Research progress on targeting effect and regulating mechanisms of the stemness of cancer stem cells / 药学学报

Cancer stem cells (CSCs) have become an important target to overcome the obstacle of tumor therapy. In recent years, many reports have shown that the heterogenicity and plasticity of CSCs, and the microenvironment interact with each other, which become important factors affecting the dynamic conversion of CSCs. Therefore, we should not only focus on the stem characteristics of CSCs, but also consider the factors related to the regulation of the dynamic transformation of CSCs stemness. The signaling pathways, epithelial-mesenchymal transition (EMT) and the niche of CSCs, are proved to play an important role in the regulation of stemness of CSCs. The aspects are important in the studies of tumor therapy by targeting CSCs. This article summarizes the mechanisms for regulation of the stemness of cancer stem cells and the progress in the studies of targeting cancer stem cells with a focus on the CSCs dynamic regulation.

Reversing multidrug resistance by tyrosine kinase inhibitors / 癌症

Recently, a large number of tyrosine kinase inhibitors(TKIs) have been developed as anticancer agents. These TKIs can specifically and selectively inhibit tumor cell growth and metastasis by targeting various tyrosine kinases and thereby interfering with cellular signaling pathways. The therapeutic potential of TKIs has been hindered by multidrug resistance(MDR), which is commonly caused by overexpression of ATP-binding cassette(ABC) membrane transporters. Interestingly, some TKIs have also been found to reverse MDR by directly inhibiting the function of ABC transporters and enhancing the efficacy of conventional chemotherapeutic drugs. In this review, we discuss ABC transporter-mediated MDR to TKIs and MDR reversal by TKIs.

Effect of troxerutin and cerebroproptein hydrolysate injection on platelet aggregation and thrombosis / 中国实验血液学杂志

This study was purposed to explore the effect of troxerotin and cerebroproptein hydrolysate injection (TCHI) on platelet aggregation in vitro and thrombosis in vivo. The inhibitory rate of TCHI at different concentrations on platelet aggregation was determined by platelet aggregometer. The relationship between dose and effect was established. The effect of troxerutin and cerebroproptein hydrolysate injection on thrombosis was determined by the carotid thrombosis model of rats. The results showed that the TCHI could inhibit thrombosis and platelet aggregation in a concentration-dependent way. When the concentration of TCHI total nitrogen was 5 µg/ml, the inhibition rate of platelet aggregation reached to the highest value of 28.61 ± 22.07%, which is 2.5 times as much as that with 100 µg/ml aspirin. It is concluded that the TCHI has antiaggregative and antithrombotic activity effects against platelet aggregation and thrombosis.

Batroxobin reduces intracellular calcium concentration and inhibits proliferation of vascular smooth muscle cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Batroxobin (BX), a serine protease used in defibrinogenation and thrombolysis, also has an effect on c-fos gene and growth factor. This study attempted to determine the effects of BX on the proliferation of vascular smooth muscle cells (VSMCs) and calcium metabolism.</p><p><b>METHODS</b>VSMCs were treated with BX at concentrations of 0.1, 0.3, or 1.0 mmol/L and cell numbers were determined at 0, 24, 48, and 72 hours. Intracellular calcium concentration ([Ca2+]i) was measured using direct fluorescence methods.</p><p><b>RESULTS</b>BX was found to suppress proliferation of VSMCs in a dose-dependent fashion with inhibition rates of 18% and 31% by 48 and 72 hours, respectively. In addition, BX decreases basal [Ca2+]i significantly. The basal level in untreated cells was 162.7 +/- 33.8 nmol/L, and decreased to 131.5 +/- 27.7 nmol/L, 128.3 +/- 28.5 nmol/L, and 125.6 +/- 34.3 nmol/L with the three concentrations of BX, respectively. Noradrenaline (NE)-induced [Ca2+]i stimulation was also attenuated by BX (0.1 mmol/L BX, 20% +/- 8% inhibition; 0.3 mmol/L BX, 54% +/- 11% inhibition; 1.0 mmol/L BX, 62% +/- 15% inhibition). The ability of NE to stimulate [Ca2+]i was attenuated in cultures in Ca(2+)-free medium, as was the ability of BX to blunt NE-induced stimulation.</p><p><b>CONCLUSION</b>These findings demonstrate that BX can effectively inhibit proliferation of VSMCs, probably by blocking the release and uptake of Ca2+, thus influencing [Ca2+]i.</p>