Inhibition of LTA4H by bestatin in human and mouse colorectal cancerResearch in context
Background: Our preclinical data showed that the leukotriene A4 hydrolase (LTA4H) pathway plays a role in colorectal cancer (CRC). High expression of LTA4H and leukotriene B4 receptor type 1 (BLT1) were also associated with CRC survival probability. Clinical samples were evaluated to determine wheth...
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Format: | Article |
Language: | English |
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Elsevier
2019-06-01
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Series: | EBioMedicine |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419303093 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Simin Zhao Ke Yao Dan Li Kangdong Liu Guoguo Jin Mingyang Yan Qiong Wu Hanyong Chen Seung Ho Shin Ruihua Bai Gangcheng Wang Ann M. Bode Ziming Dong Zhiping Guo Zigang Dong |
spellingShingle |
Simin Zhao Ke Yao Dan Li Kangdong Liu Guoguo Jin Mingyang Yan Qiong Wu Hanyong Chen Seung Ho Shin Ruihua Bai Gangcheng Wang Ann M. Bode Ziming Dong Zhiping Guo Zigang Dong Inhibition of LTA4H by bestatin in human and mouse colorectal cancerResearch in context EBioMedicine |
author_facet |
Simin Zhao Ke Yao Dan Li Kangdong Liu Guoguo Jin Mingyang Yan Qiong Wu Hanyong Chen Seung Ho Shin Ruihua Bai Gangcheng Wang Ann M. Bode Ziming Dong Zhiping Guo Zigang Dong |
author_sort |
Simin Zhao |
title |
Inhibition of LTA4H by bestatin in human and mouse colorectal cancerResearch in context |
title_short |
Inhibition of LTA4H by bestatin in human and mouse colorectal cancerResearch in context |
title_full |
Inhibition of LTA4H by bestatin in human and mouse colorectal cancerResearch in context |
title_fullStr |
Inhibition of LTA4H by bestatin in human and mouse colorectal cancerResearch in context |
title_full_unstemmed |
Inhibition of LTA4H by bestatin in human and mouse colorectal cancerResearch in context |
title_sort |
inhibition of lta4h by bestatin in human and mouse colorectal cancerresearch in context |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2019-06-01 |
description |
Background: Our preclinical data showed that the leukotriene A4 hydrolase (LTA4H) pathway plays a role in colorectal cancer (CRC). High expression of LTA4H and leukotriene B4 receptor type 1 (BLT1) were also associated with CRC survival probability. Clinical samples were evaluated to determine whether LTA4H could serve as a therapeutic target and whether leukotriene B4 (LTB4) could be used as a biomarker for evaluating the efficacy of bestatin in CRC. Methods: Patients with Stage I-III CRC did or did not receive bestatin prior to surgery. Evaluable pairwise CRC patient blood samples were collected to evaluate LTB4 concentration. Tissues were processed by immunohistochemistry to detect the LTA4H pathway and Ki-67 expression. We also determined whether LTA4H or BLT1 was associated with CRC survival probability and explored the mechanism of bestatin action in CRC. Findings: Samples from 13 CRC patients showed a significant decrease in LTB4, the LTA4H signaling pathway, and Ki-67 in the bestatin-treated group compared with the untreated group. LTA4H and BLT1 are overexpressed in CRC and associated with CRC survival probability. Bestatin effectively inhibited LTB4 and tumorigenesis in the ApcMin/+ and CRC patient-derived xenograft mouse model. Interpretation: These results demonstrate that LTB4 could serve as a biomarker for evaluating bestatin efficacy in CRC and the antitumor effects of bestatin through its targeting of LTA4H and support further studies focusing on LTA4H inhibition in CRC. Keywords: Bestatin, LTA4H, LTB4, BLT1, Colorectal cancer |
url |
http://www.sciencedirect.com/science/article/pii/S2352396419303093 |
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doaj-2ac8c422d98b4506a56f7b2077c712342020-11-25T02:43:18ZengElsevierEBioMedicine2352-39642019-06-0144361374Inhibition of LTA4H by bestatin in human and mouse colorectal cancerResearch in contextSimin Zhao0Ke Yao1Dan Li2Kangdong Liu3Guoguo Jin4Mingyang Yan5Qiong Wu6Hanyong Chen7Seung Ho Shin8Ruihua Bai9Gangcheng Wang10Ann M. Bode11Ziming Dong12Zhiping Guo13Zigang Dong14The Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States of America; Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, PR China; China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, PR China; Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan, PR ChinaThe Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States of America; China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, PR ChinaAffiliated Tumor Hospital of Zhengzhou University, Zhengzhou, Henan, PR ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, PR China; China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, PR China; Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan, PR ChinaThe Henan Orthopedic Hospital, Zhengzhou, Henan, PR ChinaChina-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, PR ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, PR China; China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, PR ChinaThe Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States of AmericaThe Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States of AmericaAffiliated Tumor Hospital of Zhengzhou University, Zhengzhou, Henan, PR ChinaAffiliated Tumor Hospital of Zhengzhou University, Zhengzhou, Henan, PR ChinaThe Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States of AmericaDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, PR China; Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan, PR China; Correspondence to: Z. Dong, Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, 100 Science Avenue, Zhengzhou, Henan 450001, PR China.The Henan Orthopedic Hospital, Zhengzhou, Henan, PR China; Correspondence to: Z. Guo, The Henan Orthopedic Hospital, 100 Yongping Road, Zhengzhou, Henan 450001, PR China.The Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States of America; China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, PR China; Correspondence to: Z. Dong, The Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States of America.Background: Our preclinical data showed that the leukotriene A4 hydrolase (LTA4H) pathway plays a role in colorectal cancer (CRC). High expression of LTA4H and leukotriene B4 receptor type 1 (BLT1) were also associated with CRC survival probability. Clinical samples were evaluated to determine whether LTA4H could serve as a therapeutic target and whether leukotriene B4 (LTB4) could be used as a biomarker for evaluating the efficacy of bestatin in CRC. Methods: Patients with Stage I-III CRC did or did not receive bestatin prior to surgery. Evaluable pairwise CRC patient blood samples were collected to evaluate LTB4 concentration. Tissues were processed by immunohistochemistry to detect the LTA4H pathway and Ki-67 expression. We also determined whether LTA4H or BLT1 was associated with CRC survival probability and explored the mechanism of bestatin action in CRC. Findings: Samples from 13 CRC patients showed a significant decrease in LTB4, the LTA4H signaling pathway, and Ki-67 in the bestatin-treated group compared with the untreated group. LTA4H and BLT1 are overexpressed in CRC and associated with CRC survival probability. Bestatin effectively inhibited LTB4 and tumorigenesis in the ApcMin/+ and CRC patient-derived xenograft mouse model. Interpretation: These results demonstrate that LTB4 could serve as a biomarker for evaluating bestatin efficacy in CRC and the antitumor effects of bestatin through its targeting of LTA4H and support further studies focusing on LTA4H inhibition in CRC. Keywords: Bestatin, LTA4H, LTB4, BLT1, Colorectal cancerhttp://www.sciencedirect.com/science/article/pii/S2352396419303093 |