AIM: To investigate the population pharmacokinetic characteristics of capecitabine and its possible influencing factors in Chinese patients of breast cancer. METHODS: 78 cases of Chinese patients with breast cancer were chosen as the objects in this study. Following treatment with capecitabine (0.6 g, 0.15 g/piece, 4 pieces, orally), blood samples were collected and concentrations of capecitabine in plasma were analyzed by high performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. The nonlinear mixed-effects software (NONMEM) was used to analyze the data and the population pharmacokinetic model was constructed accordingly. RESULTS: The final established model of absorption and elimination is one-compartment model. The clearance (CL/F) in pharmacokinetic formula of the model is as follows: CL/F=291×e

Objective:To investigate the efficacy, safety and common adverse reactions of Apatinib monotherapy in elderly patients with advanced colorectal cancer(CRC)who failed to respond to standard regimens.Methods:This was a retrospective study.A total of 106 elderly patients with advanced CRC who had failed standard regimens from January 2015 to December 2019 were included.Patients enrolled in this study received Apatinib with an initial dosage of 500 mg or 250 mg.The objective response rate(ORR)and disease control rate(DCR)were assessed after treatment with apatinib.The progression-free survival(PFS)and overall survival(OS)were evaluated during the follow-up period.Additionally, adverse reactions during treatment with apatinib were recorded.Results:The efficacy was assessed by using the best overall response during apatinib treatment.Of 106 patients, there were 9 patients with partial response(PR), 68 patients with stable disease(SD)and 29 patients with progressive disease(PD). The ORR was 8.5% and the DCR was 72.6%.The median PFS was 3.6 months and the median OS was 10.1 months.Relatively common adverse reactions in these patients were hypertension(63 patients, 59.4%)and hand-foot syndrome(HFS)(51 patients, 48.1%)during apatinib treatment.The median PFS of patients with hypertension and of patients without hypertension were 5.0 months and 3.0 months, respectively( P=0.008). The median PFS of patients with and without HFS were 5.4 months and 3.0 months, respectively( P=0.013). Conclusions:Preliminary evidence suggests that Apatinib monotherapy has good efficacy and safety in elderly patients with advanced CRC who have failed standard regimens, and patients with adverse reactions such as hypertension and HSF still have a good prognosis.

Objective To investigate the associations between CYP2A6 polymorphisms and treatment outcomes of adjuvant S-1 in postoperative gastric cancer patients.Methods 188 patients after D2 radical resection received S-1 based adjuvant chemotherapy.PBMC cell specimen were collected for the genotyping of genetic variation and CYP2A6 gene mRNA expression.Univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis,and multivariate analysis were adjusted by COX regression analysis.Results The polymorphisms included in this study were collected in the NCBI database with the minor allele frequency ＞ 10％ in Chinese population (rs8192725,rs8192720 and rs28399433),with rs8192725 only of clinical significance.The prevalence of rs8192725 in CYP2A6 were CC genotype 131 cases (69.7％),CT genotype 51 cases (27.1％),TT genotype 6 cases (3.2％),minor allele frequency of rs8192725 was 0.17.The 3 year disease-free survival (DFS) rate in patients with CT/TT genotype and CC genotype were 61.5％ and 72.5％,respectively (x2 =8.233,P =0.004).The 3 year overall survival rate of the two genotypes were 73.7％ and 79.4％ (x2 =4.863,P =0.021).CT/TT genotypes were an independent factor for DFS (OR =1.81,P =0.012).The expression of CYP2A6 in PBMC of the patients with CT/TT genotypes were significantly lower than those of the CC genotype patients (P ＜ 0.001).Conclusions After D2 gastric cancer patients treated by S-1,the polymorphism rs8192725 of CYP2A6 may effect the clinical outcomes of adjuvant chemotherapy S-1 treatment through influencing the mRNA expression of CYP2A6.

