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Antiangiogenic and antimetastatic activity of JAK inhibitor AZD1480

STAT3 has important functions in both tumor cells and the tumor microenvironment to facilitate cancer progression. The STAT regulatory kinase Janus-activated kinase (JAK) has been strongly implicated in promoting oncogenesis of various solid tumors, including the use of JAK kinase inhibitors such as... Full description

Journal Title: Cancer research 01 November 2011, Vol.71(21), pp.6601-10
Main Author: Xin, Hong
Other Authors: Herrmann, Andreas , Reckamp, Karen , Zhang, Wang , Pal, Sumanta , Hedvat, Michael , Zhang, Chunyan , Liang, Wei , Scuto, Anna , Weng, Shaobu , Morosini, Deborah , Cao, Zhu A , Zinda, Michael , Figlin, Robert , Huszar, Dennis , Jove, Richard , Yu, Hua
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1538-7445 ; PMID: 21920898 Version:1 ; DOI: 10.1158/0008-5472.CAN-11-1217
Link: http://pubmed.gov/21920898
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recordid: medline21920898
title: Antiangiogenic and antimetastatic activity of JAK inhibitor AZD1480
format: Article
creator:
  • Xin, Hong
  • Herrmann, Andreas
  • Reckamp, Karen
  • Zhang, Wang
  • Pal, Sumanta
  • Hedvat, Michael
  • Zhang, Chunyan
  • Liang, Wei
  • Scuto, Anna
  • Weng, Shaobu
  • Morosini, Deborah
  • Cao, Zhu A
  • Zinda, Michael
  • Figlin, Robert
  • Huszar, Dennis
  • Jove, Richard
  • Yu, Hua
subjects:
  • Antineoplastic Agents -- Therapeutic Use
  • Janus Kinases -- Antagonists & Inhibitors
  • Neoplasm Metastasis -- Drug Therapy
  • Neoplasm Proteins -- Antagonists & Inhibitors
  • Neovascularization, Pathologic -- Drug Therapy
  • Protein Kinase Inhibitors -- Therapeutic Use
  • Pyrazoles -- Therapeutic Use
  • Pyrimidines -- Therapeutic Use
  • Tumor Microenvironment -- Drug Effects
ispartof: Cancer research, 01 November 2011, Vol.71(21), pp.6601-10
description: STAT3 has important functions in both tumor cells and the tumor microenvironment to facilitate cancer progression. The STAT regulatory kinase Janus-activated kinase (JAK) has been strongly implicated in promoting oncogenesis of various solid tumors, including the use of JAK kinase inhibitors such as AZD1480. However, direct evidence that JAK drives STAT3 function and cancer pathogenesis at the level of the tumor microenvironment is yet to be established clearly. In this study, we show that AZD1480 inhibits STAT3 in tumor-associated myeloid cells, reducing their number and inhibiting tumor metastasis. Myeloid cell-mediated angiogenesis was also diminished by AZD1480, with additional direct inhibition of endothelial cell function in vitro and in vivo. AZD1480 blocked lung infiltration of myeloid cells and formation of pulmonary metastases in both mouse syngeneic experimental and spontaneous metastatic models. Furthermore, AZD1480 reduced angiogenesis and metastasis in a human xenograft tumor...
language: eng
source:
identifier: E-ISSN: 1538-7445 ; PMID: 21920898 Version:1 ; DOI: 10.1158/0008-5472.CAN-11-1217
fulltext: fulltext
issn:
  • 15387445
  • 1538-7445
url: Link


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titleAntiangiogenic and antimetastatic activity of JAK inhibitor AZD1480
creatorXin, Hong ; Herrmann, Andreas ; Reckamp, Karen ; Zhang, Wang ; Pal, Sumanta ; Hedvat, Michael ; Zhang, Chunyan ; Liang, Wei ; Scuto, Anna ; Weng, Shaobu ; Morosini, Deborah ; Cao, Zhu A ; Zinda, Michael ; Figlin, Robert ; Huszar, Dennis ; Jove, Richard ; Yu, Hua
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subjectAntineoplastic Agents -- Therapeutic Use ; Janus Kinases -- Antagonists & Inhibitors ; Neoplasm Metastasis -- Drug Therapy ; Neoplasm Proteins -- Antagonists & Inhibitors ; Neovascularization, Pathologic -- Drug Therapy ; Protein Kinase Inhibitors -- Therapeutic Use ; Pyrazoles -- Therapeutic Use ; Pyrimidines -- Therapeutic Use ; Tumor Microenvironment -- Drug Effects
descriptionSTAT3 has important functions in both tumor cells and the tumor microenvironment to facilitate cancer progression. The STAT regulatory kinase Janus-activated kinase (JAK) has been strongly implicated in promoting oncogenesis of various solid tumors, including the use of JAK kinase inhibitors such as AZD1480. However, direct evidence that JAK drives STAT3 function and cancer pathogenesis at the level of the tumor microenvironment is yet to be established clearly. In this study, we show that AZD1480 inhibits STAT3 in tumor-associated myeloid cells, reducing their number and inhibiting tumor metastasis. Myeloid cell-mediated angiogenesis was also diminished by AZD1480, with additional direct inhibition of endothelial cell function in vitro and in vivo. AZD1480 blocked lung infiltration of myeloid cells and formation of pulmonary metastases in both mouse syngeneic experimental and spontaneous metastatic models. Furthermore, AZD1480 reduced angiogenesis and metastasis in a human xenograft tumor...
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titleAntiangiogenic and antimetastatic activity of JAK inhibitor AZD1480
descriptionSTAT3 has important functions in both tumor cells and the tumor microenvironment to facilitate cancer progression. The STAT regulatory kinase Janus-activated kinase (JAK) has been strongly implicated in promoting oncogenesis of various solid tumors, including the use of JAK kinase inhibitors such as AZD1480. However, direct evidence that JAK drives STAT3 function and cancer pathogenesis at the level of the tumor microenvironment is yet to be established clearly. In this study, we show that AZD1480 inhibits STAT3 in tumor-associated myeloid cells, reducing their number and inhibiting tumor metastasis. Myeloid cell-mediated angiogenesis was also diminished by AZD1480, with additional direct inhibition of endothelial cell function in vitro and in vivo. AZD1480 blocked lung infiltration of myeloid cells and formation of pulmonary metastases in both mouse syngeneic experimental and spontaneous metastatic models. Furthermore, AZD1480 reduced angiogenesis and metastasis in a human xenograft tumor...
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abstractSTAT3 has important functions in both tumor cells and the tumor microenvironment to facilitate cancer progression. The STAT regulatory kinase Janus-activated kinase (JAK) has been strongly implicated in promoting oncogenesis of various solid tumors, including the use of JAK kinase inhibitors such as AZD1480. However, direct evidence that JAK drives STAT3 function and cancer pathogenesis at the level of the tumor microenvironment is yet to be established clearly. In this study, we show that AZD1480 inhibits STAT3 in tumor-associated myeloid cells, reducing their number and inhibiting tumor metastasis. Myeloid cell-mediated angiogenesis was also diminished by AZD1480, with additional direct inhibition of endothelial cell function in vitro and in vivo. AZD1480 blocked lung infiltration of myeloid cells and formation of pulmonary metastases in both mouse syngeneic experimental and spontaneous metastatic models. Furthermore, AZD1480 reduced angiogenesis and metastasis in a human xenograft tumor...
doi10.1158/0008-5472.CAN-11-1217
pmid21920898
date2011-11-01