ABSTRACT
Objective:To investigate the expression of class IIIβ-tubulin (TUBB3) in advanced gastric cancer and analyze its correlation with the chemotherapeutic effect of paclitaxel and the prognosis of patients. Methods:This study reviewed 49 cases with advanced gastric cancer, diagnosed from December 2008 to December 2011 at Shaoyang Central Hospital. All patients were treated with paclitax-el or docetaxel-based chemotherapy. TUBB3 expression was determined using immunohistochemistry. Relationships of the expression of TUBB3 protein with chemotherapy response, progression-free survival (PFS), and overall survival (OS) were analyzed. Results:Among the 46 valid cases treated with paclitaxel or docetaxel-based regimen, treatment response was as follows:complete response (CR) in 1 patient, partial response (PR) in 17 patients, stable disease (SD) in 22 patients, and progression disease (PD) in 6 patients. The overall response rate (CR+PR) was 39.13％(18/46). The chemotherapy response rates in low and high TUBB3 expression groups were 54.17％(13/24) and 22.73％(5/22), respectively (χ2=4.736, P=0.029). The patients with low TUBB3 expression had significantly longer median PFS and OS than those with high TUBB3 expression (PFS 5.9 vs. 3.9 months, P=0.032;OS 11.6 vs. 7.9 months, P=0.001). Univar-iate analysis and multivariate Cox regression analysis showed that the expression of TUBB3 was an independent prognostic factor in advanced gastric cancer. Conclusions:The present study demonstrates that TUBB3 expression in advanced gastric cancer is associated with chemotherapy response and prognosis;especifically, the low expression group had a better chemotherapy response and progno-sis than the high expression group. The result of this study may provide a new sight for tailored chemotherapy and for predicting prog-nosis of individuals with advanced gastric cancer.
ABSTRACT
Objective To determine the pathogenic mutant gene and the classification for 2 Chinese families with congenital fibrosis of the extraocular muscles (CFEOM) by using candidate genes methods.Methyls All members in the 2 Chinese families with CFEOM were collected and underwent for clinical data collection,including medical history,physical examination and 5-8 mL peripheral venous blood for DNA extraction.Exon 2,8,20,21 of KIF21A,exon 1,2,3 of PHOX2A/ARIX,exon 1,2,3,and 4 of TUBB2B and exon 1,2,3,4 of TUBB3 were selected and synthesized by PCR,and the amplified samples were purified for sequences analysis by Chromas2.3 and DNAman7.0 software.Results There were 9 members developed CFEOM in family 1,with the typical CFEOM characteristics.The mutation site was located in KIF21A (exon 21),2860C ＞ T;and 4 patients in family 2 suffered this disease,and the typical CFEOM appearance features was in 3 patients.The mutation site was located in TBUU3 (exon 4),1249 G ＞ A.Conclusion The candidate genes methods can be used to identify the pathogenic genes of pedigrees with inherited diseases effectively.Family 1 belongs to CFEOM 1A type,which is the autosomal dominant inheritance with complete penetrance,and family 2 belongs to CFEOM 3A type,whivh is the autosomal dominant inheritance with incomplete penetrance.
ABSTRACT
Background and purpose:Chemotherapy is an alternative treatment option, which could still get a therapeutic effect, when the EGFR-TKI treatment of non-small cell lung cancer failed. Studies have shown that RR, TYMS, ERCC1 and TUBB3 have respectively relationship with chemosensitivity of gemcitabine, pemetrexed, platinum-based drugs and microtubule-based chemotherapy drugs.The expression levels of these molecular markers can predict the sensitivity of these chemotherapy drugs. The patients with RRMI, TS, ERCC1 and TUBB3 higher expression have reduced chemosensitivity, and lower expression have increased sensitivity. The purpose of this study was to explore the sensitivity of tumor cell lines with acquired resistance to geiftinib caused byEGFR-T790M mutation to cisplatin, gemcitabine, pemetrexed, vinorelbine, paclitaxel and docetaxel.Methods:MTT assay was used to detect the IC50 values of cisplatin, gemcitabine, vinorelbine, paclitaxel and docetaxel, pemetrexed to PC9 and PC9/GR cells, and to explore the chemosensitivity of lung adenocarcinoma cells to these chemotherapy drugs; Luminex method was used respectively to detect the expression levels of ERCC1 mRNA, TUBB3 mRNA, TS mRNA, and RRM1 mRNA in PC9 and PC9/GR cells. Western blot was used to detect the protein expression levels of ERCC1, TUBB3, TS and RRM1 in PC9 and PC9/GR cells.Results: The IC50 values of cisplatin, gemcitabine and pemetrexed to PC9/GR cells were signiifcantly higher than those to PC9 cells (P<0.05), while the IC50 values of vinorelbine, paclitaxe and docetaxel to PC9/GR cells were signiifcantly decreased (P<0.05). Luminex method showed the expressions of ERCC1 mRNA, TS mRNA and RRM1 mRNA in PC9/GR cells were signiifcantly increased than those in PC9 cells (P<0.05), while the expression of TUBB3 mRNA was signiifcantly decreased (P<0.05). Western blot method showed the expressions of TUBB3, TS and RRM1 protein in PC9/GR cells were signiifcantly increased than those in PC9 cells (P<0.05), while TUBB3 protein expression in PC9/GR cells was signiifcantly decreased (P<0.05). Western blot method analysis result showed that the expressions of TUBB3, TS and RRM1 protein in PC9/GR cells were significantly increased than those in PC9 cells (P<0.05), while TUBB3 protein expression in PC9/GR cells was signiifcantly decreased (P<0.05). Conclusion:The chemosensitivity of lung adenocarcinoma with EGFR-T790M mutation is changed. It has decreased sensitivity to cisplatin, gemcitabine, pemetrexed and increased sensitivity to vinorelbine, paclitaxel and docetaxel. The reason of the change of chemosensitivity of geiftinib-resistant lung adenocarcinoma cell maybe related to the changes of ERCC1 mRNA, RRM1 mRNA and TS mRNA and their protein expressions.
ABSTRACT
Objective To investigate the relationship between the expression of BRCA1,β-tubulin III (TUBB3) and their efficacies with platinum-based chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods The expression levels of BRCA1 and TUBB3 were detected by immunohistochemistry. The relationship between BRCA1 and TUBB3 expressions and their efficacies were analyzed. Results The high expression rate of BRCA1 was 34.8%, and the efficacy of platinum-based chemotherapy in patients with BRCA1-lower expression is obviously better than that in patients with BRCA1-higher expression. There was a significant difference between these two groups (30.4%vs 67.4%, P=0.004). The effective rate of platinum-based chemotherapy in TUBB3-higher expression group and TUBB3-lower expression group were illustrated no significance (59.4% vs 50.0%, P=0.445). Conclusion Platinum-based chemotherapy is more suitable for the advanced NSCLC patients with lower expression of BRCA1. The expression level of BRCA1 could be used to predict the efficacy of platinum-based chemotherapy in advanced NSCLC patients.