scholarly journals Suppressive Effect of Juzentaihoto on Vascularization Induced by B16 Melanoma CellsIn VitroandIn Vivo

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Shintaro Ishikawa ◽  
Takako Ishikawa ◽  
Kazuhito Asano ◽  
Hiroshi Fujiwara ◽  
Mayumi Okada ◽  
...  
Keyword(s):  
Herbal Medicines ◽  
Suppressive Effect ◽  
B16 Melanoma ◽  
Vascular Endothelial ◽  
Internal Fluid ◽  
Cell Metastasis ◽  
Experimental Mouse ◽  
Therapeutic Mechanisms ◽  
Endothelial Growth Factor ◽  
Mouse System

Juzentaihoto (JTT) is well known to be one of Japanese herbal medicines, and used for the supplemental therapy of cancer patients with remarkable success. The present study, therefore, was undertaken to examine the possible therapeutic mechanisms of JTT on cancer using B16 melanoma cell (B16 cell)/experimental mouse system. JTT was well mixed with rodent chow at 3.0% concentrations, and was administered orally ad libitum. Administration of JTT was started one week before tumor cell injection and continued throughout the experiment. Administration of JTT into mice significantly inhibited tumor metastasis in lungs after intravenous injection of2×105B16 cells in a volume of 50 μL. JTT also significantly suppressed enlargement of tumor size in hind footpad after the subcutaneous injection of2×105(50 μL) B16 cells. In the second part of experiments, the chamber that containing B16 cells was buried in the murine back. In JTT administrated group, vascular endothelial growth factor (VEGF) of chamber internal fluid significantly decreased, and vascularization of chamber circumference was also inhibited. These results strongly suggest that oral administration of JTT caused decrease in the generation of VEGF, which is responsible for vascularization, and results in inhibition of B16 cell metastasis.

scholarly journals Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia

Blood ◽  
2009 ◽  
Vol 114 (4) ◽  
pp. 844-859 ◽  
Author(s):  
Hsin-Yu Fang ◽  
Russell Hughes ◽  
Craig Murdoch ◽  
Seth B. Coffelt ◽  
Subhra K. Biswas ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Nuclear Factor Κb ◽  
Atherosclerotic Plaques ◽  
Vascular Endothelial ◽  
Surface Receptors ◽  
Experimental Mouse ◽  
Angiopoietin 2 ◽  
Endothelial Growth Factor ◽  
Arthritic Joints

Abstract Ischemia exists in many diseased tissues, including arthritic joints, atherosclerotic plaques, and malignant tumors. Macrophages accumulate in these sites and up-regulate hypoxia-inducible transcription factors (HIFs) 1 and 2 in response to the hypoxia present. Here we show that the gene expression profile in primary human and murine macrophages changes markedly when they are exposed to hypoxia for 18 hours. For example, they were seen to up-regulate the cell surface receptors, CXCR4 and GLUT1, and the potent, tumor-promoting cytokines, vascular endothelial growth factor A, interleukin (IL)-1β and IL-8, adrenomedullin, CXCR4, and angiopoietin-2. Hypoxia also stimulated their expression and/or phosphorylation of various proteins in the nuclear factor-κB (NF-κB) signaling pathway. We then used both genetic and pharmacologic methods to manipulate the levels of HIFs-1α and 2α or NF-κB in primary macrophages to elucidate their role in the hypoxic induction of many of these key genes. These studies showed that both HIF-1 and -2, but not NF-κB, are important transcriptional effectors regulating the responses of macrophages to such a period of hypoxia. Further studies using experimental mouse models are now warranted to investigate the role of such macrophage responses in the progression of various diseased tissues, such as malignant tumors.

scholarly journals VEGF-A produced by chronically inflamed tissue induces lymphangiogenesis in draining lymph nodes

Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3158-3167 ◽  
Author(s):  
Cornelia Halin ◽  
Nadja E. Tobler ◽  
Benjamin Vigl ◽  
Lawrence F. Brown ◽  
Michael Detmar
Keyword(s):  
Lymph Nodes ◽  
Neutralizing Antibody ◽  
Delayed Type Hypersensitivity ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Protein Levels ◽  
Cell Metastasis ◽  
Endothelial Growth Factor ◽  
Draining Lymph Nodes ◽  
Inflamed Tissue

Abstract Lymphangiogenesis is involved in tumor cell metastasis and plays a major role in chronic inflammatory disorders. To investigate the role of lymphangiogenesis in inflammation, we induced and maintained delayed-type hypersensitivity (DTH) reactions in the ears of mice and then analyzed the resulting lymphangiogenesis in the inflamed tissue and draining lymph nodes (LNs) by quantitative fluorescence-activated cell sorting (FACS) and by immunofluorescence. Long-lasting inflammation induced a significant increase in the number of lymphatic endothelial cells, not only in the inflamed ears but also in the ear-draining auricular LNs. Inflammation-induced lymphangiogenesis was potently blocked by systemic administration of a vascular endothelial growth factor (VEGF)-A neutralizing antibody. Surprisingly, tissue inflammation specifically induced LN lymphangiogenesis but not LN angiogenesis. These findings were explained by analysis of both VEGF-A protein and mRNA levels, which revealed that VEGF-A was expressed at high mRNA and protein levels in inflamed ears but that expression was increased only at the protein level in activated LNs. Inflammation-induced lymphangiogenesis in LNs was independent of the presence of nodal B lymphocytes, as shown in B cell-deficient mice. Our data reveal that chronic inflammation actively induces lymphangiogenesis in LNs, which is controlled remotely, by lymphangiogenic factors produced at the site of inflammation.

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