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Shi, Liang,Chen, Zhan-Guo,Wu, Li-li,Zheng, Jian-Jian,Yang, Jian-Rong,Chen, Xiao-Fei,Chen, Zeng-Qiang,Liu, Cun-Li,Chi, Sheng-Ying,Zheng, Jia-Ying,Huang, Hai-Xia,Lin, Xiang-Yang,Zheng, Fang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23
Many chemotherapeutic agents have been successfully used to treat hepatocellular carcinoma (HCC); however, the development of chemoresistance in liver cancer cells usually results in a relapse and worsening of prognosis. It has been demonstrated that DNA methylation and histone modification play crucial roles in chemotherapy resistance. Currently, extensive research has shown that there is another potential mechanism of gene expression control, which is mediated through the function of short noncoding RNAs, especially for microRNAs (miRNAs), but little is known about their roles in cancer cell drug resistance. In present study, by taking advantage of miRNA effects on the resistance of human hepatocellular carcinoma cells line to cisplatin, it has been demonstrated that miR-340 were significantly downregulated whereas Nrf2 was upregulated in HepG2/CDDP (cisplatin) cells, compared with parental HepG2 cells. Bioinformatics analysis and luciferase assays of Nrf2-3'-untranslated region-based reporter constructor indicated that Nrf2 was the direct target gene of miR-340, miR-340 mimics suppressing Nrf2-dependent antioxidant pathway and enhancing the sensitivity of HepG2/CDDP cells to cisplatin. Interestingly, transfection with miR-340 mimics combined with miR-340 inhibitors reactivated the Nrf2 related pathway and restored the resistance of HepG2/CDDP cells to CDDP. Collectively, the results first suggested that lower expression of miR-340 is involved in the development of CDDP resistance in hepatocellular carcinoma cell line, at least partly due to regulating Nrf2-dependent antioxidant pathway.
Jian-Wei Pan,Ren-Ya Zhan,Liang Wen,Ying Tong,Shu Wan,Yong-Ying Zhou 연세대학교의과대학 2009 Yonsei medical journal Vol.50 No.4
Purpose: To describe the therapeutic effect and possibility of the ultra-early surgery for poor-grade aneurysmal subarachnoid hemorrhage (Hunt-Hess grades Ⅳ-Ⅴ). Materials and Methods: Nine cases with intracranial aneurysms, demonstrated by computed tomographic angiography (CTA), were treated by ultra-early surgery under general anesthesia within 24 hours from subarachnoid hemorrhage (SAH), 5 cases were treated within 6 hours and 4 cases in 6 - 24 hours. Preoperative Hunt-Hess grade: 6 cases were Ⅳ and 3 cases were Ⅴ. The clinical outcome was evaluated by Glasgow Outcome Scores (GOS). Results: In operation, difficult dissection occurred in 5 cases (55.6%), and rupture of aneurysm occurred and temporary obstructions were performed in 4 cases (44.4%). After clipping of aneurysm, 2 cases underwent V-P shunt because of hydrocephalus, pulmonary infection occurred in 3 cases, hypothalamus reaction accompanied with upper gastrointestinal hemorrhage in 2 cases. The clinical outcome were favorable (GOS 4 - 5) in 4 cases (44.4%), dissatisfied (GOS 2 - 3) in 3 cases (33.3%), and dead (GOS 1) in 2 cases (22.2%) when patients departed from our hospital. Conclusion: The ultra-early surgery can avoid early rebleeding of intracranial aneurysm, therefore, should be considered in the treatment of Hunt-Hess grade Ⅳ-Ⅴ intracranial aneurysms. The appliance of CTA can make it possible to use of ultra-early surgery and improve the therapeutic effect. Purpose: To describe the therapeutic effect and possibility of the ultra-early surgery for poor-grade aneurysmal subarachnoid hemorrhage (Hunt-Hess grades Ⅳ-Ⅴ). Materials and Methods: Nine cases with intracranial aneurysms, demonstrated by computed tomographic angiography (CTA), were treated by ultra-early surgery under general anesthesia within 24 hours from subarachnoid hemorrhage (SAH), 5 cases were treated within 6 hours and 4 cases in 6 - 24 hours. Preoperative Hunt-Hess grade: 6 cases were Ⅳ and 3 cases were Ⅴ. The clinical outcome was evaluated by Glasgow Outcome Scores (GOS). Results: In operation, difficult dissection occurred in 5 cases (55.6%), and rupture of aneurysm occurred and temporary obstructions were performed in 4 cases (44.4%). After clipping of aneurysm, 2 cases underwent V-P shunt because of hydrocephalus, pulmonary infection occurred in 3 cases, hypothalamus reaction accompanied with upper gastrointestinal hemorrhage in 2 cases. The clinical outcome were favorable (GOS 4 - 5) in 4 cases (44.4%), dissatisfied (GOS 2 - 3) in 3 cases (33.3%), and dead (GOS 1) in 2 cases (22.2%) when patients departed from our hospital. Conclusion: The ultra-early surgery can avoid early rebleeding of intracranial aneurysm, therefore, should be considered in the treatment of Hunt-Hess grade Ⅳ-Ⅴ intracranial aneurysms. The appliance of CTA can make it possible to use of ultra-early surgery and improve the therapeutic effect.
