Tajima Hidehiro, Ohta Tetsuo, Kitagawa Hirohisa, Okamoto Koichi, Sakai Seisho, Kinoshita Jun, Makino Isamu, Furukawa Hiroyuki, Hayashi Hironori, Nakamura Keishi, Oyama Katsunobu, Inokuchi Masafumi, Nakagawara Hisatoshi, Fujita Hideto, Takamura Hiroyuki, Ninomiya Itasu, Fushida Sachio, Tani Takashi, Fujimura Takashi, Kitamura Seiko, Ikeda Hiroko, Tsuneyama Koichi
Department of Gastroenterologic Surgery Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, Kanazawa.
Oncol Lett. 2012 Jun;3(6):1186-1190. doi: 10.3892/ol.2012.657. Epub 2012 Mar 26.
We examined the pathological effects of preoperative neoadjuvant chemotherapy (NAC) and the expression of markers of apoptosis, epithelial-to-mesenchymal transition (EMT) and cancer stem cells in resected pancreatic cancer specimens from patients treated with gemcitabine as NAC. Immunohistochemical expression of the apoptosis marker M30, EMT marker Snail and stem cell marker CD44 in surgically resected pancreatic cancer specimens were compared between patients treated (NAC group n=13) and not treated (control group n=21) with gemcitabine. In the NAC group, the tumor specimens showed tumor cell injury; however, there was no significant reduction of serosal, retroperitoneal, perineural or vascular invasion, lymph node metastasis or tumor size. The expression frequencies of M30 and CD44 were significantly higher in the NAC group (61.5 and 53.8%) compared to the control group (9.5 and 14.3%); however, no significant difference in Snail expression was noted between the two groups (53.8 versus 42.9%). Gemcitabine induced apoptosis of pancreatic cancer cells in vivo; however, it did not reduce the tumor burden. Moreover, the residual cancer tissues were rich in chemoresistant cancer stem cells. By contrast, marked EMT of cancer cells was observed in the specimens from the groups treated and not treated with gemcitabine.
我们研究了术前新辅助化疗(NAC)的病理效应,以及吉西他滨作为NAC用于治疗的患者的切除胰腺癌标本中凋亡、上皮-间质转化(EMT)和癌症干细胞标志物的表达情况。比较了接受吉西他滨治疗的患者(NAC组,n = 13)和未接受吉西他滨治疗的患者(对照组,n = 21)手术切除的胰腺癌标本中凋亡标志物M30、EMT标志物Snail和干细胞标志物CD44的免疫组化表达。在NAC组中,肿瘤标本显示出肿瘤细胞损伤;然而,浆膜、腹膜后、神经周围或血管侵犯、淋巴结转移或肿瘤大小均无显著降低。与对照组(9.5%和14.3%)相比,NAC组中M30和CD44的表达频率显著更高(分别为61.5%和53.8%);然而,两组之间Snail表达无显著差异(分别为53.8%和42.9%)。吉西他滨在体内诱导胰腺癌细胞凋亡;然而,它并未减轻肿瘤负担。此外,残留癌组织富含化疗耐药的癌症干细胞。相比之下,在接受和未接受吉西他滨治疗的组的标本中均观察到癌细胞明显的EMT。