Anticoagulants in cancer treatment: malignancy as a solid phase coagulopathy

Zacharski, Leo R.

doi:10.1016/s0304-3835(02)00258-6

Cited by 72 publications

(72 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, in the present study, we found that lung cancer cell lines, particularly small cell lung cancer cell lines, can also express the mRNA and protein of TAFI, suggesting that malignant cells may also be a direct source of this fibrinolytic inhibitor in cancer patients. In agreement with this, previous studies have also demonstrated that lung cancer cells, in particular small cell lung cancer cells, are capable of directly producing and releasing other pro-coagulant factors, such as tissue factor and proteases [1,5]. More abundant expression of TAFI antigen from small cell lung cancer cells may explain the significantly increased circulating levels of TAFI in patients with small cell lung cancer compared to those with adenocarcinoma and epidermoid carcinoma observed in the present study.…”

Section: Discussionsupporting

confidence: 92%

“…More abundant expression of TAFI antigen from small cell lung cancer cells may explain the significantly increased circulating levels of TAFI in patients with small cell lung cancer compared to those with adenocarcinoma and epidermoid carcinoma observed in the present study. In addition to causing systemic activation of the blood coagulation system, secretion of TAFI from cancer cells may increase intra-tumoral fibrin deposition and thus promote the growth and dissemination of tumor cells [1].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have demonstrated the tendency of clotting and fibrinolytic disorders to develop in patients with malignancy [1,2] The clinical presentation of thrombotic alterations in cancer patients may vary from the classic picture of consumptive coagulopathy or thromboembolism to low-grade intravascular coagulation [3,4]. Specific conditions associated with cancer, such as stasis due to prolonged immobilization, surgery, infections, vascular endothelium injury due to chemotherapeutic agents, and abnormalities of the blood coagulation system, contribute to the hypercoagulable and thrombophilic state of patients with cancer [5,6].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Increased circulating levels of thrombin‐activatable fibrinolysis inhibitor in lung cancer patients

et al. 2004

View full text Add to dashboard Cite

Impairment of fibrinolytic function plays an important role in the mechanism of thrombotic disorders in cancer patients. This study assessed the circulating level of thrombin-activatable fibrinolysis inhibitor in patients with lung cancer and its expression by several lung cancer cell lines. The plasma concentrations of thrombin-activatable fibrinolysis inhibitor were significantly increased in lung cancer patients compared to healthy subjects. The concentration of thrombin-activatable fibrinolysis inhibitor was particularly higher in patients with small cell carcinoma compared to those with adenocarcinoma or squamous cell carcinoma, and in cancer patients that responded to chemotherapy compared to nonresponders. In vitro studies showed more expression of thrombin-activatable fibrinolysis inhibitor in small cell carcinoma than in adenocarcinoma cell lines and more expression in lung cancer cell lines sensitive to anti-cancer agents than in resistant cell lines. This study suggests that thrombin-activatable fibrinolysis inhibitor, in part secreted from lung cancer cells, may play a role in the pathogenesis of thrombotic disorders in lung cancer patients.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Increased circulating levels of thrombin‐activatable fibrinolysis inhibitor in lung cancer patients

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Several individual constituents of thrombin-generating pathways have been implicated in neoplasia including coagulation factors VIIa, IXa, Xa and thrombin (IIa) (1)(2)(3)(4)(5). Thrombin in particular has multiple cellular effects including induction of cell proliferation and motility, enhancement of vascular permeability, deposition of matrix fibrin, promotion of tumor cell seeding, adhesion to endothelium and extracellular matrix and enhancement of the metastatic capacity of tumors (6,7).…”

Section: Introductionmentioning

confidence: 99%

“…Among the PAR family members, PAR 1 (11,12), PAR 3 (13) and PAR 4 (14) are targeted mainly by thrombin. PAR 2 (15) can be activated by trypsin, mast cell tryptase, neutrophil proteinase 3, tissue factor/factor VIIa/factor Xa, human kallikrein-related peptidases and membrane-tethered serine proteinase-1/matriptase 1, but not by thrombin (9,10). In the setting of cancer, the ability of thrombin to act via PARs was highlighted by the demonstration of PAR 1 expression in carcinosarcoma and melanoma cells (16), and during the last few years, growing evidence for a function of the PAR family in neoplasia has been obtained (17).…”

Section: Introductionmentioning

confidence: 99%

Green tea polyphenol epigallocatechin-3-gallate inhibits thrombin-induced hepatocellular carcinoma cell invasion and p42/p44-MAPKinase activation

Kaufmann

Henklein²,

Henklein³

et al. 2009

Oncol Rep

View full text Add to dashboard Cite

Abstract.Thrombin has been recently demonstrated to promote hepatocellular carcinoma (HCC) cell migration by activation of the proteinase-activated receptor (PAR) subtypes PAR 1 and PAR 4 suggesting a role of these proteinasereceptor systems in HCC progression. In this study, we investigated the effect of (-)-epigallocatechin-3-gallate (EGCG), the major polyphenolic compound of green tea on thrombin-PAR 1 /PAR 4 -mediated hepatocellular carcinoma cell invasion and p42/p44 MAPKinase activation. In this study we used the permanent liver carcinoma cell line HEP-3B and two primary cultures established from surgically resected HCCs. We found that stimulation of HCC cells with thrombin, the PAR 1 -selective activating peptide, TFLLRN-NH 2 , and the PAR 4 -selective activating peptide, AYPGKF-NH 2 , increased cell invasion across a Matrigel-coated membrane barrier and stimulated activation of p42/p44 MAPKinase phosphorylation. Both the effects on p42/p44 MAPKinases, and on cell invasiveness induced by thrombin and the PAR 1/4 subtype-selective agonist peptides were effectively blocked by EGCG. The results clearly identify EGCG as a potent inhibitor of the thrombin-PAR 1 /PAR 4 -p42/p44 MAPKinase invasive signaling axis in hepatocellular carcinoma cells as a previously unrecognized mode of action for EGCG in cancer cells. Moreover, the results suggest that (-)-epigal-locatechin-3-gallate might have therapeutic potential for hepatocellular carcinoma.

show abstract