1.Effect of CYP3A4*18B, CYP3A5*3 gene polymorphism on dosage and concentration of tacrolimus in renal transplant patients.
Lin ZHU ; Hongtao SONG ; Qinghua WANG ; Weizhen WU ; Shunliang YANG ; Jianming TAN
Acta Pharmaceutica Sinica 2012;47(7):878-83
The effect of CYP3A4*18B and CYP3A5*3 on concentration/dosage x body surface area ratios (C/D'), adverse effects and acute rejection of tacrolimus in renal transplant patients were investigated. The CYP3A4*18B genotypes of 227 renal transplant patients were determined by PCR-RFLP method. The differences of C/D' ratios, adverse reactions and acute rejection were compared among all of the genotype groups treated with tacrolimus. The frequencies of CYP3A4*18 and CYP3A5*3 alleles in renal transplant patients were 30.8% and 74.2%, respectively. No significant association was found between the C/D's of tacrolimus and CYP3A4*18B genotypes when they were classified by two CYP3A5 genotypes (P > 0.05). While after the effects of CYP3A4*18B genotype were eliminated, the C/D' ratio of tacrolimus in patients with CYP3A5*1/*1 and *1/*3 genotype group was significantly lower than those with CYP3A5*3/*3 genotype groups (P < 0.01). There is no significant difference in adverse effects and acute rejection among different genotypes (P > 0.05).
2.Expression and clinical significance of minichromosome maintenance protein 3(MCM3) in gastric cancer tissues
Si LI ; Xiaolong LI ; Rui SONG ; Xueqian CHEN ; Weizhen YANG ; Yang LIU
International Journal of Biomedical Engineering 2022;45(1):36-40,46
Objective:To study the expression level and clinical significance of minichromosome maintenance protein 3(MCM3) in human gastric cancer.Methods:The expression levels of MCM3 mRNA and protein in gastric cancer and adjacent normal tissues were analyzed using public databases such as TCGA, CCLE and HPA. The clinicopathological features of 69 patients with gastric cancer were retrospectively analyzed, and the expression levels of MCM3 protein in tumor tissues and adjacent normal tissues were detected by immunohistochemical staining, and the relationship between it and clinicopathological features was analyzed. The interaction network of MCM3 proteins was analyzed using the STRING database.Results:The expression levels of MCM3 mRNA and protein in gastric cancer tissues were significantly higher than those in adjacent normal tissues ( P<0.05), and its high expression was correlated with the size of gastric cancer tumors ( P<0.05). In gastric cancer tissue, the expression of MCM3 was correlated with the expression level of proliferating cell nuclear antigen (PCNA) ( R=0.61, P<0.01), and there may be a protein-protein interaction. Conclusions:MCM3 plays an important role in gastric cancer by interacting with PCNA, and it is expected to become a new diagnostic and therapeutic target.
3.Correlation of Th1/Th2 and Th17/Treg with treatment efficacy of PD-1 inhibitor in advanced non-small cell lung cancer patients complicated with chronic obstructive pulmonary disease
Weizhen SONG ; Jiangnan ZHENG ; Xiaoting ZHOU ; Lingyun DONG
Cancer Research and Clinic 2023;35(9):675-679
Objective:To investigate the relationship between peripheral blood helper T cell 1/helper T cell 2 (Th1/Th2), helper T cell 17/regulatory T cell (Th17/Treg) and efficacy of programmed death receptor 1 (PD-1) inhibitor in patients with advanced non-small cell lung cancer (NSCLC) combined with chronic obstructive pulmonary disease (COPD).Methods:The clinical data of 107 patients with advanced NSCLC combined with COPD who were admitted to Suzhou Ninth Hospital Affiliated to Soochow University from April 2021 to September 2022 were retrospectively analyzed. The patients were treated with PD-1 inhibitor, and they were categorized into the disease control group (82 cases) and the disease progression group (25 cases) according to the clinical efficacy. Th1/Th2, Th17/Treg and clinical data of patients before treatment were compared between the two groups, and logistic regression was used to analyze the independent influencing factors of patients' PD-1 inhibitor efficacy.Results:Th1/Th2 and Th17/Treg before treatment in the disease control group were higher than those in the disease progression group (12.49±1.14 vs. 7.04±1.06, t = 21.26, P < 0.001; 0.14±0.03 vs. 0.09±0.04, t = 6.72, P < 0.001). The proportions of patients with TNM stage Ⅳ, lymph node metastasis and brain metastasis in the disease progression group were higher than those in the disease control group (all P < 0.01). The results of multivariate logistic regression analysis showed that pre-treatment Th1/Th2 ( OR = 0.744, 95% CI 0.685-0.799, P < 0.001), pre-treatment Th17/Treg ( OR = 0.514, 95% CI 0.465-0.552, P < 0.001), TNM stage ( OR = 1.258, 95% CI 1.049-1.656, P = 0.048), lymph node metastasis ( OR = 1.790, 95% CI 1.223-2.734, P = 0.005), and brain metastasis ( OR = 1.640, 95% CI 1.184-2.348, P = 0.005) were independent influencing factors of PD-1 inhibitor efficacy in patients with advanced NSCLC combined with COPD. Conclusions:Patients with advanced NSCLC combined with COPD who have high Th1/Th2 and Th17/Treg before treatment have good outcomes with PD-1 inhibitor therapy.