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| 1 | Guanylyl cyclase C signaling axis and colon cancer prevention显示文摘Colorectal cancer(CRC) is a major cause of cancerrelated mortality and morbidity worldwide. While improved treatments have enhanced overall patient outcome, disease burden encompassing quality of life, cost of care, and patient survival has seen little benefit. Consequently, additional advances in CRC treatments remain important, with an emphasis on preventative measures. Guanylyl cyclase C(GUCY2C), a transmembrane receptor expressed on intestinal epithelial cells, plays an important role in orchestrating intestinal homeostatic mechanisms. These effects are mediated by the endogenous hormones guanylin(GUCA2A) and uroguanylin(GUCA2B), which bind and activate GUCY2 C to regulate proliferation, metabolism and barrier function in intestine. Recent studies have demonstrated a link between GUCY2 C silencing and intestinal dysfunction, including tumorigenesis. Indeed, GUCY2 C silencing by the near universal loss of its paracrine hormone ligands increases colon cancer susceptibility in animals and humans. GUCY2C's role as a tumor suppressor has opened the door to a new paradigm for CRC prevention by hormone replacement therapy using synthetic hormone analogs, such as the FDA-approved oral GUCY2 C ligand linaclotide(Linzess^(TM)). Here we review the known contributions of the GUCY2 C signaling axis to CRC, and relate them to a novel clinical strategy targeting tumor chemoprevention. | Amanda M Pattison Dante J Merlino Erik S Blomain Scott A Waldman | 2016 | World Journal of Gastroenterology2016，22，36： | 2 |
| 2 | 鸟苷酸环化酶C及其内生性配体在人胃癌和癌前病变组织中的表达及临床意义显示文摘目的 :研究鸟苷酸环化酶C(guanylyl cyclase C,GC-C)和两个配体内生性肽类激素鸟苷素(guanylin,GN)和尿鸟苷素(uroguanylin,UGN)在胃癌、肠上皮化生和异型增生组织中的表达及与胃癌生物学行为之间的关系,并探讨其临床意义。方法:采用实时荧光定量聚合酶链反应法(real-time quantitative polymerase chain reaction,q RT-PCR)检测胃癌(60例)、肠上皮化生(23例)、异型增生(25例)和远癌胃(30例)组织中GC-C、GN和UGN m RNA的表达。进一步对三者与临床病理参数的关系及三者间的相关性进行分析。结果:q RT-PCR显示,GC-C和GN m RNA在肠上皮化生、异型增生及胃癌中高表达,而远癌胃组织中则不表达(均P=0.000 0)。GC-C和GN m RNA在肠型胃癌中的表达高于弥漫型(P=0.000 4和0.000 8),与年龄、性别、病灶大小、临床病理分期、分化程度、淋巴结转移和浸润深度等因素无关(均P>0.05)。在肠上皮化生、异型增生和胃癌组织中GC-C和GN的表达呈正相关(r=0.682 9、0.495 4和0.777 4,P=0.000 3、0.011 8和0.000 0)。而UGN在远癌胃组织、肠上皮化生、异型增生及胃癌组织中都有表达,差异无统计学意义(均P>0.05)。结论:胃黏膜癌变过程中GC-C的异位表达与其内生性配体GN的表达有关,检测两者的变化将有助于胃癌高危人群监测和胃癌早期诊断。 | 蒋伟 张健锋 张弘 朱惠君 倪润洲 毛振彪 | 2015 | 南通大学学报(医学版)2015，35，5： | 0 |
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