cell invasion induced by hypoxia.