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This study aimed to assess the effects of curcumin on lymphatic vessel density (LVD) in an in vivo model of gastric cancer using the gastric cancer cell line, SGC-7901. Gastric tumor-bearing nude mice were treated with saline or 40, 80, or 160 mg kg(-1) day(-1) curcumin for 8 weeks. The results indicated that the tumor volumes were significantly lower in mice treated with 80 and 160 mg kg(-1) day(-1) curcumin as compared with that of the control group (both P < 0.001). In addition, both 80 and 160 mg kg(-1) day(-1) curcumin significantly reduced LVD (both P < 0.01). Although immunohistochemical analysis showed that curcumin did not significantly alter the expression of prospero homeobox 1 (Prox-1), podoplanin, and vascular endothelial growth factor receptor 3 (VEGFR-3), 160 mg kg(-1) day(-1) curcumin significantly decreased the expression of Prox-1, podoplanin, and VEGFR-3 levels as detected by Western blot analysis (P ≤ 0.03). Downregulation of lymphatic vessel endothelial receptor 1 (LYVE-1), Prox-1, podoplanin, and VEGFR-3 mRNA expression by curcumin was also detected (all P < 0.05). Furthermore, the apoptosis rates of tumor cells increased with curcumin in a concentration-dependent manner (all P < 0.001). Thus, curcumin may inhibit gastric cancer lymph node metastasis. Our findings provide theoretical evidence and an experimental basis for further analysis of the clinical application of curcumin in the therapy of gastric cancer.
This study aimed to assess the effects of curcumin on lymphatic vessel density (LVD) in an in vivo model of gastric cancer using the gastric cancer cell line, SGC-7901. Gastric tumor-bearing nude mice were treated with saline or 40, 80, or 160 mg kg(-1) day(-1) curcumin for 8 weeks. The results indicated that the tumor volumes were significantly lower in mice treated with 80 and 160 mg kg(-1) day(-1) curcumin as compared with that of the control group (both P < 0.001). In addition, both 80 and 160 mg kg(-1) day(-1) curcumin significantly reduced LVD (both P < 0.01). Although immunohistochemical analysis showed that curcumin did not significantly alter the expression of prospero homeobox 1 (Prox-1), podoplanin, and vascular endothelial growth factor receptor 3 (VEGFR-3), 160 mg kg(-1) day(-1) curcumin significantly decreased the expression of Prox-1, podoplanin, and VEGFR-3 levels as detected by Western blot analysis (P ≤ 0.03). Downregulation of lymphatic vessel endothelial receptor 1 (LYVE-1), Prox-1, podoplanin, and VEGFR-3 mRNA expression by curcumin was also detected (all P < 0.05). Furthermore, the apoptosis rates of tumor cells increased with curcumin in a concentration-dependent manner (all P < 0.001). Thus, curcumin may inhibit gastric cancer lymph node metastasis. Our findings provide theoretical evidence and an experimental basis for further analysis of the clinical application of curcumin in the therapy of gastric cancer.
The lymphatic system is the primary pathway of metastasis for most human cancers. Recent research efforts in studying lymphangiogenesis have suggested the existence of a relationship between lymphatic vessel density and patient survival. However, current methodology of lymphangiogenesis quantification is still characterised by high intra-and interobserver variability. For the amount of lymphatic vessels in a tumour to be a clinically useful parameter, a reliable quantification technique needs to be developed. With this consensus report, we therefore would like to initiate discussion on the standardisation of the immunohistochemical method for lymphangiogenesis assessment. Metastasis is the leading cause of cancer mortality. Metastatic cancer cells can escape from their site of origin and spread to distant organs through invasion of the vascular system and/or the lymphatic system. Tumour vascularisation is widely accepted as a bona fide indicator of tumour growth, metastases and patient survival. In 1996, Peter Vermeulen et al (1996) published a first international consensus on the methodology and criteria of the evaluation of angiogenesis quantification in solid tumours and 5 years later, a second consensus report, in which new concepts and mechanisms of tumour vascularisation were integrated, appeared (Vermeulen et al, 2002). Both reports were aimed at improving the standardisation of angiogenesis quantification in order to allow intratumourous microvessel density to be applied as a prognostic indicator and, moreover, as a reliable predictor of the risk of malignant transformation of premalignant lesions and of response to cancer treatment. Contrary to angiogenesis, the de novo formation of lymphatic vessels or lymphangiogenesis and its role in promoting the metastatic spread of tumour cells has only recently become a focal point of cancer research with an increasing number of studies showing a relationship between patient survival and lymphatic density in different tumour types. In order to confirm the potential prognostic value of lymphangiogenesis in patients with cancer, a quantification method that is characterised by a low intra-and interobserver variability needs to be developed. In this first consensus report, we would like to provide an overview of current concepts of the lymphatic vasculature and its regulating factors and propose guidelines for the estimation of the ongoing lymphangiogenesis in solid human tumour sections.
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