80 research outputs found
Targeted gene therapy of nasopharyngeal cancer in vitro and in vivo by enhanced thymidine kinase expression driven by human TERT promoter and CMV enhancer
<p>Abstract</p> <p>Background/Aim</p> <p>To explore the therapeutic effects of thymidine kinase (TK) expressed by enhanced vector pGL3-basic- hTERTp-TK-EGFP-CMV driven by human telomerase reverse transcriptase promoter (hTERTp) as well as cytomegalovirus immediate early promoter enhancer (CMV).</p> <p>Materials/Methods</p> <p>Enhanced TK-EGFP expression was confirmed by fluorescent microscopy, real time PCR and telomerase activity. Its effects were examined by survival of tumor cells NPC 5-8F and MCF-7, index of xenograft implanted in nude mice and histology.</p> <p>Results</p> <p>Compared with non-enhanced vector pGL3-basic-TK-hTERTp-EGFP, TK expressed by the enhanced vector significantly decreased NPC 5-8F and MCF-7 cell survival rates after ganciclovir (GCV) treatment (p < 0.001) and tumor progress in nude mice with NPC xenograft and treated with GCV, without obvious toxicity to mouse liver and kidney.</p> <p>Conclusion</p> <p>The enhanced TK expression vector driven by hTERTp with CMV enhancer has brighter clinical potentials in nasopharyngeal carcinoma therapy than the non-enhanced vector.</p
Super-W(infinity) Asymptotic Symmetry of Higher-Spin AdS(3) Supergravity
We consider (2+1)-dimensional (N, M)-extended higher-spin anti-de Sitter
supergravity and study its asymptotic symmetries. The theory is described by
the Chern-Simons action based on a real, infinite-dimensional higher-spin
superalgebra. We specify consistent boundary conditions on the higher-spin
super-gauge connection corresponding to asymptotically anti-de Sitter
spacetimes. We then determine the residual gauge transformations that preserve
these asymptotic conditions and compute their Poisson bracket algebra. We find
that the asymptotic symmetry is enhanced from the higher-spin superalgebra to
some (N,M)-extended super-W(infinity) nonlinear superalgebra. The latter has
the same classical central charge as pure Einstein gravity. Special attention
is paid to the (1,1)-case. Truncation to the bosonic sector yields the
previously found W(infinity) algebra, while truncation to the underlying
finite-dimensional superalgebra reproduces the N-extended superconformal
algebra (in its nonlinear version for N>2). We discuss string theory
realization of these higher-spin anti-de Sitter supergravity theories as well
as relations to previous treatments of super-W(infinity) in the literature.Comment: References added. (N>2)-Extended supersymmetric models argued to be
rigid with respect to lambda-deformation. Comments on G(3)-case adde
Effects of histone deacetylase inhibitor FR901228 on expression level of telomerase reverse transcriptase in oral cancer
We speculated whether or not the expression level of telomerase reverse transcriptase (hTERT) would be modulated by agents targeting epigenetics in oral cancer cell lines. Although hTERT is known to be targeted by epigenetic changes, it remains unclear how chemoagents targeting epigenetics work on hTERT transcription. In the present study, the epigenetic effects of histone deacetylase (HDAC) inhibitor FR901228 on hTERT transcription were analysed by RT-PCR in oral cancer cell lines. The mRNA expression of hTERT was upregulated after exposure to FR901228 in hTERT-negative Hep2 cells, even in the hTERT highly expressed SAS and KB cells. Moreover, co-treatment of protein synthesis inhibitor cycloheximide (CHX) resulted in the induction of hTERT transcription by FR901228. This suggests that the induction of hTERT by FR901228 requires de novo protein synthesis to some extent and is more likely a direct than an indirect effect on epigenetic changes such as histone acetylation / deacetylation. We further examined the effect of FR901228 on c-myc protein, which is one of the main hTERT transcription activators. FR901228 repressed c-myc protein only in the absence of CHX, dependent of the enhancement of de novo protein synthesis. Our results indicate that c-myc protein is repressed indirectly by FR901228 but may not contribute FR901228-induced hTERT transcription. The present study showed that the HDAC inhibitor FR901228 induced the hTERT gene by a complex mechanism that involved other transcription factors except for c-myc, in addition to the inhibition of histone deacetylation
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