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靶向钙/钙调蛋白依赖性激酶I和II作为子宫内膜癌潜在的抗增殖治疗方法。

Targeting calcium/calmodulin-dependence kinase I and II as a potential anti-proliferation remedy for endometrial carcinomas.

作者信息

Takai Noriyuki, Ueda Tami, Nasu Kaei, Yamashita Satoko, Toyofuku Mayo, Narahara Hisashi

机构信息

Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, 1-1 Idaigaioka, Hasama-machi, Yufu-shi, Oita, Japan.

出版信息

Cancer Lett. 2009 May 18;277(2):235-43. doi: 10.1016/j.canlet.2008.12.018. Epub 2009 Jan 24.

Abstract

Calcium/calmodulin-dependent kinase (CaMK) I and II expression in endometrial cancer cells correlates with the malignant potential of this tumor, and CaMKI and II are potential therapeutic targets in endometrial cancer. CaMKI and II expression was significantly associated with PCNA-labeling index, clinical stage, histological grade, the presence of invasion to greater than one-half the myometrium, and clinical outcome. All endometrial cancer cell lines examined were sensitive to the growth-inhibitory effect of KN-93, a membrane-permeant CaMKs-selective inhibitor that is competitive with calmodulin. KN-93 induced the G0/G1 arrest and apoptosis, rising hopes that KN-93 may become a useful treatment for endometrial cancers.

摘要

钙/钙调蛋白依赖性激酶(CaMK)I和II在子宫内膜癌细胞中的表达与该肿瘤的恶性潜能相关,且CaMKI和II是子宫内膜癌潜在的治疗靶点。CaMKI和II的表达与增殖细胞核抗原(PCNA)标记指数、临床分期、组织学分级、肌层浸润超过一半的情况以及临床结局显著相关。所有检测的子宫内膜癌细胞系均对KN-93(一种可透过细胞膜的、与钙调蛋白竞争性结合的CaMKs选择性抑制剂)的生长抑制作用敏感。KN-93诱导细胞停滞于G0/G1期并引发凋亡,这让人们燃起了KN-93可能成为子宫内膜癌有效治疗手段的希望。

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