AIM: To investigate the in vitro antitumor effect of adenovirus-mediated small interfering RNAs (siRNAs) on pancreatic cancer and the associated mechanism. METHODS: A 63-nucleotide (nt) oligonucleotide encoding K-rasv...AIM: To investigate the in vitro antitumor effect of adenovirus-mediated small interfering RNAs (siRNAs) on pancreatic cancer and the associated mechanism. METHODS: A 63-nucleotide (nt) oligonucleotide encoding K-rasval12 and specific siRNA were introduced into pSilencer 3.1-H1, then the H1-RNA promoter and siRNA coding insert were subcloned into pAdTrack to get plasmid pAdTrackH1-Avasval12. After homologous recombination in bacteria and transfections of such plasmids into a mammalian packaging cell line 293, siRNA expressing adenovirus Adh1-K-rasval12 was obtained. Stable suppression of K-rasval12 was detected by Northern blot and Western blot. Apoptosis in Panc-1 cells was detected by flow cytometry. RESULTS: We obtained adenovirus AdHl-K-rasval12 carrying the pSilencer 3.1-H1 cassette, which could mediate gene silencing. Through siRNA targeted K-rasval12, the oncogenic phenotype of cancer cells was reversed. Flow cytometry showed that apoptotic index of Panc-1 cells was significantly higher in the AdH1-K-rasval12-treatment group (18.70% at 72 h post-infection, 49.55% at 96 h post-infection) compared to the control groups (3.47%, 3.98% at 72 and 96 h post-infection of AdH1-empty, respectively; 4.21%, 3.78% at 72 and 96 h post-infection of AdHl-p53, respectively) (P<0.05). CONCLUSION: These results demonstrate that adenoviral vectors can be used to mediate RNA interference (RNAi) to induce persistent loss of functional phenotypes. In gene therapy, the selective down-regulation of only the mutant version of a gene allows for highly specific effects on tumor cells, while leaving the normal cells untouched. In addition, the apoptosis of pancreatic cancer cell line Panc-1 can be induced after AdH1-K-rasval12 infection. This kind of adenovirus based on RNAi might be a promising vector for cancer therapy.展开更多
The phenomenon of the resonant activation （RA） of a particle over a fluctuating potential barrier with a four-value noise is investigated. It is shown that the mean first passage time （MFPT） displays six minima as...The phenomenon of the resonant activation （RA） of a particle over a fluctuating potential barrier with a four-value noise is investigated. It is shown that the mean first passage time （MFPT） displays six minima as the function of the transition rates γ1, γ2, γ3, γ4, γ5, and 76 of the four-value noise, respectively. In addition, the effect of other parameters of the system, such as the noise strength D of the additive Gaussian white noise and the parameter value a, b, c, and d of the four-value noise, on the RAs is also investigated.展开更多
Based on a membrane-bulk coupling cell model proposed by Gomez-Marin et al. [ Phys. Rev. Lett. 98 （2007） 168303], the cooperative effects of noise and coupling on the stochastic dynamical behavior are investigated. ...Based on a membrane-bulk coupling cell model proposed by Gomez-Marin et al. [ Phys. Rev. Lett. 98 （2007） 168303], the cooperative effects of noise and coupling on the stochastic dynamical behavior are investigated. For parameters in a certain region, the oscillation can be induced by the cooperative effect of noise and coupling. Whether considering the coupling or not, corresponding coherence resonance phenomena are observed. Furthermore, the effects of two coupling parameters, cell size L and coupling intensity k, on the noise-induced oscillation of membranes are studied. Contrary effects of noise are found in and out of the deterministic oscillatory regions.展开更多
In this paper, we derive a unified scattering theory model for current noise based on the equivalent contact model of the scattering region. Our model seamlessly covers the whole range of transport regimes from cohere...In this paper, we derive a unified scattering theory model for current noise based on the equivalent contact model of the scattering region. Our model seamlessly covers the whole range of transport regimes from coherent transport to incoherent transport and it also includes the effects of Pauli exclusion and Coulomb interaction on shot noise.展开更多
