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Role of homeobox gene A5 in multidrug resistance of human small cell lung cancer cells.

Faman XIAO ; Zhenzhu CHEN ; Xiangping ZENG ; Yifeng BAI ; Linlang GUO ; Yufa LI

Journal of Southern Medical University.2013;33(11):1665-1668.

OBJECTIVETo investigate the role of homeobox gene A5 (HOXA5) in multidrug resistance of human small cell lung cancer (SCLC) cells and the possibility of using HOXA5 as the therapeutic targets for SCLC treatment.

METHODSWe examined HOXA5 mRNA and protein expressions in chemosensitive human SCLC cells (H69) and the multidrug-resistant SCLC cells (H69AR) using quantitative real-time PCR and immunoblotting. HOXA5 expression was then enhanced or suppressed by transfection of the cells with HOXA5 expression plasmids or small interference RNA (siRNA), and the chemosensitivity of transfected cells to cisplatin (DDP) and etoposide (VP-16) was evaluated using cell counting kit-8 (CCK8) assay.

RESULTSH69 cells showed a 8.99-fold higher expression of HOXA5 than H69AR cells. HOXA5 knockdown caused obvious reductions in the chemosensitivity of H69 cells to DDP and VP-16 with increased cells in G0/G1 phase; conversely, HOXA5 enhancement resulted in an increased sensitivity of H69AR cells to DDP and VP-16.

CONCLUSIONHOXA5 may play an important role in multidrug resistance of SCLC and can be a potential therapeutic target in clinical treatment of SCLC.

Antineoplastic Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Line, Tumor ; Cell Survival ; drug effects ; Cisplatin ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Etoposide ; pharmacology ; Homeodomain Proteins ; genetics ; metabolism ; Humans ; Immunoblotting ; Lung Neoplasms ; metabolism ; pathology ; Plasmids ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Real-Time Polymerase Chain Reaction ; Small Cell Lung Carcinoma ; metabolism ; pathology ; Transfection

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Effects of glucagon-like peptide-1 on liver oxidative stress, TNF-α and TGF-β1 in rats with non-alcoholic fatty liver disease.

Huiting GAO ; Lishu XU ; Dongfeng LI ; Lichang GUANG ; Weiping DENG

Journal of Southern Medical University.2013;33(11):1661-1664.

OBJECTIVETo investigate the effects of glucagon-like peptide-1 (GLP-1) on liver oxidative stress, TNF-α and TGF-β1 in rats with diet-induced non-alcoholic fatty liver disease (NAFLD).

METHODSThirty male rats were randomly divided into 3 equal groups and fed for 16 weeks with normal diet (ND), high-fat diet (HFD), or high-fat diet with intraperitoneal injection of liraglutide (GLP-1, administered in the later 4 weeks). The rats were then sacrificed to obtain blood samples and liver tissues for analyzing the levels of blood aminotransferase (ALT), triglyceride (TG), and total-cholesterol (TC) using an automatic biochemical analyzer and the levels of superoxide dismutase (SOD), malondial-dehyde (MAD), free fatty acid (FFAs), TNF-α in the liver homogenates and TGF-β1 in serum by radioimmunoassay or ELISA.

RESULTSCompared with ND group, HFD group showed significantly increased body weight, liver index, serum levels of ALT, TG, TC, and TGF-β1, and TG, TC, MAD, FFAs, and TNF-α in the liver homogenates, with also significantly increased degree of hepatic steatosis and inflammation activity (P<0.05) and lowered level of SOD. All these changes were markedly ameliorated in GLP-1 group (P<0.05).

CONCLUSIONLiraglutide can reduce high-fat diet-induced hepatic steatosis, improve oxidative stress and lipid peroxidation, and decrease TGF-β1 and TNF-α levels in serum and liver homogenates, suggesting its potential as a therapeutic agent for NAFLD.

Alanine Transaminase ; blood ; Animals ; Cholesterol ; blood ; metabolism ; Fatty Acids, Nonesterified ; metabolism ; Hypoglycemic Agents ; pharmacology ; Liraglutide ; pharmacology ; Liver ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Non-alcoholic Fatty Liver Disease ; blood ; metabolism ; pathology ; Oxidative Stress ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Transforming Growth Factor beta1 ; blood ; Triglycerides ; blood ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

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Combined endoscopic-laparoscopic techniques for one-stage treatment of concomitant cholelithiasis and choledocholithiasis.

