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Background This study was to investigate the influence of physiological changes and the expression of MRP2 efflux transporter on the pharmacokinetics of norfloxacin after acute exposure to high altitude 4300 m. Methods and Results The rats were randomly divided into high altitude group and plain group. Blood gas and biochemical analysis showed that the physiological parameters significantly changed at high altitude. The mRNA and protein expression of MRP2 in high altitude group were higher than plain group in rat small intestine and kidney, while was reduced in rat liver. The AUC, K a and C max of norfloxacin were significantly reduced in high altitude group (p < 0.05). However, the MRT, CL, t 1/2 and Vd were significantly increased (p < 0.05). Conclusions These results indicate that physiological indicators and expression levels of drug transporters MRP2 are changed in responded to high altitude, to severely affect norfloxacin pharmacokinetics. These changes may provide basis and new ideas to adjust the dosage and administration, so as to promote rational drug use in the high altitude. [ABSTRACT FROM AUTHOR]

Abstract: Patients with non-small cell lung cancer (NSCLC) who have activating epidermal growth factor receptor (EGFR) mutations benefit from treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs), namely, gefitinib and erlotinib. However, these patients eventually develop resistance to EGFR-TKIs. About 50% of this acquired resistance may be the result of a secondary mutation in the EGFR gene, such as the one corresponding to T790M. In our previous study, we found that combined treatment with fulvestrant and gefitinib decreases the proliferation of H1975 NSCLC cells, compared to treatment with either fulvestrant or gefitinib alone; however, the molecular mechanism for the improved effects of the combination treatment are still unknown. In this study, we confirmed that fulvestrant increases the gefitinib sensitivity of H1975 cells and found that let-7c was most upregulated in the fulvestrant-treated cells. Our data revealed that let-7c increases gefitinib sensitivity by repressing RAS and inactivating the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways. Taken together, our findings suggest that let-7c plays an important role in fulvestrant-induced upregulation of gefitinib sensitivity in H1975 cells. [Copyright &y& Elsevier]

Abstract: We conducted this study to evaluate the expression of leptin and its receptor, OB-Rb in gastric cancer and their relationship to clinicopathological features, VEGF and HER-2 expression, as well as the prognostic value. One hundred and ten gastric cancer specimens were detected for leptin, OB-Rb, VEGF and HER-2 by immunohistochemistry (IHC), and 96 specimens of normal gastric mucosa served as the control. The expression level of leptin, OB-Rb and HER-2 in gastric tissues were significantly higher than normal tissues (49.1% vs. 34.0%, 60.9% vs. 46.0%, 19.1% vs. 8.0%, P <0.05). There was a correlation between the expression of leptin and HER-2, both of which were significantly associated with invasion depth, lymph node metastasis, AJCC stage and VEGF expression. However, there was no correlation between OB-Rb expression and all clinicopathological features. Cox regression analyses showed that age, tumor size, histological grade, serosa invasion, AJCC stage, chemotherapy, leptin and HER-2 overexpression were prognostic factors. The survival of patients with leptin positive expression was significantly poorer than those with negative expression (OS: 20.0months vs. 32.5months, FPS: 12.0months vs. 18.0months, P <0.01). Leptin, rather than OB-Rb, played an important role in the progression and angiogenesis of gastric cancer, and was a prognostic factor for poor outcome. [Copyright &y& Elsevier]

Abstract: CD44 molecule plays critical role in distant malignant metastasis. It is expressed in standard form (CD44s) or variant form (CD44v). Tumor necrosis factor-α (TNF-α) is highly expressed in the cancer microenvironment. TNF-α was reported to modulate CD44 expression in several kinds of cancer. However, little is known about pathological role of TNF-α in breast cancer (BC) cells. In the current investigation, we investigated the effect of TNF-α on BC cells (MCF-7 and MDA-MB-231) viability, CD44 expression, and in vitro migration. We found that TNF-α down-regulated CD44s expression, up-regulated CD44v3 and CD44v6 expression through JNK pathway in MCF-7 cells. In MDA-MB-231 cells, TNF-α up-regulated CD44s, CD44v3 and CD44v6 expression via p38 pathway. These data indicate important role of CD44 molecule in BC pathology. [Copyright &y& Elsevier]