BACKGROUND: KRAS mutation plays an important role in the pathogenesis of pancreatic cancer. However, the role of wild-type KRAS in the progression of pancreatic cancer remains unknown. The present study was to investi...BACKGROUND: KRAS mutation plays an important role in the pathogenesis of pancreatic cancer. However, the role of wild-type KRAS in the progression of pancreatic cancer remains unknown. The present study was to investigate the expression of the Ras GTPase activating protein (DAB2IP) in pancreatic cancer and its clinical significance. METHODS: The expression of DAB2IP in pancreatic cancer cell lines and normal human pancreatic ductal epithelial cells was analyzed by Western blotting and realtime quantitative reverse transcription-PCR (qRT-PCR). The KRAS mutational types of pancreatic cancer tissues obtained from pancreatic cancer patients (n=20) were also analyzed. Subsequently, DAB2IP expression was detected in pancreatic cancer tissues, adjacent and normal pancreatic tissues (n=2) by immunohistochemistry, and the relationship between DAB2IP expression and the clinical characteristics of patients was evaluated. RESULTS: Western blotting and qRT-PCR results showed that DAB2IP expression in pancreatic cancer cells with wild-type KRAS was lower than that in those with mutation-type KRAS and normal human pancreatic ductal epithelial cells (P【0.05). Immunohistochemistry showed that DAB2IP expression was lower in pancreatic cancer tissues than that in adjacent and normal pancreatic tissues (Z=-4.000, P=0.000). DAB2IP expression was lower in pancreatic cancer patients with the wild-type KRAS gene than that in those with KRAS mutations (WilcoxonW=35.000, P=0.042). Furthermore,DAB2IP expression in patients with perineurial invasion was lower than that in those without invasion (WilcoxonW=71.500, P=0.028). DAB2IP expression was lower in patients with more advanced stage than that in those with early clinical stage (WilcoxonW=54.000, P=0.002). CONCLUSIONS: DAB2IP expression was reduced in patients with pancreatic cancer compared with those with no cancer. DAB2IP expression was correlated with the KRAS gene, perineurial invasion and clinical stage of the disease. Our data indicated that DAP2IP expression can be used as a potential prognostic indicator and a promising molecular target for therapeutic intervention in patients with pancreatic cancer.展开更多
AIM: To observe the growth inhibitory effect of wild-type Kras2 gene on a colonic adenocarcinoma cell line Caco-2. METHODS: Recombinant plasmid pCI-neo-Kras2 with wild type Kras2 open reading frame was constructed. Th...AIM: To observe the growth inhibitory effect of wild-type Kras2 gene on a colonic adenocarcinoma cell line Caco-2. METHODS: Recombinant plasmid pCI-neo-Kras2 with wild type Kras2 open reading frame was constructed. The Caco-2 cells were transfected with either pCI-neo or pCI-neo-Kras2 using Lipofectamine 2000. The expression of wild type Kras 2 was examined by Northern blot analysis. And the expression of wild type Kras2 protein was examined by Western blot analysis. The effects of wild-type Kras2 on cell proliferation were analyzed by monotetrazolium (MTT) assay, meanwhile analyses of cell cycle and spontaneous apoptosis rate were carried out by flow cytometry (FCM). RESULTS: The plasmid of pCI-neo-Kras 2 was successfully established. The growth rate of cells transfected with pCI-neo-Kras2 was significantly lower than the control cells transfected with the empty pCI-neo vector (P < 0.05). Cell cycle analysis revealed arrest of the pCI-neo-Kras2 transfected cells in G0/G1 phases, decreased DNA synthesis and decreased fractions of cells in S phase. The proliferative index of cells transfected with pCI-neo-Kras2 was decreased compared with the control cells (49.78% vs 64.21%),while the apoptotic rate of Caco-2 cells with stable Kras 2 expression increased (0.30% vs 0.02%). CONCLUSION: The wild-type Kras2 gene effectively inhibits the growth of the colonic adenocarcinoma cell line Caco-2.展开更多
Objective: Panitumumab administered as monotherapy in colorectal cancer(CRC) has shown response and disease stabilization rates of approximately 30%. The current study aimed to evaluate the progression-free survival(P...Objective: Panitumumab administered as monotherapy in colorectal cancer(CRC) has shown response and disease stabilization rates of approximately 30%. The current study aimed to evaluate the progression-free survival(PFS) and overall survival(OS) of patients with metastatic colorectal cancer(mCRC) treated with panitumumab every 3 weeks as a second line treatment.Methods: This study is a retrospective analysis of 18 patients, aged more than 18 years, with wild-type KRAS exon 2 mCRC treated with panitumumab as a second-line single agent after progression on first-line chemotherapy.Results: The median number of courses received was 10(range, 4-29), and the median duration of treatment was 30 weeks(range,12-96 weeks). After a median follow-up period of 13 months, the median PFS was 6 months(range, 4.3-7.7 months) and the median OS was 11 months(range, 7.4-14.5 months). The median PFS was 4 months for patients with < grade 2 skin toxicity and 6months(range, 4.5-7.5 months) for patients with ≥ grade 2 skin rash(P=0.05). The median OS was 9 months(range, 6.4-11.5months) and 14 months(range, 11.6-16.3 months) for the two groups of patients(P=0.002).Conclusions: Panitumumab given every 3 weeks is effective and well tolerated in patients with advanced CRC that progressed after standard chemotherapy.展开更多
