Heterogeneity-related anticancer therapy response differences in metastatic colon carcinoma: new hints to tumor-site-based personalized cancer therapy.

BACKGROUND/AIMS: Heterogeneity in primary tumor and related metastases may result in different response to anticancer therapy. Previous work revealed that there were heterogeneity in primary colon carcinoma and matched lymphatic and hepatic metastases. Whether such heterogeneity in primary colon carcinoma and corresponding lymphatic and hepatic metastases would result in different response to anticancer therapy is unknown. METHODOLOGY: To investigate whether the heterogeneity in primary colon carcinoma and matched lymphatic and hepatic metastases would result in different response to anticancer therapy, patient-derived tumor tissue (PDTT) xenograft models of colon carcinoma with lymphatic and hepatic metastases were used to evaluate the response to VEGF-targeted therapy (bevacizumab) in combination with chemotherapy (capecitabine). RESULTS: All xenografts of primary colon carcinoma and corresponding lymphatic and hepatic metastases in nude mice responded to VEGF-targeted therapy in combination with chemotherapy. However, chemotherapy alone resulted in significantly higher tumor growth inhibition rate in xenogfafts of primary colon carcinoma than that of corresponding lymphatic and hepatic metastasis (p < 0.01). VEGF-targeted therapy in combination with chemotherapy resulted in significantly higher tumor growth inhibition rate in xenogfafts of colon carcinoma lymphatic metastasis than that of corresponding primary colon carcinoma and hepatic metastasis (p < 0.001). CONCLUSIONS: Our results demonstrate that primary colon carcinoma and its corresponding lymphatic and hepatic metastases have different response rate to chemotherapy and to VEGF-targeted therapy in combination with chemotherapy. This study provides us new hints to tumor-site-based personalized cancer therapy in metastatic colon carcinoma.

Yangxueqingnao particles inhibit rat vascular smooth muscle cell proliferation induced by lysophosphatidic acid.

OBJECTIVE: To observe the effect of Yangxueqingnao particles on rat vascular smooth muscle cell (VSMC) proliferation induced by lysophosphatidic acid (LPA). METHODS: The amount of (3)H-TdR ((3)H-thymidine) admixed in cultured rat VSMC was measured and mitogen-activated protein kinase (MAPK) activity and lipid peroxidation end product malondialdehyde (MDA) content of the VSMC were assayed. RESULTS: 1x10(-9), 1x10(-8), 1x10(-7) mol/L LPA in a concentration dependent manner, induced the amount of (3)H-TdR admixed, MAP kinase activity, and MDA content of the cultured rat VSMC to increase. However, 5%, 10%, and 15% Yangxueqingnao serum preincubation resulted in a decrease of 23.0%, 42.0%, and 52.0% (P<0.01) respectively in the amount of (3)H-TdR admixed, a decline in VSMC MAP kinase activity of 13.9% (P<0.05), 29.6% (P<0.01), and 48.9% (P<0.01) respectively, and also, a decrease in MDA content of VSMC of 19.4%, 24.7%, and 43.2% (P<0.01) respectively, in the 1x10(-7) mol/L LPA-treated VSMC. CONCLUSIONS: LPA activates the proliferation and lipid peroxidation of VSMC in a concentration dependent manner. The LPA-induced VSMC proliferation is related to the activity of MAP kinases, enzymes involved in an intracellular signalling pathway. The results of the present study showed that Yangxueqingnao particles can effectively inhibit LPA-induced VSMC proliferation, MAP kinase activation, and reduce lipid peroxidative lesion.

[Effect of Chrysanthemum morifolium Ramat on apoptosis of bovine aortic smooth muscle cells]

OBJECTIVE: To observe the effect and the mechanism of Chrysanthemum morifolium Ramat on apoptosis of bovine aortic smooth muscle cells. METHODS: Vascular smooth muscle cells were isolated from thoracic aorta of fetal calf and cultured, then incubated with different concentration of Chrysanthemum morifolium Ramat. Apoptosis was measured by flow cytometry. SOD and MDA were measured by spectrophotometer. RESULTS: We found that: (1) the number of apoptotic cells was reduced from (4.425+/-0.624)% to (2.875+/-0.640)% in Chrysanthemum morifolium Ramat group, in a concentration dependent manner; (2) the value of SOD was increased from (1.683+/-0.149)X10(4) U/L to (2.297+/-0.230)X104 U/L and the value of MDA was reduced from(166.454+/-56.805)&mgr;mol/L to (73.068+/-27.203)&mgr;mol/L in Chrysanthemum morifolium Ramat group, also in a concentration dependent manner. CONCLUSION: Chrysanthemum morifolium Ramat can inhibit apoptosis of vascular smooth muscle cells in a concentration-dependent manner.