...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular cancer therapeutics >Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment.
【24h】

Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment.

机译：PF-562,271抑制粘着斑激酶可抑制胰腺癌的生长和转移，同时改变肿瘤的微环境。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Current therapies for pancreatic ductal adenocarcinoma (PDA) target individual tumor cells. Focal adhesion kinase (FAK) is activated in PDA, and levels are inversely associated with survival. We investigated the effects of PF-562,271 (a small-molecule inhibitor of FAK/PYK2) on (i) in vitro migration, invasion, and proliferation; (ii) tumor proliferation, invasion, and metastasis in a murine model; and (iii) stromal cell composition in the PDA microenvironment. Migration assays were conducted to assess tumor and stromal cell migration in response to cellular factors, collagen, and the effects of PF-562,271. An orthotopic murine model was used to assess the effects of PF-562,271 on tumor growth, invasion, and metastasis. Proliferation assays measured PF-562,271 effects on in vitro growth. Immunohistochemistry was used to examine the effects of FAK inhibition on the cellular composition of the tumor microenvironment. FAK and PYK2 were activated and expressed in patient-derived PDA tumors, stromal components, and human PDA cell lines. PF-562,271 blocked phosphorylation of FAK (phospho-FAK or Y397) in a dose-dependent manner. PF-562,271 inhibited migration of tumor cells, cancer-associated fibroblasts, and macrophages. Treatment of mice with PF-562,271 resulted in reduced tumor growth, invasion, and metastases. PF-562,271 had no effect on tumor necrosis, angiogenesis, or apoptosis, but it did decrease tumor cell proliferation and resulted in fewer tumor-associated macrophages and fibroblasts than control or gemcitabine. These data support a role for FAK in PDA and suggest that inhibitors of FAK may contribute to efficacious treatment of patients with PDA.
机译：胰腺导管腺癌（PDA）的当前疗法靶向单个肿瘤细胞。局灶性粘附激酶（FAK）在PDA中被激活，其水平与存活率成反比。我们研究了PF-562,271（FAK / PYK2的小分子抑制剂）对（i）体外迁移，侵袭和增殖的影响; （ii）在鼠模型中的肿瘤增殖，侵袭和转移; （iii）PDA微环境中的基质细胞组成。进行迁移测定以评估响应细胞因子，胶原蛋白和PF-562,271作用的肿瘤和基质细胞迁移。使用原位鼠模型评估PF-562,271对肿瘤生长，侵袭和转移的影响。增殖测定法测量了PF-562271对体外生长的影响。免疫组织化学用于检查FAK抑制对肿瘤微环境的细胞组成的影响。 FAK和PYK2被激活并在患者衍生的PDA肿瘤，基质成分和人PDA细胞系中表达。 PF-562,271以剂量依赖的方式阻断了FAK（磷酸-FAK或Y397）的磷酸化。 PF-562,271抑制肿瘤细胞，与癌症相关的成纤维细胞和巨噬细胞的迁移。用PF-562,271小鼠治疗导致肿瘤生长，侵袭和转移减少。 PF-562,271对肿瘤坏死，血管生成或细胞凋亡没有影响，但确实降低了肿瘤细胞的增殖，并导致肿瘤相关的巨噬细胞和成纤维细胞少于对照组或吉西他滨。这些数据支持FAK在PDA中的作用，并表明FAK的抑制剂可能有助于有效治疗PDA患者。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号