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이령아(Ryung-Ah Lee),이은정(Eun-Joung Lee),강보영(Bo Young Kang),김광호(Kwang Ho Kim) 대한외과학회 2007 Annals of Surgical Treatment and Research(ASRT) Vol.72 No.3
Purpose: There is a need for sensitive, specific diagnostic and prognostic molecular markers that can monitor the early patterns of gene expression in non-invasive exfoliated colonocytes shed in stools. It has been estimated that approximately 1010 normal adult colonic epithelial cells, each having a lifespan of 3∼4 days, are shed from the lower two-thirds of colon crypts daily; thus, the development of a screening test using colonocytes is an realistic goal. Due to the characteristics of stools, few studies have been conducted on RNA based detection methods. Herein, a mass RNA analysis, using stools in colorectal cancer, is reported. Methods: The study included 15 colorectal cancer patients, and 15 control patients without neoplastic disease. RNA was isolated from routinely collected stool samples using a modified method. The expression levels of survivin, livin, Akt-1, caveolin, histone deacetylase (HDAC)1, matrix metalloproteinases (MMP)-2, MMP-7, MMP-9, MMP-12, hepatoma derived growth factor (HDGF), peptideYY, hypoxia-inducible factor (HIF)-1, epidermal growth factor receptor (EGFR), N-cadherin, catenin-β, inducible nitric oxide synthase (iNOS), ring-3, enolase-1β, insulin-like growth factor binding protein (IGFBP)-2, tissue inhibitors of metalloproteinase (TIMP)-1 and EphB2 were determined by reverse transcriptasepolymerase chain reactions (RT-PCR). Results: The rates of expression of fecal survivin, livin and Akt-1 assays for colorectal cancer were all 93%; whereas, those of the fecal caveolin, HDAC1, MMP-2, HDGF and peptideYY assays for colorectal cancer were 13, 6, 20, 6 and 6%, respectively. The remaining 13 assays did not show any expression in either the colorectal or normal groups. The expression levels of survivin, livin and Akt-1 were higher in the colorectal cancer than normal group in a semiquantitative analysis (P<0.05). Conclusions: These fecal survivin, livin and Akt-1 assays had both high expression rate and levels (colorectal cancer as distinguished from normal group) for detecting colorectal cancer; although, a larger study will be necessary to assess the expression rates and levels.
이령아(Ryung-Ah Lee) 대한종양외과학회 2005 Korean Journal of Clinical Oncology Vol.1 No.2
표적치료(targeted therapy)는 특정 질병을 유발하는 신호전달체계의 분자적 수준에서 유전자나 단백질 등을 표적으로 하여 전체 신호전달과정을 차단시킴으로써 병의 진행을 막고 치유를 도모하고자 고안된 새로운 치료방법이다. 표적치료제(targeted agent)는 표적치료를 위해 사용되는 약제를 종합적으로 의미하는 용어이다. 유방암 치료에서의 trastuzumab의 상업적 성공 이후 수많은 표적치료제가 개발되었거나 개발중에 있다. 표적치료제의 개발에서 이상적인 표적을 결정하는 것이 중요한데 이상적인 표적은 중요 장기에서는 발현되지 않고 암세포에서만 발현되고 암세포의 성장과 분열에 결정적인 역할을 하는 것이라야 한다. 더불어서 표적 자제의 활성도의 측정이 가능하고 측정된 결과가 임상적인 예후와 관련이 있으면 더 좋다. 현재 공식적으로 인정되어 있는 항체형 표적치료제는 미국에서 8종, 유럽에서 1종으로 모두 9종으로 alentuzumab, rituximab, trastuzumab, cetuximab, ibritumomab, gemtuzumab, tositumomah, edrecolomab, bevacizumab등이다. 그 외 imatinib, erlotinib, gefitinib, bortezomib등의 소분자치료제들도 개발되어 있다. 표적치료제는 각각의 종양에서 그 분자적 성질에 따라 개별화된 치료를 할 수 있다는 점에서 기존의 치료제들과 차별화된다. 항체를 이용한 치료제나 소분자 치료제 모두 완벽한 종양치료를 위한 발전의 일보로 생각되며 지금까지의 성공적인 치료제의 개발로 미루어 미래에는 더 많은 약제들이 성공할것으로 예측된다. 향후 몇 년간은 많은 표적치료제의 상업화에 따라 동반된 진단기법의 개발과 유사약제의 개발 등 많은 변화가 있을 것으로 예상되며 이러한 pharmacogenomics의 발전이 암환자의 예후를 향상시키는 결정적인 변화의 전환점이 되기를 기대한다. The target therapy is a new therapeutic approach blocking the molecular pathway that is associated with the initiation and progression processes of various diseases. The targeted agents are recently developed new drugs for target therapy. The definition of targeted agents is complex but it is used intermingly in medical and research field. Many targeted agents is now developed or in developing after tremendous commercial success of trastuzumab in terms of treatment of breast cancer. The most important issue in drug development is selection of ideal target related to molecular events of specific disorders. The ideal features of anticancer target is a macromolecule that is crucial to the malignant phenotype and is not expressed in vital organs, that has biological relevance that can be measured reproducibly in readily obtained clinical specimens and that is correlated well with clinical prognosis. There are 8 anticancer antibodies such as alentuzumab, rituximab, trastuzumab, cetuximab, ibritumomab, gemtuzumab, tositumomab, bevacizumab approved by FDA for sales in Unites States and edrecolomab approved in Europe. Small molecule inhibitors such as imatinib mesylate, erlotinib, gefitinib, bortezomib are developed as well to manage of hemotologic malignancies. The targeted agent is differentiated from previously existed agents in terms of individualization of personals according to their molecular characteristics in various malignancies. New current interest to targeted agents in oncology field has been desirable stimulus for the evolving field of pharmacogenomics. During next several years, many new drugs will be passed through the approval process and enter the market acoompanied with associated specialized diagnostic tests. The affirmative competition in oncology drug development would be welcomed to improve the outcome of patients and to reduce morbidity.