基金supported by grants from the Project of International Cooperation in Guangzhou Province (2010B050700014)the Science and Technology Planning Project of Guangzhou(2011J4100006)
文摘BACKGROUND: KRAS mutation plays an important role in the pathogenesis of pancreatic cancer. However, the role of wild-type KRAS in the progression of pancreatic cancer remains unknown. The present study was to investigate the expression of the Ras GTPase activating protein (DAB2IP) in pancreatic cancer and its clinical significance. METHODS: The expression of DAB2IP in pancreatic cancer cell lines and normal human pancreatic ductal epithelial cells was analyzed by Western blotting and realtime quantitative reverse transcription-PCR (qRT-PCR). The KRAS mutational types of pancreatic cancer tissues obtained from pancreatic cancer patients (n=20) were also analyzed. Subsequently, DAB2IP expression was detected in pancreatic cancer tissues, adjacent and normal pancreatic tissues (n=2) by immunohistochemistry, and the relationship between DAB2IP expression and the clinical characteristics of patients was evaluated. RESULTS: Western blotting and qRT-PCR results showed that DAB2IP expression in pancreatic cancer cells with wild-type KRAS was lower than that in those with mutation-type KRAS and normal human pancreatic ductal epithelial cells (P【0.05). Immunohistochemistry showed that DAB2IP expression was lower in pancreatic cancer tissues than that in adjacent and normal pancreatic tissues (Z=-4.000, P=0.000). DAB2IP expression was lower in pancreatic cancer patients with the wild-type KRAS gene than that in those with KRAS mutations (WilcoxonW=35.000, P=0.042). Furthermore,DAB2IP expression in patients with perineurial invasion was lower than that in those without invasion (WilcoxonW=71.500, P=0.028). DAB2IP expression was lower in patients with more advanced stage than that in those with early clinical stage (WilcoxonW=54.000, P=0.002). CONCLUSIONS: DAB2IP expression was reduced in patients with pancreatic cancer compared with those with no cancer. DAB2IP expression was correlated with the KRAS gene, perineurial invasion and clinical stage of the disease. Our data indicated that DAP2IP expression can be used as a potential prognostic indicator and a promising molecular target for therapeutic intervention in patients with pancreatic cancer.
基金a grant from National Natural Science Foundation of China for Young Scholars, No. 30200326
文摘AIM: To observe the growth inhibitory effect of wild-type Kras2 gene on a colonic adenocarcinoma cell line Caco-2. METHODS: Recombinant plasmid pCI-neo-Kras2 with wild type Kras2 open reading frame was constructed. The Caco-2 cells were transfected with either pCI-neo or pCI-neo-Kras2 using Lipofectamine 2000. The expression of wild type Kras 2 was examined by Northern blot analysis. And the expression of wild type Kras2 protein was examined by Western blot analysis. The effects of wild-type Kras2 on cell proliferation were analyzed by monotetrazolium (MTT) assay, meanwhile analyses of cell cycle and spontaneous apoptosis rate were carried out by flow cytometry (FCM). RESULTS: The plasmid of pCI-neo-Kras 2 was successfully established. The growth rate of cells transfected with pCI-neo-Kras2 was significantly lower than the control cells transfected with the empty pCI-neo vector (P < 0.05). Cell cycle analysis revealed arrest of the pCI-neo-Kras2 transfected cells in G0/G1 phases, decreased DNA synthesis and decreased fractions of cells in S phase. The proliferative index of cells transfected with pCI-neo-Kras2 was decreased compared with the control cells (49.78% vs 64.21%),while the apoptotic rate of Caco-2 cells with stable Kras 2 expression increased (0.30% vs 0.02%). CONCLUSION: The wild-type Kras2 gene effectively inhibits the growth of the colonic adenocarcinoma cell line Caco-2.
文摘Objective: Panitumumab administered as monotherapy in colorectal cancer(CRC) has shown response and disease stabilization rates of approximately 30%. The current study aimed to evaluate the progression-free survival(PFS) and overall survival(OS) of patients with metastatic colorectal cancer(mCRC) treated with panitumumab every 3 weeks as a second line treatment.Methods: This study is a retrospective analysis of 18 patients, aged more than 18 years, with wild-type KRAS exon 2 mCRC treated with panitumumab as a second-line single agent after progression on first-line chemotherapy.Results: The median number of courses received was 10(range, 4-29), and the median duration of treatment was 30 weeks(range,12-96 weeks). After a median follow-up period of 13 months, the median PFS was 6 months(range, 4.3-7.7 months) and the median OS was 11 months(range, 7.4-14.5 months). The median PFS was 4 months for patients with < grade 2 skin toxicity and 6months(range, 4.5-7.5 months) for patients with ≥ grade 2 skin rash(P=0.05). The median OS was 9 months(range, 6.4-11.5months) and 14 months(range, 11.6-16.3 months) for the two groups of patients(P=0.002).Conclusions: Panitumumab given every 3 weeks is effective and well tolerated in patients with advanced CRC that progressed after standard chemotherapy.