A Characterization of the Coagulant and Fibrinolytic Profile of Human Pancreatic Carcinoma Cells

Kakkar, Ajay K.; Chinswangwatanakul, Vitoon; Tebbutt, S.; Lemoine, Nick R.; Williamson, R. C. N.

doi:10.1159/000022375

Cited by 11 publications

(8 citation statements)

References 17 publications

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confidence: 92%

“…We observed that MP-TF activity in cancer patients with VTE is higher than in matched cancer patients without VTE. This finding strongly supports previous observations of a relationship between elevated MP-TF activity and VTE in patients with cancer from small studies of selected cancer patients [1,[4][5][6].It is interesting that the large majority of patients who develop VTE during chemotherapy have normal MP-TF activity, suggesting that an acute thrombotic event itself is not the cause of an elevated MP-TF activity. Our data point to a contribution of cancer cells themselves as (in) direct cause of elevated MP-TF activity and ask for novel studies better designed to study prospectively the relationship between chemotherapy, elevated MP-TF activity and venous thrombosis.…”

supporting

confidence: 90%

“…Although recombinant asTF shortened the clotting time of platelet poor plasma [1], asTF was enriched in human thrombi [1] and triggered activation of factor (F)X when secreted by human umbilical vein endothelial cells (HUVEC) [4], asTF expressed by human embryonic kidney (HEK) cells failed to activate FX [5]. To further explore the putative role of asTF in coagulation, we studied the procoagulant properties of asTF cloned from HUVEC in an expression model of MIA PaCa-2 cells, a human pancreatic TF-deficient cell line [2,[6][7][8]. Using these cells, confounding factors such as concurrent expression of TF are excluded.…”

mentioning

confidence: 99%

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Human alternatively spliced tissue factor is not secreted and does not trigger coagulation

Böing

Hau

Sturk

et al. 2009

Journal of Thrombosis and Haemostasis

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1-74) in patients (n = 68) with normal MP-TF activity (P = 0.028). In the group of 51 patients who presented with VTE, survival was significantly worse in patients with elevated MP-TF activity than in those with normal MP-TF activity (P = 0.010). In univariate analysis only tumour type, thrombosis and MP-TF activity were significantly associated with survival. In multivariate analysis, adjustment for tumour type, age and stage, did not affect the association between MP-TF activity and mortality (P < 0.015).The present study is the largest series of unselected patients with both cancer and VTE, in whom MP-TF activity has been measured in the acute phase of thrombosis. The strength of the present study is that we did not select for any tumour type but instead investigated all cancer patients who presented with acute VTE irrespective of the type of malignancy. We observed that MP-TF activity in cancer patients with VTE is higher than in matched cancer patients without VTE. This finding strongly supports previous observations of a relationship between elevated MP-TF activity and VTE in patients with cancer from small studies of selected cancer patients [1,[4][5][6].It is interesting that the large majority of patients who develop VTE during chemotherapy have normal MP-TF activity, suggesting that an acute thrombotic event itself is not the cause of an elevated MP-TF activity. Our data point to a contribution of cancer cells themselves as (in) direct cause of elevated MP-TF activity and ask for novel studies better designed to study prospectively the relationship between chemotherapy, elevated MP-TF activity and venous thrombosis. AcknowledgementsThis study was financially supported by a grant of the Dutch Cancer Foundation KWF/NKB UL-2006-3618. Disclosure of Conflict of InterestsThe authors state that they have no conflict of interest.

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supporting

confidence: 92%

supporting

confidence: 90%

mentioning

confidence: 99%

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Human alternatively spliced tissue factor is not secreted and does not trigger coagulation

Böing

Hau

Sturk

et al. 2009

Journal of Thrombosis and Haemostasis

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“…The mechanisms by which TFPI is increased in patients with cancer is not fully understood; however, increased synthesis by tumour cells or host cells is likely. Tumour‐associated macrophages 39 and various cancer cells have been shown to express TFPI 18, 142, 143, whereas small lung cell carcinoma, renal cell carcinoma and malignant melanoma did not 39. The absence of appropriately configured TF–FVII : Xa complex, required for TFPI‐binding, may be the cause.…”

Section: The Clinical Value Of Tfpimentioning

confidence: 99%

Tissue factor pathway inhibitor: structure, biology and involvement in disease

Lwaleed

Bass

2005

The Journal of Pathology

175

120

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Tissue factor (TF)-initiated coagulation plays a significant role in the pathophysiology of many diseases, including cancer and inflammation. Tissue factor pathway inhibitor (TFPI) is a plasma Kunitz-type serine protease inhibitor, which modulates initiations of coagulation induced by TF. In a factor (F) Xa-dependent feedback system, TFPI binds directly and inhibits the TF-FVII/FVIIa complex. Normally, TFPI exists in plasma both as a full-length molecule and as variably carboxy-terminal truncated forms. TFPI also circulates in complex with plasma lipoproteins. The levels and the dual inhibitor effect of TFPI on FXa and TF-FVII/FVIIa complex offers insight into the mechanisms of various pathological conditions triggered by TF. The use of selective pharmacological inhibitors has become an indispensable tool in experimental haemostasis and thrombosis research. In vivo administration of recombinant TFPI (rTFPI) in an experimental animal model prevents thrombosis (and re-thrombosis after thrombolysis), reduces mortality from E. coli-induced-septic shock, prevents fibrin deposition on subendothelial human matrix and protects against disseminated intravascular coagulation (DIC). Thus, TFPI may play an important role in modulating TF-induced thrombogenesis and it may also provide a unique therapeutic approach for prophylaxis and/or treatment of various diseases. In this review, we consider structural and biochemical aspects of the TFPI molecule and detail its inhibitory mechanisms and therapeutic implications in various disease conditions.

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“…Офици-ально датой ее признания считается 1865 г., когда французский врач А. Труссо опубликовал лекцию, в которой описал несколько случаев пальпируемых опухолей брюшной полости, сопровожда-ющихся наличием поверхностных тромбофлебитов, высказав ги-потезу о возможной гиперкоагуляции, связанной с опухолью [5]. Впоследствии эта гипотеза нашла подтверждение, но при этом было показано и противоположное влияние компонентов систе-мы свертывания на прогрессию опухоли [6,7]. На сегодняшний день многие механизмы этой двусторонней взаимосвязи уже из-учены.…”

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