thromboplastin and Intestinal-Neoplasms

Recombinant nematode anticoagulant protein c2 (rNAPc2) is a specific inhibitor of tissue factor (TF)/factor VIIa complex with novel antithrombotic activity. TF is highly expressed in human colorectal tumors, and levels are positively correlated with disease progression.. To explore the therapeutic potential and mechanism of action of rNAPc2 during tumor growth and metastasis, we tested rNAPc2 in several experimental colorectal cancer models in mice.. Administration of rNAPc2 inhibited pulmonary metastasis in mice systemically disseminated with CT26 murine colon carcinoma cells in a dose-dependent fashion. Combining rNAPc2 with the cytotoxic agent 5-fluorouracil or bevacizumab (humanized anti-vascular endothelial growth factor monoclonal antibody) resulted in additive growth inhibition and simultaneous reduction of microvessel density in HCT116 human colorectal tumor xenografts in nude mice. Furthermore, rNAPc2 potentiated CPT-11 in inhibiting hepatic metastasis in nude mice with portal vein injection of HCT116 tumor cells. Long-term administration of rNAPc2 significantly suppressed spontaneous formation of intestinal tumors in Apc(Min/+) mice. Using a RNA interference approach, we showed that TF expression is necessary for rNAPc2-mediated inhibition of HCT116 human colorectal tumor xenograft growth in nude mice, indicating that the antitumor effect of rNAPc2 may be transduced through TF that is expressed on tumor cells.. rNAPc2 is a potent anticancer agent when used in combination with chemotherapy or antiangiogenic therapy in mouse models of colorectal cancer, and TF positivity appears to be required for its activity.

Topics: Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bevacizumab; Cell Line, Tumor; Colorectal Neoplasms; Disease Progression; Female; Fluorouracil; Helminth Proteins; Humans; Intestinal Neoplasms; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Thromboplastin; Xenograft Model Antitumor Assays

Tissue factor (TF), which normally safeguards vascular integrity by inducing hemostasis upon injury, has received widespread attention in the pathogenesis of cancer progression and metastasis. Aberrantly expressed TF in cancer cells has been reported to be associated with advanced stages of malignancy in various cancers.. The expression of TF and microvessel density (MVD) were immunohistochemically evaluated in 207 gastric cancers, and their relationship with clinicopathological features was examined.. TF was preferentially expressed (41.8%) in intestinal-type cancer at a significantly higher rate than that in diffuse-type cancer (12.1%, P<0.0001). The expression of TF was associated with advanced stage of disease and showed a positive correlation with a higher rate of lymphatic and venous invasion and lymphatic metastasis in intestinal-type, but not in diffuse-type carcinoma. Moreover, TF expression was associated with high MVD in the tumor and a worse outcome only in intestinal-type carcinoma.. TF may be critically involved in tumor progression in intestinal-type, but not in diffuse-type, gastric carcinoma. The difference in clinical features between these two histological types might be partially dependent on TF expression profile.

Topics: Adenocarcinoma; Aged; Carcinoma, Signet Ring Cell; Female; Gastrectomy; Humans; Intestinal Neoplasms; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Microcirculation; Middle Aged; Neoplasm Invasiveness; Prognosis; Stomach Neoplasms; Thromboplastin

To study the changes of hemostatic molecular markers in patients with gastric or intestinal cancer for elucidating their clinical significance.. The plasma levels of tissue factor (TF), thrombin antithrombin complex (TAT), tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), urokinase plasminogen activator receptor (u-PAR) and plasmin antiplasmin complex (PAP) were measured by ELISA. Gene transcription of TF, t-PA, u-PA mRNA were detected by real-time RT-PCR.. The plasma levels of TF, TAT, u-PA, u-PAR and PAP were elevated in gastric or intestinal cancer patients (P < 0.05), while u-PA, u-PAR remarkably increased in patients with local infiltration, lymph node involvement or distal metastasis (P < 0.01). Plasma level of TF, TAT, PAP were remained higher than control even after surgery. TF, u-PA mRNA were higher (P < 0.01) and t-PA was lower (P > 0.05) in gastric or intestinal cancer compared to normal tissue.. Their existed over expression of TF and u-PA, increasing formation of thrombin and plasminogen in gastric or intestinal cancer patients. Hypercoagulability and hyperfibrinolysis were important factors related with metastasis potential of gastric or intestinal cancer. t-PA may be a character of well differentiated tissue. Quantitative detection of TF and u-PA gene expression by the method of real-time RT-PCR is feasible for them as observation markers in gastric or intestinal cancer patients.

Topics: Adult; Blood Coagulation; Female; Humans; Intestinal Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stomach Neoplasms; Thromboplastin; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

Topics: Adenoma; Biomarkers, Tumor; Humans; Intestinal Neoplasms; Intestine, Large; Male; Neoplasms; Prognosis; Prostatic Neoplasms; Thromboplastin