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Glioma is the most common primary intracranial malignancy in the central nervous system. At present, the most important treatment option is surgical resection of the tumor combined with radiotherapy and chemotherapy. The principle of operation is to remove the tumor to the maximal extent on the basis of preserving brain function. However, prominent invasive and infiltrative proliferation of glioma tumor cells into the surrounding normal tissues frequently reduces the efficacy of treatment. This in turn worsens the prognosis, because the tumor cannot be completely removed, which can readily relapse. Chemotherapeutic agents when applied individually have demonstrated limited efficacy for the treatment of glioma. However, multiple different chemotherapeutic agents can be used in combination with other treatment modalities to improve the efficacy while circumventing systemic toxicity and drug resistance. Therefore, it is pivotal to unravel the inhibitory mechanism mediated by the different chemotherapeutic drugs on glioma cells in preclinical studies. The aim of the present review is to provide a summary for understanding the effects of different chemotherapeutic drugs in glioma, in addition to providing a reference for the preclinical research into novel chemotherapeutic agents for future clinical application.

Epigenetics have been demonstrated to play a pivotal role in the progression of multiple cancers. Our previous study has demonstrated that microvesicles (MVs) derived from K562 cells could malignantly transform normal hematopoietic cells. The aim of this section was to elucidate the epigenetic effects of RNA in K562-MVs. We altered some epigenetic RNAs (miR-106a-5p, miR-106b-5p and lincPOU3F3) in K562-MVs and followed the process of transformation. Global DNA methylation and DNA methyltransferase (DNMT) levels were observed respectively. Our findings revealed that increased miR-106a/b in K562-MVs accelerated the transformation process (8.33±0.94 vs. 13.29±1.28 days; P

In the periphery of pancreatic ductal adenocarcinoma (PDAC), high accumulation of tumor-associated macrophages (TAMs), which exhibit M2 phenotype, has been shown to be correlated with extra-pancreatic invasion, lymph vessel invasion, lymph node involvement and shortened survival time. However, mechanisms by which tumor cells educate and reprogram TAMs remain largely unclear. The phenotype of TAMs in PDAC tissues was confirmed by immunofluoresence and confocal microscopy. Human CD14+ monocytes were incubated with recombinant human REG4 (rREG4) before being stimulated with LPS and IL-10 and IL-6 were measured with ELISA. A panel of M1 and M2 genes were measured by quantitative real-time PCR. Panc1, AsPC1 and BxPC3 cells were cultured in the conditioned medium (CM) and treated with REG4. The macrophages were infected with CREB shRNA or cultured by the CM of Panc1 cells infected with REG4 shRNA. The expression of CD163, CD206 and REG4 and the phosphorylation levels of epidermal growth factor receptor (EGFR), AKT and cAMP response element-binding protein (CREB) in cells were assessed with western blotting. Cell proliferation and invasiveness were also assessed. The rREG4 or the conditioned medium of Panc1 cells which secreted REG4 induced the polarization macrophages to M2 phenotype. Treatment of human macrophages with REG4 resulted in phosphorylation of EGFR, AKT and CREB. The latter was responsible for REG4-mediated macrophage polarization to M2. The conditioned medium of macrophages treated with rREG4 promoted the proliferation and invasion of pancreatic cancer cell lines. REG4, overexpressed in PDAC and secreted by cancer cells, promoted macrophage polarization to M2, through at least in part, activation of ERK1/2 and CREB and changed the microenvironment to facilitate cancer growth and metastasis.

The expression of CD9 has been shown to be inversely associated with pancreatic cancer metastasis but the underlying mechanism remains incompletely understood. Using the two closely associated pancreatic cancer cell lines, PaTu-8898s and PaTu-8898t, which are metastatic and non-metastatic, respectively, we showed that the PaTu-8988s cells expressed a lower level of CD9 but had higher prolifera- tion and migration rates than the PaTu-8898t cells. An inverse correlation between CD9 expression and the cell surface level of epidermal growth factor receptor (EGFR) was observed in both cell lines. In the PaTu-8898s cells, overexpression of CD9 decreased the cell surface expression of EGFR, associated with increased expression of dynamin-2, whereas in the PaTu-8898t cells, knockdown of CD9 with RNA interference (RNAi) increased the cell surface expression of EGFR, associated with decreased expression of dynamin-2. However, the total EGFR level did not change by manipulation of CD9 expres- sion, suggesting that CD9 plays a role in EGFR endocytosis. Furthermore, in the PaTu-8898ts cells, CD9 overexpression decreased the cell proliferation and migration, which were reversed by EGFR overexpression, whereas in the PaTu-8898t cells, CD9 knockdown enhanced the cell proliferation and migration which were blocked by EGFR RNAi both in vitro and in vivo. Thus, in pancreatic cancer cells, downregulation of CD9 may play a role in cancer growth and metastasis through, at least in part, enhancing cell surface expression of EGFR.