The prothrombotic state in cancer: pathogenic mechanisms

Cicco, Marcello De

doi:10.1016/j.critrevonc.2003.10.003

Cited by 213 publications

(144 citation statements)

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“…Tissue factor, a transmembrane receptor lipophilic phospholipoprotien with potent procoagulant activity, reportedly becomes constitutively expressed in some cancer tissues (Rao, 1992;De Cicco, 2004). Expression of TF on tumour cells, tumour-associated macrophages and endothelial cells is upregulated in response to cytokines, such as tumour necrosis factor and interleukin-1 (Grignani and Maiolo, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Regarding the mechanisms underlying VTE formation in cancer patients, several tumour cell procoagulant activities have been identified that may act at steps in blood coagulation pathways (De Cicco, 2004). Numerous studies have suggested that tissue factor (TF) may play an important role in the pathogenesis of hypercoagulable states in patients with cancer (Rao, 1992), and TF expression has been confirmed in some cancer tissues by immunohistochemistry (Callander et al, 1992;Ueno et al, 2000).…”

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confidence: 99%

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Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer

et al. 2007

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Ovarian cancer, and clear cell carcinoma in particular, reportedly increases the risk of venous thromboembolism (VTE). However, the mechanisms remain unclear. Tissue factor (TF) supposedly represents a major factor in the procoagulant activities of cancer cells. The present study examined the involvement of TF expression in VTE for patients with ovarian cancer. Subjects comprised 32 consecutive patients (mean age 49.8 years) with histologically confirmed ovarian cancer. Presence of VTE was examined using a combination of clinical features, D-dimer levels and venous ultrasonography. Immunohistochemical analysis was used to evaluate TF expression into 4 degrees. Venous thromboembolism was identified in 10 of the 32 patients (31%), including five of the 11 patients with clear cell carcinoma. Tissue factor expression was detected in cancer tissues from 24 patients and displayed significant correlations with VTE development (P ¼ 0.0003), D-dimer concentration (P ¼ 0.003) and clear cell carcinoma (Po0.05). Multivariate analysis identified TF expression as an independent predictive factor of VTE development (Po0.05). Tissue factor (TF) expression is a possible determinant of VTE development in ovarian cancer. In particular, clear cell carcinoma may produce excessive levels of TF and is more likely to develop VTE.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer

et al. 2007

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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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“…Individuals with cancer have an increased risk of developing thrombosis, and activation of the coagulation system accelerates cancer progression (Rickles et al 2003). Many tumors cause coagulation dysfunction leading to production of procoagulant substances (De Cicco 2004). SCUBE1 may be a procoagulant substance in cancer.…”

Section: Introductionmentioning

confidence: 99%

Elevated Serum Levels of SCUBE1, a Marker for Coagulation, in Patients with Breast Cancer

Topcu

Kavgacı

Özdemir

et al. 2015

Tohoku J. Exp. Med.

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Breast cancer (BC) is the most common cancer among women and a major cause of death. Signal Peptide-Cub-Epidermal growth factor domain-containing protein-1 (SCUBE1) is secreted under hypoxia and inflammatory conditions from platelet alpha granules. Its biological function is uncertain, although it may be a procoagulant substance in cancer patients. SCUBE1 is useful for identifying thrombotic diseases, including cancers and acute coronary syndromes. D-dimer reflects the relationship between coagulation activation and fibrinolysis; namely, thrombosis and D-dimer levels are closely linked. This is the first investigation of the potential diagnostic and prognostic value of SCUBE1 levels in patients with BC. Fifty patients and 33 age-matched and body mass index-matched healthy controls were enrolled. Blood samples were collected before chemotherapy regimens commenced. Serum SCUBE1 and D-dimer levels were measured before adjuvant chemotherapy and were compared to the healthy controls. SCUBE1 levels were determined using an enzyme-linked immunosorbent assay (ELISA) method. SCUBE1 and D-dimer levels were significantly higher in patients than in the controls (p = 0.03 and p < 0.001, respectively). A cut-off value of 1.55 ng/mL for SCUBE1 was associated with 62% sensitivity and 72.7% specificity and with positive predictive value of 77.5% and negative predictive value of 55.8%. Two patients with high SCUBE1 and D-dimer levels also developed pulmonary embolism. SCUBE1 may indicate hypercoagulability in patients with BC and thus help identify patients at greater risk of thrombosis and requiring anti-thrombosis treatment. SCUBE1 may also be used as an assistant test for identifying patients at risk of BC.

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The prothrombotic state in cancer: pathogenic mechanisms

Cited by 213 publications

References 103 publications

Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer

Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer

Crosstalk between cancer and haemostasis

Elevated Serum Levels of SCUBE1, a Marker for Coagulation, in Patients with Breast Cancer

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