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1.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-875786

ABSTRACT

Objective@#To analyze the CYP2C19 gene polymorphism in patients with upper digestive system diseases in Anhui Province, so as to provide evidence for individual treatment.@*Methods@#The 307 patients with upper digestive system diseases in the Department of Gastroenterology, The 901st Hospital of Combined Service Force of People's Liberation Army were selected. The CYP2C19 genotypes were detected by DNA microarray microarray. The CYP2C19 genotypes and metabolic types in different genders, ages and diseases were analyzed.@*Results@# There were 197 males ( 64.17% ) and 110 females ( 35.83% ) , with the age of ( 58.00±16.13 ) years old. The gene frequency of CYP2C19*1, CYP2C19*2 and CYP2C19*3 was 62.70%, 32.25% and 5.05%, respectively. There were 119 cases (38.76%) of *1/*1 ( 636GG, 681GG ), 129 cases ( 42.02% ) of *1/*2 ( 636GG, 681GA ) , 18 cases (5.86%) of *1/*3 ( 636GA, 681GG ) , 29 cases ( 9.45% ) of *2/*2 ( 636GG, 681AA ) , 11 cases ( 3.58% ) of *2/*3 ( 636GA, 681GA ) , and 1 cases ( 0.33% ) of *3/*3 ( 636AA, 681GG ). In terms of metabolisms, there were 119 cases ( 38.76% ) of fast metabolism type, 147 cases (47.88%) of intermediate metabolism type and 41 cases (13.35%) of slow metabolism type. There were no significant differences in CYP2C19 genotypes and metabolic types among the patients with different gender, age and digestive system diseases ( P>0.05 ).@*Conclusion@#The CYP2C19 genotypes of patients with upper digestive system diseases were polymorphic, mainly the fast metabolism type and the intermediate metabolism type, which could provide reference for the clinical medication of individualized treatment of proton pump inhibitors.

2.
Mol Med Rep ; 15(3): 1297-1304, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28138714

ABSTRACT

The present study aimed to investigate whether overexpression of integrin-linked kinase (ILK) affects drug resistance to temozolomide (TMZ) in glioma cells. To do this, a plasmid containing the ILK gene was transfected into the SHG­44 human glioma cell line, and cells were subsequently cultured in the absence or presence of TMZ. The expression levels of ILK, multidrug resistance­associated protein (MRP) and multi­drug resistance protein (MDR) were assessed in these cells. Cell growth and apoptosis were measured by MTT and Hoechst staining, and flow cytometry, respectively. In addition, the expression levels of B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated x protein (Bax), and caspase­3 activity, were evaluated. The ILK­overexpressing SHG­44 cell was successfully constructed, and demonstrated increased expression levels of ILK, MDR and MRP compared with untransfected cells. Cell growth in the ILK+TMZ group was significantly greater, and the percentage of apoptotic cells in the ILK+TMZ group was significantly reduced, compared with the p enhanced green fluorescent protein (EGFP)­C1+ TMZ empty vector control group. Expression levels of the anti­apoptotic protein Bcl­2 were significantly increased and those of the pro­apoptotic protein Bax were significantly decreased (P<0.01) in the ILK+TMZ group compared with the pEGFP­C1+TMZ group. In addition, the activity of caspase­3 in ILK+TMZ group was significantly decreased compared with the pEGFP­C1+TMZ group (P<0.01). Overexpression of ILK therefore promoted the proliferation of SHG­44 human glioma cells, reduced apoptosis and reduced sensitivity to TMZ via decreasing the activity of caspase­3.


Subject(s)
Antineoplastic Agents, Alkylating/pharmacology , Brain Neoplasms/genetics , Dacarbazine/analogs & derivatives , Drug Resistance, Neoplasm/genetics , Gene Expression , Glioma/genetics , Protein Serine-Threonine Kinases/genetics , Brain Neoplasms/metabolism , Caspase 3/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Dacarbazine/pharmacology , Drug Resistance, Multiple/genetics , Glioma/metabolism , Humans , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Temozolomide , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism
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