Background and purpose: Aurora kinases, frequently detected to be over-expressed in some human tumors, regulate many essential events during tumor cell mitosis progression and have been regarded as potentially important targets for cancer therapy. This study was designed to detect Aurora-B expression in cervical carcinoma, explore the relation Aurora-B expression and clinicopathologic feature. So, Aurora-B kinase inhibition ZM447439 was used to investigate the effect of ZM447439 on SiHa cell line and the synergy effect with paclitaxel. Methods:Detected Aurora-B protein in cervical carcinoma(70 patients), CINⅡ(46 patients) and normal cervix(21patients) by immunohistochemistry. The inhibitory effects of ZM447439 and paclitaxel in SiHa cell line were investigated by MTT based assay, The expression of apoptosis associated protein was measured by Western blot. Results:The rate of Aurora-B expression is 71.43%in cervical cancer, with no signiifcant correlation to clinical stage, age, lymph node metastasis, vascular invasion (P>0.05). Aurora-A protein expression has significant correlation to pathological type and grade(P<0.05). Enhanced antiproliferative effects were found when SiHa cells were cultured with ZM447439. Synergic effect of ZM447439 combined with paclitaxel was found in SiHa cell line(Q>1.15). The level of P53 was increased significantly through ZM447439 treatments with Western blot. Conclusion: Our data provides strong evidence that high expression of Aurora-B in cervical cancer. The targeted Aurora-B inhibitors, ZM447439, can enhance paclitaxel anti-tumor activity in cervical cancer.

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 1 (VEGFR1) pathways-related genes and the risk of pre-eclampsia. METHODS: In total 178 pregnant women with pre-eclampsia (case group) and 100 healthy pregnant women (control group) during the third trimester were enrolled. The SNPs of VEGF rs3025039, rs2010963 and VEGFR1 rs3812867, rs55875014 and rs722503 loci were determined by PCR-restriction fragment length polymorphism (PCR-RFLP) assay. The levels of serum VEGF and sVEGFR1 were also determined. And their association with pre-eclampsia was analyzed. RESULTS: The systolic blood pressure, diastolic blood pressure and sVEGFR1 of the case group were significantly higher than those of the control group, while the VEGF level was significantly lower than that in the control group (P<0.05). Allelic frequencies of the VEGF (rs3025039, rs2010963) and VEGFR1 (rs3812867, rs55875014, rs722503) have fit the Hardy-Weinberg equilibrium (P>0.05). The frequency of T allele of VEGF at rs3025039 locus in the case group was higher than that in the control group (P<0.05). There were significant differences in VEGF at rs3025039 locus under dominant and co-dominant models in case group (P<0.05). Compared with those with CC, the risk was higher in patients with CT or TT genotypes (P<0.05). The systolic and diastolic blood pressure and sVEGFR1 in pre-eclampsia pregnant women with CT or TT genotypes were significantly higher than those with the CC genotype, while their VEGF level was significantly lower (P<0.05). No significant difference was found in allelic frequencies of other four loci between the two groups (P>0.05). CONCLUSION Polymorphisms of rs3025039 locus of VEGF gene is associated with the occurrence of pre-eclampsia. The variant at this locus may affect the activity of VEGF and influence the development of pre-eclampsia.
Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Pre-Eclampsia/genetics* ; Pregnancy ; Vascular Endothelial Growth Factor A/genetics* ; Vascular Endothelial Growth Factor Receptor-1/genetics* ; Vascular Endothelial Growth Factors/genetics*

Objective:To study the clinical characteristics of Lynch syndrome-associated endometrial cancer in elderly patients and the relationship of the disease with MSH2 gene mutations in patients' families.Methods:Clinical data of 473 elderly patients with endometrial cancer admitted to our hospital between January 2016 and January 2021 were retrospectively analyzed.MSH2 gene mutations were detected and verified by DNA sequence analysis, real-time quantitative PCR and reverse transcription PCR.Patients were divided into a Lynch syndrome group and a non-Lynch syndrome group, and the clinicopathological features of the two groups were compared.Results:Of 473 endometrial carcinoma patients, 46(9.7%)had embryogenic mutations of the MMR gene and were diagnosed with Lynch syndrome, with 18, 6, 24 and 10 patients carrying MLH1, PMS2, MSH2 and MSH6 mutations, respectively.There were 3 mutations in the MSH2 gene, including exon 7 1380C>A, exon 12 2011A>G and exon 13 2756A→AC.The proportions of patients with G3 grade endometrioid adenocarcinoma, lower uterine segment involvement and a history of Lynch syndrome-associated malignant tumors in the Lynch syndrome group were significantly higher than those in the non-Lynch syndrome group( χ2=8.935, 8.303, 9.770, all P<0.05). Conclusions:Poorly differentiated endometrioid adenocarcinoma, predisposition to lower uterine segment involvement and familial inheritance are the main clinical manifestations of Lynch syndrome-associated endometrial carcinoma in elderly patients, with the most common mutations seen in the MSH2 gene.