Thrombotic and Inflammatory Mediators in Cancer Patients Are Downregulated by Enoxaparin. Biochip and Protein Array Analysis

The pathogenesis of cancer is known to upregulate inflammatory and thrombotic processes which contribute to the increased mortality in these patients. We hypothesized that the baseline inflammatory and thrombotic mediators are upregulated in cancer and treatment with LMWHs such as enoxaparin may downregulate these mediators. Methods: To test this hypothesis plasma samples were retrospectively analyzed from an open label multi dose active comparator parallel design study in which all patients (n=110) were initially treated with enoxaparin (1-1.5 mg/kg sc) for 5 days. These patients were subdivided into two groups. Group A continued to receive enoxaparin whereas Group B received warfarin. Baseline blood samples, 5 days and 12 weeks post treatment samples were analyzed using bio chip arrays (Randox analyzer) and protein chip array using surface enhanced laser desorption ionization (SELDI) technique.Results: In the cerebral biochip array analysis, levels of CRP, TNFRI, D DIMER, NGAL and TM were elevated at baseline which reduced after treatment with enoxaparin at three months except for NSE and TNFRI. In the cytokine biochip array, IL2, IL4, IL6, IL8, IL10, VEGF, IFNG, TNFA, IL1A, IL1B, MCP1 and EGF showed marked upregulation at baseline with enoxaparin treatment resulting in a decrease of IL6 alone. In contrast the warfarin treated group, both the cerebral and cytokine biochip array showed only marginal decreases.The baseline plasma samples from the patients recruited with multiple cancers in the Oncenox study showed a greater prevalence of the 11.6kDa biomarker (76%) with average amplitude of 23.6. The samples collected after 3 Months of enoxaparin treatment revealed markedly reduced prevalence (38%) and average amplitude of 5.4, whereas the warfarin treated group showed a modest decline in the 11-6kD a biomarker with a 52% prevalence and an average amplitude of 18.2. Conclusions: These results confirm that inflammatory and thrombotic mediators are differentially downregulated by treatment with enoxaparin in comparison to warfarin. The biochip and protein arrays provide unique tools to profile the known mediators and identify newer biomarkers. which may be useful in differentiating target sites for the newer drugs in cancer management.

No relevant conflicts of interest to declare.