1.Lidamycin inhibits the proliferation of HERG K+ channel highly expressing cancer cells and shows synergy with anticancer drugs.
Boyang SHANG ; Yue SHANG ; Yongsu ZHEN ; Shuzhen CHEN
Acta Pharmaceutica Sinica 2011;46(11):1321-5
This study is to investigate inhibitory effects of lidamycin (LDM) on the proliferation of HERG K+ channel highly expressing cancer cells and its synergy with anticancer drugs. MTT assay was used to examine the inhibitory effects of lidamycin combined with various anticancer drugs on the proliferation of human lung cancer A549 cells, human colon cancer HT-29 cells and herg-stably-transfected A549 cells. Using the xenograft model of subcutaneously transplanted HT-29 in nude mice, inhibitory effect was appraised in vivo. The coefficient of drug interaction (CDI) was used to evaluate the synergistic effect of drug combination. LDM significantly inhibited the proliferation ofA549 cells and HT-29 cells with IC50 values of 2.14 and 4.64 ng mL(-1), respectively. The efficacy in HT-29 cells with high HERG potassium expression level is less potent than that in A549 cells with low expression level. In terms of IC50 values, LDM suppressed the growth of herg-stably-transfected A549 cells less potently than pCDNA3.1-stably-transfected A549 cells. There existed synergistic effects in the combinations of fluorouracil (5-FU) and LDM, doxorubicin (DOX) and LDM, or hydroxycamptothecine (HCPT) and LDM. CDI values of the combinations of 5-FU and LDM were more than 0.75. CDI values of LDM and DOX were more than 0.70, but some CDI values of LDM and HCPT were less than 0.70. As for the CDI values, synergistic effects of the combination of LDM and HCPT were the most potent of the three groups. There is no relationship between the inhibitory effect of the growth of cancer cells by 5-FU and HERG potassium expression level. HERG expression level negatively correlated with inhibitory effect on the proliferation of cancer cells by DOX. HERG expression levels and chemosensitivity were positively correlated for HCPT. In the model of subcutaneously xenograft transplanted HT-29 in vivo, LDM and/or HCPT effectively inhibited the growth of HT-29 in nude mice, and the optimum CDI of the combination of LDM and HCPT was less than 1. HERG expression level negatively correlates the chemosensitivity of cancer cells to LDM. There exist synergistic effects in vitro and in vivo in the combination of LDM and HCPT, which inhibitory effects of the proliferation of cancer cells positively modulated by HERG potassium expression level. HERG K+ channel may become a target of combined therapy for choosing anticancer drugs.
2.Anticancer Effects of the Single-chain Fv Fragment scFv (3G11) Against Type Ⅳ Collagenase in Combination with Cisplatin
Qingfang MIAO ; Boyang SHANG ; Yongsu ZHEN
Journal of Medical Research 2006;0(03):-
Objective To explore the effect of recombinant scFv (3G11)directed against type IV collagenase in combination with cisplatin on the therapy of hepatocellular carcinoma.Methods The effects of cisplatin on the type IV collagenase secreted by cancer cells were investigated by gelatin zymography analysis and Western-blot.The antitumor activity of scFv (3G11)in combination with cisplatin was evaluated by MTT assay in vitro and a mouse hepatoma 22 model in vivo.Results Cisplatin inhibited the activity of type IV collagenase.ScFv (3G11)in combination with cisplatin showed significant inhibition effects on the growth of hepatocellular carcinoma both in vitro and in vivo.The coefficient of drug interaction(CDI)was less than 1.Conclusions ScFv (3G11)in combination with cisplatin demonstrated synergetic effects on the therapy of hepatocellular carcinoma.
5.Ethical Investigations and Considerations of Clinical Trials of TCM in Diabetic Nephropathy Management
Zhen WANG ; Jianwei SHANG ; Jinzhou TIAN ; Hongfang LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2013;(4):739-742
With the high incidence of diabetic nephropathy, the clinical trials of traditional Chinese medicine (TCM) in diabetic nephropathy area play an important role in the development of this subject. Therefore, follow-ing the principles of medical ethics, issues of fully understanding professional requirements of ethics review for clinical research of diabetic nephropathy and the protection of patients' rights are questions which should be solved. This article was based on the investigations on ethical needs of experts and patients in diabetic nephropathy area of TCM clinical trials . Discussions and considerations were made on results . A the more per-fect and regulated medical informed consent formwork for diabetic nephropathy of TCM clinical trials was made based on these consultations .
