The epidermal growth factor receptor (EGFR) provides a rational target for cancer therapy as it is commonly overexpressed in a variety of solid tumors, and its deregulation is correlated with resistance to chemotherapy and radiotherapy and a poor prognosis. Cetuximab (C255), a specific monoclonal antibody directed against EGFR, is synergistic with chemotherapy and radiotherapy and has been licensed for the treatment of irinotecan refractory colorectal cancer (CRC) and squamous cell cancer of the head and neck (SCCHN), which express EGFR. In addition, the clinical trials about cetuximab for the treatment of non-small cell lung cancer (NSCLC), breast and pancreas carcinoma are ongoing, and cetuximab has been proven to a novel strategy for the treatment of cancer with the overexpression of EGFR.

Multidrug resistance(MDR)of tumor cells has become the main impediment that influence the curative effect of cancer chemotherapy. Although there are many mechanisms can generate the multidrug resistance, the overexpression of P-glycoprotein encoded by the multidrug resistance-1(mdr1) gene is the main cause in the formation of MDR. Seaching for innocuous and effective reversal of MDR is not only a method of improving the efficiency of cancer chemotherapy but also the problem desiderated to be resolved in chemotherapy domain.

Objective To investigate whether gemcitabine (GEM) could enhance radiosensitivity of human non-small cell lung cancer cells and its related mechanism.Methods Clonogenic assay was used to analyze radiosensitivity enhancement by GEM on p53 mutant human lung adenocarcinoma cell line 973.Alterations of cell cycle distribution and apoptosis were measured by flow cytometry.Results Mild radiosesitizing effect was observed when 10 nmol/L GEM was administrated before or after irradiation.Marked radiosesitizing effect was demonstrated when 100 nmol/L GEM was administrated before or after irradiation, with much stronger effect of pre-irradiation GEM treatment.Mutation of p53 gene affected cell cycle redistribution and cell apoptosis, but had no relationship with radiosensitivity enhancement of GEM.Conclusions 100 nmol/L GEM could significantly enhance radiosensitivity of human lung cancer cells.However, this effect may not be associated with p53 gene mutation, cell cycle redistribution or cell apoptosis.

AIM: To explore the effect of L-carnitine on nuclear factor of activated T-cells, cytoplasmic 3 (NFATc3) in cardiomyocytes under H2O2 stimulation.METHODS: Primary cultured neonatal rat myocardial cells were stimulated by H2 O2 at concentration of 200μmol/L for 12 h to induce oxidative stress injury.In treatment group, L-carni-tine and cyclosporin A ( CsA) , a specific inhibitor of calcineurin ( CaN) , were administered 30 min prior to H2 O2 stimula-tion.After treatment, total, cytoplasmic and nuclear NFATc3 protein levels were determined by Western blotting.The method of immunofluoresence was used to evaluate the distribution of NFATc3.RESULTS: H2 O2 treatment produced no effect on the expression of total NFATc3, but caused its translocation from the cytosolic to nuclear compartment, which was greatly blunted by L-carnitine pretreatment.CONCLUSION:L-carnitine antagonized oxidative stress injury via alleviating NFATc3 nuclear translocation.

Objective To investigate the efficacy of zoledronic acid in the treatment of senile unstable femoral intertrochanteric fractures with anatomical locking plate. Methods 67 patients were randomly divided into two groups. Five days after the operation, group A received one intravenous injection of 5 mg zoledronic acid, while patients in group B did not receive the injection. The two groups were compared in terms of hospitalization time, complications, limb weight-bearing time, fracture healing time, hip function score after operation, preoperative and postoperative serum calcium and serum ALP, bone mineral density of proximal femur before operation and 1 year after operation. Results There were no statistically significant differences between the two groups in age, type of fracture, hospital stay, partial weight-bearing time, fracture healing time, hip function at 1 month and 1 year after operation, preoperative bone mineral density and blood calcium. But the differences were statistically different in hip function at 3 months after operation , averaged bone mineral density of proximal femur and serum ALP 1 year after operation. Moreover, 5 patients in group A developed muscle pain or fever after intravenous injection of zoledronic acid. Conclusion The locking plate combined with zoledronic acid injection in treatment of elderly patients with unstable femoral intertrochanteric fracture could inhibit bone loss, increase bone mineral density, and accelerate limb function recovery after operation. On the other hand, Zoledronic acid has a high incidence of adverse reaction.

We aimed at analyzing the structure of extracellular polysaccharide A from Grifola frondosa (EXGFP-A) and testing its immunomodulatory activity. Structural analysis shows that EXGFP-A was a contained α-D-glucoside bond and pyranose ring. GC analysis reveals that EXGFP-A was mainly composed of rhamnose, arabinose, xylose, mannose, glucose, galactose, by the molar ratio of 0.28:0.31:0.30:0.06:7.98:0.61. The results of MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay indicates when EXGFP-A was at a concentration of 80 μg/mL and treatment time of 48 h, RAW264.7 cells proliferation index reached a maximum of 137.5%. Meanwhile, the AO staining showed that EXGFP-A activated RAW264.7 cells and improved the level of intracellular nucleic acid metabolism. In addition, in a certain range of concentration, EXGFP-A was able to increase the release of NO in RAW264.7 cells, and upregulate the mRNA expression of immunological factor TNF-α, IL-1β, IL-6, IL-12, IFN-γ and iNOS of RAW264.7 cells. Our results confirm that EXGFP-A had immunomodulatory activity. Our findings provided scientific basis for the structural analysis and application of Grifola frondosa polysaccharide.
Animals ; Cytokines ; metabolism ; Grifola ; chemistry ; Mice ; Nitric Oxide Synthase Type II ; metabolism ; Polysaccharides ; immunology ; RAW 264.7 Cells

Arsenic trioxide (ATO) is used as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, increasing drug resistance is reducing its efficacy. Therefore, a better understanding of ATO resistance mechanism is required. In this study, we established an ATO-resistant human epidermoid carcinoma cell line, KB/ATO, from its parental KB-3-1 cells. In addition to ATO, KB/ATO cells also exhibited cross-resistance to other anticancer drugs such as cisplatin, antimony potassium tartrate, and 6-mercaptopurine. The arsenic accumulation in KB/ATO cells was significantly lower than that in KB-3-1 cells. Further analysis indicated that neither application of P-glycoprotein inhibitor, breast cancer resistant protein (BCRP) inhibitor, or multidrug resistance protein 1 (MRP1) inhibitor could eliminate ATO resistance. We found that the expression level of ABCB6 was increased in KB/ATO cells. In conclusion, ABCB6 could be an important factor for ATO resistance in KB/ATO cells. The ABCB6 level may serve as a predictive biomarker for the effectiveness of ATO therapy.