E-Only Section

Formation of new blood vessels from preexisting vasculature is an indispensable process in tumor initiation, invasion, and metastasis. Novel therapeutic approaches target endothelial cells involved in the process of angiogenesis, due to their genetic stability relative to the rapidly mutating drug-resistant cancer cells. In the present study, we investigated the effect of an active fraction from Emilia sonchifolia, belonging to the family Asteraceae, a plant well known for its antiinflammatory and antitumor effects, on the inhibition of tumor-specific angiogenesis. Administration of the active fraction from E sonchifolia (AFES; 5 mg/kg, body weight, intraperitoneally) containing the major compound γ-humulene significantly inhibited B16F10 melanomainduced capillary formation in C57BL/6 mice. The level of serum vascular endothelial growth factor and serum proinflammatory cytokines such as interleukin-1β, interleukin-6, tumor necrosis factor-α, and granulocytemacrophage colony-stimulating factor were also reduced significantly. At the same time, administration of AFES significantly enhanced the production of antiangiogenic factors such as tissue inhibitor of matrix metalloproteinase-1. Dose-dependent reduction can be seen in the budding and expansion of microvessels from rat thoracic aorta by AFES treatment. Inhibition of the activation of proenzyme to active enzyme of matrix metalloproteinase along with a successful reduction of proliferation, invasion, and migration of human umbilical vein endothelial cells demonstrated the antiangiogenic effect of AFES in vitro. To date, no study has examined the antiangiogenic activity of this plant with already wellknown anti-inflammatory and antitumor effects. Results obtained in the present study by using both in vivo and in vitro angiogenic models altogether proved the inhibitory effect of AFES on tumor-specific neovessel formation. Immune Cell–Conditioned Media Suppress Prostate Cancer PC-3 Cell Growth Correlating With Decreased Proinf lammatory/Anti-inflammatory Cytokine Ratios in the Media Using 5 Selected Crude Polysaccharides Hsiao-Chien Lin, MS1 and Jin-Yuarn Lin, PhD1 DOI: 10.1177/1534735415627923 Abstract Five different crude polysaccharides from guava seed (GSPS), bitter buckwheat (BBPS), common buckwheat (CBPS), red Formosa lambsquarters (RFLPS), and yellow Formosa lambsquarters (YFLPS) were isolated to treat human prostate cancer PC-3 cells via direct action or tumor immunotherapy. The splenocyteand macrophageconditioned media (SCM and MCM) were prepared using individual selected polysaccharides, and then SCM or MCM was further collected to treat PC-3 cells. The relationship between PC-3 cell growth and Th1/Th2 cytokines in SCM as well as proinflammatory/antiinflammatory cytokine secretion profiles in MCM were delineated. The results showed that all 5 selected polysaccharides did not significantly inhibit PC-3 cell growth via direct action. However, SCM or MCM cultured in the absence or presence of 5 selected polysaccharides significantly (P < .05) inhibited PC-3 cell growth. MCM cultured with 5 polysaccharides dose dependently enhanced their inhibitory effects on the viabilities of PC-3 cells than those cultured without polysaccharides. There was a significant (P < .05) negative correlation between PC-3 cell viabilities and (interleukin [IL]-6 + tumor necrosis factor [TNF]-α)/ IL-10 level ratios in the corresponding MCM, implying that macrophages suppress PC-3 cell growth through decreasing secretion ratios of proinflammatory/antiinflammatory cytokines in a tumor microenvironment.Five different crude polysaccharides from guava seed (GSPS), bitter buckwheat (BBPS), common buckwheat (CBPS), red Formosa lambsquarters (RFLPS), and yellow Formosa lambsquarters (YFLPS) were isolated to treat human prostate cancer PC-3 cells via direct action or tumor immunotherapy. The splenocyteand macrophageconditioned media (SCM and MCM) were prepared using individual selected polysaccharides, and then SCM or MCM was further collected to treat PC-3 cells. The relationship between PC-3 cell growth and Th1/Th2 cytokines in SCM as well as proinflammatory/antiinflammatory cytokine secretion profiles in MCM were delineated. The results showed that all 5 selected polysaccharides did not significantly inhibit PC-3 cell growth via direct action. However, SCM or MCM cultured in the absence or presence of 5 selected polysaccharides significantly (P < .05) inhibited PC-3 cell growth. MCM cultured with 5 polysaccharides dose dependently enhanced their inhibitory effects on the viabilities of PC-3 cells than those cultured without polysaccharides. There was a significant (P < .05) negative correlation between PC-3 cell viabilities and (interleukin [IL]-6 + tumor necrosis factor [TNF]-α)/ IL-10 level ratios in the corresponding MCM, implying that macrophages suppress PC-3 cell growth through decreasing secretion ratios of proinflammatory/antiinflammatory cytokines in a tumor microenvironment. Chemopreventive Activity of MGN-3/ Biobran Against Chemical Induction of Glandular Stomach Carcinogenesis in Rats and Its Apoptotic Effect in Gastric