کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4303917 1288490 2009 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of Tissue Factor—Factor VIIa Proteolytic Activity Blunts Hepatic Metastasis in Colorectal Cancer
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی عمل جراحی
پیش نمایش صفحه اول مقاله
Inhibition of Tissue Factor—Factor VIIa Proteolytic Activity Blunts Hepatic Metastasis in Colorectal Cancer
چکیده انگلیسی

BackgroundExpression of the principal initiator of coagulation, tissue factor (TF), by colorectal cancer (CRC) cells is involved in tumoral angiogenesis and metastasis progression, after binding of factor VIIa (FVIIa) to TF and generation of TF-FVIIa activity. We thus hypothesized that inhibition of the TF pathway by active site-blocked FVIIa (FFR-FVIIa) may prevent the development of hepatic metastasis in CRC.MethodsRat tumoral cells (DHDK12 proB cells) expressing high levels of TF were injected in the portal vein in syngenic BDIX rats. Rats received intraperitoneal injection of either FFR-FVIIa, from d 3 to d 7 (adjuvant treatment) (n = 19), or solvent buffer (n = 18) (control group). Additionally, cancer cells were infused subcutaneously in 20 other rats, which were assigned to FFR-FVIIa adjuvant treatment (n = 10), or buffer treatment (n = 10). Macroscopic and histological analysis was performed at d 14.ResultsIn the control group, infusion of cancer cells resulted in development of macroscopic hepatic tumors in 17/18 rats. In the adjuvant FFR-FVIIa group, macroscopic hepatic tumors were visible on the liver surface in 3/19 rats (P = 0.002 versus control). All rats with subcutaneous injection of proB cells exhibited macroscopic tumors, with no significant difference between the control and the treated ones.ConclusionInhibition of the proteolytic activity of TF-FVIIa complex blunted hematogenous hepatic metastasis, suggesting that TF-FVIIa is a relevant target for the prevention of hepatic metastasis in CRC. TF-blocking agents should be investigated as adjuvant treatment in this setting.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Surgical Research - Volume 153, Issue 2, 15 May 2009, Pages 239–245
نویسندگان
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