Analysis of incidence and clinical outcomes in patients with thromboembolic events and invasive exocrine pancreatic cancer

Epstein, Andrew S.; Soff, Gerald A.; Capanu, Marinela; Crosbie, Christopher; Shah, Manish A.; Kelsen, David P.; Denton, Brian T.; Gardos, Stuart; O’Reilly, Eileen M.

doi:10.1002/cncr.26600

Cited by 89 publications

(88 citation statements)

References 30 publications

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“…Unlike other factors (stage, major surgery, and chemotherapy) which have been already shown in previous studies, 25–27 the tumor site (pancreatic head) as a risk factor for VTE seems to be unfamiliar. We hypothesized that pancreatic head cancer might be frequently associated with early detection at relatively early stage because of symptoms and signs such as pain, jaundice, or Courvoisier's sign.…”

Section: Discussionmentioning

confidence: 65%

Characteristics of Venous Thromboembolism in Pancreatic Adenocarcinoma in East Asian Ethnics

Lee

Jun-Hyeon

et al. 2016

Medicine

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Section: Discussionmentioning

confidence: 65%

Characteristics of Venous Thromboembolism in Pancreatic Adenocarcinoma in East Asian Ethnics

Lee

Jun-Hyeon

et al. 2016

Medicine

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“…Pancreatic cancer, in particular, is strongly associated with a hypercoagulable state and venous thromboembolism. The reported incidence of venous thromboembolism following a pancreatic cancer diagnosis is 5%–26%, with rates of 57% in older autopsy studies 4. Arterial thromboembolism is less well documented in cancer, but is increasingly recognised.…”

Section: Discussionmentioning

confidence: 99%

Recurrent brain ischaemia and deep vein thrombosis: the clot thickens

et al. 2017

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“…Pancreatic cancer is among the most common malignancies associated with thromboembolic events [5] and these events confer a significantly worse prognosis [6].…”

Section: Introductionmentioning

confidence: 99%

Protease-activated receptor 2 suppresses lymphangiogenesis and subsequent lymph node metastasis in a murine pancreatic cancer model

et al. 2014

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Protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that functions as a cell-surface sensor for coagulation factors and other proteases associated with the tumour microenvironment. Pancreatic cancer cells express high levels of PAR-2 and activation of PAR-2 may induce their proliferation and migration. Interestingly, however, PAR-2 expression is increased in stroma-rich pancreatic cancer regions, suggesting a potential role of PAR-2 in the tumour microenvironment. Here, we assessed the importance of PAR-2 in the stromal compartment by utilizing an orthotopic pancreatic cancer model, in which tumour cells are PAR-2-positive, whereas stromal cells are PAR-2-negative. We assessed tumour weight and volume and analysed proliferation and (lymph)angiogenesis both in vivo and in vitro. We show that genetic ablation of PAR-2 from the stromal compartment inhibits primary tumour growth, which is accompanied by reduced vascularization in primary tumours and reduced in tube formation of vascular endothelial cells in vitro. In contrast to smaller primary tumours, the number of lymph node metastases was increased in PAR-2-deficient animals, which was accompanied by an increased number of lymphatic vessels. In vitro tube-formation assays show that PAR-2 does not inhibit the intrinsic tube-forming capacity of lymphatic endothelial cells, but that PAR-2 actually inhibits cancer cell-induced tube formation. Overall, stromal PAR-2 thus plays a dual role in pancreatic cancer development by potentiating primary tumour growth but limiting lymphangiogenesis and subsequent lymph node metastasis. Our data identify a novel role of PAR-2 in the tumour microenvironment and pinpoint PAR-2 as a negative regulator of lymphangiogenesis.

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Analysis of incidence and clinical outcomes in patients with thromboembolic events and invasive exocrine pancreatic cancer

Cited by 89 publications

References 30 publications

Characteristics of Venous Thromboembolism in Pancreatic Adenocarcinoma in East Asian Ethnics

Characteristics of Venous Thromboembolism in Pancreatic Adenocarcinoma in East Asian Ethnics

Recurrent brain ischaemia and deep vein thrombosis: the clot thickens

Protease-activated receptor 2 suppresses lymphangiogenesis and subsequent lymph node metastasis in a murine pancreatic cancer model

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