AIM： To investigate potential antitumor effects of rAd-p53 by determining if it enhanced sensitivity of gastric cancer cells to chemotherapy. METHODS： Three gastric cancer cell lines with distinct levels of differen...AIM： To investigate potential antitumor effects of rAd-p53 by determining if it enhanced sensitivity of gastric cancer cells to chemotherapy. METHODS： Three gastric cancer cell lines with distinct levels of differentiation were treated with various doses of rAd-p53 alone, oxaliplatin （OXA） alone, or a combination of both. Cell growth was assessed with an 3-（4,5）-dimethylthiahiazo （-z-yl）-3,5-diphenytetrazoli- umromide assay and the expression levels of p53, Bax and Bcl-2 were determined by immunohistochemistry. The presence of apoptosis and the expression of caspase-3 were determined using flow cytometry. RESULTS： Treatment with rAd-p53 or OXA alone inhibited gastric cancer cell growth in a time- and dose- dependent manner; moreover, significant synergistic effects were observed when these treatments were combined. Immunohistochemical analysis demonstrated that treatment with rAd-p53 alone, OXA alone or combined treatment led to decreased Bcl-2 expression and increased Bax expression in gastric cancer cells.Furthermore, flow cytometry showed that rAd-p53 alone, OXA alone or combination treatment induced apoptosis of gastric cancer cells, which was accompa- nied by increased expression of caspase-3. CONCLUSION： rAd-p53 enhances the sensitivity of gastric cancer cells to chemotherapy by promoting apoptosis. Thus, our results suggest that p53 gene therapy combined with chemotherapy represents a novel avenue for gastric cancer treatment.展开更多
Objective: To investigate the therapeutic effect of Yuchang suppository on experimental ulcerative colitis rats and the effect of PPARγ/NF-KB signaling pathway. Methods: The UC rat model was replicated by 2.4.6-trini...Objective: To investigate the therapeutic effect of Yuchang suppository on experimental ulcerative colitis rats and the effect of PPARγ/NF-KB signaling pathway. Methods: The UC rat model was replicated by 2.4.6-trinitrobenzenesulfonic acid (TNBS)/ethanol method and randomly divided into normal control group, model group, high-dose group of Yuchang suppository, middle dose group , Low-dose group and sulfasalazine group, 8 rats in each group. After 14 days of treatment, the general condition of the rats was observed and the disease activity index was scored. The changes of serum TNF-α, IL-1β and IL-6 levels were detected by ELISA. The colonic mucosal injury index (CMDI) score and colon were observed by colon specimens. Histopathological changes;RT-PCR and Western blot were used to detect the expression of PPARγ and NF-KB genes and proteins in colon tissue. Results: Compared with the normal control group, the DAI and CMDI scores in the model group and the levels of serum TNF-α, IL-1β, IL-6, NF-κB p65 mRNA and protein in colon tissue were significantly increased, PPAR. - γ mRNA and protein expression levels were significantly reduced. The levels of IL-1β, IL-6, TNF-α and the expression of NF-κB p65 mRNA and protein in colon tissue were lower than those in the model group, and the expression levels of PPARγ mRNA and protein were high. In the model group. In the improvement of NF-κBp65 and PPAR-γ gene and protein expression in rat colonic mucosa, the high-dose group and the middle-dose group were significantly better than the low-dose group. Conclusion:Yuchang suppository can significantly improve the symptoms and histopathology of UC model rats. The mechanism may be through activation of PPARγ, blocking the activation of NF-κB signaling pathway, and down-regulating inflammatory factors such as TNF-α and IL-1β. The expression is such that the inflammatory response is alleviated or eliminated, thereby achieving the therapeutic effect of UC.展开更多
Background： Previous data are controversial about the association of renal artery stenosis （RAS） with clinical outcome in patients with heart failure. Definition of RAS in previous studies might not be appropriate....Background： Previous data are controversial about the association of renal artery stenosis （RAS） with clinical outcome in patients with heart failure. Definition of RAS in previous studies might not be appropriate. By definition of RAS with renal duplex sonography, we investigated the association of RAS with clinical outcome in patients with heart failure. Methods： In this retrospective study, we identified 164 patients with heart failure （New York Heart Association classification ≥11; left ventricular ejection fraction 〈50%） who had received renal duplex sonography during hospital stay. RAS was defined as renal-aortic ratio 〉3.5 or a peak systolic velocity ≥200 cm/s （or both）, or occlusion of the renal artery. Categorical data of patients were compared using the Chi-square test or Fisher＇s exact test. Cox proportional hazards regression modeling technique was used to investigate the prognostic significance of possible predictors. Results： Finally, 143 patients were enrolled, Median follow-up time was 32 months （1-53 months）. Twenty-two patients were diagnosed as RAS by renal duplex sonography, including 13 unilateral RAS （3 left RAS, l0 right RAS） and 9 bilateral RAS. There were more all-cause mortality and cardiovascular death in patients with RAS than patients without RAS. By multivariate analysis, RAS was a significant predictor for all-cause death and cardiovascular death （hazard ratio [HR] = 4.155, 95% confidence interval [（7/]： 1.546-1 1. 164, P = 0.005; and MR = 3.483, 95% CI： 1.200-10.104, P = 0.022, respectively）. As for composite endpoint events, including death, nonfatal myocardial infarction, ischemic stroke or intracranial hemorrhage, rehospitalization for cardiac failure, and renal replacement therapy, only angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker was significant predictor. RAS was not a significant predictor for composite endpoint events. Conclusions： Our data suggested that RAS is associated with a poorer clinical outcome in patients with heart failure.展开更多
