Procoagulant factors in patients with cancer

Molnar, Soledad; Guglielmone, Hugo; Lavarda, Marcelo; Rízzí, María; Jarchum, Gustavo

doi:10.1080/10245330701521416

Cited by 24 publications

(27 citation statements)

References 12 publications

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“…These disorders of coagulation leading to DIC in lung cancer might be attributed to the fact that chronic inflammation increases thrombin production, which is reflected in TAT levels. Another mechanism for increased thrombin production in lung cancer could be activation of the X factor by elevated cancer procoagulant level, which may affect the coagulation system however, we did not evaluate cancer procoagulant in this study. Nevertheless, elevated thrombin levels from chronic inflammation in lung cancer increases fibrinogen and fibrin levels, which promotes the production of FDP and D‐dimer.…”

Section: Discussionmentioning

confidence: 98%

Risk factors for disseminated intravascular coagulation in patients with lung cancer

et al. 2018

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BackgroundThe mortality rate from disseminated intravascular coagulation (DIC) is higher in patients with lung cancer than in non‐lung cancer patients. Moreover, the prevalence of DIC varies among the pathologic types of lung cancer. This study analyzed the relationship between coagulation factors and the pathologic types of lung cancer.MethodsTwenty‐six patients with progressive, inoperable stage IIB or higher lung cancer (20 men, 6 women; mean age 71 years; 11 Adeno, 10 squamous cell carcinoma, and 5 small cell carcinoma) and five healthy volunteers without respiratory disease (3 men, 2 women; mean age 72 years) were enrolled in the study. Blood samples were collected at lung cancer diagnosis, before treatment.ResultsWhite blood cell count, platelet count, serum C‐reactive protein, fibrin/fibrinogen degradation products, fibrinogen, thrombin‐antithrombin complex, and D‐dimer levels differed significantly between lung cancer patients and the control group, but not among the pathologic types of lung cancer. Thrombomodulin levels were significantly higher in patients with Adeno and squamous cell carcinoma than in those with small cell carcinoma (P < 0.05 and P < 0.01, respectively). Antithrombin levels were significantly lower in patients with squamous cell carcinoma than in those with Adeno (P < 0.05).ConclusionCoagulation disorders may develop secondary to chronic inflammation in patients with progressive lung cancer. DIC in lung cancer may be attributed to changes in anticoagulation factors, such as thrombomodulin and antithrombin, but not in other coagulation factors.

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Section: Discussionmentioning

confidence: 98%

Risk factors for disseminated intravascular coagulation in patients with lung cancer

et al. 2018

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“…Specifically, the tumor-associated protease cancer procoagulant is secreted from numerous malignancies including colorectal cancer into the bloodstream [21]. Under in vivo conditions this can cause paraneoplastic coagulopathy throughout cleavage and activation of the coagulation factor X heavy chain (P00742) [22]. The reporter peptide CP-RP comprises the cleavage site WKPYDAAD that is part of the coagulation factor X and is preferably cleaved in serum specimens of tumor patients [8].…”

Section: Discussionmentioning

confidence: 99%

Functional protease profiling with reporter peptides in serum specimens of colorectal cancer patients: demonstration of its routine diagnostic applicability

