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腹腔内应用牛磺罗定/肝素对腹腔镜手术大鼠黏附分子表达及结肠癌的影响

Influence of intraperitoneal application of taurolidine/heparin on expression of adhesion molecules and colon cancer in rats undergoing laparoscopy.

作者信息

Bobrich Eva, Braumann Chris, Opitz Isabelle, Menenakos Charalambos, Kristiansen Glen, Jacobi Christoph A

机构信息

Department of General, Visceral, Vascular and Thoracic Surgery, Universitaetsmedizin Berlin, Medical Faculty Charité, Humboldt University, Schumannstr, Berlin, Germany.

出版信息

J Surg Res. 2007 Jan;137(1):75-82. doi: 10.1016/j.jss.2006.07.013. Epub 2006 Nov 15.

Abstract

BACKGROUND

Recent experimental studies have shown that intraperitoneal administration of taurolidine/heparin causes a reduction of local tumor growth after laparoscopy in rat models. It might be that the anti-adherent activities of these agents are responsible for this effect. In this study we investigated the adhesion molecules E-cadherin, beta1-integrin, and CD44.

MATERIALS AND METHODS

Following a 10,000 colon adenocarcinoma cells' (DHD/K12/TRb) intraperitoneal application a cecum resection and a partial parietal peritoneum resection (1 x 1 cm) were performed using a three trocar technique in 30 BD IX rats. After randomization in two groups, the cecum suture line and the parietal peritoneal defect were either lavaged with 1 mL of 0.5% taurolidine/10 IU heparin or with equal amounts of 0.9% normal saline solution. Rats were sacrificed four weeks after operation and total tumor growth was determined. E-cadherin, beta1-integrin, and CD44 were assessed immunohistochemically on the tumor tissue.

RESULTS

The expression of E-cadherin was significantly reduced to 46.7% (complete loss of staining) in the taurolidine/heparin group. Although no significant difference was detected concerning the beta1-integrin and CD44 expression, a slightly reduced expression level with 26.7% of negative staining in metastases of the taurolidine/heparin group was observed. The total tumor weight (171.1 +/- 181.2 mg) as well as the total number of tumor lesions was also reduced by the substances compared to the control group (283.2 +/- 91.4 mg).

CONCLUSIONS

Taurolidine/heparin led to a significant reduction of local tumor growth. Additionally a reduction of the expression of E-cadherin was observed. However, the biological behavior of this molecule is multivariant, controversial and still unclear. Further studies should elucidate its role in the epithelial tumor genesis.

摘要

背景

最近的实验研究表明,在大鼠模型中,腹腔镜检查后腹腔内注射牛磺罗定/肝素可使局部肿瘤生长减缓。可能是这些药物的抗粘连活性导致了这种效果。在本研究中,我们调查了黏附分子E-钙黏蛋白、β1整合素和CD44。

材料与方法

在30只BD IX大鼠中,采用三套管技术,腹腔注射10000个结肠腺癌细胞(DHD/K12/TRb)后,进行盲肠切除术和部分壁层腹膜切除术(1×1 cm)。随机分为两组后,用1 mL 0.5%牛磺罗定/10 IU肝素或等量的0.9%生理盐水冲洗盲肠缝合线和壁层腹膜缺损处。术后四周处死大鼠,测定肿瘤总生长情况。对肿瘤组织进行免疫组织化学评估E-钙黏蛋白、β1整合素和CD44。

结果

在牛磺罗定/肝素组中,E-钙黏蛋白的表达显著降低至46.7%(染色完全缺失)。虽然在β1整合素和CD44表达方面未检测到显著差异,但在牛磺罗定/肝素组转移灶中观察到表达水平略有降低,阴性染色率为26.7%。与对照组(283.2±91.4 mg)相比,这些物质还使肿瘤总重量(171.1±181.2 mg)以及肿瘤病灶总数减少。

结论

牛磺罗定/肝素可使局部肿瘤生长显著减缓。此外,观察到E-钙黏蛋白的表达降低。然而,该分子的生物学行为是多变量的,存在争议且仍不清楚。进一步的研究应阐明其在上皮肿瘤发生中的作用。

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