Objective: To investigate the effect of VEGFR2 gene polymorphism V297I on the clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with bevacizumab combining with chemotherapy. Methods:Atotal of 135 patients with advanced NSCLC, who were treated by bevacizumab plus platinum-based chemotherapy for first-line regimen, were included in this study. PCR-RFLP assay was used to detect the VEGFR2 genotypes in peripheral blood of patients and qPCR was used to detect the VEGFR2 mRNA in the cancer tissues of NSCLC patients. Logistic regression analysis was used to analyze the correlation between gene polymorphism and other variants, Kaplan-Meier assay to analyze the correlation between genotype and prognosis, and Cox regression model to analyze the risk factors for patients’PFS. Results: Of the polymorphisms analyzed, only polymorphism V297I was found to be of clinical significance. V297I locates in the coding region of VEGFR2, and it’s prevalence in the study population was as follows: CC genotype in 99 cases (73.33%), CT genotype in 33 cases (24.44%) and TT genotype in 3 cases (2.23%); the frequency of minor allele was 0.14, and the distribution of three genotypes was in accordance with Hardy-Weinberg equilibrium (P>0.05). The overall objective remission rate (ORR) of the 135 patients was 45.93%, the median progression free survival (mPFS) was 8.2 months and the median overall survival (mOS) was 20.8 months. The ORR, mPFS and mOS of patients with CT/TT genotype and CC genotype were 41.67%, 6.2 months, 18.9 months and 47.47%, 8.9 months and 21.5 months, respectively (all P<0.05).Additionally, the mRNAexpression of VEGFR2 in cancer tissues of the patients with CT/TT genotype was significantly higher than those with CC genotype (P< 0.01). The risk factors for patients’PFS included V297I, gender and ECOG score. Conclusion:Among advanced NSCLC patients treated by bevacizumab plus platinum-based chemotherapy, the polymorphism V297I of VEGFR2 may impact the clinical outcomes and prognosis of NSCLC patients treated with bevacizumab first line treatment by influencing the mRNAexpression of VEGFR2.

Objective: To investigate the association between genetic variation of kinase insert domain receptor (KDR) and the prognosis in colorectal cancer (CRC) patients received 5-FU based adjuvant chemotherapy. Methods: The clinical data of 176 CRC patients, who underwent surgical treatment at the Department of Anus and Intestine Surgery, People’s Hospital of Zhengzhou during January 2012 and December 2017, were retrospectively analyzed, and 93 cases of tumor tissues were collected for this study. The genotype of KDR polymorphism locus was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). qPCR was used to detect the expression of KDR mRNAin colorectal cancer tissues. The correlation between the polymorphism genotypes and other variables was analyzed by logistic regression model. The expression of different genotypes of KDR was analyzed by nonparametric test. The relationship between KDR genotype and prognosis of patients was analyzed by Kaplan-Meier survival analysis, and the other variables were adjusted by Cox risk scale model. Results: Of the polymorphisms analyzed, only rs2071559 was of clinical significance. The distribution frequency of KDR rs2071559 in 176 CRC patients was as follows: TT genotype in 95 cases (53.98%), TC genotype in 70 cases (39.77%) and CC genotype in 11 cases (6.25%); the minor allele frequency was 0.26; and the distribution of three genotypes was in accordance with Hardy-Weinberg's Equilibrium (P=0.690). The median disease free survival (mDFS) of patients carrying C allele and wild type TT genotype was 4.4 and 3.2 years, respectively (P<0.05); The median overall survival (mOS) of patients with TC/CC genotype and TT genotype was 5.2 and 4.0 years, respectively (P<0.05). After COX model modification, the effect of TC/CC genotype on mOS was still statistically significant (OR=0.55, P<0.05). The mRNA expression of KDR in cancer tissues of the patients with TC/CC genotypes were significantly lower than those of the wild type TT genotype (P<0.01). Conclusion: The polymorphism of KDR rs2071559 is associated with clinical outcomes in patients with colorectal cancer. KDR rs2071559 may affect the prognosis of colorectal cancer patients by affecting the mRNAexpression of KDR.

