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人胃癌中的幽门螺杆菌状态与血管生成因子

H pylori status and angiogenesis factors in human gastric carcinoma.

作者信息

Mangia Anita, Chiriatti Annalisa, Ranieri Girolamo, Abbate Ines, Coviello Maria, Simone Giovanni, Zito Francesco Alfredo, Montemurro Severino, Rucci Antonello, Di Leo Alfredo, Tommasi Stefania, Berloco Pasquale, Xu Jian Ming, Paradiso Angelo

机构信息

Clinical Experimental Oncology Laboratory, National Cancer Institute, Via Amendola 209, Bari 70126, Italy.

出版信息

World J Gastroenterol. 2006 Sep 14;12(34):5465-72. doi: 10.3748/wjg.v12.i34.5465.

Abstract

AIM

To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density (MVD), thymidine phosphorylase (TP), vascular endothelial growth factor receptor-1 (VEGF-R1), p53 and circulating VEGF levels.

METHODS

Angiogenic markers were analyzed immunohistochemically in 56 primary gastric cancers. H pylori cytotoxin (vacA) and the cytotoxin-associated gene (cagA) amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELISA, respectively.

RESULTS

A total of 69% of patients were positive for circulating IgG antibodies against H pylori. cagA-positive H pylori strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was significantly associated with cagA (P = 0.0001). MVD was significantly correlated with both tumor VEGF expression (r = 0.361, P = 0.009) and serum VEGF levels (r = -0.347, P = 0.041). Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level (P = 0.026).

CONCLUSION

H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic characteristics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical disease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent.

摘要

目的

研究胃癌患者中幽门螺杆菌的表达与原发性肿瘤血管生成标志物的关系,如微血管密度(MVD)、胸苷磷酸化酶(TP)、血管内皮生长因子受体-1(VEGF-R1)、p53和循环VEGF水平。

方法

对56例原发性胃癌进行免疫组织化学分析血管生成标志物。采用PCR检测幽门螺杆菌细胞毒素(vacA)和细胞毒素相关基因(cagA)扩增情况。分别采用ELISA法检测39例和38例患者血清幽门螺杆菌IgG抗体及血清/血浆循环VEGF水平。

结果

共有69%的患者抗幽门螺杆菌循环IgG抗体呈阳性。41%的胃癌患者中发现cagA阳性幽门螺杆菌菌株。50%的患者中发现vacA;在vacA阳性患者中s1菌株表达更高。s1菌株的存在与cagA显著相关(P = 0.0001)。MVD与肿瘤VEGF表达(r = 0.361,P = 0.009)和血清VEGF水平(r = -0.347,P = 0.041)均显著相关。相反,VEGF-R1表达和MVD均与p53表达无关。然而,除血浆VEGF水平外(P = 0.026),幽门螺杆菌与任何血管生成标志物均无关。

结论

幽门螺杆菌抗原与较高的血浆VEGF水平相关,但与血管生成特征无关。可以推测,幽门螺杆菌对血管生成的毒性作用发生在临床前疾病早期或长期侵袭性感染中,但仅在高幽门螺杆菌IgG水平持续存在时。

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