Mast Cell Tumors in Mongolian Gerbils Infected with Helicobacter pylori that had been Pretreated with 30% NaCl
Mast Cell Tumors in Mongolian Gerbils Infected with Helicobacter pylori that had been Pretreated with 30% NaCl
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肥大%20细胞%20肿瘤%20in%20蒙古%20沙鼠%20感染%20with%20幽门螺杆菌%20that%20had%20been%20预处理%20with%2030%%20NaCl
DOI：
10.1111/hel.12049
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发表时间：
2013-06
期刊：
影响因子：
4.4
通讯作者：
Yuan, Yuan
中科院分区：
文献类型：
--
作者：
Liu, Yunen;Piao, Ying;Gong, Yuehua;Dong, Nannan;Yuan, Yuan
编辑认为，肥大细胞是一种来源于骨髓的炎性细胞[1]。患有肥大细胞瘤的患者通常有不同的临床结果，一些患者尽管接受了治疗，但存活时间只有几个月[2]。幽门螺杆菌在调节胃炎症中起着重要作用。幽门螺杆菌也被证明与高盐饮食有协同作用，这增加了胃萎缩和肠化生的产生。我们的体外实验结果证实，经30%浓度的盐处理后，幽门螺杆菌毒素水平保持在较高水平[3]。本文报道了蒙古沙土鼠在感染幽门螺杆菌后肥大细胞肿瘤的发生发展，直到最近才有文献报道幽门螺杆菌是否为肥大细胞肿瘤的潜在危险因素。从人胃癌患者中分离出幽门螺杆菌，在添加20%胎牛血清和30%浓度盐的布鲁氏菌双相培养板上进行微需氧培养。收集细菌，最终浓度调整为1 910个活细菌/毫升。幽门螺杆菌的鉴定是基于典型的菌落形态、革兰氏染色和阳性尿素酶试验。20只动物接种幽门螺杆菌(1910CFU，0.5mL)，20只动物注射等量生理盐水，1次/d，连续3d。在73周结束时，所有活着的动物都被完全尸检。所有标本均经福尔马林固定、石蜡包埋、苏木精-伊红染色。此外，对胃组织进行AB/PAS、Giemsa和免疫组织化学染色，包括幽门螺杆菌免疫球蛋白(1：100；丹麦达科，Glostrup)、Syn(1：50；细胞信号技术，美国马萨诸塞州丹弗斯)、角蛋白和增殖细胞核抗原(1：100；基因公司，香港，中国)。在本研究中，Giemsa和免疫组织化学染色证实，幽门螺杆菌大量定植于粘液层，少数与胃粘膜紧密附着。Hp感染组100%(20/20)出现肥大细胞样瘤2例(10%)，对照组为0/20(0%)。显微镜下，肿瘤样细胞胞核圆形，细胞边界模糊。几乎所有的肿瘤细胞都含有大量以嗜碱性为主的颗粒。Giemsa染色显示胞质嗜碱性颗粒有密集或疏松分布两种不同的形态特征。这些颗粒对阿尔新蓝呈阳性反应，对PAS呈阴性反应。蒙古沙鼠也有明显的肥大细胞亚群，空肠中的肥大细胞对糜酶和类胰蛋白酶呈强阳性，而舌和皮肤中的肥大细胞基本上都不表达这两种酶[4]。我们的结果表明，该肿瘤的角蛋白、Syn和增殖细胞核抗原均为阴性，不能与幽门螺杆菌感染引起的类癌相鉴别，诊断为肥大细胞瘤。自发性肥大细胞瘤的发生率很低，仅有1例(1/387，2.6%)被报道[5]。肥大细胞瘤的生物学行为取决于细胞形态和增殖细胞核抗原的表达。纺锤形和非典型的肥大细胞特征往往与更具侵袭性的临床结果相关[6]。此外，在动物的胃、肝、脾、肺和脑中系统地观察到肥大细胞瘤(图1)。由于其具有伸展和移动的功能，因此很难准确确定原发部位。慢性胃炎、萎缩性胃炎和肠化生的发生率在幽门螺杆菌感染组显著增加，而对照组仅见轻度胃炎(数据未显示)。尽管很难根据这组有限的数据得出确凿的结论，但这些观察表明，幽门螺杆菌、30%高盐预处理与播散性肥大细胞肿瘤的发展之间可能存在联系。如果结果得到证实，则需要对预处理的分子效应进行表征，以开始了解其发病机制。
To the Editor, Mast cells are one of the inflammatory cells derived from bone marrow [1]. Patients bearing mast cell tumor often have different clinical outcomes, and some patients survive only a few months despite therapy [2]. Helicobacter pylori plays an important role in the regulation of gastric inflammation. Helicobacter pylori has also been shown to have a synergistic interaction with a high salt diet, which enhances the production of gastric atrophy and intestinal metaplasia. Our results in vitro previously confirmed that H. pylori toxin level was remained at high levels after pretreated with 30% concentration salt [3]. Here, we report development of mast cell tumors in Mongolian gerbils after H. pylori infection, whether H. pylori, pretreated with 30% concentration salt, being a potential risk factor for mast cell tumor has not yet been reported until recently. Helicobacter pylori, isolated from a human gastric cancer patient, were grown under microaerobic conditions on biphasic Brucella culture plates supplemented with 20% fetal calf serum and 30% concentration salt. The bacteria were harvested, and the final concentration was adjusted to 1 9 10 viable bacteria/mL. Helicobacter pylori were identified on the basis of typical colony morphology, Gram straining, and a positive urease test. A total of 20 animals were inoculated with H. pylori (1 9 10 CFU, 0.5 mL), and 20 received the same volume of saline, once a day for three consecutive days. All living animals were completely necropsied at the end of 73 weeks. All specimens