6.Treatment scheme selection strategy and progress of elderly femoral neck fracture of Garden type II
Baitong LI ; Tianyi ZHOU ; Zhen LIU ; Jian SHANG
Chinese Journal of Tissue Engineering Research 2017;21(3):445-449
BACKGROUND: There are various treatment methods for femoral neck fracture in the elderly, and they have advantages and disadvantages, especially for the elderly type of stable femoral neck fractures Garden type II of treatment options. OBJECTIVE: To summarize the current main clinical methods of senile femoral neck fractures of Garden type II, compare the advantages and disadvantages of internal fixation and joint replacement, and provide the best treatment for orthopedic surgeons. METHODS: We retrieved PubMed database. Key words were elderly femoral neck fracture, Garden type II, selection strategy and progress. Combining with the clinical cases encountered in the comparative analysis, the relevant discussion was analyzed. RESULTS AND CONCLUSION: Although the risk of surgery and the pain of non-surgical patients in early stage, the effects are not ideal. Internal fixation of Garden type II femoral neck fracture and joint replacement in elderly patients is controversial. For the elderly and Garden type II femoral neck fractures, the rate of revision after cannulated screw fixation was significantly higher than that of hip replacement. Both cement-type and biological-type implant prosthesis can improve hip function largely, and reduce non-surgical complications, and finally get a satisfactory clinical effect. The clinician should make the best treatment plan according to the patient’s age, bone condition, fracture type and physical condition.
7.Silver nanoparticles and anti-bacterial silver coating:research and development
Lianchun XU ; Jian SHANG ; Ye SUN ; Xinguang HAN ; Zhen LIU
Chinese Journal of Tissue Engineering Research 2016;20(25):3793-3800
BACKGROUND: Current numerous studies have confirmed that silver nanoparticles have been extensively applied due to their good anti-bacterial performances. OBJECTIVE: To summarize the overseas and domestic research and development of anti-bacterial silver coating based on the anti-bacterial mechanism and bio-safety of silver nanoparticles as wel as progression of anti-bacterial silver coating. METHODS: The first author retrieved the databases of Web of Science, PubMed and CNKI for relative articles published from January 1976 to January 2015. The keywords were “silver nanoparticles, titanium al oy, implant, antibacterial properties, biosecurity, coating” in English and Chinese, respectively. RESULTS AND CONCLUSION: Because of their smal dimension and quantum effects, as wel as great specific surface area, silver nanoparticles can be in close contact with pathogenic microorganisms to exert biological effects. Additional y, silver nanoparticles exhibit the excellent resistance to bacteria, fungi, viruses and cancer cel s. However, most of their mechanisms of biological effects remain unclear, and there are unresolved problems about the slow-release time of silver nanoparticles in vivo and how to control the slow-release silver ions. Besides, there are fewer long-term animal experiments. Therefore, a large number of laboratory and clinical studies are needed to ensure that silver nanoparticles cannot cause adverse reactions during long-term administration and how to reduce their toxicity.
8.Effects of Shuangshen Ningxin capsule on ventricular remodeling and wall motion in myocardial ischemic miniature swine induced by thrombus
Zhen YU ; Jianxun LIU ; Xinzhi LI ; Xiaohong SHANG ; Lifang YAO
Chinese Pharmacological Bulletin 1987;0(02):-
Aim To observe the improved effects of Shuangshen Ningxin capsule on ventricular remodeling and wall motion in myocardial ischemic miniature swine induced by thrombus.Methods Myocardial ischemic model miniature swine induced by self-thrombus via cardiac catheter in left anterior descending coronary artery(LAD)were administrated Shuangshen Ningxin capsule for 6 days.The changes of cardiac form,left heart systolic and diastolic function,left ventricular wall motion were observed by the technology of conventional ultrasound and Doppler tissue imaging.Results 6 days after myocardial ischemia and administration,miniature swine of model group showed ventricular wall thinning,chambers heart dilating,ventricle remodeling and wall motion weak,but Shuangshen Ningxin capsule obviously lowered left ventricular internal diameter at end-diastole(LVIDd),left ventricular internal diameter at end-systole(LVIDs),end-systolic volume(ESV),end-diastolic volume(EDV)and isovolumic relaxation time(IVRT),and increased ejection fraction(EF),tissue velocity and tissue trace of left ventricle anterior wall cardiac apex segment.Conclusion Shuangshen Ningxin capsule has anti-myocardial ischemia effect by improving left ventricular remodeling,increasing left cardiac work,improving left heart systolic and diastolic function and increasing left ventricular wall motion.
