Background： As the clinical value of cytokeratin-19 （CK 19） and thymidine kinase-1 （TK1 ） in advanced gastrointestinal cancer remains controversial, we investigated their expression and clinical significance in t...Background： As the clinical value of cytokeratin-19 （CK 19） and thymidine kinase-1 （TK1 ） in advanced gastrointestinal cancer remains controversial, we investigated their expression and clinical significance in this disease. Methods： A total of 171 advanced gastrointestinal cancer patients were prospectively enrolled in this study. The mRNA level of CK 19 was detected using quantitative real-time reverse transcription-polymerase chain reaction （PCR） in all patients, along with a control group of fifty healthy individuals. Furthermore, detection of TK1 protein was carried out in 96 patients using a chemiluminescence dot blot assay. The primary endpoint was overall survival （OS） time. Results： Positive CKl 9 mRNA expression was detected in 74 （43.3%） of the 171 patients and positive TK1 expression was detected in 66 （68.8%） of the 96 patients. Furthermore, of the 96 patients, 36 （37.5%） were positive for both TK1 protein and CK19 mRNA, 30 （31.3%） were negative for TK1 protein, and 15 （15.6%） were negative for TKl protein and positive for CK19 mRNA. The results indicated that patients who were positive for CK 19 mRNA expression had significantly shorter OS times than those who were negative for it （median OS 7.7 vs. 9.7 months, respectively; P = 0.02）. Moreover, patients who were positive tbr CK 19 mRNA and TK 1 protein expression had shorter OS times （median OS 6.1 months） than those who were positive for CKl9 mRNA and negative for TKl protein expression （median OS 9.1 months; P： 0.028）. Positive CK 19 mRNA expression was significantly associated with shorter OS in the univariate analysis （P = 0.027）. Based on a multivariate Cox regression analysis, CK19 mRNA together with TK1 protein expression （P = 0.024） was an independent predictor for OS in gastrointestinal cancer patients. Conclusions： Our results suggest that positive expression ofCKl9 mRNA and TK1 protein is closely correlated with poor prognosis in advanced gastrointestinal cancer. Furthermore, both CKl9 and TKl are possible gastrointestinal cancer biomarkers.展开更多
Summary:Acute respiratory distress syndrome(ARDS)is associated with a mortality of 45%.Our previous rescarch indicated that anti-vascular endothelial growth factor(VEGF)could maintain the normal structure and function...Summary:Acute respiratory distress syndrome(ARDS)is associated with a mortality of 45%.Our previous rescarch indicated that anti-vascular endothelial growth factor(VEGF)could maintain the normal structure and function of the respiratory barrier.However,systemic application of VEGF antagonists would lead to animal death.This study attempts to study the targeted drug delivery for ARDS.In this study,we used soluble fims-like tyrosine kinase-1(sFlt)-targeted ultrasound microbubbles to antagonize the effect of VEGF on lung tissue.Ninety male BALB/C mice were randomly assigned to 6 groups:phosphate buffer saline(PBS)group(PBS+PBS);blank group(PBS+empty microbubbles);lipopolysaccharide(LPS)group(LPS+PBS);ARDS group(LPS tempty microbubbles);control group(PBS+sFlt microbubbles);and treatment group(LPS+sFIt microbubbles).After administration of LPS or PBS in the corresponding groups,the sFlt-targeted microbubbles or empty microbubbles were injected into the blood circulation.Then the lungs were irradiated with ultrasound,which ruptured the drug-loaded microbubbles and helped release drugs to the lung tissues targeted.The lung injury score,lung wet/dry ratio(W/D),liver and kidney functions,and the mortality of the mice in all groups were investigated at the predetermined time point.The difference in mortality between groups was examined by Fisher test.Other data were analyzed by onc-way analysis of variance(ANOVA).A value of P<0.05 indicates that the difference was significant.The results showed that the PaO2 levels were normal in the PBS group,the blank group,and the control group.The LPS group and ARDS group showed significant hypoxia.PaO2 was improved significantly in the treatment group.The lung injury score and W/D were normal in the PBS group,the blank group,and the control group.The lung injury score and W/D increased significantly in the LPS group and ARDS group and decreased in the treatment group(P<0.05).The mortality rate of the ARDS model was 60%(95%confidence interval 47.5%-72.5%),and that with sFlt-targeted microbubbles was significantly lower at only 40%(95%confidence interval 27.5%-52.5%,P<0.05).It was concluded that anti-VEGF with sFIt targeted ultrasound microbubbles attenuated the lung injury and ultimately reduced the 7-day mortality effectively.It might be a suitable therapeutic tool for the treatment of ARDS.展开更多
