Pathogenesis, clinical and laboratory aspects of thrombosis in cancer

Franchini, Massimo; Montagnana, Martina; Targher, Giovanni; Manzato, Franco; Lippi, Giuseppe

doi:10.1007/s11239-007-0028-6

Cited by 61 publications

(51 citation statements)

References 96 publications

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“…The activation of coagulation in cancer patients is widely implicated in both tumour progression and the development of thrombosis [31]. High levels of plasma D-dimer have been associated with poor prognosis in several malignant diseases, including lung pancreas, prostate, gastric, colorectal, and breast cancer [19, 20, 32, 33].…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of plasma D-dimer predict a worse outcome in patients with nasopharyngeal carcinoma

et al. 2014

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BackgroundHemostatic alterations occur during the development of cancer. Plasma D-dimer is a hypercoagulability and fibrinolytic system marker that is increased in patients with various solid tumours. The aim of this study was to evaluate the hemostatic status of nasopharyngeal carcinoma (NPC) patients by assessing plasma D-dimer levels to investigate its value as a prognostic marker.MethodsWe retrospectively analysed 717 patients with nasopharyngeal carcinoma, and we applied Cox regression and log-rank tests to assess the association of D-dimer levels with disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS). D-dimer levels were measured using a quantitative D-dimer latex agglutination assay.ResultsUsing the 3rd quartile values (0.8 μg/L) as the optimal cut-offs, we found that patients with high D-dimer levels have a shorter 3-year DFS, (79%, 95%CI (73.1–84.9)) vs. (69%, 95%CI (59.2–78.8)), DMFS (87%, 95%CI (83.1–90.9)) vs. (77%, 95%CI (69.2–84.8)), and overall survival (82%, 95%CI (76.1–87.9)) vs. (76%, 95%CI (66.2–85.8)). Multivariate analysis revealed that pre-treatment D-dimer levels and EBV DNA were significant independent factors for DFS, DMFS, and OS in NPC patients. Subgroup analyses indicated that the plasma D-dimer levels could effectively stratify patient prognosis for early cancer, advanced stage cancer, and patients with EBV DNA ≥4000 copies/ml.ConclusionsHigh D-dimer levels were associated with poor disease-free survival, distant metastasis-free survival, overall survival, and increased risk of mortality in NPC patients. Prospective trials are required to assess the prognostic value of D-dimer levels.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-583) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Elevated levels of plasma D-dimer predict a worse outcome in patients with nasopharyngeal carcinoma

et al. 2014

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“…Cancer activates the coagulation cascade and conversely, coagulation factors play a role in the progression of cancer [12]. A number of genes mediating inflammation and coagulation have been shown to be differentially expressed in the peritoneal tissues of EOC patients compared to benign stroma [13].…”

Section: Introductionmentioning

confidence: 99%

Thrombin promotes epithelial ovarian cancer cell invasion by inducing epithelial-mesenchymal transition

Zhong

Zhang

et al. 2013

J Gynecol Oncol

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ObjectiveOver-expression of thrombin in ovarian cancer cells is associated with poor prognosis. In this study, we investigated the role of thrombin in inducing epithelial-mesenchymal transition (EMT) in SKOV3 epithelial ovarian cancer cells.MethodsAfter thrombin treatment SKOV3 cells were subjected to western blots, reverse-transcription PCR, and enzyme-linked immunosorbent assay to quantify EMT-related proteins, mRNA expression of SMAD2, DKK1, and sFRP1, and the secretion of matrix metalloproteinases (MMPs) and cytokines. Meanwhile, invasion ability was evaluated using transwell assays.ResultsThe results indicated a dose- and time-dependent down-regulation of E-cadherin and upregulation of N-cadherin and vimentin in thrombin-treated SKOV3 cells, compared with the thrombin-free control group (p<0.05). There was a dose- and time-dependent increase in the levels of SMAD2 and DKK1 mRNAs and a decrease in the levels of sFRP1 mRNA in thrombin-treated SKOV3 cells compared to control cells (p<0.05). Thrombin-treated SKOV3 cells exhibited increased secretion of MMP-9, MMP-2, interleukin (IL)-8, and IL-6 and increased invasion compared to untreated cells (p<0.05). Thrombin altered the morphology of SKOV3 cells to a spindle-like phenotype. Addition of hirudin to thrombin-treated cells reversed the effects of thrombin.ConclusionThrombin induced EMT and promoted the invasion of SKOV3 cells, possibly via distinct signaling pathways. Hirudin inhibited the effects of thrombin, suggesting that anticoagulant therapy could be a novel therapeutic strategy for ovarian carcinoma.

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“…While, in a subgroup of cancer patients, activation of the coagulation protease cascade may become clinically apparent as venous or arterial thromboembolism or decompensated disseminated intravascular coagulation (DIC), almost all patients with advanced tumours show laboratory evidence of low-grade systemic coagulation activation, as indicated, for example, by elevated plasma D-dimer (4,5). In this regard it is noteworthy that several studies have linked enhanced intravascular coagulation activation to adverse clinical outcomes in patients with various types of malignancies (6)(7)(8)(9).…”

Section: Zusammenfassungmentioning

confidence: 99%

“…In most cancer patients, systemic inflammation is reflected by laboratory evidence of an acute-phase reaction, as indicated by elevated levels of fibrinogen and C-reactive protein, and becomes microscopically apparent by enhanced infiltration of the tumour microenvironment by lymphocytes, macrophages, and polymorphonuclear leukocytes (4,5,17). While inflammation plays a critical role in molecular carcinogenesis (18,19), as clinically illustrated, for example, by the high incidence of colorectal cancer in patients suffering from ulcerative colitis, malignant tumours are typically referred to as wounds that never heal due to constant irritation of the surrounding organ tissue.…”

Section: Zusammenfassungmentioning

confidence: 99%

Crosstalk between cancer and haemostasis

Bokemeyer¹

2012

Hamostaseologie

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SummaryCancer is characterized by bidirectional interrelations between tumour progression, coagulation activation, and inflammation. Tissue factor (TF), the principal initiator of the coagulation protease cascade, is centrally positioned in this complex triangular network due to its pleiotropic effects in haemostasis, angiogenesis, and haematogenous metastasis. While formation of macroscopic thrombi is the correlate of cancer-associated venous thromboembolism (VTE), a major healthcare burden in clinical haematology and oncology, microvascular thrombosis appears to be critically important to blood-borne tumour cell dissemination. In this regard, expression of TF in malignant tissues as well as shedding of TFbearing microparticles into the circulation are thought to be regulated by defined genetic events relevant to pathological cancer progression, thus directly linking Trousseau’s syndrome to molecular tumourigenesis.Because pharmacological inhibition of the TF pathway in selective tumour types and patient subgroups would be in line with the modern concept of individualized, targeted anti-cancer therapy, this review will focus on the role of TF in tumour biology and cancer-associated VTE.

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Pathogenesis, clinical and laboratory aspects of thrombosis in cancer

Cited by 61 publications

References 96 publications

Elevated levels of plasma D-dimer predict a worse outcome in patients with nasopharyngeal carcinoma

Elevated levels of plasma D-dimer predict a worse outcome in patients with nasopharyngeal carcinoma

Thrombin promotes epithelial ovarian cancer cell invasion by inducing epithelial-mesenchymal transition

Crosstalk between cancer and haemostasis

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