INVOLVEMENT OF INFLAMMATORY REACTIONS AND ELEVATED CELL-PROLIFERATION IN THE DEVELOPMENT OF BLADDER-CANCER IN SCHISTOSOMIASIS PATIENTS
INVOLVEMENT OF INFLAMMATORY REACTIONS AND ELEVATED CELL-PROLIFERATION IN THE DEVELOPMENT OF BLADDER-CANCER IN SCHISTOSOMIASIS PATIENTS
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DOI：
10.1016/0027-5107(94)90248-8
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发表时间：
1994-03-01
期刊：
影响因子：
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通讯作者：
ANWAR, WA
中科院分区：
文献类型：
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作者：
ROSIN, MP;ZAKI, SSED;ANWAR, WA
埃及血吸虫感染与膀胱癌密切相关。尽管人们对这种关联提出了多种解释，但这种关系的本质仍然没有得到解决。本文探讨了这样的假设：炎症和细胞增殖增加在感染患者膀胱癌的发展中起主要作用，可能是通过增加尿路上皮的遗传不稳定性水平来实现的。该论文详细介绍了我们实验室为检验这一假设而进行的体内和体外研究。这些研究包括群体研究，其中使用脱落尿路上皮细胞的微核（MN）测试来分析受感染个体膀胱中的染色体断裂情况。该方法还包括在温哥华对长期导管引流患者进行的平行研究，该人群与血吸虫病患者有许多相似之处。在体外研究中，我们将膀胱细胞与活化的中性粒细胞或模拟炎症的实验条件共同孵育。这些研究表明，炎症细胞在被激活时可以诱导膀胱细胞中的微核，并且这种反应与 11 号染色体上的位点有关，11 号染色体是膀胱癌发生过程中通常发生改变的染色体。使用的最后一种方法是测定血吸虫病患者档案活检中的染色体变化（MN 频率和染色体数量改变）和增殖水平（增殖细胞核抗原的表达）。初步结果表明，这些患者在膀胱炎期间发生细胞增殖失调。这种改变对染色体断裂水平的影响程度尚未确定。
Schistosoma haematobium infection is strongly associated with urinary bladder cancer. Although numerous explanations have been proposed for this association, the nature of this relationship remains unresolved. This paper explores the hypothesis that inflammation and elevated cell proliferation play a major role in the development of bladder cancer in infected patients, possibly by increasing the level of genetic instability in the urothelium. The paper details in vivo and in vitro studies being done in our laboratories to test this hypothesis. These studies include population studies in which chromosomal breakage in the bladder of infected individuals is assayed using the micronucleus (MN) test on exfoliated urothelial cells. The approach also includes parallel studies in Vancouver with patients with long-term catheter drainage, a population with many similarities to schistosomiasis patients. In the in vitro studies we are co-incubating bladder cells with activated neutrophils or experimental conditions simulating inflammation. These studies show that inflammatory cells when activated can induce micronuclei in bladder cells and that this response is associated with loci on chromosome 11, a chromosome commonly altered during bladder carcinogenesis. A final approach being used is to assay chromosomal change (MN frequencies and numerical chromosome alterations) and level of proliferation (expression of proliferating cell nuclear antigen) in archival biopsies from schistosomiasis patients. Preliminary results show that a dysregulation of cell proliferation is occurring during cystitis in these patients. The extent to which this alteration affects the level of chromosomal breakage is yet to be determined.