ABSTRACT
HuR (human antigen R), an mRNA-binding protein responsible for poor prognosis in nearly all kinds of malignancies, is a potential anti-tumor target for drug development. While screening HuR inhibitors with a fluorescence polarization (FP) based high-throughput screening (HTS) system, the clinically used drug eltrombopag was identified. Activity of eltrombopag on molecular level was verified with FP, electrophoretic mobility shift assay (EMSA), simulation docking and surface plasmon resonance (SPR). Further, we showed that eltrombopag inhibited cell proliferation of multiple cancer cell lines and macrophages, and the anti-tumor activity was also demonstrated in a 4T1 tumor-bearing mouse model. The data showed that eltrombopag was efficient in reducing microvessels in tumor tissues. We then confirmed the HuR-dependent anti-angiogenesis effect of eltrombopag in 4T1 cells and RAW264.7 macrophages with qRT-PCR, HuR-overexpression and HuR-silencing assays, RNA stability assays, RNA immunoprecipitation and luciferase assays. Finally, we analyzed the anti-angiogenesis effect of eltrombopag on human umbilical vein endothelial cells (HUVECs) mediated by macrophages with cell scratch assay and Matrigel angiogenesis assay. With these data, we revealed the HuR-dependent anti-angiogenesis effect of eltrombopag in breast tumor, suggesting that the existing drug eltrombopag may be used as an anti-cancer drug.
ABSTRACT
In spite of the serious effects on the patient's quality of life, the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) remains a trouble problem. With the development of new agents, the acute and delayed CINV have been significantly improved in response rate, however the controlling of nausea and breakthrough CINV are undesirable. Recently, olanzapine has been demonstrated effectively in the prevention and treatment of CINV, especially in nausea, that can improve the quality life of patients as well. The paper sketches the mechanism of CINV and mainly summarizes the progress in prevention and treatment of olanzapine in CINV.
ABSTRACT
Objective To provide references for enriching and innovating patterns of TCM syndrome differentiation by exploring the relationship between pathological changes and TCM syndrome differentiation of delayed graft function (DGF) after renal transplantation. Methods Totally 57 patients with DGF after renal transplantation who were diagnosed by pathological biopsy were also diagnosed by TCM doctors to obtain TCM syndromes. And the pathological diagnoses were compared with the distribution of TCM syndromes to discuss the relationship between them. Results All the patients were classified into four TCM syndromes:spleen-kidney qi deficiency, liver-kidney yin deficiency, qi-stagnation and blood stasis, and deficiency of both qi and yin. The results of pathological biopsy were as follows:acute tubular necrosis, calcineurin inhibitor toxicity and acute rejection. Quantitative corresponding relation was found between the pathological diagnoses and the TCM syndromes. Conclusion There are inner links between pathological diagnosis and TCM syndromes of DGF, which can be references for diagnosis and treatment of TCM syndrome differentiation.