Abstract:
Ghrelin is a hormone with multiple physiologic functions, including promotion of growth hormone release, stimulation of appetite and regulation of energy homeostasis. Treatment with ghrelin/ghrelin-receptor agonists is a prospective therapy for disease-related cachexia and malnutrition. In vitro studies have shown high expression of ghrelin in cancer tissue, although its role including its impact in cancer risk and progression has not been established. We performed a systematic literature review to identify peer-reviewed human or animal in vivo original research studies of ghrelin, ghrelin-receptor agonists, or ghrelin genetic variants and the risk, presence, or growth of cancer using structured searches in PubMed database as well as secondary searches of article reference lists, additional reviews and meta-analyses. Overall, 45 (73.8%) of the 61 studies reviewed, including all 11 involving exogenous ghrelin/ghrelin-receptor agonist treatment, reported either a null (no statistically significant difference) or inverse association of ghrelin/ghrelin-receptor agonists or ghrelin genetic variants with cancer risk, presence or growth; 10 (16.7%) studies reported positive associations; and 6 (10.0%) reported both negative or null and positive associations. Differences in serum ghrelin levels in cancer cases vs controls (typically lower) were reported for some but not all cancers. The majority of in vivo studies showed a null or inverse association of ghrelin with risk and progression of most cancers, suggesting that ghrelin/ghrelin-receptor agonist treatment may have a favorable safety profile to use for cancer cachexia. Additional large-scale prospective clinical trials as well as basic bioscientific research are warranted to further evaluate the safety and benefits of ghrelin treatment in patients with cancer.
摘要:
Ghrelin是一种具有多种生理功能的激素,包括促进生长激素的释放,刺激食欲和调节能量稳态。用ghrelin/ghrelin受体激动剂治疗是疾病相关恶病质和营养不良的前瞻性治疗。体外研究表明ghrelin在癌组织中高表达,尽管其作用,包括其对癌症风险和进展的影响尚未确定。我们进行了系统的文献综述,以确定同行评审的人或动物体内ghrelin的原始研究研究,ghrelin受体激动剂,或ghrelin遗传变异和风险,存在,或使用PubMed数据库中的结构化搜索以及文章参考列表的二次搜索,额外的评论和荟萃分析。总的来说,审查的61项研究中有45项(73.8%),包括所有涉及外源性生长素释放肽/生长素释放肽受体激动剂治疗的11项,报告了ghrelin/ghrelin受体激动剂或ghrelin遗传变异与癌症风险的无效(无统计学差异)或负相关,存在或生长;10项(16.7%)研究报告了正相关;6项(10.0%)报告了负或零和正相关。报道了一些但并非所有癌症的癌症病例与对照(通常较低)中血清生长素释放肽水平的差异。大多数体内研究表明,生长素释放肽与大多数癌症的风险和进展呈零或负相关。这表明ghrelin/ghrelin受体激动剂治疗癌症恶病质可能具有良好的安全性。需要进行其他大规模前瞻性临床试验以及基础生物科学研究,以进一步评估ghrelin治疗癌症患者的安全性和益处。