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首页> 外文期刊>Current therapeutic research, clinical and experimental. >Ajili, F.a b , Boubaker, S.b , Derouiche, A.c , Ali, M.B.a , Mustapha, I.B.a , Cherif, M.c , Chebil, M.c , Mannai, M.d , Barbouche, M.-R.a Relationship between toll-like receptor 2 nonsynonymous single nucleotide polymorphisms and the effectiveness of Bacille Calmette-Guérin immunotherapy in preventing recurrence of superficial bladder cancer: A prospective study
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Ajili, F.a b , Boubaker, S.b , Derouiche, A.c , Ali, M.B.a , Mustapha, I.B.a , Cherif, M.c , Chebil, M.c , Mannai, M.d , Barbouche, M.-R.a Relationship between toll-like receptor 2 nonsynonymous single nucleotide polymorphisms and the effectiveness of Bacille Calmette-Guérin immunotherapy in preventing recurrence of superficial bladder cancer: A prospective study

机译：Ajili，Fab，Boubaker，Sb，Derouiche，Ac，Ali，MBa，Mustapha，IBa，Cherif，Mc，Chebil，Mc，Mannai，Md，Barbouche，M.-Ra之间的联系，在收费型受体2非同义单核苷酸多态性之间卡米尔-卡梅特-瓜林免疫疗法在预防浅表性膀胱癌复发中的作用和有效性：前瞻性研究

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Background: Intravesical Bacille Calmette-Guérin (BCG) immunotherapy has been used for several decades as a prophylactic approach against recurrence of superficial bladder cancer. However, its effectiveness has been both variable and unpredictable. Typically, cancer BCG-immunotherapy aims to redirect or modulate both innate and adaptive immune responses. The consequences of gene polymorphisms in several key immuno-regulatory molecules on the heterogeneity of the response to BCG-immunotherapy have been investigated. Objective: The aim of this study was to evaluate the association of toll-like receptor (TLR) 2 polymorphisms (arginine to glutamine substitution at position 753 [Arg753Gln] and arginine to tryptophan substitution at position 677 [Arg677Trp]) and the outcome of BCG-immunotherapy. Methods: This prospective study was conducted during a 3-year period from June 2006 to July 2009. Consecutive patients were recruited during a 1-year period and followed for 2 years at the Department of Urology, Charles Nicolle Hospital, Tunis, Tunisia. Patients with superficial bladder tumors at stage Ta (noninvasive papillary carcinoma) or T1 (where the tumor has grown from the layer of cells lining the bladder into the connective tissue below but has not grown into the muscle layer of the bladder) of any grade were eligible; carcinoma in situ cases were excluded. The TLR2 Arg753Gln and Arg677Trp polymorphisms were studied in peripheral blood DNA from patients treated with BCG-immunotherapy after transurethral resection. Results: A total of 112 consecutive patients were enrolled (101 men and 11 women; mean age, 63.9 years [range, 25-85 years]) and completed the 2-year followup. Polymerase chain reaction amplification followed by direct sequencing of the region containing the TLR2 single-nucleotide polymorphism (SNP) of interest did not detect Arg753Gln or Arg677Trp in any of the study participants belonging to either of 2 groups: responders (n = 67) and nonresponders (n = 45) to BCG-immunotherapy. Conclusions: No patients included in the study were found to have the 2 known TLR2 nonsynonymous SNPs, and the relative importance of these polymorphisms could not be definitely determined. However, a significant proportion of patients without these polymorphisms responded to BCG-immunotherapy, suggesting that these genetic variants are not critical in the effectiveness of this approach for preventing recurrence of the tumor.
机译：背景：膀胱内BacilleCalmette-Guérin（BCG）免疫疗法已被用作预防浅表性膀胱癌复发的方法。但是，其有效性既可变又不可预测。通常，癌症BCG免疫疗法旨在改变或调节先天和适应性免疫应答。已经研究了几种关键的免疫调节分子中的基因多态性对BCG免疫疗法反应异质性的影响。目的：本研究旨在评估toll样受体（TLR）2多态性（精氨酸与位置753 [Arg753Gln]上的谷氨酰胺取代和精氨酸与677位[Arg677Trp]上的色氨酸取代之间的关联）和BCG的结果-免疫疗法。方法：这项前瞻性研究在2006年6月至2009年7月的3年中进行。在1年期间招募了连续患者，并在突尼斯的Charles Nicolle医院泌尿外科随访了2年。患有任何程度的Ta（非侵入性乳头状癌）或T1期的浅表性膀胱肿瘤（其中肿瘤已经从衬在膀胱内的细胞层生长到下方的结缔组织，但尚未生长到膀胱的肌肉层）的患者合格;排除原位癌病例。经尿道切除后经BCG免疫治疗的患者外周血DNA中研究了TLR2 Arg753Gln和Arg677Trp多态性。结果：共有112例患者入组（男101例，女11例;平均年龄63.9岁，范围25-85岁），并完成了2年的随访。聚合酶链反应扩增后，直接测序包含目标TLR2单核苷酸多态性（SNP）的区域，在属于以下两组的任何研究参与者中均未检测到Arg753Gln或Arg677Trp：应答者（n = 67）和无应答者（n = 45）接受BCG免疫疗法。结论：研究中没有患者发现有2种已知的TLR2非同义SNP，并且这些多态性的相对重要性尚不确定。然而，相当大比例的没有这些多态性的患者对BCG免疫疗法有反应，这表明这些遗传变异对这种方法预防肿瘤复发的有效性并不关键。

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