We report isolation of a novel tumor-reversing gene, tentatively named SVS-1, encoding a protein of 820 amino acids with localization on the plasma membrane as a type I transmembrane protein.

The effect of the benzylic structure of lignan on antioxidant activity was evaluated. Secoisolariciresinol (1) and 3,4-bis(4-hydroxy-3-methoxybenzyl)tetrahydrofuran (2), which have two secondary benzylic positions without oxygen, showed the highest antioxidant activity. Optically active verrucosin (4) was synthesized for the first time in this experiment.

(1-4) Class I enzymes (topo I, EC 5.99.1.2) act by making a transient break in one DNA strand, allowing the DNA to swivel and release torsional strain, changing the linking number by steps of one.(2,4) Class II enzymes (topo II, EC 5.99.1.3) make transient breaks in both strands of one DNA molecule, allowing the passage of another DNA duplex through the gap, changing the linking number by steps of two.(1-3) These enzymes are crucial for cellular genetic processes such as DNA replication, transcription, recombination, and chromosome segregation at mitosis.It has long been accepted that topos are valuable targets of cancer chemotherapeutics.(2-5) Several classes of topo inhibitors have been introduced into cancer clinics as potent anticancer drugs, including camptothecin (CPT) derivatives (e.g. irinotecan and topotecan) inhibiting topo I (4) and anthracyclines (e.g. doxorubicin and mitoxantorone), epipodophyllotoxins (e.g. etoposide , aminoacridines (e.g. m-AMSA) and ellipticines targeting topo II.(4,5) These agents are active in both hematological and solid malignancies. The activity of these agents is thought to result from stabilization of the DNA /topo cleavable complex (CC), an intermediate in the catalytic cycle of the enzymes, (2,5,6) resulting ultimately in apoptosis. A number of new topo inhibitors have recently been reported that do not stabilize CC. Thus, two general mechanistic classes of topo inhibitors, especially for topo II, have recently been described: (7) (1) classical topo 'poisons' that stabilize CC and stimulate single-or double-strand cleavage of DNA, such as CPT and its derivatives, indolocarbazoles for topo I, and for topos I and II; and (2) catalytic inhibitors that prevent the catalytic cycle of the enzymes at steps other than cleavage intermediates, such as dioxopiperazines, (7,9,10) aclarubicin, (11) intoplicin, (12) and F11782.(13) Some of these compounds are dual inhibitors of topos I and II. The catalytic inhibitors of topo II, merbarone (14,15) and dioxopiperazines, (9,10) have been extensively studied and have been shown to inhibit the reopening of the closed clamp formed by the enzyme around DNA by inhibiting the ATPase activity of the enzyme, thus sequestering the enzyme within the cell. (7,16,17)

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We focused on the biological activity of the collagen extracts obtained from the giant edible jellyfish, Nemopilema nomurai. Jellyfish collagen extracts stimulates the production of immunoglobulins (Igs) and cytokines by human hybridoma cells and human peripheral blood lymphocytes. Therefore, we examined the immunoregulatory function of jellyfish collagen extracts in mice. Intake of jellyfish collagen extracts facilitated the Ig production activity of lymphocytes from spleen and Peyer's patch. Furthermore, the levels of Igs in the serum clearly increased after the administration of jellyfish collagen extracts. Intake of bovine collagen from Achilles' tendon also activated lymphocytes activity in mice. The activity of total and antigen-specific Ig production in splenocytes from OVA-challenged mice was also enhanced by collagen intake. However, the total and OVA-specific IgE levels in the serum were not affected by the collagen intake. These results suggested that jellyfish collagen extracts stimulates an immune response in vivo, without inducing allergic complications.

Lysozyme from hen egg has been reported to possess an anti-inflammatory effect. However, little is known about its detailed mechanism. The mechanism of anti-inflammatory effect of lysozyme was examined in this study. When mouse macrophage-like cell line RAW264.7 cells and mouse peritoneal macrophages were activated with lipopolysaccharide (LPS) and then treated with lysozyme, the production of tumor necrosis factor-α and interleukin-6 was significantly suppressed. The effect was induced by suppressing the gene expression levels of both cytokines. Phagocytosis activity of peritoneal macrophages was not altered by the treatment with lysozyme, suggesting that lysozyme shows the anti-inflammatory effect without inhibiting the phagocytotic response of macrophages. In addition, lysozyme inhibited phosphorylation of c-jun N-terminal kinase (JNK) and was taken up by macrophages within 1 h after treatment of the cells with lysozyme. Overall results suggest that lysozyme is taken up intracellularly and suppresses LPS-induced inflammatory responses by inhibiting JNK phosphorylation.