ABSTRACT
PURPOSE: Current treatment of glioblastoma after surgery consists of a combination of fractionated radiotherapy and temozolomide. However, it is difficult to completely remove glioblastoma because it has uncertain boundaries with surrounding tissues. Moreover, combination therapy is not always successful because glioblastoma has diverse resistances. To overcome these limitations, we examined the combined effects of chemotherapy and knockdown of mitogen-activated protein kinase phosphatase-1 (MKP-1). MATERIALS AND METHODS: We used ten different anti-cancer drugs (cisplatin, cyclophosphoamide, doxorubicin, epirubicin, etoposide, 5-fluorouracil, gemcitabine, irinotecan, mitomycin C, and vincristine) to treat glioblastoma multiforme (GBM) cells. Knockdown of MKP-1 was performed using siRNA and lipofectamine. The basal level of MKP-1 in GBM was analyzed based on cDNA microarray data obtained from the Gene Expression Omnibus (GEO) databases. RESULTS: Anti-cancer drug-induced cell death was significantly enhanced by knockdown of MKP-1, and this effect was most prominent in cells treated with irinotecan and etoposide. Treatment with these two drugs led to significantly increased phosphorylation of c-Jun N-terminal kinase (JNK) in a time-dependent manner, while pharmacological inhibition of JNK partially inhibited drug-induced cell death. Knockdown of MKP-1 also enhanced drug-induced phosphorylation of JNK. CONCLUSION: Increased MKP-1 expression levels could be the cause of the high resistance to conventional chemotherapeutics in human GBM. Therefore, MKP-1 is an attractive target for overcoming drug resistance in this highly refractory malignancy.
Subject(s)
Humans , Apoptosis , Camptothecin , Cell Death , Dacarbazine , Deoxycytidine , Doxorubicin , Drug Resistance , Drug Resistance, Multiple , Dual Specificity Phosphatase 1 , Epirubicin , Etoposide , Fluorouracil , Gene Expression , Glioblastoma , JNK Mitogen-Activated Protein Kinases , Lipids , Mitomycin , Oligonucleotide Array Sequence Analysis , Phosphorylation , Phosphotransferases , Protein Kinases , RNA, Small InterferingABSTRACT
Objective To evaluate the reliability and clinical application of measuring blood glucose and urea with electrodes and end reaction methods. Method Using the electrodes and end reaction methods, blood glucose and urea were measured respectively. The results and the relativity between the two methods were compared. Result Comparing the two methods for GLU and UREA, the correlative factors were 0.990 1 and 0.989 1 respectively. They had fairly good comparability. The linear ranges of their regression equations met the clinical needs. With favorable accuracy, the correlative factors were above 0.997 9. Conclusion The electrodes method was rapid and accurate, which was suitable for emergency tests. The ending reaction methods was fairly stable and has less interfering factors, which was fit for the routine use.
ABSTRACT
Objective To investigate the relationship between sICAM-1 and colorectal carcinoma metastasis. Methods ELISA was used to detect sICAM-1 level in specimens from 50 cases colorectal cancer patients' serum and 30 cases controls. Results Serum sICAM-1 level in colorectal cancer was significantly higher than that in controls (P 0.05), that in patients with metastasis was significantly higher than that in control(P