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2016 ; 7
(51
): 85291-85305
Nephropedia Template TP
gab.com Text
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Thrombin inhibition and cisplatin block tumor progression in ovarian cancer by
alleviating the immunosuppressive microenvironment
#MMPMID27852034
Alexander ET
; Minton AR
; Peters MC
; van Ryn J
; Gilmour SK
Oncotarget
2016[Dec]; 7
(51
): 85291-85305
PMID27852034
show ga
Cancer is often associated with an increased risk of thrombotic complications
which can be aggravated by treatment with chemotherapeutics such as cisplatin.
Multiple lines of evidence suggest that thrombin activity promotes tumor growth
and metastasis. We examined the effect of co-treatment with dabigatran etexilate,
a direct thrombin inhibitor, and cisplatin using the murine ID8 ovarian cancer
model. Mice receiving co-treatment with both dabigatran etexilate and low dose
cisplatin had significantly smaller tumors, developed less ascites and had lower
levels of circulating activated platelets and tissue factor (TF) positive
microparticles than those treated with dabigatran etexilate or cisplatin alone.
Co-treatment with dabigatran etexilate and cisplatin significantly decreased the
number of Gr1+/CD11b+ myeloid derived suppresser cells and CD11b+/CD11c+
dendritic cells in the ascites of ID8 tumor-bearing mice. Co-treatment also
significantly reduced levels of pro-tumorigenic cytokines including TGF-?, VEGF,
IL-6, IL-10, and MCP-1 in the ascites while increasing IFN-? production by CD8+
effector T cells in the tumor ascites. These results demonstrate that
co-treatment with dabigatran etexilate significantly augments the anti-tumor
activity of cisplatin in ovarian tumor progression by alleviating the
immunosuppressive microenvironment, suggesting that thrombin may be a potential
therapeutic target for treatment of ovarian cancer.