文摘Background： As the clinical value of cytokeratin-19 （CK 19） and thymidine kinase-1 （TK1 ） in advanced gastrointestinal cancer remains controversial, we investigated their expression and clinical significance in this disease. Methods： A total of 171 advanced gastrointestinal cancer patients were prospectively enrolled in this study. The mRNA level of CK 19 was detected using quantitative real-time reverse transcription-polymerase chain reaction （PCR） in all patients, along with a control group of fifty healthy individuals. Furthermore, detection of TK1 protein was carried out in 96 patients using a chemiluminescence dot blot assay. The primary endpoint was overall survival （OS） time. Results： Positive CKl 9 mRNA expression was detected in 74 （43.3%） of the 171 patients and positive TK1 expression was detected in 66 （68.8%） of the 96 patients. Furthermore, of the 96 patients, 36 （37.5%） were positive for both TK1 protein and CK19 mRNA, 30 （31.3%） were negative for TK1 protein, and 15 （15.6%） were negative for TKl protein and positive for CK19 mRNA. The results indicated that patients who were positive for CK 19 mRNA expression had significantly shorter OS times than those who were negative for it （median OS 7.7 vs. 9.7 months, respectively; P = 0.02）. Moreover, patients who were positive tbr CK 19 mRNA and TK 1 protein expression had shorter OS times （median OS 6.1 months） than those who were positive for CKl9 mRNA and negative for TKl protein expression （median OS 9.1 months; P： 0.028）. Positive CK 19 mRNA expression was significantly associated with shorter OS in the univariate analysis （P = 0.027）. Based on a multivariate Cox regression analysis, CK19 mRNA together with TK1 protein expression （P = 0.024） was an independent predictor for OS in gastrointestinal cancer patients. Conclusions： Our results suggest that positive expression ofCKl9 mRNA and TK1 protein is closely correlated with poor prognosis in advanced gastrointestinal cancer. Furthermore, both CKl9 and TKl are possible gastrointestinal cancer biomarkers.
基金This study was supported by Scientific Research Fund of Hubei Provincial Department of Education(No.B2016081)Young Scholar Research Grant of Chinese Anesthesiologist Association(No.21700007).
文摘Summary:Acute respiratory distress syndrome(ARDS)is associated with a mortality of 45%.Our previous rescarch indicated that anti-vascular endothelial growth factor(VEGF)could maintain the normal structure and function of the respiratory barrier.However,systemic application of VEGF antagonists would lead to animal death.This study attempts to study the targeted drug delivery for ARDS.In this study,we used soluble fims-like tyrosine kinase-1(sFlt)-targeted ultrasound microbubbles to antagonize the effect of VEGF on lung tissue.Ninety male BALB/C mice were randomly assigned to 6 groups:phosphate buffer saline(PBS)group(PBS+PBS);blank group(PBS+empty microbubbles);lipopolysaccharide(LPS)group(LPS+PBS);ARDS group(LPS tempty microbubbles);control group(PBS+sFlt microbubbles);and treatment group(LPS+sFIt microbubbles).After administration of LPS or PBS in the corresponding groups,the sFlt-targeted microbubbles or empty microbubbles were injected into the blood circulation.Then the lungs were irradiated with ultrasound,which ruptured the drug-loaded microbubbles and helped release drugs to the lung tissues targeted.The lung injury score,lung wet/dry ratio(W/D),liver and kidney functions,and the mortality of the mice in all groups were investigated at the predetermined time point.The difference in mortality between groups was examined by Fisher test.Other data were analyzed by onc-way analysis of variance(ANOVA).A value of P<0.05 indicates that the difference was significant.The results showed that the PaO2 levels were normal in the PBS group,the blank group,and the control group.The LPS group and ARDS group showed significant hypoxia.PaO2 was improved significantly in the treatment group.The lung injury score and W/D were normal in the PBS group,the blank group,and the control group.The lung injury score and W/D increased significantly in the LPS group and ARDS group and decreased in the treatment group(P<0.05).The mortality rate of the ARDS model was 60%(95%confidence interval 47.5%-72.5%),and that with sFlt-targeted microbubbles was significantly lower at only 40%(95%confidence interval 27.5%-52.5%,P<0.05).It was concluded that anti-VEGF with sFIt targeted ultrasound microbubbles attenuated the lung injury and ultimately reduced the 7-day mortality effectively.It might be a suitable therapeutic tool for the treatment of ARDS.
