Objective To investigate the effects of hypoxic conditions on expressions of hypoxia-inducible factor 1α (HIF-1α) and P-glycoprotein (P-gp),and the relationship between HIF-1α and P-gp.Methods Tumor tissues from 54 cases of patients with colonic neoplasm in Xingtai People's Hospital were selected after operation from June 2013 to June 2015.The expressions of HIF-1α and P-gp in colonic tumor tissues were detected by using immunohistochemistry,and their correlations to clinical and pathologic features were analysed.The expressions of HIF-1α and P-gp in colonic tumor cell lines under normoxia and hypoxia conditions were detected by using cell smear method,and correlation between HIF-1α expression and P-gp expression was analysed.Results Among tumor tissues from 58 cases of patients with colonic neoplasm,the positive rate of HIF-1α expression was 58.62％,and that of P-gp expression was 46.55％.The positive rates of HIF-1α and P-gp expressions of patients on the Dukes stage C+D were significantly higher than those of patients on A+B phase (P＜0.05).Additionally,the positive rates of HIF-1α and P-gp expressions of patients with lymphatic metastasis were significantly higher than those of patients without lymphatic metastasis (P＜0.05).The HIF-1α expression was positively correlated with the P-gp expression (r=0.574,P＜0.01).For the same cell lines,the expression levels of HIF-1α and P-gp under hypoxia condition were significantly higher than those under normoxia condition,there were statistically significant differences (P＜0.01).While,under the same oxygen conditions,no statistically significant difference was found in expression levels of HIF-1 and P-gp among different colonic tumor cell lines (P＞0.05).Conclusion Overexpression and coexpression of HIF-1α and P-gp exist in colon cancer.The expression levels of HIF-1α and P-gp in patients with different Dukes stages and patients with or without lymph node metastasis are significantly different,and positive correlation is observed between the expression of HIF-1α and P-gp.Hypoxia condition can induce an increase in expressions of HIF-1α and P-gp in colonic tumor cells.

To search for potent drugs against non-small-cell lung cancer(NSCLC),a series of hybrids(9a-9e, 10a-10e and 11a-11e﹚ from anilinopyrimidines and diazeniumdiolates were designed and synthesized.The MTT assay was employed to evaluate their antiproliferative activity against H1975 cells harboring epithelial growth factor receptor(EGFR)L858R/T790M mutation.The results showed that compounds 9a-9e displayed remarkable inhibitory activity on H1975 cells.Among these compounds, the most potent was compound 9b(IC50=0.65 μmol/L),which was superior to the positive control gefitinib.Additionally,molecular docking study indicated that 9b could bind with EGFR T790M by forming hydrogen bond, electrostatic interactions, et al, suggesting that compound 9b may be a potential anti-NSCLC agent for further investigation.

PURPOSE: The incidence of allergen specific immunotherapy-related systemic reactions (SRs) varies among different studies, and many factors are likely to contribute to SRs. This study aims to investigate the incidence, characteristics, and risk factors of SRs to standardize dust mite-specific subcutaneous immunotherapy (SCIT) in Central China. METHODS: All patients receiving standardized dust mites (100-100,000 SQ-U/mL; Alutard SQ, Hørsholn, Denmark) immunotherapy were followed up. Recorded data included demographics, diagnosis, patient status, pulmonary function testing results before and after each injection, allergen dosage, and details of SRs. RESULTS: From June 2011 to August 2014, a total of 208 patients received 4,369 injections; 27 (13.0%) patients experienced 48 (1.1%) systemic reactions. Most of the SRs were grade 2 reactions (n=30, 62.5%), followed by grade 1 (n=11, 22.9%), grade 3 (n=7, 14.6%), and no fatal reactions occurred. Forty-six SRs (95.8%) occurred within 30 minutes. Higher SR rates were associated with high concentration extracts (100,000 SQ-U/mL), injections with concomitant local reactions (LRs), children, asthma and high sensitivity (skin prick test 3+/4+ and/or sIgE≥17.5 kUA/L) (P<0.05). The estimated odds of SRs increased in children (OR=6.57; 95% CI: 1.88-22.97, P=0.003), asthmatic patients (OR=4.10; 95% CI: 1.72-9.80, P=0.002), and injections with LRs (OR=2.41; 95% CI: 1.33-4.36, P=0.004). CONCLUSIONS: The incidence of SRs to dust mite SCIT was low, and multiple factors were associated with the increased incidence of SRs. Children, asthmatics and patients with concomitant LR may be prone to develop SRs.
Asthma ; Child ; China ; Demography ; Dermatophagoides pteronyssinus ; Diagnosis ; Dust* ; Follow-Up Studies* ; Humans ; Immunotherapy* ; Incidence ; Mites* ; Respiratory Function Tests ; Risk Factors