Association between increased tumor necrosis factor alpha levels and acquired activated protein C resistance in patients with metastatic colorectal cancer

Ferroni, Patrizia; Riondino, Silvia; Portarena, Ilaria; Formica, Vincenzo; Farina, Francesca; Martini, Francesca; Massimiani, Gioia; Palmirotta, Raffaele; Roselli, Mario

doi:10.1007/s00384-012-1493-8

Cited by 16 publications

(14 citation statements)

References 27 publications

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“…Also, when comparing pre-and post-CRT levels of these cytokines, a significant increase in post-CRT IL-6 was observed in the Low-R, corroborating this hypothesis. IL-6 levels were also reported to be associated with poor prognosis in various types of cancer, including pancreatic, breast, ovarian and esophageal (15,35), and increased levels of TNF-α have been shown to correlate with poor prognosis in colorectal cancer patients (36,37). IL-6 has been shown to be associated with tumor stage, metastasis and survival of colorectal cancer patients (13)(14)(15)35).…”

Section: D Venous Invasionmentioning

confidence: 98%

Changes in the plasma levels of cytokines/chemokines for predicting the response to chemoradiation therapy in rectal cancer patients

et al. 2013

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In the present study, we aimed to characterize the predictive value of cytokines/chemokines in rectal cancer (RC) patients receiving chemoradiation therapy (CRT). Blood samples were obtained pre- and post-CRT from 35 patients with advanced RC, who received neoadjuvant CRT followed by surgery, and the correlation between plasma levels of cytokines/chemokines and the response to CRT was analyzed. The pre-CRT levels of soluble CD40-ligand (sCD40L) and the post-CRT levels of chemokine ligand-5 (CCL-5) were significantly associated with the depth of tumor invasion and with venous invasion. In addition, a significant decrease in sCD40L and CCL-5, as well as in platelet counts, was associated with a favorable response to CRT. A significant correlation between pre-CRT platelet counts and sCD40L was observed in patients with a favorable response. By contrast, higher post-CRT interleukin (IL)-6 was associated with a poor response. Platelets, immune system and cancer cells, cross-linked through various cytokines/chemokines, appear to play an important role in the response to CRT, and by understanding their roles, new approaches for the improvement of the therapy might be proposed.

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Section: D Venous Invasionmentioning

confidence: 98%

Changes in the plasma levels of cytokines/chemokines for predicting the response to chemoradiation therapy in rectal cancer patients

et al. 2013

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“…A number of small case-control studies demonstrated increased levels of pro-inflammatory, or decreased levels of anti-inflammatory, cytokines in patients at risk for DVT ( 61 , 63 , 45 ). Although in a larger, prospective population-based case-control study, no such associations were found ( 37 ).…”

Section: Cytokines and Vtementioning

confidence: 99%

Cytokines, Adhesion Molecules, and Matrix Metalloproteases as Predisposing, Diagnostic, and Prognostic Factors in Venous Thrombosis

et al. 2018

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The inflammatory response is a well-established part of, and a prerequisite for, venous thrombosis. To better understand the pathophysiology of venous thrombosis and to identify improved diagnostic biomarkers, further studies of the relationship between inflammation and coagulation are needed. We review previous studies concerning inflammatory biomarkers in venous thromboembolism, in particular cytokines, soluble adhesion molecules and matrix metalloproteases as predisposing, diagnostic and prognostic factors in venous thrombosis. Elevated cytokines and genetic alterations coding for cytokines are found in several patient cohorts which indicate that cytokines are involved as predisposing factors in venous thrombosis development. Increased levels of pro-inflammatory cytokines are detected both in animal models and in patients with acute venous thrombosis and clinical trials, although currently without evident diagnostic value. Adhesion molecules are crucial in the development of venous thrombosis, especially P-selectin seems important in initiating leukocyte accumulation and adhesion to endothelium for subsequent platelet accumulation. Several studies have demonstrated increased soluble P-selectin levels in patients with venous thrombosis, emphasizing its potential role as diagnostic marker and also as a therapeutic target. Matrix metalloproteases are essential effectors during venous thrombosis resolution and may impact vessel wall fibrosis, and together with their natural occurring inhibitors are crucial in acute and chronic thrombosis pathophysiology. Furthermore, studies in animal models of venous thrombosis have demonstrated anti-inflammatory treatment to be effective in terms of thrombus resolution and reduction of vessel wall damage, without increase in bleeding risk during the course of treatment. Thus, soluble mediators should be further investigated both as possible biomarkers and therapeutic targets in venous thromboembolic disease.

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“…PrC performs cytoprotective and antimetastatic effects independently of coagulation [37]. Association between increased incidence of thrombotic events and acquired resistance to PrC (APC), unrelated to factor V Leiden, has been observed in multiple myeloma and colorectal cancer [38,39]. There could be mechanisms of cell resistance due to the modification of the endothelial receptor and induction of APC under the influence of tumor proinflammatory cytokines [39,40].…”

Section: Suppression Of Natural Anticoagulant Mechanismsmentioning

confidence: 99%

Hemostatic System in Malignancy: Providing the “Soil” in Metastatic Niche Formation

Beleva¹,

Попов²,

Grudeva-Popova³

2016

Tumor Metastasis

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Malignancy arises and progresses in tight association with changes in the tumor microenvironment and deregulation of hemostatic system. Cancer induces hemostatic imbalance through production and secretion of procoagulant substances, suppression of anticoagulant mechanisms, endothelial activation, and angiogenic switch. Cancer cells are equipped with certain coagulation signaling receptors such as tissue factor TF and urokinase plasminogen activator receptor uPAR . Tissue factor as major initiator of coagulation, TF is considered the main cause for hypercoagulability in cancer. Constitutive TF expression by cancer cells is a hallmark of malignancy rendering tumors proangiogenic and prometastatic. TF fosters metastasis through coagulation-dependent pathways leading to fibrin deposition in the evolving premetastatic niche. TF has been identified as an independent predictor for metastatic development and adverse prognosis. uPAR Tissue overexpression of uPAR is demonstrated in almost all human cancers and is associated with advanced disease. Increased uPAR expression is driven by molecular events involving K-ras and SRC oncogenes. Transactivation of these receptors, mediated by binding to hemostatic proteins, activates intracellular signaling pathways, modulates gene expression and facilitates processes of tumor initiation, epithelial-to-mesenchymal transition, anoikis, and metastasis. By manipulating hemostatic processes, tumor induces tolerant host environment necessary for evasion of defense attacks, survival, and progression.

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Association between increased tumor necrosis factor alpha levels and acquired activated protein C resistance in patients with metastatic colorectal cancer

Cited by 16 publications

References 27 publications

Changes in the plasma levels of cytokines/chemokines for predicting the response to chemoradiation therapy in rectal cancer patients

Changes in the plasma levels of cytokines/chemokines for predicting the response to chemoradiation therapy in rectal cancer patients

Cytokines, Adhesion Molecules, and Matrix Metalloproteases as Predisposing, Diagnostic, and Prognostic Factors in Venous Thrombosis

Hemostatic System in Malignancy: Providing the “Soil” in Metastatic Niche Formation

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