基金Supported by National Natural Science Foundation of China, No.30271473
文摘AIM: To investigate the in vitro antitumor effect of adenovirus-mediated small interfering RNAs (siRNAs) on pancreatic cancer and the associated mechanism. METHODS: A 63-nucleotide (nt) oligonucleotide encoding K-rasval12 and specific siRNA were introduced into pSilencer 3.1-H1, then the H1-RNA promoter and siRNA coding insert were subcloned into pAdTrack to get plasmid pAdTrackH1-Avasval12. After homologous recombination in bacteria and transfections of such plasmids into a mammalian packaging cell line 293, siRNA expressing adenovirus Adh1-K-rasval12 was obtained. Stable suppression of K-rasval12 was detected by Northern blot and Western blot. Apoptosis in Panc-1 cells was detected by flow cytometry. RESULTS: We obtained adenovirus AdHl-K-rasval12 carrying the pSilencer 3.1-H1 cassette, which could mediate gene silencing. Through siRNA targeted K-rasval12, the oncogenic phenotype of cancer cells was reversed. Flow cytometry showed that apoptotic index of Panc-1 cells was significantly higher in the AdH1-K-rasval12-treatment group (18.70% at 72 h post-infection, 49.55% at 96 h post-infection) compared to the control groups (3.47%, 3.98% at 72 and 96 h post-infection of AdH1-empty, respectively; 4.21%, 3.78% at 72 and 96 h post-infection of AdHl-p53, respectively) (P<0.05). CONCLUSION: These results demonstrate that adenoviral vectors can be used to mediate RNA interference (RNAi) to induce persistent loss of functional phenotypes. In gene therapy, the selective down-regulation of only the mutant version of a gene allows for highly specific effects on tumor cells, while leaving the normal cells untouched. In addition, the apoptosis of pancreatic cancer cell line Panc-1 can be induced after AdH1-K-rasval12 infection. This kind of adenovirus based on RNAi might be a promising vector for cancer therapy.
基金National Natural Science Foundation of China under Grant No.10375009K.C.Wong Magna Fund in Ningbo University of ChinaNational Natural Science Foundation of China under Grant No.10647134
文摘The phenomenon of the resonant activation （RA） of a particle over a fluctuating potential barrier with a four-value noise is investigated. It is shown that the mean first passage time （MFPT） displays six minima as the function of the transition rates γ1, γ2, γ3, γ4, γ5, and 76 of the four-value noise, respectively. In addition, the effect of other parameters of the system, such as the noise strength D of the additive Gaussian white noise and the parameter value a, b, c, and d of the four-value noise, on the RAs is also investigated.
基金supported by the National Natural Science Foundation of China under Grant No.10575041
文摘Based on a membrane-bulk coupling cell model proposed by Gomez-Marin et al. [ Phys. Rev. Lett. 98 （2007） 168303], the cooperative effects of noise and coupling on the stochastic dynamical behavior are investigated. For parameters in a certain region, the oscillation can be induced by the cooperative effect of noise and coupling. Whether considering the coupling or not, corresponding coherence resonance phenomena are observed. Furthermore, the effects of two coupling parameters, cell size L and coupling intensity k, on the noise-induced oscillation of membranes are studied. Contrary effects of noise are found in and out of the deterministic oscillatory regions.
基金This research was financially supported by Scientific Research Fund of Shaanxi Provincial Education Department （Grant No. 2013K1115） ,the National Natural Science Foundation of China （Grant No. 61106062）, the Fundamental Research Funds for the Central Universities （Grant No. K50511050007）, and the Fundamental Research Funds for AnKang University （Grant No. AYQDZR201206）.
文摘In this paper, we derive a unified scattering theory model for current noise based on the equivalent contact model of the scattering region. Our model seamlessly covers the whole range of transport regimes from coherent transport to incoherent transport and it also includes the effects of Pauli exclusion and Coulomb interaction on shot noise.
