To investigate the mutation status of epidermal growth factor receptor (EGFR) and KRAS gene in patients with non-small cell lung cancer (NSCLC) in Xuanwei, Yunnan and to correlate the mutation status with clinicopathologic features.Mutation status of exons 18, 19, 20 and 21 of EGFR, and codons 12, 13 of KRAS in 63 cases of NSCLC were analyzed by gene sequencing and ARMS-Taqman probe method. Correlation with patients' clinicopathological characteristics was performed.EGFR and KRAS mutations were present in 55.6% (35/63) and 6.3% (4/63), respectively. EGFR gene mutations were present, including exon 18 G719X in 14.3% (5/35), exon 19 in 14.3% (5/35), exon 20 S768I and T790M in 20.0% (7/35), exon 21 L858R in 31.4% (11/35), exon 18 G719X and exon 20 S768I double mutation in 17.1% (6/35), and exon 20 T790M and exon 21 L858R double mutation in 2.9% (1/35). KRAS mutations were seen in codon 12 in 3 of 4 cases, and codon 13 in 1 of 4 cases. EGFR mutations were mutually exclusive with KRAS mutations. According to statistic analysis, EGFR mutations were associated with the histological types of NSCLC(P<0.05), but without correlation with patient's gender, age, smoking status and lymph node metastasis(P>0.05). KRAS mutations in NSCLC had no correlation with the clinical pathologic characteristics of the patients.A higher frequency of EGFR exon 18 G719X and 20 exon S768I mutations are found in the patients in Xuanwei, Yunnan. EGFR mutations are associated with histologic types of NSCLC, but without correlation with patient's gender, age, smoking status and lymph node metastasis. KRAS mutation in NSCLC has no correlation with the clinicopathologic characteristics of the patients.
We previously found that genetic polymorphisms in gene coding for histamine H4 receptors were related to the risk and malignant degree of breast cancer. The roles of polymorphisms in other histamine-related genes, such as histidine decarboxylase (HDC), histamine N-methyltransferase (HNMT) and histamine H3 receptor (HRH3), remain unexplored. The aim of this study is to analyze the clinical associations of polymorphisms in HDC, HNMT and HRH3 with breast cancer. Two hundred and one unrelated Chinese Han breast cancer patients and 205 ethnicity-matched health controls were recruited for case-control investigation. Genomic DNA from the participants was extracted and 5 single nucleotide polymorphisms (SNPs) in HDC, HNMT and HRH3 were genotyped. We found that polymorphisms of HNMT and HRH3 were irrelevant with breast cancer in the present study. However, the T allele of rs7164386 in HDC significantly decreased the risk of breast cancer (adjusted odds ratios [ORs], 0.387; 95% confidence intervals [CIs], 0.208–0.720; P = 0.003). Furthermore, for HDC haplotypes, the CG haplotype of rs7164386-rs7182203 was more frequent among breast cancer patients (adjusted OR, 1.828; 95% CI, 1.218–2.744; P = 0.004) while the TG haplotype was more frequent among health controls (adjusted OR, 0.351; 95% CI, 0.182–0.678; P = 0.002). These findings indicated that polymorphisms of HDC gene were significantly associated with breast cancer in Chinese Han population and may be novel diagnostic or therapeutic targets for breast cancer. Further studies with larger participants worldwide are still needed for conclusion validation.
Objective
To explore the effect of fibroblast growth factor receptors 1 -dominant negativestrategy(FGFR1-DN)on alkaline phosphatase(ALP)activity of bone marrow stromal stem cells(BMSCs)after osteogenic induction.
Methods
BMSCs were transfected with eukaryotic expression plasmid pcDNA3. 1(+)-DN FGFR1 and pcDNA3. 1(+)-FGFR1. The experiment was conducted in 4 groups: FGFR1-DN transfection group, FGFR1 transfection group, pcDNA3. 1(+)empty vector transfection group and non-transfection group. The ALP activity of BMSCs was detected in logarithmic growth phase after osteogenic culture. The qualitative detection of ALP activity was carried out immunohistochemically while the quantitative detection by cALP kit. The ALP activity was compared between the 4 groups at 7 and 14 days after osteogenic induction.
Results
Compared with 7 days, the ALP activity at 14 days was significantly increased in the4 groups, and the increase in FGFR1-DN transfection group was significantly higher than in the other 3 groups(P< 0. 05). At both 7 and 14 days, the ALP activity in FGFR1-DN transfection group was the highest while that in FGFR1 transfection group was the lowest(P< 0. 05).
Conclusions
FGFR1-DN can promote the ALP activity of BMSCs during osteogenesis. This may provide an experimental basis for the joint application oflocal gene therapy and tissue engineering and for construction of tissue engineered bone with better biocom-patibility.
Key words:
Bone marrow cells; Fibroblast growth factors; Fibroblast growth factor receptor 1; Dominant negative effect
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