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김치홍,박손야영주,유진영 대한암학회 2013 Cancer Research and Treatment Vol.45 No.2
Purpose This study was conducted in order to investigate the significance of transforming growth factor β1 (TGFβ1) and E-cadherin proteins in tumor progression of lung adenocarcinoma and to evaluate their differential expression in association with morphologic characteristics. Materials and Methods A total of 65 pulmonary adenocarcinomas were reclassified according to the new classification system proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. Tumor samples from 20 adenocarcinomas in situ (AIS, formerly bronchioloalveolar carcinoma [BAC]),9 minimally invasive adenocarcinomas (MIA, formerly BAC with ≤ 5 mm invasion), 17lepidic predominant adenocarcinomas (LPA, formerly mixed adenocarcinoma showing nonmucinous BAC features with >5 mm invasion), and 19 invasive adenocarcinomas with no BAC features were analyzed by immunohistochemistry for expression of TGFβ1 and E-cadherin proteins. Results TGFβ1 expression was detected in 46% (21/46) of noninvasive elements and 87%(39/45) of invasive elements (p=0.001). E-Cadherin expression was less frequent in invasive components than in noninvasive components (38% vs. 65%, p=0.009). Negative correlation was identified between TGFβ1 expression and E-cadherin expression in noninvasive elements (p=0.022). More importantly, significantly higher frequency of TGFβ1 expression was observed in noninvasive components of LPA (14/17, 82%),compared with those of either AIS (5/20, 25%) or MIA (2/9, 22%) (p=0.008). Conclusion Our data indicate involvement of both TGFβ1 and E-cadherin proteins in tumor progression of pulmonary adenocarcinoma. It is noteworthy that TGFβ1 up-regulation precedes alveolar destruction by invasion of tumor cells. TGFβ1 may thus have the potential to improve lung adenocarcinoma diagnostics and therapeutics.
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김치홍,김승훈,박손야영주,유진영,김훈교 대한암학회 2015 Cancer Research and Treatment Vol.47 No.4
Purpose Mutation-specific antibodies have recently been developed for identification of epidermalgrowth factor receptor (EGFR) mutations by immunohistochemistry (IHC). This study wasdesigned to investigate whether the type of specimen (biopsy vs. resection) would make adifference in determining mutation status by IHC, and to evaluate whether biopsies are suitablefor detection of mutant EGFR protein. Materials and MethodsIHC was performed using mutation-specific antibodies for E746-A750 deletion (DEL) andL858R point mutation (L858R) in biopsies and tissue microarrays of resected tumors from154 patients with pulmonary adenocarcinoma. Results were then compared with DNAsequencing data. ResultsMolecular-based assays detected EGFR mutations in 62 patients (40.3%), including 14(9.1%) with DEL, and 31 (20.1%) with L858R. IHC with two mutation-specific antibodiesshowed a homogeneous staining pattern, and correctly identified EGFRmutation status in89% (137/154). Overall (biopsy/resection) sensitivity, specificity, positive predictive value,and negative predictive value were 75.6% (78.3%/72.7%), 94.5% (90.9%/96.3%), 85%(78.3%/88.9%), and 90.4% (90.9%/89.7%), respectively. ConclusionOur data showed that IHC using EGFR mutation–specific antibodies is useful for detectionof EGFRmutations with high specificity and good sensitivity not only for resection specimensbut also for biopsy materials. Therefore, IHC using EGFRmutation–specific antibodies maypreclude a second biopsy procedure to obtain additional tissues for identification of EGFRmutations by molecular assays in biopsies from advanced cancer, particularly when tumorcells in the samples are limited.
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