Objective:Oral fluoropyrimidine S-1 contains tegafur,gimeracil,and oteracil;among them,tegafur is the major active pre-cursor,which is metabolized to 5-fluorouracil by cytochrome P4502A6(CYP2A6).We examined the associations between CYP2A6 poly-morphisms and the treatment outcomes of adjuvant S-1 in patients with gastric cancer.Methods:Two hundred patients diagnosed with pathological stageⅡ-Ⅲgastric cancer were included in this study,and they received adjuvant S-1(40 mg/m2,bid,days 1-28,ev-ery 6 weeks for eight cycles)after curative surgery.Additionally,we analyzed the wild-type allele(W)(CYP2A6*1)and four variant al-leles(V)(CYP2A6*4,*7,*9,and*10).Results:Two hundred patients were enrolled in this study between November 2007 and July 2013.With a median follow-up of 46.4 months(range:12.5-80.1),the 3-year relapse-free survival(RFS)and overall survival(OS)rates were 83.1%(95% confidence interval(CI),77.7%-88.5%)and 94.8%(95% CI,91.6%-98.0%),respectively.However,RFS differed signifi cantly according to the CYP2A6 genotype.The 3-year RFS rates were 95.9% for W/W,83.1% for W/V,and 72.5% for V/V(P=0.032)gen-otypes.Grades 3 and 4 overall toxicity did not differ according to genotype for any grade(P=0.628 and P=0.227,respectively).Conclu-sions:CYP2A6 genotypes correlate with the outcome of S-1 chemotherapy,wherein patients with the variant genotypes show worse prognosis.Additionally,polymorphism detection may be used as a biomarker to guide clinical chemotherapy choices for adjuvant ad-ministration of gastric cancer therapy.

Objective: To inrestigate the association between thymidine phosphorylase (TYMP) polymorphisms and efficacy of postop-erative capecitabine-based adjuvant chemotherapy in colorectal cancer (CRC) patients. Methods: Two hundred and thirty-five patients with colorectal cancer who received surgical treatment and adjuvant chemotherapy between January 2010 and December 2016 from People's Hospital of Zhengzhou, were included in this study. Peripheral blood and postoperative tissue specimens of the CRC patients were collected for genotyping polymorphisms and measuring TYMP mRNA expression, respectively. The correlation between the poly-morphisms and efficacy of postoperative chemotherapy in CRC patients was analyzed. Results: The prevalence of 5633C>T in TYMP gene among the CRC patients was as follows: CC genotype, 149 cases (63.40%); CT genotype, 73 cases (31.06%); and TT genotype, 13 cases (5.54%); the minor allele frequency of 5633C>T was 0.21. Survival analysis of the patients revealed that the median overall sur-vival (OS) of patients with the CT/TT genotype and those with the CC genotype was 5.9 and 4.5 years, respectively; the result was sta-tistically significant (P=0.009). Following adjustment in multivariate Cox regression analysis, the CT/TT genotype was found to be an in-dependent favorable factor for OS (HR=0.67, P=0.015). Additionally, of the 87 postoperative tissue specimens, results show that the levels of TYMP mRNA in cancer tissues of patients with the CT/TT genotype were significantly higher than those with the CC genotype (P=0.019). Conclusions: TYMP mRNA expression may be influenced by the 5633C>T polymorphism, making CRC patients benefit from capecitabine treatment.

[Abstract] Objective: To investigate the relationship between expression of MICA/B (MHC class I chain-related proteinA/B) and disease-free survival (DFS) of patients with HER2+(human epidermal growth factor receptor 2) breast cancer tissue. Methods: Twenty six cases of corresponding para-cancerous tissue and 100 cases of HER2+ breast cancer tissue that preserved in wax at Zhengzhou People’ s Hospital Affiliated to Southern Medical University from January 2009 to June 2010 were collected for this study. Expression of MICA/ B in these tissue samples was detected by immunohistochemistry; and the relationship between MICA/B expression with clinicopathologic features as well as DFS was analyzed with Kaplan-Meier survival curve. Results: The expression of MICA/B in adjacent paracancerous tissues was negative (0/26), however, it was highly positive in cancer tissues (92/100), and the percentage with high expression was 65%(65/100), the difference was significant (P<0.05). High MICA/B expression rate in stage I was significantly higher than that in stage Ⅱ-Ⅲ (77.55% vs 52.94%， P<0.05), and the high expression rate in stage T1 was also significantly higher than that in stage T2-T4 (75.00% vs 52.27%， P<0.05). High MICA/B expression rate in ER+, PR+ group (with positive number≥1%) was significantly lower than that in ER- , PR-group (ER： 52.38% vs 74.14%，PR： 51.35% vs 73.02%， all P<0.05). MICA/B expression was correlated with clinical stages, the expression of ER, PR and tumor size (all P<0.05), but not associated with menopausal status, histological grade and lymph node metastasis (all P>0.05). Over-expression of MICA/B was closely associated with much better 6-year DFS rate in patients no matter with or without targeted therapy (the targeted group: 90.6% vs 72.2%; the untargeted group: 78.4% vs 58.8%, all P<0.05). Conclusion: Over-expression of MICA/B in HER2+ breast cancer tissue is closely related to DFS, which may be served as a potential prognosis indicator for patients with HER2+ breast cancer.

