| Gastric cancer is one of the most common diseases that greatly threaten human life. According to the statistical data, the incidence of gastric cancer accounts the first in alimentary tract and the third of total carcinomas, which is increasing steadly. Surgical resection, of which the relapse and metastasis are common, is the main therapeutic method for gastric cancer by now. The five-year survival rate of advanced gastric cancer with radical resection is 40%. Relapse and metastasis are main causes of death for gastric cancer patients and lymphatic metastasis is the most important way. Invasion and metastasis that are the leading cause for tumor death are important biological features of malignant tumor. Invasion and metastasis are closely related processes during tumor growth and invasion is an intrinsic factor of tumor metastasis. Passing through the biological barrier is the committed step for the dynamic process of invasion and metastasis. Firstly, cancer cells adhere to the basement membrane and (or) extracellular matrix, then several proteinases are released and activated to degrade the basement membrane and extracellular matrix, at last, cancer cells migrate to target tissues and clone into metastatic focus with the aid of chemokines, autocrine and paracrine growth factors. Cancer cells may invade lymphatic vessels directly and both the primary and newly born lymphatic vessels are the pathway for lymphatic metastasis of cancer cells. Shedding from primary region, cancer cells may be transferred to hilum of lymph node through blood circulation and be captured in lymph nodes to form metastasis. The more of the invaded cancer cells in blood vessels, the more of the possibility of lymph node involved. But the incidence of this indirect metastasis way is fairly small than the former. So, with regard to gastric cancer, the lymphatic metastasis will be affected by the expression of adhesive and invasive related factors, the microvessel density and lymphatic microvessel density of tumor. d-Limonene is purified monoterpene from tangerine peel, its scientific name is 1-methyl-4- isopropyl- cyclohexene, molecular formula is C10H16, and molecular weight is 136.23. The content of d-limonene in tangerine peel essential oil is more than 90 percent and the purity is more than 97 percent. d-Limonene has prevention and cure effects on chemo-induced breast cancer, liver cancer, lung cancer, gastric cancer, colon cancer and pancreatic cancer in rodent animal. With the poisonless, extensive and edible features, d-limonene receives widely attention. The anticancer mechanisms of d-limonene include: induce the expression of metabolic enzyme to detoxicate the carcinogen; induce the apoptosis and redifferentiation of cancer cells and (or) inhibit the isopropylizasion of protein transferase for cell growth. But, with respect to the metastasis, especially lymphatic metastasis, study on the effect of d-limonene has never been reported now. Recently, study for cancer lymphatic metastasis receives much more attention. Several specific markers for lymphatic vessel endothelium such as vascular endothelial growth factor receptor 3 (VEGFR-3), LYVE-1, and Podoplanin have been identified which make the differentiation of lymphatic vessel and blood vessel into realization. Up to now, few are known for the mechanisms of tumor lymphatic metastasis. At present, vascular endothelial growth factor C (VEGF-C), a member of vascular endothelial growth factor family, is regarded as specific growth factor for lymphatic endothelium. VEGF-C may activate its specific receptor VEGFR-3, which located in lymphatic endothelial cells, to induce the proliferation of lymphatic endothelial cells and the lymphangiogenesis through MEK/ERK and PI3-kinase/AKT pathway. For lymphatic vessels lack of tight junction and continuous basement membrane, it is easy for tumor cells to enter the lymphatic vessels through intercellular space. The bond of VEGF-C expressed by tumor cell to its receptor VEGFR-3 may promote the lymphangiogenesis and the increased lymphat... |
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