Fu, Si-Rui,Zhang, Ying-Qiang,Li, Yong,Hu, Bao-Shan,He, Xu,Huang, Jian-Wen,Zhan, Mei-Xiao,Lu, Li-Gong,Li, Jia-Ping Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7
Background: Sorafenib is a promising drug for advanced hepatocellular carcinoma (HCC); however, treatment may be discontinued for multiple reasons, such as progressive disease, adverse events, or the cost of treatment. The consequences of sorafenib discontinuation and continuation are uncertain. Materials and Methods: We retrospectively analyzed 88 HCC patients treated with sorafenib from July 2007 to January 2013. Overall survival (OS), post-disease progression overall survival (pOS), and time to disease progression (TTP) were compared for survival analysis. Cox proportional hazard regression was performed to assess the effect of important factors on OS in the overall patient population and on pOS in patients who continued sorafenib treatment. Results: Sorafenib was discontinued and continued in 24 and 64 patients, respectively. The median OS (355 vs 517 days respectively; p=0.015) and median post-PD OS (260 vs 317 days, respectively; p=0.020) were statistically different between the discontinuation and continuation groups. Neither the median time to first PD nor the time to second PD were significantly different between the 2 groups. In the discontinuation group, 3 of the 24 patients (12.5%) suffered disease outbreaks. In Cox proportional hazard regression analysis after correction for confounding factors, BCLC stage (p=0.002) and PD site (p=0.024) were significantly correlated with pOS in patients who continued sorafenib treatment. Conclusions: Sorafenib discontinuation may cause HCC flares or outbreaks. It is advisable to continue sorafenib treatment after first PD, particularly in patients with Barcelona Clinic Liver Cancer stage B disease or only intrahepatic PD.
( Hong-xu Yang ),( Yue Shang ),( Quan Jin ),( Yan-ling Wu ),( Jian Liu ),( Chun-ying Qiao ),( Zi-ying Zhan ),( Huan Ye ),( Ji-xing Nan ),( Li-hua Lian ) 한국응용약물학회 2020 Biomolecules & Therapeutics(구 응용약물학회지) Vol.28 No.4
In current study, we aimed to investigate whether the gentiopicroside (GPS) derived from Gentiana manshurica Kitagawa could block the progression of alcoholic hepatic steatosis to fibrosis induced by chronic ethanol intake. C57BL/6 mice were fed an ethanol- containing Lieber-DeCarli diet for 4 weeks. LX-2 human hepatic stellate cells were treated with GPS 1 h prior to transforming growth factor-β (TGF-β) stimulation, and murine hepatocyte AML12 cells were pretreated by GPS 1 h prior to ethanol treatment. GPS inhibited the expression of type I collagen (collagen I), α-smooth muscle actin (α-SMA) and tissue inhibitor of metal protease 1 in ethanol-fed mouse livers with mild fibrosis. In addition, the imbalanced lipid metabolism induced by chronic ethanol-feeding was ameliorated by GPS pretreatment, characterized by the modulation of lipid accumulation. Consistently, GPS inhibited the expression of collagen I and α-SMA in LX-2 cells stimulated by TGF-β. Inhibition of lipid synthesis and promotion of oxidation by GPS were also confirmed in ethanol-treated AML12 cells. GPS could prevent hepatic steatosis advancing to the inception of a mild fibrosis caused by chronic alcohol exposure, suggesting GPS might be a promising therapy for targeting the early stage of alcoholic liver disease.
( Feng Yun Gong ),( Ding Yu Zhang ),( Jiang Guo Zhang ),( Li Li Wang ),( Wei Li Zhan ),( Jun Ying Qi ),( Jian Xin Song ) 생화학분자생물학회(구 한국생화학분자생물학회) 2014 BMB Reports Vol.47 No.4
To gain insights into the effect of MexB gene under the short interfering RNA (siRNA), we synthesized 21 bp siRNA duplexes against the MexB gene. RT-PCR was performed to determine whether the siRNA inhibited the expression of MexB mRNA. Changes in antibiotic susceptibility in response to siRNA were measured by the E-test method. The efficacy of siRNAs was determined in a murine model of chronic P. aeruginosa lung infection. MexB-siRNAs inhibited both mRNA expression and the activity of P. aeruginosa in vitro. In vivo, siRNA was effective in reducing the bacterial load in the model of chronic lung infection and the P. aeruginosa-induced pathological changes. MexB-siRNA treatment enhanced the production of inflammatory cytokines in the early infection stage (P < 0.05). Our results suggest that targeting of MexB with siRNA appears to be a novel strategy for treating P. aeruginosa infections. [BMB Reports 2014; 47(4): 203-208]