Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary tumor in the central nervous system. One of the most widely used chemotherapeutic drugs for GBM is temozolomide, which is a DNA-alkylating agent and its efficacy is dependent on MGMT methylation status. Little progress in improving the prognosis of GBM patients has been made in the past ten years, urging the development of more effective molecular targeted therapies. Hyper-activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is frequently found in a variety of cancers including GBM, and it plays a central role in the regulation of tumor cell survival, growth, motility, angiogenesis and metabolism. Numerous PI3K inhibitors including pan-PI3K, isoform-selective and dual PI3K/mammalian target of rapamycin (mTOR) inhibitors have exhibited favorable preclinical results and entered clinical trials in a range of hematologic malignancies and solid tumors. Furthermore, combination of inhibitors targeting PI3K and other related pathways may exert synergism on suppressing tumor growth and improving patients’ prognosis. Currently, only a handful of PI3K inhibitors are in phase I/II clinical trials for GBM treatment. In this review, we focus on the importance of PI3K/Akt pathway in GBM, and summarize the current development of PI3K inhibitors alone or in combination with other inhibitors for GBM treatment from preclinical to clinical studies.
In conclusion, myricetin is a multi-targeted drug that has potent anti-migratory and antiinvasive effects on GBM cells, and suppresses formation of lamellipodia and focal adhesions, suggesting that it may serve as an alternative option for GBM treatment.
Using slag and metakaoline as raw materials , different modules of water glass as activator ,a new type of cementitious material—slag-based geopolymer was prepared. The fluidity of slag-based geopolymer paste and optimum content of superplasticizer in slag-based geopolymer mortar being as evaluation standard, adaptablities of slag-based geopolymer to naphthalene superplasticizer and melamine superplasticizer were studied. The results have shown that both naphthalene superplasticizer and melamine superplasticizer with slag-based geopolymer were adaptable well, obvious saturated points and optimum contents to two kinds of superplasticizers were performed.
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