isoglobotrihexosylceramide and Neoplasm-Metastasis

isoglobotrihexosylceramide has been researched along with Neoplasm-Metastasis* in 1 studies

Other Studies

1 other study(ies) available for isoglobotrihexosylceramide and Neoplasm-Metastasis

Article	Year
Enhanced antitumor effects by chemical modified IGb3 analogues. Molecular cancer therapeutics, 2011, Volume: 10, Issue:8 Certain glycolipid antigens for natural killer T (NKT) cells can direct the overall cytokine balance of the immune response. However, the molecular mechanism of Th1- or Th2-biased cytokine secretion by NKT cells is still unknown. Previously, we synthesized isoglobotrihexosylceramide (iGb3) analogues by introducing a hydroxyl group at C4 on the ceramide portion of iGb3 to produce 4-HO-iGb3 or to further deoxylation on the terminal galactose to produce 4'''-dh-iGb3. Both modified iGb3, especially 4'''-dh-iGb3, stimulated more IFN-γ production by hepatic NKT cells, and thus elicited preferential Th1 responses. Here, we found that 4'''-dh-iGb3-loaded bone marrow-derived dendritic cells (DC) could significantly inhibit growth of subcutaneous melanoma and suppress lung metastasis in C57BL/6 mice compared with unmodified iGb3-loaded DCs. In investigating the mechanisms of this improved activity, we found that 4'''-dh-iGb3 stimulation increased STAT1 signaling by NKT cells, whereas the phosphorylation of Th2 type cytokine-associated transcription factor STAT6 signaling was not affected. Analysis of the structures of iGb3 and 4'''-dh-iGb3 revealed that 4'''-dh-iGb3 provides greater stability and affinity between glycolipid and CD1d or NKT TCR complex than iGb3. Thus, 4'''-dh-iGb3 can improve the antitumor effects of a DC-based vaccine possibly by stabilizing the CD1d/glycolipid/TCR complex and stimulating IFN-γ signaling of NKT cells. Furthermore, chemical modification of iGb3 can elicit Th1-biased responses by NKT cells, and 4'''-dh-iGb3 combined with a DC vaccine may serve as a potent new NKT-based therapy against tumors and infectious diseases. Topics: Animals; Antigens, CD1d; Antineoplastic Agents; Binding Sites; Dendritic Cells; Globosides; Killer Cells, Natural; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Models, Molecular; Neoplasm Metastasis; Protein Binding; Receptors, Antigen, T-Cell, alpha-beta; STAT1 Transcription Factor; T-Box Domain Proteins; Trihexosylceramides	2011

Article

Year

Enhanced antitumor effects by chemical modified IGb3 analogues.

Molecular cancer therapeutics, 2011, Volume: 10, Issue:8

Certain glycolipid antigens for natural killer T (NKT) cells can direct the overall cytokine balance of the immune response. However, the molecular mechanism of Th1- or Th2-biased cytokine secretion by NKT cells is still unknown. Previously, we synthesized isoglobotrihexosylceramide (iGb3) analogues by introducing a hydroxyl group at C4 on the ceramide portion of iGb3 to produce 4-HO-iGb3 or to further deoxylation on the terminal galactose to produce 4'''-dh-iGb3. Both modified iGb3, especially 4'''-dh-iGb3, stimulated more IFN-γ production by hepatic NKT cells, and thus elicited preferential Th1 responses. Here, we found that 4'''-dh-iGb3-loaded bone marrow-derived dendritic cells (DC) could significantly inhibit growth of subcutaneous melanoma and suppress lung metastasis in C57BL/6 mice compared with unmodified iGb3-loaded DCs. In investigating the mechanisms of this improved activity, we found that 4'''-dh-iGb3 stimulation increased STAT1 signaling by NKT cells, whereas the phosphorylation of Th2 type cytokine-associated transcription factor STAT6 signaling was not affected. Analysis of the structures of iGb3 and 4'''-dh-iGb3 revealed that 4'''-dh-iGb3 provides greater stability and affinity between glycolipid and CD1d or NKT TCR complex than iGb3. Thus, 4'''-dh-iGb3 can improve the antitumor effects of a DC-based vaccine possibly by stabilizing the CD1d/glycolipid/TCR complex and stimulating IFN-γ signaling of NKT cells. Furthermore, chemical modification of iGb3 can elicit Th1-biased responses by NKT cells, and 4'''-dh-iGb3 combined with a DC vaccine may serve as a potent new NKT-based therapy against tumors and infectious diseases.

Topics: Animals; Antigens, CD1d; Antineoplastic Agents; Binding Sites; Dendritic Cells; Globosides; Killer Cells, Natural; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Models, Molecular; Neoplasm Metastasis; Protein Binding; Receptors, Antigen, T-Cell, alpha-beta; STAT1 Transcription Factor; T-Box Domain Proteins; Trihexosylceramides

2011