Contribution of angiogenesis to the progression of colon cancer: possible inhibitory effect of angiogenesis inhibitor TNP-470 on tumor growth and hepatic metastasis.

The contribution of angiogenesis to tumor growth and hepatic metastasis of colorectal cancer was investigated by means of immunohistochemical study and in vitro and in vivo experiments. Colorectal cancer specimens from 30 patients with hepatic metastasis and 39 patients without hepatic metastasis were studied by staining with antibodies against factor VIII-related antigen. Microvessel count in patients with liver metastasis was significantly higher than in those without liver metastasis (p<0.005). The effect of TNP-470 was evaluated with in vitro and in vivo experiments using human colon cancer cell line, LM and the highly hepatic metastasis cell line, LM-H5. The effect of TNP-470 on the proliferation of the cancer cells and human umbilical vein endothelial cells (HUVECs) was examined. TNP-470 inhibited more sensitively the proliferation of HUVECs than cancer cells in vitro. IC50 was approximately 3 pg/ml in HUVECs and approximately 2 microg/ml in cancer cells. The effect of TNP-470 on the growth of xenografts and liver metastases by LM-H5 in nude mice was examined. TNP-470 (30 mg/kg) was administered by subcutaneous injection every third day for 4 weeks. TNP-470 inhibited both the growth of xenograft and the hepatic metastasis. The number of metastatic foci in the liver was 78.2+/-30.1 in the control group and 20.6+/-16.5 in the treated group. These results suggest that TNP-470 is a potent agent to inhibit tumor growth and hepatic metastasis of colon cancer.

The assessment of trigeminal sensory nerve paraesthesia after bilateral sagittal split osteotomy: modified somatosensory evoked potentials recording method.

Trigeminal neurosensory impairment is frequently observed following orthognathic surgery. The purpose of the present study is to visualize the degree of trigeminal nerve impairment following bilateral sagittal split osteotomy (BSSO). Twenty patients who underwent BSSO were in the present study. To record the modified somatosensory evoked potentials (SEP), two electrostimulation clips were applied. One clip was placed on the mucous surface of the lower lip and the other was placed on the skin surface. Each contact surface contained a separate 2 mm diameter silver anode and cathode attached to a 5 x 15 mm basement plate. The results obtained using this method revealed that complete recovery from neural impairment was observed in 7 cases (36.8%) on the right operative side and 4 (20.0%) on the left side at 6 months postoperatively. A definite delay in latency was observed on the left operative side at all the examination periods. The recovery period evaluated by the SEP method was longer than that of the objective two-point discrimination thresholds. Clinical records obtained showed considerable implications for trigeminal nerve function after BSSO.