期刊
GUT
卷 70, 期 9, 页码 1713-1723出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/gutjnl-2020-320608
关键词
-
资金
- Japanese Society for the Promotion of Science Kakenhi [26430107, 17K07155]
- Fugaku Trust for Medicinal Research
- Grants-in-Aid for Scientific Research [26430107, 17K07155] Funding Source: KAKEN
PDAC is the deadliest cancer and frequently associated with CAT. This study found that inhibition of VCAM-1 can effectively treat PDAC and CAT in mice, leading to extended survival time. Increase of plasma ANP and sVCAM-1 may serve as diagnostic markers for CAT in PDAC.
Objective Pancreatic ductal adenocarcinoma (PDAC) is the deadliest cancer. Cancer-associated thrombosis/thromboembolism (CAT), frequently observed in PDAC, is known as a poor prognostic factor. Here, we investigated the underlying mechanisms between PDAC and CAT, and performed a trial of therapeutic approach for PDAC using a genetically engineered mouse model, PKF (Ptf1a(cre/+);LSL-Kras(G12D/+);Tgfbr2(flox/flox)). Design Presence of CAT in PKF mice was detected by systemic autopsy. Plasma cytokines were screened by cytokine antibody array. Murine and human plasma atrial natriuretic peptide (ANP) and soluble vascular cell adhesion molecule 1 (sVCAM-1) were determined by ELISA. Distribution of VCAM-1 in PKF mice and human autopsy samples was detected by immunohistochemistry. PKF mice were treated with anti-VCAM-1 antibody and the effects on survival, distribution of CAT and the tumour histology were analysed. Results We found spontaneous CAT with cardiomegaly in 68.4% PKF mice. Increase of plasma ANP and sVCAM-1 was observed in PKF mice and PDAC patients with CAT. VCAM-1 was detected in the activated endothelium and thrombi. Administration of anti-VCAM-1 antibody to PKF mice inhibited tumour growth, neutrophil/macrophage infiltration, tumour angiogenesis and progression of CAT; moreover, it dramatically extended survival (from 61 to 253 days, p<0.01). Conclusion Blocking VCAM-1/sVCAM-1 might be a potent therapeutic approach for PDAC as well as CAT, which can contribute to the prognosis. Increase of plasma ANP and sVCAM-1 might be a diagnostic approach for CAT in PDAC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据