Junzheng WU ; Xiaofei XU ; Hao LIU ; Guoxin LI

Journal of Southern Medical University.2013;33(11):1656-1660.

OBJECTIVETo assess the clinical effects of combined endoscopic-laparoscopic technique for one-stage treatment of cholelithiasis with concomitant choledocholithiasis.

METHODSA retrospective analysis was conducted of the clinical data of 30 patients (Group A) with cholelithiasis and choledocholithiasis receiving one-stage laparoscopic cholecystectomy (LC) combined with intraoperative encoscopic retrograde cholangio-pancreatography (ERCP) and 32 patients (Group B) receiving LC combined with 1aparoscopic common bile duct exploration. The operative time, blood loss, conversion to open surgery rate, time to postoperative ambulation, calculi residual rate, hospitalization cost and length of hospital stay were analyzed comparatively.

RESULTSThere were statistically differences between the two groups in hospitalization cost and length of hospital stay (P<0.05) but not in the other indices (P>0.05).

CONCLUSIONCombined endoscopic-laparoscopic techniques can be a safe and feasible option for one-stage treatment of concomitant cholelithiasis and choledocholithiasis to allow rapid postoperative recovery with a shortened hospital stay.

Adult ; Aged ; Cholangiopancreatography, Endoscopic Retrograde ; methods ; Cholecystectomy, Laparoscopic ; methods ; Choledocholithiasis ; complications ; surgery ; Cholelithiasis ; complications ; surgery ; Combined Modality Therapy ; Female ; Humans ; Laparoscopy ; methods ; Length of Stay ; economics ; Male ; Middle Aged ; Postoperative Complications ; Retrospective Studies

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Establishment of a rabbit model of cardiopulmonary bypass in acute cerebral embolism phase.

Wenkui MO ; Liangyong HE ; Qunqing CHEN ; Yusheng YAN ; Jian TONG ; Hua MENG ; Fuli ZHANG

Journal of Southern Medical University.2013;33(11):1652-1655.

OBJECTIVETo establish a stable and feasible rabbit model of cardiopulmonary bypass (CPB) in acute cerebral embolism phase for studying the effects of CPB on brain tissues and the timing of surgical intervention of acute cerebral embolism.

METHODSFifty-four rabbits were randomized into group A (n=18) to receive CPB without middle cerebral artery occlusion (MCAO) and group B to undergo CPB at 24 h (group B1, n=18) or 1 week (group B2, n=18) after MCAO. Through a supraorbital margin approach, electrocoagulation was carried out to occlude the main stem of the left MCA under direct vision to establish MCAO. Magnetic resonance imaging (MRI) was performed at both 24 h and 1 week after MCAO, and the severity of cerebral embolization was evaluated. CPB was established by cannulation of the ascending aorta and the right atrium through a median sternotomy incision. MRI was performed at 2 h after CPB to observe the brain tissues.

RESULTSMCAO was successfully established in groups B1 and B2, and all the rabbits survived after MCAO. In both groups A and B, MRI examination detected no cerebral hemorrhage or new embolism 2 h after CPB.

CONCLUSIONSWe have established a stable and feasible CPB model in rabbits with acute cerebral embolism to allow study of the mechanisms of CPB-related organ damage and its interventions.

Animals ; Cardiopulmonary Bypass ; Disease Models, Animal ; Electrocoagulation ; Female ; Infarction, Middle Cerebral Artery ; etiology ; physiopathology ; Magnetic Resonance Imaging ; Male ; Middle Cerebral Artery ; surgery ; Rabbits ; Random Allocation

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Application of three-dimensional visualization technology for laparoscopic resection of cystic carcinoma in the pancreatic body and tail.

Baohua HOU ; Peng CUI ; Zhixiang JIAN ; Shaojie LI ; Wei CHEN ; Yingliang OU ; Jinrui OU

Journal of Southern Medical University.2013;33(11):1648-1651.

OBJECTIVETo study the application of three-dimensional visualization technology for laparoscopic resection of cystic carcinoma in the pancreatic body and tail.

METHODSSix cases of cystic carcinoma in the pancreatic body and tail treated between Nov, 2009 and Mar, 2011 were retrospectively analyzed. The original image data of 64-slice spiral CT were collected and using adaptive region growing algorithm, the serial CT images were segmented and automatically extracted to obtain the 3-dimensional reconstruction images with customized image manipulation software. The specific surgical approach (the trocar position) and surgical procedure were planned based on the reconstructed mode.

