Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A lipoteichoic acid-related molecule OK-PSA is an active component of OK-432, a Streptococcus-derived anticancer immunotherapeutic agent. In the present study, we first examined the effect of OK-PSA on the maturation of dendritic cells (DCs) in vitro by using the DCs derived from 5 healthy donors and 10 patients with head and neck cancer with or without expression of toll-like receptor 4 (TLR4) or MD-2 mRNA. OK-PSA treatment effectively increased the surface expression of MHC class II, CD80, CD83, and CD86. OK-PSA-stimulated DCs secreted the cytokines that can induce helper T-cell 1 (Th1)-type T-cell response, and stimulated allogeneic T cells to produce IFN-gamma and to elicit an allogeneic antigen-specific cytotoxicity. These activities almost depended on expression of TLR4 and MD-2 genes. We next investigated the in vivo anticancer effect of intratumoral administration of syngeneic DCs followed by OK-PSA against established tumors in mice. C57BL/6 mice, which express wild-type TLR4, and C57BL/6-derived TLR4-knockout (TLR4(-/-)) mice were used. Although OK-PSA accelerated the antitumor effect of intratumoral DC administration in wild-type mice bearing syngeneic tumors, the antitumor effect of OK-PSA as well as of the combination therapy with DCs and OK-PSA was not significant in TLR4(-/-) mice. Interestingly, an administration of wild-type-mouse-derived DCs followed by OK-PSA exhibited a marked antitumor effect even in the TLR4(-/-) mice. These findings suggest that OK-PSA may be a potent adjuvant for local DC therapy, and that DC therapy followed by OK-PSA is able to elicit anticancer activity even in a TLR4-deficient host when TLR4 is expressed only in DCs injected intratumorally.
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PMID:Expression of toll-like receptor 4 on dendritic cells is significant for anticancer effect of dendritic cell-based immunotherapy in combination with an active component of OK-432, a streptococcal preparation. 1528 56

A lipoteichoic acid-related molecule OK-PSA is an active component of OK-432. In the in vitro experiments, OK-PSA enhanced expression of MHC class II, CD80 and CD86, as well as IL-12 production on dendritic cells (DCs) were derived from wild-type mice, but not from TLR4-deficient (TLR4-/-) mice. Next we examined the in vivo anti-cancer effect of intratumoral administration of syngeneic DCs followed by OK-PSA against established tumors in mice. Although OK-PSA augmented anti-tumor effect of DC administration in tumor-bearing wild-type mice, anti-tumor effect of DCs and OK-PSA was not significant in TLR4-/- mice. Interestingly, an administration of wild-type mice-derived DCs followed by OK-PSA exhibited a marked anti-tumor effect even in TLR4-/- mice. These findings suggest that OK-PSA may be a potential adjuvant for local DC therapy, and that DC therapy followed by OK-PSA is able to elicit anti-cancer activity even in TLR4-deficient host when TLR4 is expressed only in DCs injected intratumorally.
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PMID:[Anti-cancer effect of an intratumoral injection of dendritic cells expressing TLR4 in combination with an active component of OK-432 in TLR4-deficient mice]. 1555 10