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Toll 样受体 9 在弥漫性大 B 细胞淋巴瘤中的表达:进一步探讨 NFκB 通路中的 CpG 寡脱氧核苷酸。

Expression of Toll-like receptor9 in diffuse large B-cell lymphoma: further exploring CpG oligodeoxynucleotide in NFκB pathway.

机构信息

Department of Pathology, Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

出版信息

APMIS. 2012 Nov;120(11):872-81. doi: 10.1111/j.1600-0463.2012.02915.x. Epub 2012 May 28.

Abstract

Human Toll-like receptors (TLRs) that recognize a variety of pathogen-associated molecular patterns are associated with activation and immunogenic response in lymphoid neoplasms, but rarely explored in diffuse large B-cell lymphoma (DLBCL). We conducted this study to evaluate the expression of TLR9 in and potential treatment of DLBCL with TLR9 agonist - CpG oligodeoxynucleotide (ODN). The real-time quantitative reverse transcription-polymerase chain reaction was carried out to detect TLR9 expression in 41 formalin-fixed paraffin-embedded samples. The transformation of immunophenotype and NFκB pathway of DLBCL upon CpG ODN stimulation were investigated by a DLBCL cell line. TLR9 was commonly detected in DLBCL with relative mRNA levels above 1.0 × 10(-2) in 35 of 41 cases (85.36%). It was suspected that a high proportion of DLBCL to be activated by CpG stimulation. In vitro study with a DLBCL cell line revealed an increased CD20, but decreased BCL-6 and MUM1/IRF4 expression after treatment with CpG ODN. The NFκB pathway was initially activated, but finally suppressed upon CpG ODN stimulation. The proliferation of tumor cells was also inhibited by long time incubation. These findings provide new insights into the role of TLR9 in DLBCL and potential implication of TLR9 agonist in the treatment of DLBCL.

摘要

人类 Toll 样受体 (TLRs) 能够识别多种病原体相关的分子模式,与淋巴肿瘤的激活和免疫应答有关,但在弥漫性大 B 细胞淋巴瘤 (DLBCL) 中很少被研究。我们进行这项研究是为了评估 TLR9 在 DLBCL 中的表达,并利用 TLR9 激动剂——CpG 寡脱氧核苷酸 (ODN) 对其进行潜在治疗。采用实时定量逆转录聚合酶链反应检测 41 例福尔马林固定石蜡包埋样本中 TLR9 的表达。通过 DLBCL 细胞系研究 CpG ODN 刺激对免疫表型和 NFκB 通路的转化。在 41 例病例中,有 35 例(85.36%)的 TLR9 相对 mRNA 水平高于 1.0×10(-2),提示 CpG 刺激可激活相当大比例的 DLBCL。体外研究显示,DLBCL 细胞系经 CpG ODN 处理后,CD20 表达增加,但 BCL-6 和 MUM1/IRF4 表达减少。NFκB 通路最初被激活,但随后被 CpG ODN 刺激抑制。长时间孵育也抑制了肿瘤细胞的增殖。这些发现为 TLR9 在 DLBCL 中的作用提供了新的见解,并提示 TLR9 激动剂在 DLBCL 治疗中的潜在意义。

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