【作者】 吴武军；

【导师】 曾健；

【作者基本信息】 广西医科大学 ， 普通外科胃肠腺体， 2004， 硕士

【摘要】 目的 探讨活性炭微粒-表阿霉素(charcoal activated absorbing epirubicin,Epi-CH)混悬液对乳腺癌腋窝转移淋巴结中癌细胞凋亡和增殖的作用。 方法 60例临床检查或B超探查腋窝淋巴结肿大的乳腺癌病人随机分为两组，治疗组40例，对照组20例。在改良根治术前48-72h治疗组于瘤床或肿瘤周围注射Epi-CH 10mg，对照组注射表阿霉素水溶液10mg，术后清点清除的腋窝淋巴结总数和黑染淋巴结数。用高效液相色谱法(外标法)测定治疗组黑染和未黑染淋巴结中表阿霉素的含量。用末端转移酶标记法(Tunel)检测腋窝淋巴结凋亡指数(apoptosis index,AI)，用免疫组化S-P法检测腋窝淋巴结增殖指数(proliferation index,PI)及凋亡相关蛋白bc1-2、bax、C-myc、Fas、Fas-L的表达。用SPSS10.0软件包进行统计学处理。 结果 治疗组共清扫腋淋巴结650个，平均每例15.20±1.22个；对照组共清扫232个，平均11.16±1.43个，治疗组平均数多于对照组(p＜0.01)。治疗组中腋窝淋巴结的黑染率为88.8％(577/650)；黑染淋巴结癌转移率为37.9％(219/577)，未黑染淋巴结转移率为24.7％(18/73)，黑染淋巴结癌转移率明显增高(p＜0.05)；直径≤1.0cm淋巴结黑染率为91.60％(475/519)，直径＞1.0cm淋巴结黑染率为77.9％(102/131)，前者高于后者(p＜0.01)。治疗组注射Epi-CH后48—72h内黑染淋巴结中表阿霉素的浓度平均为443.0±广西医科大学2001级硕士研究生学位论文123.Ing/g，未黑染组淋巴结浓度平均为31，8士11 .gng/g，前者是后者的14.3倍，有显著性差异印<0.01)。治疗组35例腋窝淋巴结阳性病人癌巢丰富的黑染癌转移淋巴结48个与对照组巧例病人阳性淋巴结24个癌细胞的Al、Pl和凋亡相关蛋白bcl一2、bax、c一yc、Fas、Fas一比较，治疗组Al明显升高印<0.01)，pl明显下降(P<0.05)、bel一2、 bax、Fas一L蛋白表达上升(p<0.05)，而C劝yc、Fas蛋白表达无明显变(P>0.05)。结论应用自行研制的活性炭一表阿霉素混悬液进行乳腺癌淋巴化疗，可以增加手术清除的腋窝淋巴结数目，提高腋窝淋巴结清除率;活性炭能够携带表阿霉素并停留在腋窝淋巴结内，显著增加表阿霉素在局部淋巴结中的浓度，并诱导淋巴结内癌细胞凋亡增加和增殖减少;活性炭一表阿霉素混悬液的淋巴化疗作用可能是通过上调bax、Fas一L蛋白表达来完成。活性炭一表阿霉素混悬液对乳腺癌的淋巴化疗具有化疗效果肯定、化疗药物用量少、毒副作用低、临床使用方便的优点，值得临床推广应用。更多还原

【Abstract】 Objectives To investigate the chemotherapeutic effect of charcoal activated absorbing epirubicin suspension (Epi-CH) on the axillary metastasis lymph nodes in patients with breast cancer.Methods 60 patients with breast cancer were divided into two groups randomly. 40 patients (Epi-CH group) were injected Epi-CH 10mg into the region around the tumor or biopsy excision. 20 patients (control group) were injected epirubicin lOmg into the same region. After 48-72 hours, the modified radical mastectomy was operated. The axillary lymph nodes and the staining lymph nodes were calculated. The concentration of epiribicin in lymph nodes was measured by high performance liquid chorography (HPLC). The apoptosis index (AI) was detected by terminal deoxynucleotidy trans ferase mediated digoxigenin-dUTP nick end labeling (Tunel). The proliferation index (PI) and the expressions of apoptosis related gene proteins(including bcl-2, bax, C-myc, Fas, Fas-L) were detected by S-P. Statistical analysis was performed using SPSS 10.0. Results The average number of dissected lymph nodes in Epi-CH group was 15.20\1.22, and that in control group was 11.10\1.43, The average number ofdissected lymph nodes in Epi-CH group was markedly higher (p < 0.01) .In Epi-CH group, the staining rate of axillary lymph nodes was 88.8% (577/650). The metastasis rate of staining lymph nodes (219/577) was significantly higher than that of non-staining lymph nodes (18/73) (p < 0.05). The proportion of the staining lymph nodes with diameter > 1.0cm(102/131) was lower than that with diameter ≤ 1.0cm (475/519). In Epi-CH group, The concentration of epirubicin in staining lymph nodes (443.0 ± 123.1ng/g) was higher significantly than that of non-blackened (31.8±11.9ng/g) (p < 0.01). AI of blackened lymph nodes in Epi-CH group (9.5% ±2.1%) was increased remarkable than that in control(3.8% ±1.4%) (p < 0.01). PI of blackened lymph nodes in Epi-CH group (60.1 % ± 12.1 %) was decreased significantly than that in control group(73.5%±12.4%) (p < 0.05). The expressions of bcl-2, bax, Fas-L gene protein in Epi-CH group were up-regulated(p < 0.05), but those of C-myc and Fas was not different between two groups (p > 0.05).Conclusions The study indicates that lymphatic chemotherapy using Epi-CH can increase the dissected lymph nodes during modified mastectomy, rise the concentration of epirubicin in axillary lymph nodes, enhance the cancer cell apoptosis and reduce the cancer cell proliferation. The lymphatic chemotherapy effects of Epi-CH result from up-regulation of expressions of bax and Fas-L geneproteins.更多还原