BACKGROUND Hereditary diffuse gastric cancer(HDGC)is a familial cancer syndrome often associated with germline mutations in the CDH1 gene.However,the frequency of CDH1 mutations is low in patients with HDGC in East As...BACKGROUND Hereditary diffuse gastric cancer(HDGC)is a familial cancer syndrome often associated with germline mutations in the CDH1 gene.However,the frequency of CDH1 mutations is low in patients with HDGC in East Asian countries.Herein,we report three cases of HDGC harboring a missense CDH1 variant,c.1679C>G,from a single Japanese family.CASE SUMMARY A 26-year-old female(Case 1)and a 51-year-old male(father of Case 1),who had a strong family history of gastric cancer,were diagnosed with advanced diffuse gastric cancer.After genetic counselling,a 25-year-old younger brother of Case 1 underwent surveillance esophagogastroduodenoscopy that detected small signet ring cell carcinoma foci as multiple pale lesions in the gastric mucosa.Genetic analysis revealed a CDH1 c.1679C>G variant in all three patients.CONCLUSION It is important for individuals suspected of having HDGC to be actively offered genetics evaluation.This report will contribute to an increased awareness of HDGC.展开更多
文摘目的：探讨肾间质纤维化过程中，ILK 及其相关蛋白 PKB 、α‐SMA 、E‐cadherin 的表达及意义，以及给予 PI3K 抑制剂（沃特曼宁）干预治疗的效果，为临床诊治提供一线索。方法本组以96只2～3周龄幼年 SD 雌性大鼠为实验动物，采用单侧输尿管结扎（UUO）制作肾间质纤维化模型。将大鼠随机分为三组：对照组（A 组）、UUO未治疗组（B 组）、UUO 治疗组（C 组）。每组于造模成功后第1w 、2w 、3w 、4w 采用免疫组化染色检测左肾组织 ILK 、PKB 、α‐SMA 及 E‐cadherin 的表达。采用 SPSS17．0对数据结果进行统计学分析。结果 B 组 ILK 、PKB 及α‐SMA的表达随着实验时间的延续表达呈上升趋势，各时间点与 A 组相比差异有统计学意义（P＜0．05）；E‐cadherin 的表达呈下降趋势，各时间点与 A 组相比差异有统计学意义（P＜0．05）。 C 组 ILK 、PKB 及α‐SMA 的表达随着实验时间的延续表达上调明显减缓，各时间点与 B 组相比差异有统计学意义（P＜0．05），在第3w 、4w ILK 与 PKB 的表达与 A 组相比差异有统计学意义（P ＜0．05），在第2w 、3w 、4w α‐SMA 的表达与 A 组相比差异有统计学意义（P＜0．05）；E‐cadherin 的表达下调与 B 组相比明显减缓，在第2w 、3w 、4w 与 A 组和 B 组相比差异均有统计学意义（P＜0．05）。相关性分析发现 B 组 ILK 与 PKB 、‐SMA 的表达呈正相关（P＜0．05），与 E‐Cadherin 的表达呈负相关（P＜0．05）。结论 ILK 参与了肾间质纤维化的发生发展，给予 PI3K 抑制剂沃特曼宁（wortmannin）干预治疗可以延缓肾脏疾病的进展，有望为临床治疗提供新的靶点。
文摘BACKGROUND Hereditary diffuse gastric cancer(HDGC)is a familial cancer syndrome often associated with germline mutations in the CDH1 gene.However,the frequency of CDH1 mutations is low in patients with HDGC in East Asian countries.Herein,we report three cases of HDGC harboring a missense CDH1 variant,c.1679C>G,from a single Japanese family.CASE SUMMARY A 26-year-old female(Case 1)and a 51-year-old male(father of Case 1),who had a strong family history of gastric cancer,were diagnosed with advanced diffuse gastric cancer.After genetic counselling,a 25-year-old younger brother of Case 1 underwent surveillance esophagogastroduodenoscopy that detected small signet ring cell carcinoma foci as multiple pale lesions in the gastric mucosa.Genetic analysis revealed a CDH1 c.1679C>G variant in all three patients.CONCLUSION It is important for individuals suspected of having HDGC to be actively offered genetics evaluation.This report will contribute to an increased awareness of HDGC.