were formalin fixed, embedded in paraffin, and stained with hematoxylin and eosin (H&E). Moreover, gastric tissues were stained with AB/PAS, Giemsa, and immunohistochemistry including H. pylori IgG (1:100; DAKO, Glostrup, Denmark), Syn (1:50; Cell Signaling Technology, Danvers, MA, USA), keratin, and PCNA (1:100; Gene Company, Hong Kong, China). In this study, Giemsa and immunohistochemical staining confirmed that a large number of H. pylori colonized in the mucus layer and a few were closely adhered to the gastric mucosa. Two of 20 (10%) mast cell-like tumor were observed in 100% (20/20) of the H. pylori-infected group vs 0/20(0%)in the sham inoculated animals. Microscopically, tumor-like cells bear round nuclei and rather indistinct cell borders. Nearly all of the neoplastic cells contained numerous predominantly basophilic granules. Giemsa staining showed cytoplasmic basophilic granules had two different morphological characteristics, intensely or loosely distribution. These granules were positive for alcian blue, but were negative for PAS. Mongolian gerbils also had distinct mast cell subsets and mast cells in the jejunum were strongly positive for chymase and tryptase, whereas those in tongue and skin were essentially negative for both proteases [4]. Our results showed that the tumors were negative for keratin, Syn, and PCNA to differential diagnosis from carcinoid resulting from H. pylori infection in the stomach and the tumors were diagnosed as mast cell tumors. The incidence of spontaneous mast cell tumor is rare as only one case (1/387, 2.6%) has been reported [5]. The biological behavior of mast cell tumors depends on cell morphology and PCNA expression. Spindled and atypical mast cell features tend to correlate with more aggressive clinical outcome [6]. In addition, mast cell tumor was observed systemically in stomach, liver, spleen, lung, and brain of the animals (Fig. 1). It was difficult to determine accurately the primary site because of its function of extending and movement. The incidence of chronic gastritis, atrophic gastritis as well as intestinal metaplasia was significantly increased in H. pylori-infected group, and only slight gastritis was observed in the control group (data not shown). Although it is difficult to draw firm conclusions based on this limited set of data, these observations suggest a possible connection between H. pylori, pretreatment with 30% high salt, and the development of disseminated mast cell tumors. If the results are confirmed, the molecular effects of the pretreatment need to be characterized to begin to understand the pathogenesis.
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影响因子：
2.4
作者：
M. A. Guzmán-Silva
通讯作者：
M. A. Guzmán-Silva
DOI：
10.2741/231
发表时间：
2011-06
期刊：
Frontiers in bioscience
影响因子：
--
作者：
M. Jamur;C. Oliver
通讯作者：
M. Jamur;C. Oliver
影响因子：
2.4
作者：
M. Diamantidis;A. Myrou;G. Kaiafa;V. Kaloutsi;G. Karayannopoulou;A. Theodoridis;A. Adamidou;A. Papadopoulos;D. Grekas
通讯作者：
M. Diamantidis;A. Myrou;G. Kaiafa;V. Kaloutsi;G. Karayannopoulou;A. Theodoridis;A. Adamidou;A. Papadopoulos;D. Grekas
暴露于高盐的幽门螺杆菌的生物学和毒力特征的变化。
DOI：
--
发表时间：
2011
期刊：
Asian Pacific J Cancer Prev
影响因子：
--
作者：
徐莹;景晶晶;宫月华;徐倩;张文陆;朴英;王艳丽;袁媛
通讯作者：
袁媛
影响因子：
2.8
作者：
Y. Nawa;Y. Horii;M. Okada;N. Arizono
通讯作者：
Y. Nawa;Y. Horii;M. Okada;N. Arizono