@article{oai:ycu.repo.nii.ac.jp:00000905,
 author = {佐伯, 博行 and SAEKI, Hiroyuki},
 issue = {2},
 journal = {横濱醫學, The Yokohama medical journal},
 month = {Mar},
 note = {HER2(human epidermal growth factor receptor 2)は細胞膜貫通型チロシンキナーゼ受容体であり細胞の増殖,分化に関与している.膵癌の19.6～47.6%にHER2過剰発現が認められるがHerceptin(trastuzumab)の有効性や化学療法との併用効果に関しては不明である.今回,ヒト膵癌培養細胞株TRGを用いてHerceptinと5-FU(5-fluorouracil)の細胞傷害効果および併用効果をin vitroで検討した.TRG細胞はRT-PCR,Flow cytometryでHER2過剰発現が認められた.TRG細胞にHerceptinまたは5-FUを処理するとそれぞれ濃度依存性の細胞傷害効果が認められた.Herceptinと5-FUを併用処理するとそれぞれ単独処理よりも強い細胞傷害効果が認められた.Herceptinの抗体依存性細胞傷害活性(ADCC)を分析するためにTRG細胞にHerceptinまたは5-FUを処理した後,末梢血単核球(PBMC)を作用させた.PBMCの添加によりHerceptin,5-FUの細胞傷害効果は増強されたがHerceptinの方が増強効果が強く,ADCCの関与が示唆された.TRG細胞に5-FUを処理するとTRG細胞のHER2発現量が増加した.その結果Herceptinの細胞傷害効果が増強され5-FUとHerceptinの併用効果が得られたと考えられた.今回の研究でHerceptinと5-FUの併用療法はHER2を過剰発現する膵癌に対して有効な治療法となりうる可能性が示唆された., HER2, a transmembrane growth factor receptor, is overexpressed in 21 - 48% of pancreatic cancer. However, the efficacy of anti-HER2 antibody, Herceptin (trastuzumab), for pancreatic cancer patients has not been fully evaluated. In this study, the cytotoxic effect of Herceptin in combination with 5-FU (5-fluorouracil) for HER2 overexpressing human pancreatic cancer in vitro was investigated, using the human pancreatic adenocarcinoma cell line, TRG. The TRG cell line was positive for HER2 mRNA in RT-PCR analyses and overexpressed HER2 protein in flow cytomerty analyses. Either Herceptin or 5-FU concentration-dependently inhibited the growth of TRG cells. Combination of Herceptin and 5-FU resulted in significant inhibition of growth of TRG cells compared to either agent alone. We added peripheral blood mononuclear cells (PBMC) to TRG cells after treatment with Herceptin or 5-FU in order to analyze the effect of antibody-dependent cellular cytotoxicity (ADCC) by the chemotherapeutics. Incubation with PBMC enhanced the antiproliferative effect of Herceptin more than that of 5-FU, which could be the result of ADCC induced by Herceptin. This study showed that combination therapy with Herceptin and 5-FU could be effective for HER2 overexpressing pancreatic cancer patients., 8, KJ00004192672, 原著, ORIGINAL ARTICLE},
 pages = {111--119},
 title = {HER2を過剰発現する膵癌に対するHerceptin (trastuzumab), 5-FU (5-fluorouracil)併用療法の細胞傷害効果},
 volume = {56},
 year = {2005},
 yomi = {サエキ, ヒロユキ}
}