Gocyk W, Nikliński T, Olechnowicz H, Duda A, Bielański W, Konturek P C, Konturek S J
Department of Thoracosurgery, District Hospital, Cracow, Poland.
Med Sci Monit. 2000 Nov-Dec;6(6):1085-92.
Tumors arising in the lungs are in over 90% bronchogenic carcinomas that have been attributed predominantly to tobacco smoking, asbestos or air pollution but little is known about endogenous factors that could facilitate their development and invasiveness. The lungs originate embryologically from the same endoderm cells which form the epithelia lining the digestive tract, where gastrin is the major proliferative stimulus.
Since lung cancer patients were recruited mostly among smokers, who also have been found to exhibit significantly higher infection rate of Helicobacter pylori (HP) infection than non-smokers and, as since the HP-infected subjects show enhanced plasma levels of gastrin, we decided 1) to compare the seroprevalence of HP and the expression of its cytotoxin, CagA, in lung cancer patients with those in the age- and gender-matched controls without cancer: 2) to determine the gene expression for gastrin and its receptors (CCKB-R) in lung cancer, 3) to assess the gastrin levels in plasma bronchial lavage and in tumor tissue and 4) to examine the expression of cyclooxygenase (COX)-1 and COX-2 in cancer tissue resection margin and intact bronchial mucosa.
The trial material included 50 patients with lung carcinoma and 100 age- and gender-matched controls. Anti-HP and anti-CagA IgG seroprevalence was estimated by specific antisera using ELISA tests. Gene expression of gastrin, CCKB-R, COX-1 and COX-2 was examined using RT-PCR, while gastrin was measured by specific RIA.
The seroprevalence of HP, especially that expressing CagA, is significantly higher in lung cancers than in healthy controls. Both gastrin and CCKB-R mRNA were detected in the cancer tissue and at the resection margin and similarly COX-2 mRNA was expressed in most cancers and resection margin but not in bronchial mucosa where only COX-1 was found. The lung cancer tissue and resection margin contained many folds larger amounts of immunoreactive gastrin than intact bronchial mucosa.
肺部出现的肿瘤超过90%是支气管源性癌，主要归因于吸烟、接触石棉或空气污染，但对于可能促进其发展和侵袭性的内源性因素却知之甚少。肺在胚胎学上起源于与形成消化道上皮相同的内胚层细胞，在消化道中胃泌素是主要的增殖刺激因子。
由于肺癌患者大多是吸烟者，且发现他们幽门螺杆菌（HP）感染率明显高于非吸烟者，又因为HP感染患者的胃泌素血浆水平升高，我们决定：1）比较肺癌患者与年龄和性别匹配的无癌对照者中HP的血清流行率及其细胞毒素CagA的表达；2）确定肺癌中胃泌素及其受体（CCKB-R）的基因表达；3）评估血浆、支气管灌洗液和肿瘤组织中的胃泌素水平；4）检测癌组织切除边缘和完整支气管黏膜中环氧合酶（COX）-1和COX-2的表达。
试验材料包括50例肺癌患者和100例年龄和性别匹配的对照者。使用ELISA试验通过特异性抗血清估计抗HP和抗CagA IgG的血清流行率。使用RT-PCR检测胃泌素、CCKB-R、COX-1和COX-2的基因表达，而胃泌素通过特异性RIA进行测定。
肺癌患者中HP的血清流行率，尤其是表达CagA的HP的血清流行率，显著高于健康对照者。在癌组织和切除边缘均检测到胃泌素和CCKB-R mRNA，同样，大多数癌症和切除边缘均表达COX-2 mRNA，但在仅发现COX-1的支气管黏膜中未表达。肺癌组织和切除边缘所含免疫反应性胃泌素比完整支气管黏膜多许多倍。