Findeisen

Costina

Yepes

et al. 2012

J Exp Clin Cancer Res

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BackgroundThe progression of many solid tumors is characterized by the release of tumor-associated proteases and the detection of tumor specific proteolytic activity in serum specimens is a promising diagnostic tool in oncology. Here we describe a mass spectrometry-based functional proteomic profiling approach that tracks the ex-vivo degradation of a synthetic endoprotease substrate in serum specimens of colorectal tumor patients.MethodsA reporter peptide (RP) with the amino acid sequence WKPYDAAD was synthesized that has a known cleavage site for the cysteine-endopeptidase cancer procoagulant (EC 3.4.22.26). The RP was added to serum specimens from colorectal cancer patients (n = 30), inflammatory controls (n = 30) and healthy controls (n = 30) and incubated under strictly standardized conditions. The proteolytic fragment of the RP was quantified with liquid chromatography / mass spectrometry (LC/MS).ResultsRP-spiking showed good intra- and inter-day reproducibility with coefficients of variation (CVs) that did not exceed a value of 10%. The calibration curve for the anchor peptide was linear in the concentration range of 0.4 – 50 μmol/L. The median concentration of the RP-fragment in serum specimens from tumor patients (TU: 17.6 μmol/L, SD 9.0) was significantly higher when compared to non-malignant inflammatory controls (IC: 11.1 μmol/L, SD 6.1) and healthy controls (HC: 10.3 μmol/L, SD 3.1). Highest area under receiver operating characteristic (AUROC) values were seen for discrimination of TU versus HC (0.89) followed by TU versus IC (0.77). IC and HC could barely be separated indicated by an AUROC value of 0.57. The proteolytic activity towards the RP was conserved in serum specimens that were kept at room temperature for up to 24 hours prior to the analysis.ConclusionThe proteolytic cleavage of reporter peptides is a surrogate marker for tumor associated proteolytic activity in serum specimens of cancer patients. A simple, robust and highly reproducible LC/MS method has been developed that allows the quantification of proteolytic fragments in serum specimens. The preanalytical impact of sample handling is minimal as the tumor-associated proteolytic activity towards the reporter peptide is stable for at least up to 24 h. Taken together, the functional protease profiling shows characteristics that are in line with routinely performed diagnostic assays. Further work will focus on the identification of additional reporter peptides for the construction of a multiplex assay to increase diagnostic accuracy of the functional protease profiling.

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“…Upregulation of tissue factor (TF), the primary initiator of the coagulation cascade, has a key role in this process (Molnar et al, 2007). In normal physiological conditions, TF, a 47 kDa transmembrane protein, is constitutively expressed by subendothelial cells (such as pericytes, smooth muscle cells and fibroblasts), whereas vascular endothelial cells (ECs) and intravascular cells do not express TF (Abe et al, 1999).…”

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confidence: 99%

Angiogenesis is associated with the onset of hyperplasia in human ductal breast disease

et al. 2009

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BACKGROUND: The precise timing of the angiogenic switch and the role of angiogenesis in the development of breast malignancy is currently unknown. METHODS: Therefore, the expression of CD31 (pan endothelial cells (ECs)), endoglin (actively proliferating ECs), hypoxia-inducible factor-1 (HIF-1a), vascular endothelial growth factor-A (VEGF) and tissue factor (TF) were quantified in 140 surgical specimens comprising normal human breast, benign and pre-malignant hyperplastic tissue, in situ and invasive breast cancer specimens. RESULTS: Significant increases in angiogenesis (microvessel density) were observed between normal and benign hyperplastic breast tissue (Po0.005), and between in situ and invasive carcinomas (Po0.0005). In addition, significant increases in proliferating ECs were observed in benign hyperplastic breast compared with normal breast (Po0.05) cancers and in invasive compared with in situ cancers (Po0.005). Hypoxia-inducible factor-1a, VEGF and TF expression were significantly associated with increases in both angiogenesis and proliferating ECs (Po0.05). Moreover, HIF-1a was expressed by 60 -75% of the hyperplastic lesions, and a significant association was observed between VEGF and TF in ECs (Po0.005) and invasive tumour cells (Po0.01). CONCLUSIONS: These findings are the first to suggest that the angiogenic switch, associated with increases in HIF-1a, VEGF and TF expression, occurs at the onset of hyperplasia in the mammary duct, although the greatest increase in angiogenesis occurs with the development of invasion.

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Procoagulant factors in patients with cancer

Cited by 24 publications

References 12 publications

Risk factors for disseminated intravascular coagulation in patients with lung cancer

Risk factors for disseminated intravascular coagulation in patients with lung cancer

Functional protease profiling with reporter peptides in serum specimens of colorectal cancer patients: demonstration of its routine diagnostic applicability

Angiogenesis is associated with the onset of hyperplasia in human ductal breast disease

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