目的 探讨纳米炭吸附氟尿嘧啶淋巴靶向化疗对胃癌转移淋巴结、胃癌组织及正常胃组织中细胞凋亡率(apoptosis index,AI)的影响。方法 我院36例胃癌患者分为淋巴靶向化疗(lymph node-targeted chemotherapy, LNTC)组和对照组,每组18例。LNTC组先以纳米炭吸附氟尿嘧啶行淋巴靶向化疗后再行手术,对照组直接手术。术毕即取胃癌组织、转移淋巴结及正常胃组织,以Tunel-AP法检测其中的细胞凋亡率情况。结果 LNTC组胃癌组织及转移淋巴结中AI为(17.30±3.50)%及(32.64±4.72)%,对照组胃癌组织及转移淋巴结中AI为(4.81±2.76)%及(7.03±2.15)%。LNTC组胃癌组织及转移淋巴结中AI均高于对照组,两组间差异有统计学意义(P<0.05).LNTC组正常胃组织中AI为(13.73±3.60)%,对照组正常胃组织中AI为(14.10±3.87)%, 两组间AI无明显差异(P>0.05)。结论 纳米炭吸附氟尿嘧啶能靶向作用于胃癌组织及转移淋巴结,使其凋亡率升高, 促进肿瘤细胞死亡,而对正常胃组织的细胞凋亡无明显影响。
Abstract
Objective To investigate the efficacy of 5-fluorouracil-loaded carbon nanoparticles, the targeted chemotherapeutic drug, on apoptosis index of cells in metastatic lymph nodes, gastric cancer and the normal gastric tissues. Methods Thirty-six patients with gastric cancer in this department were divided into lymph node-targeted chemotherapy group (n=18) and control group (n=18). The chemotherapy group had operation after the lymphatic target chemotherapy with 5-fluorouracil-loaded carbon nanoparticles. However, in control group, the patients were operated directly. The apoptosis index of cells in gastric carcinoma tissues, metastatic lymph nodes, and the normal gastric tissues after the operation were detected by TUNEL. Results In the lymph node-targeted chemotherapy group, apoptosis index(AI) of cells in gastric carcinoma tissues and metastatic lymph nodes were (17.30±3.50)% and (32.64±4.72)%, respectively, however, in the control group these were (4.81±2.76)% and (7.03±2.15)%, respectively. Consequently, the apoptosis index of cells in gastric carcinoma tissues and metastatic lymph nodes in the lymph node-targeted chemotherapy group was higher than that in the control group (P<0.05). Meanwhile, in the lymph node-targeted chemotherapy group, the AI of cells in normal gastric tissues was (13.73±3.60)%; however in the control group, the apoptosis index of cells in nomal gastric tissues was (14.10±3.87)% . There was no significant difference in the apoptosis index between the two groups (P>0.05). Conclusions 5-Fluorouracil-loaded carbon nanoparticles can target gastric carcinoma tissues and metastatic lymph nodes, therefore, increasing the apoptosis index which can promote tumor cell death. However, it has no obvious effect on the apoptosis index in normal gastric tissues.
关键词
胃癌 /
纳米炭 /
氟尿嘧啶 /
凋亡淋巴靶向化疗
Key words
gastric carcinoma /
carbon nanoparticles /
5-fluorouracil /
apoptosis lymphatic target chemotherapy
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参考文献
[1] Saka M, Katai H, Fukagawa T, et al.Recurrence in early gastric cancer with lymph node metastasis[J]. Gastric Cancer, 2008, 11(4):214-218.
[2] Shiraishi N, Sato K, Yasuda K, et al.Multivariate prognostic study on large gastric cancer[J]. J Surg Oncol, 2007, 96(1):14-18.
[3] Yokota T, Saito T, Narushima Y, et al.Lymph-node staining with activated carbon CH40:a new method for axillarylymph-node dissection in breast cancer[J]. Can J Surg, 2000, 43(3):191-196.
[4] Okamoto K, Sawai K, Minato H, et al.Number and anatomical extent of lymph node metastases in gastric cancer: analysis using intra-lymph node injection of activated carbon particles (CH 40) [J]. Jpn J Clin Oncol, 1999, 29(2):74-77.
[5] 王 强, 胃肠外科学[M] .北京: 人民军医出版社, 2001:45-47.
[6] 蔡长茂,李 威. 纳米炭在普外科恶性肿瘤诊治中的应用.中华实用诊断与治疗杂[J]. 2010,24(9): 833-834.
[7] Ishii H H, Gobé G C, Pan W, et al.Apoptosis and cell proliferation in the development of gastric carcinomas: associations with c-myc and p53 protein expression[J]. J Gastroenterol Hepatol, 2002, 17(9):966-972.
[8] 岑延增 ,罗云生, 孙 涛, 等.细胞凋亡相关基因bc1-2/bax在胃癌组织中表达探讨[J].广西医科大学学报, 2005, 22(2): 206-209.
[9] 彭朝龙,贺卫东. 1062例胃癌淋巴结转移相关因素分析[J], 医师进修杂志,2003, 26(2):35-36.
[10] 张家平. 淋巴化疗与静脉化疗对胃癌淋巴转移灶细胞凋亡的影响[J]. 临床和实验医学杂志, 2011,10(7):497-499.
[11] 刘海峰,刘为纹,房殿春. 5-氟脲嘧啶诱导人胃癌细胞凋亡的研究[J],第三军医大学学报,1999, 21(10):720-722.
[12] Reed J C, Miyashita T, Krajewski S, et al.Bcl-2 family proteins and the regulation of programmed cell death in leukemia and lymphoma [J]. Cancer Treat Res, 1996, 84:31-72.
[13] 黄 斌,李 昂,张 波,等. 纳米炭吸附5-FU淋巴靶向化疗对胃癌组织及转移淋巴结bcl-2、bax及caspase-3表达的影响[J].中国普外基础与临床杂志,2009,16(1):18-22.
[14] Salomons G S,Brady H J,Verwijs Janssen M, et al.The baxα:bcl-2 ratio modulates the response to dexa-methasone in leukemic cells and is highly variable in childhood acute leukemia [J]. Int J Cancer, 1997, 71(6):959-965.
[15] Sharma S,Singh R L,Kakkar P.Modulation of Bax/Bcl-2 and caspases by probiotics during acetaminophen induced apoptosis in primary hepatocytes [J]. Food Chem Toxicol, 2010, 49(4):770-779.
[16] Zhang Y,Jiang Q,Wang N, et al.Effects of taspine on proliferation and apoptosis by regulating caspase-3 expression and the ratio of Bax/Bcl-2 in A431 cells [J].Phytother Res, 2010, 25(3):357-364.
[17] 王海斌, 王 黔, 于 扬,等. 胃癌术中黏膜下注射5-Fu行淋巴化疗后胃周淋巴结检测的临床意义[J]. 2008,33(2):193-195.
[18] Minato H, Sawai K, Takahashi T, et al.Survival of patients with gastric cancer treated with intra-lymph nodal injection of activated carbon particles absorbed mitomycin C [J]. Gan To Kagaku Ryoho,1994, 21(13):2263-2265.
[19] Hagiwara A, Takahashi T, Kojima O, et al.Prophylaxis with carbon-adsorbed mitomycin against peritoneal recurrence of gastric cancer [J]. Lancet, 1992;339(8794):629-631.
[20] Takahashi T, Hagiwara A, Shimotsuma M, et al.Prophylaxis and treatment of peritoneal carcinomatosis: intraperitoneal chemotherapy with mitomycin C bound to activated carbon particles [J]. World J Surg, 1995,19(4):565-569.
(2012-08-22