Objective:To investigate the effects of Fructus Corni extract on the B7-H6 expression in primary liver cancer cells of rats. Methods:Sixty SD rats were randomly divided into three groups, namely, model, matrine, and Cornus officinalis. The rat model bear-ing the primary liver cancer was induced by diethylnitrosamine, except for the rats in the control group. The rats in both the matrine and Cornus officinalis groups were fed with matrine and Cornus officinalis. The rats in model groups were fed with 0.9％sodium chlo-ride solution. The number of hepatocellular carcinoma nodules was calculated, and the tumor growth inhibition rate was also calculat-ed. The pathological changes of hepatic tissues in rats of each group were observed by hematoxylin and eosin staining. The expression levels of B7-H6 in these three groups were determined by immunohistochemistry and Western blot. Results:The number of liver nod-ules of the matrine and Fructus Corni group rats was lower than that of the model group (P<0.05). The tumor inhibition rate of the Cor-nus group was significantly higher than that of the matrine group (P<0.05). The tumor growth inhibition rate of the Cornus officinalis group was significantly higher than that of the matrine group (P<0.05). Immunohistochemistry showed that the positive expression of B7-H6 in the Cornus officinalis group and the matrine group was significantly higher than that in the model group (P<0.05), and the positive expression of B7-H6 in the Cornus officinalis group was significantly higher than that in the matrine group (P<0.05). Similarly, the protein expression of B7-H6 in the Cornus officinalis and matrine groups was significantly higher than that in the model group (P<0.05) by Western blot, while the protein expression of B7-H6 in the Cornus officinalis group was significantly higher than that in the matrine group (P<0.05). Conclusion:Fructus Corni extract may inhibit the growth of hepatocellular carcinoma through upregulating the B7-H6 expression.

Objective:To explore the effect of paclitaxel (PTX) and cisplatin (DDP) on the expression of NKG2D ligands of hu-man esophagus carcinoma cell EC9706 and on the cytotoxicity of cytokine-induced killer (CIK) cells, as well as to discuss its molecu-lar mechanisms. Methods: The half maximal inhibitory concentration (IC50) values of PTX and DDP against EC9706 cells for 24 h were measured by MTT assay. The expression levels of NKG2D ligands (MICA, MICB, ULBP1, ULBP2, and ULBP3) on the EC9706 cell surface before and after 24 h culture with 1/2 IC50 of PTX or DDP were assayed by flow cytometry. Cytotoxicity of CIK cells against EC9706 cells before and after 24 h culture with 1/2 IC50 PTX or DDP was analyzed by lactate dehydrogenase release assay at an effector to target cell ratio (E:T) of 20:1 and 30:1, respectively. The expression levels of DNA damage repair genes (ATM, ATR, CHK1, CHK2, and p53) of EC9706 cells before and after 24 h incubation with 1/2 IC50 PTX or DDP were detected by quantitative fluorescent PCR. Results:The IC50 values of PTX and DDP were 10 and 5μg/mL, respectively. MICB, ULBP2, and ULBP3 on EC9706 cells were upregulated after 24 h culture with 1/2 IC50 PTX (P<0.05), and the expression levels of MICA, MICB, ULBP2, and ULBP3 were higher after 24 h culture with 1/2 IC50 DDP (P<0.05). Cytotoxicity of CIK cells against EC9706 cells cultured with 1/2 IC50 of PTX or DDP at E:T of 20:1 and 30:1 was significantly enhanced compared with those untreated (P<0.05). The expression levels of DNA damage repair genes did not significantly increase after 24 h treatment with 1/2 IC50 PTX (P>0.05), whereas ATM, ATR, CHK1, and CHK2 were over-expressed after 24 h treatment with 1/2 IC50 DDP (P<0.05). Conclusion:PTX or DDP can enhance the susceptibility of EC9706 cells to CIK cell-mediated lysis by upregulating the expression of NKG2D ligands through activating DNA damage repair genes.