9.Fetal echocardiography for diagnosis of coronary artery fistula
Zhen, XIAO ; Ning, SHANG ; Xiaoyan, MA ; Yanxia, GUO ; Chunyan, OUYANG
Chinese Journal of Medical Ultrasound (Electronic Edition) 2015;(1):46-49
ObjectiveTo explore the ultrasound characteristics of coronary artery fistula to improve its prenatal diagnosis.MethodsImaging data for 12 fetuses with coronary artery fistula who underwent fetal echocardiography at our hospital from June 2005 to December 2013 were retrospectively analyzed to summarize the ultrasound characteristics of coronary artery fistula.ResultsOf the 12 fetuses, 7 were confirmed with coronary artery fistula by echocardiography after birth, and the remaining 5 were aborted due to other cardiac abnormalities (since an autopsy was not performed, the diagnosis of coronary artery fistula could not be confirmed). Of the 7 confirmed cases, 1 had left coronary artery-to-right atrium fistula, 3 had left coronary artery-to-right ventricle fistula, and 3 had right coronary artery-to-right ventricle fistula; 1 had left coronary artery-to-right ventricle fistula with muscular ventricular septal defect, and 6 had simple coronary fistula. Two-dimensional ultrasound examination revealed that coronary arteries were displayed in all cases, and the diameter ranged from 1.8 to 4.0 mm. Color Doppler ultrasound clearly showed the fistula size, course and the situation fistulas drained into heart chambers. Diastolic regurgitation signal could be detected in the ascending aorta and aortic arch.ConclusionCoronary artery fistula can be diagnosed by color Doppler ultrasound combined with spectral Doppler ultrasound when the fetal coronary artery expands.
10.Lidamycin inhibits the proliferation of HERG K+ channel highly expressing cancer cells and shows synergy with anticancer drugs.
Bo-yang SHANG ; Yue SHANG ; Yong-su ZHEN ; Shu-zhen CHEN
Acta Pharmaceutica Sinica 2011;46(11):1321-1325
This study is to investigate inhibitory effects of lidamycin (LDM) on the proliferation of HERG K+ channel highly expressing cancer cells and its synergy with anticancer drugs. MTT assay was used to examine the inhibitory effects of lidamycin combined with various anticancer drugs on the proliferation of human lung cancer A549 cells, human colon cancer HT-29 cells and herg-stably-transfected A549 cells. Using the xenograft model of subcutaneously transplanted HT-29 in nude mice, inhibitory effect was appraised in vivo. The coefficient of drug interaction (CDI) was used to evaluate the synergistic effect of drug combination. LDM significantly inhibited the proliferation ofA549 cells and HT-29 cells with IC50 values of 2.14 and 4.64 ng mL(-1), respectively. The efficacy in HT-29 cells with high HERG potassium expression level is less potent than that in A549 cells with low expression level. In terms of IC50 values, LDM suppressed the growth of herg-stably-transfected A549 cells less potently than pCDNA3.1-stably-transfected A549 cells. There existed synergistic effects in the combinations of fluorouracil (5-FU) and LDM, doxorubicin (DOX) and LDM, or hydroxycamptothecine (HCPT) and LDM. CDI values of the combinations of 5-FU and LDM were more than 0.75. CDI values of LDM and DOX were more than 0.70, but some CDI values of LDM and HCPT were less than 0.70. As for the CDI values, synergistic effects of the combination of LDM and HCPT were the most potent of the three groups. There is no relationship between the inhibitory effect of the growth of cancer cells by 5-FU and HERG potassium expression level. HERG expression level negatively correlated with inhibitory effect on the proliferation of cancer cells by DOX. HERG expression levels and chemosensitivity were positively correlated for HCPT. In the model of subcutaneously xenograft transplanted HT-29 in vivo, LDM and/or HCPT effectively inhibited the growth of HT-29 in nude mice, and the optimum CDI of the combination of LDM and HCPT was less than 1. HERG expression level negatively correlates the chemosensitivity of cancer cells to LDM. There exist synergistic effects in vitro and in vivo in the combination of LDM and HCPT, which inhibitory effects of the proliferation of cancer cells positively modulated by HERG potassium expression level. HERG K+ channel may become a target of combined therapy for choosing anticancer drugs.
Aminoglycosides
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administration & dosage
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pharmacology
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Animals
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Antibiotics, Antineoplastic
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administration & dosage
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pharmacology
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Antineoplastic Agents, Phytogenic
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administration & dosage
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Antineoplastic Combined Chemotherapy Protocols
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pharmacology
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Camptothecin
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administration & dosage
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analogs & derivatives
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Cell Line, Tumor
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Cell Proliferation
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drug effects
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Doxorubicin
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administration & dosage
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Drug Synergism
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ERG1 Potassium Channel
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Enediynes
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administration & dosage
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pharmacology
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Ether-A-Go-Go Potassium Channels
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metabolism
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Fluorouracil
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administration & dosage
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HT29 Cells
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Humans
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Lung Neoplasms
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metabolism
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pathology
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Xenograft Model Antitumor Assays