半胱氨酰白三烯受体CysLT1R在大肠癌组织中的表达及临床意义

目的研究半胱氨酰白三烯受体(CysLT1R)在大肠癌组织中的表达及其与大肠癌临床病理特征之间的关系。方法选取46例大肠癌、32例癌旁组织、15例腺瘤性息肉手术切除标本,采用免疫组织化学法检测各组织中CysLT1R的表达水平。结果 CysLT1R在大肠癌组织、癌旁组织及腺瘤性息肉中的阳性表达率分别为67.39%,40.62%,40.0%,癌组织中CysLT1R的阳性表达率高于癌旁组织、腺瘤性息肉组织(P<0.05)。大肠癌组织中CysLT1R的表达程度与肿瘤大小、组织学分级、淋巴结转移及临床分期有关(均P<0.05)。结论 CysLT1R表达与大肠癌分化程度、肿瘤大小、淋巴结转移及临床分期有关。CysLT1R可能参与大肠癌发生发展。

新型选择性半胱氨酰白三烯受体1(CysLT1R)拮抗剂的设计合成及构效关系研究

半胱氨酰白三烯(CysLTs)是炎症脂介质,其受体(CysLTsR)在哮喘、过敏性鼻炎和癌症等疾病的发生发展中发挥重要作用.已发现3-取代1H-吲哚-2-羧酸衍生物具有半胱氨酰白三烯受体1(CysLT1R)拮抗活性,但较差的溶解度限制了其进一步研究.基于已有研究基础继续进行结构优化,设计合成了多个系列化合物,其中3-{2-[(1E)-3-({3-[(1E)-2-(7-氯喹啉-2-基)乙烯基]苯基}氨基)-3-氧亚基丙-1-烯基]苯基}丙酸(T9)展现出良好的选择性CysLT1受体拮抗活性和改善的溶解度,其IC50值为(0.0066±0.0023)μmol/L,在水中溶解度为4.16×10^(-5) g/mL.

Cysteinyl leukotrienes and their receptors: Bridging inflammation and colorectal cancer

Long-standing inflammation has emerged as a hallmark of neoplastic transformation of epithelial cells and may be a limiting factor of successful conventional tumor therapies.A complex milieu composed of distinct stromal and immune cells,soluble factors and inflammatory mediators plays a crucial role in supporting and promoting various types of cancers.An augmented inflammatory response can predispose a patient to colorectal cancer(CRC).Common risk factors associated with CRC development include diet and lifestyle,altered intestinal microbiota and commensals,and chronic inflammatory bowel diseases.Cysteinyl leukotrienes are potent inflammatory metabolites synthesized from arachidonic acid and have a broad range of functions involved in the etiology of various pathologies.This review discusses the important role of cysteinyl leukotriene signaling in linking inflammation and CRC.