基金Supported by Xuzhou Science and Technology Development Fund,No. XM07C039
文摘AIM： To investigate potential antitumor effects of rAd-p53 by determining if it enhanced sensitivity of gastric cancer cells to chemotherapy. METHODS： Three gastric cancer cell lines with distinct levels of differentiation were treated with various doses of rAd-p53 alone, oxaliplatin （OXA） alone, or a combination of both. Cell growth was assessed with an 3-（4,5）-dimethylthiahiazo （-z-yl）-3,5-diphenytetrazoli- umromide assay and the expression levels of p53, Bax and Bcl-2 were determined by immunohistochemistry. The presence of apoptosis and the expression of caspase-3 were determined using flow cytometry. RESULTS： Treatment with rAd-p53 or OXA alone inhibited gastric cancer cell growth in a time- and dose- dependent manner; moreover, significant synergistic effects were observed when these treatments were combined. Immunohistochemical analysis demonstrated that treatment with rAd-p53 alone, OXA alone or combined treatment led to decreased Bcl-2 expression and increased Bax expression in gastric cancer cells.Furthermore, flow cytometry showed that rAd-p53 alone, OXA alone or combination treatment induced apoptosis of gastric cancer cells, which was accompa- nied by increased expression of caspase-3. CONCLUSION： rAd-p53 enhances the sensitivity of gastric cancer cells to chemotherapy by promoting apoptosis. Thus, our results suggest that p53 gene therapy combined with chemotherapy represents a novel avenue for gastric cancer treatment.
文摘Objective: To investigate the therapeutic effect of Yuchang suppository on experimental ulcerative colitis rats and the effect of PPARγ/NF-KB signaling pathway. Methods: The UC rat model was replicated by 2.4.6-trinitrobenzenesulfonic acid (TNBS)/ethanol method and randomly divided into normal control group, model group, high-dose group of Yuchang suppository, middle dose group , Low-dose group and sulfasalazine group, 8 rats in each group. After 14 days of treatment, the general condition of the rats was observed and the disease activity index was scored. The changes of serum TNF-α, IL-1β and IL-6 levels were detected by ELISA. The colonic mucosal injury index (CMDI) score and colon were observed by colon specimens. Histopathological changes;RT-PCR and Western blot were used to detect the expression of PPARγ and NF-KB genes and proteins in colon tissue. Results: Compared with the normal control group, the DAI and CMDI scores in the model group and the levels of serum TNF-α, IL-1β, IL-6, NF-κB p65 mRNA and protein in colon tissue were significantly increased, PPAR. - γ mRNA and protein expression levels were significantly reduced. The levels of IL-1β, IL-6, TNF-α and the expression of NF-κB p65 mRNA and protein in colon tissue were lower than those in the model group, and the expression levels of PPARγ mRNA and protein were high. In the model group. In the improvement of NF-κBp65 and PPAR-γ gene and protein expression in rat colonic mucosa, the high-dose group and the middle-dose group were significantly better than the low-dose group. Conclusion:Yuchang suppository can significantly improve the symptoms and histopathology of UC model rats. The mechanism may be through activation of PPARγ, blocking the activation of NF-κB signaling pathway, and down-regulating inflammatory factors such as TNF-α and IL-1β. The expression is such that the inflammatory response is alleviated or eliminated, thereby achieving the therapeutic effect of UC.
文摘Background： Previous data are controversial about the association of renal artery stenosis （RAS） with clinical outcome in patients with heart failure. Definition of RAS in previous studies might not be appropriate. By definition of RAS with renal duplex sonography, we investigated the association of RAS with clinical outcome in patients with heart failure. Methods： In this retrospective study, we identified 164 patients with heart failure （New York Heart Association classification ≥11; left ventricular ejection fraction 〈50%） who had received renal duplex sonography during hospital stay. RAS was defined as renal-aortic ratio 〉3.5 or a peak systolic velocity ≥200 cm/s （or both）, or occlusion of the renal artery. Categorical data of patients were compared using the Chi-square test or Fisher＇s exact test. Cox proportional hazards regression modeling technique was used to investigate the prognostic significance of possible predictors. Results： Finally, 143 patients were enrolled, Median follow-up time was 32 months （1-53 months）. Twenty-two patients were diagnosed as RAS by renal duplex sonography, including 13 unilateral RAS （3 left RAS, l0 right RAS） and 9 bilateral RAS. There were more all-cause mortality and cardiovascular death in patients with RAS than patients without RAS. By multivariate analysis, RAS was a significant predictor for all-cause death and cardiovascular death （hazard ratio [HR] = 4.155, 95% confidence interval [（7/]： 1.546-1 1. 164, P = 0.005; and MR = 3.483, 95% CI： 1.200-10.104, P = 0.022, respectively）. As for composite endpoint events, including death, nonfatal myocardial infarction, ischemic stroke or intracranial hemorrhage, rehospitalization for cardiac failure, and renal replacement therapy, only angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker was significant predictor. RAS was not a significant predictor for composite endpoint events. Conclusions： Our data suggested that RAS is associated with a poorer clinical outcome in patients with heart failure.
