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- 발행기관 : Cancer Research UK (검색결과 4 건)
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Lee, H E,Kim, M A,Lee, H S,Jung, E-J,Yang, H-K,Lee, B L,Bang, Y-J,Kim, W H Cancer Research UK 2012 The British journal of cancer Vol.107 No.2
Background:The aim of this study was to compare gene copy number (GCN) and protein expression of MET and to evaluate their prognostic roles in gastric carcinomas.Methods:MET protein expression and gene amplification (GA) status were determined by immunohistochemistry (IHC) and silver in-situ hybridisation (SISH), respectively, in a large series of gastric carcinoma.Results:Protein overexpression was observed in 104 of 438 cases, with IHC 2+ in 94 and IHC 3+ in 10, and high polysomy of chromosome 7 and GA were found in 61 and 13 of 381, respectively. Direct comparison revealed a significant correlation between high level of protein expression and increased GCN. All cases with GA showed protein overexpression. Furthermore, all with IHC 3+ showed GA except 1, even which could be categorised as GA according to the ASCO/CAP guideline for human epidermal growth factor receptor 2 assessment. IHC 3+ and GA were significantly associated with poor prognosis.Conclusion:MET IHC reflects well on GA, and therefore, it could be a primary screening test for patient selection for anti-MET therapy if GA is a major determinant of drug responsiveness. Also, the prognostic role of MET indicates that anti-MET therapy is a very promising modality in adjuvant treatment for gastric cancer.
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Lee, D-W,Han, S-W,Lee, H J,Rhee, Y-Y,Bae, J M,Cho, N-Y,Lee, K-H,Kim, T-Y,Oh, D-Y,Im, S-A,Bang, Y-J,Jeong, S-Y,Park, K J,Park, J-G,Kang, G H,Kim, T-Y Cancer Research UK 2013 The British journal of cancer Vol.108 No.10
Background:There have been controversies in prognostic impact of mucinous histology on colorectal cancer, and its implication in patients treated with adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is unclear.Methods:Stage II and III colorectal cancer patients who underwent curative resection followed by adjuvant FOLFOX were included. Patients were grouped according to the mucinous content: >50%, mucinous adenocarcinoma (MAC); <50%, adenocarcinoma with intermediated mucinous component (AIM); and without any mucinous component, non-MAC (NMA). Clinicopathological features and disease-free survival (DFS) were compared.Results:Among a total of 521 patients, 27 patients (5.2%) had MAC, 41 patients (7.9%) had AIM, and 453 patients (86.9%) had NMA. Mucinous adenocarcinoma and AIM had higher frequency of proximal location and microsatellite instability, but lower frequency of angiolymphatic invasion. Disease-free survival was significantly worse in the MAC compared with NMA (3-year DFS 57% and 86%, respectively; P<0.001) and AIM (3-year DFS 87%, P=0.01 vs MAC). Multivariate analysis revealed MAC as an independent negative prognostic factor of DFS (adjusted hazard ratio 7.96, 95% confidence interval 3.76–16.8).Conclusion:Adenocarcinoma with intermediated mucinous component and MAC have distinct clinicopathological features compared with NMA. Mucinous adenocarcinoma has an adverse prognostic impact on stage II or III colorectal cancer treated with adjuvant FOLFOX.
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Choi, C H,Choi, J-J,Park, Y-A,Lee, Y-Y,Song, S Y,Sung, C O,Song, T,Kim, M-K,Kim, T-J,Lee, J-W,Kim, H-J,Bae, D-S,Kim, B-G Cancer Research UK 2012 The British journal of cancer Vol.107 No.1
Background:The purpose of this study was to identify genes that are differentially expressed in chemosensitive serous papillary ovarian carcinomas relative to those expressed in chemoresistant tumours.Methods:To identify novel candidate biomarkers, differences in gene expression were analysed in 26 stage IIIC/IV serous ovarian adenocarcinomas (12 chemosensitive tumours and 14 chemoresistant tumours). We subsequently investigated the immunohistochemical expression of GRIA2 in 48 independent sets of advanced ovarian serous carcinomas.Results:Microarray analysis revealed a total of 57 genes that were differentially expressed in chemoresistant and chemosensitive tumours. Of the 57 genes, 39 genes were upregulated and 18 genes were downregulated in chemosensitive tumours. Five differentially expressed genes (CD36, LIFR, CHL1, GRIA2, and FCGBP) were validated by quantitative real-time PCR. The expression of GRIA2 was validated at the protein level by immunohistochemistry, and patients with GRIA2 expression showed a longer progression-free and overall survival (P=0.051 and P=0.031 respectively).Conclusions:We found 57 differentially expressed genes to distinguish between chemosensitive and chemoresistant tumours. We also demonstrated that the expression of GRIA2 among the differentially expressed genes provides better prognosis of patients with advanced serous papillary ovarian adenocarcinoma.
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Phase I/II study of S-1 combined with weekly docetaxel in patients with metastatic gastric carcinoma
Park, S R,Kim, H K,Kim, C G,Choi, I J,Lee, J S,Lee, J H,Ryu, K W,Kim, Y-W,Bae, J-M,Kim, N K Cancer Research UK 2008 The British journal of cancer Vol.98 No.8
We designed a phase I/II trial of S-1 combined with weekly docetaxel to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in metastatic gastric carcinoma (MGC). Patients with measurable disease received S-1 orally b.i.d. on days 1–14 and docetaxel intravenously on days 1 and 8 every 3 weeks. In phase I (n=30), each cohort received escalating doses of S-1 (30–45 mg m<SUP>−2</SUP> b.i.d.) and docetaxel (25–40 mg m<SUP>−2</SUP>); MTD was 45 mg m<SUP>−2</SUP> b.i.d. S-1/35 mg m<SUP>−2</SUP> docetaxel and RD was 40 mg m<SUP>−2</SUP> b.i.d. S-1/35 mg m<SUP>−2</SUP> docetaxel. Dose-limiting toxicities included grade 3 elevated liver enzymes, gastric perforation, grade 3 diarrhoea/fatigue, febrile neutropenia with grade 3 anorexia/fatigue, and neutropenic infection with grade 3 stomatitis/anorexia. In phase II (n=52), the overall response rate was 66.7% (95% confidence interval (CI): 53.8–79.6%) and the median time to progression and overall survival were 6.5 months (95% CI: 4.9–8.1) and 13.7 months (95% CI: 9.9–17.5), respectively. The most common grade 3/4 toxicity was neutropenia (29.4%), and febrile neutropenia/neutropenic infection occurred in 19.6% of patients. Non-haematological toxicities were generally mild. There was one treatment-related death due to pneumonitis. S-1 combined with weekly docetaxel is active in MGC with moderate toxicities.British Journal of Cancer (2008) 98, 1305–1311. doi:10.1038/sj.bjc.6604312 www.bjcancer.com Published online 25 March 2008
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