当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF COLORECTAL DISEASE期刊下所有文献 > Association between increased tumor necrosis factor alpha levels and acquired activated protein C resistance in patients with metastatic colorectal cancer.

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

Abstract：

PURPOSE:The purpose of this study was to investigate the possible association between tumor necrosis factor-α (TNF-α) levels and defects in the activated protein C (APC) system as a determinant of venous thromboembolism (VTE) in metastatic colorectal cancer patients (mCRC) undergoing chemotherapy. METHODS:TNF-α levels (measured by immunoassay) and abnormalities in the APC system [evaluated by an APC-dependent thrombin generation assay (ThromboPath-ThP)] were evaluated in 45 mCRC patients undergoing chemotherapy. VTE events were recorded during follow-up. RESULTS:TNF-α levels were increased (p < 0.01), and APC functionality was decreased (p < 0.0001) in mCRC patients compared to age- and sex-matched controls. An inverse correlation was observed between TNF-α and APC impairment in mCRC (p < 0.0001). TNF-α was confirmed as an independent predictor (p = 0.007) for APC abnormalities at multivariate regression analysis. Nine (20 %) of 45 mCRC patients experienced VTE during chemotherapy. Bayesian analysis of combined ThP/TNF-α showed a positive predictive value of 0.67 in predicting VTE (p = 0.01). Cox proportional hazards survival analysis confirmed the predictive value of combined ThP/TNF-α determination in VTE risk assessment of mCRC patients (either negative vs. both positive: HR = 0.02; p = 0.001), and Kaplan-Meier analysis demonstrated that mCRC patients with either negative TNF-α or ThP values prior to chemotherapy were less likely to experience VTE (13 %) than patients with abnormalities of both markers (67 %, p = 0.002). CONCLUSIONS:These results suggest that the host inflammatory response to cancer cells and/or tumor-derived cytokines could be responsible for an impairment of the APC system and a switch toward a pro-thrombotic state, which might predispose to the occurrence of VTE in mCRC patients undergoing chemotherapy.

journal_name

Int J Colorectal Dis

journal_title

International journal of colorectal disease

authors

Ferroni P,Riondino S,Portarena I,Formica V,La Farina F,Martini F,Massimiani G,Palmirotta R,Guadagni F,Roselli M

doi

10.1007/s00384-012-1493-8

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

1561-7

issue

eissn

0179-1958

issn

1432-1262

journal_volume

pub_type

杂志文章

在线工具

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