RESULTSThe reconstructed 3-dimensional model clearly displayed cystic carcinoma in the pancreatic body and tail and the adjacent organs, showing distinct relationship between the cystoma and the splenic artery and vein. All the patients successfully underwent laparoscopic resection of the pancreatic body and tail without perioperative death. The spleen was preserved in 5 cases and removed in 1 case due to mucinous cystadenocarcinoma. The overall rate of pancreatic fistulae was 33.3% without incidences of postoperative hemorrhage. The average hospital stay of the patients was 12 days.

CONCLUSIONThree-dimensional reconstruction based on pancreatic CT data provides valuable assistance for laparoscopic resection of cystic carcinoma in the pancreatic body and tail.

Adult ; Aged ; Computer Simulation ; Cystadenocarcinoma, Mucinous ; diagnostic imaging ; surgery ; Cystadenoma, Mucinous ; diagnostic imaging ; surgery ; Cystadenoma, Serous ; diagnostic imaging ; surgery ; Female ; Humans ; Imaging, Three-Dimensional ; Laparoscopy ; adverse effects ; methods ; Length of Stay ; Male ; Middle Aged ; Pancreas ; diagnostic imaging ; surgery ; Pancreatectomy ; adverse effects ; methods ; Pancreatic Fistula ; etiology ; Pancreatic Neoplasms ; diagnostic imaging ; surgery ; Retrospective Studies ; Spleen ; surgery ; Tomography, Spiral Computed

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Synthesis and characterization of PEG-b-(PG-g-PEI) for gene delivery.

Ning HE ; Hechun SUN ; Huanxi XU ; Xiaoman DONG ; Zhangzhang SHAO

Journal of Southern Medical University.2013;33(11):1643-1647.

OBJECTIVETo synthesize a biodegradable non-viral gene carrier with a high transfection efficiency and a low cytotoxicity.

METHODSPoly(ethylene glycol)-block-(poly(L-glutamic acid)-graft-polyethylenimine) was prepared via ammonolysis of poly(ethylene glycol)-block-poly (γ-benzyl L-glutamate) with the low-molecular-mass polyethylenimine (600 Da). The synthesized copolymer was characterized by 1H nuclear magnetic resonance spectroscopy and gel permeation chromatography. The polyplex micelle from PEG-b-(PG-g-PEI) and plasmid DNA (pDNA) was studied using dynamic light scattering, zeta-potential measurements, and gel retardation assay. The in vitro cytotoxicity and transfection efficiency of PEG-b-(PG-g-PEI) were tested by MTT assay and luciferase assay in HEK 293T cells using PEI (25 kDa) as the control.

RESULTSPEG-b-(PG-g-PEI) could efficiently condense DNA into nanosized particles with positive surface charges when the N/P ratio of polymer and DNA was above 5:1. The zeta potential of the polyplexes was about 25 mV, and the particle size was 120 nm at a N/P ratio of 10. The cell toxicity and gene transfection evaluations showed a lower cytotoxicity and a higher gene transfection efficiency of the copolymer than PEI 25000 in HEK 293T cells.

CONCLUSIONSThe polymer can be used as a potential non-viral gene carrier for gene therapy.

Cell Survival ; Gene Transfer Techniques ; Genetic Vectors ; Glutamic Acid ; chemistry ; HEK293 Cells ; Humans ; Particle Size ; Plasmids ; Polyethylene Glycols ; chemical synthesis ; chemistry ; Polyethyleneimine ; analogs & derivatives ; chemical synthesis ; chemistry ; Polyglutamic Acid ; analogs & derivatives ; chemical synthesis ; chemistry ; Polymers ; Transfection

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Absorption, distribution and elimination of (59)Fe- corn polysaccharide iron complex in rats: a study with radioactivity isotope tracing.

Yuyan ZHOU ; Jianmin LIAO ; Zilong SHEN

Journal of Southern Medical University.2013;33(11):1638-1642.

OBJECTIVETo establish a method for detecting plasma concentration of corn polysaccharide iron complex (CPIC) and investigate its absorption, distribution and elimination in rats.

METHODSUsing radioactivity isotope tracing method, we detected the radioactivity of (59)Fe-CPIC in the plasma of rats at different time points by gavages of 3 doses (28.0, 14.0, and 7.0 mg/kg) (59)Fe-CPIC in SD rats. The pharmacokinetic parameters was obtained using DAS 2.0 program for analysis of tissue distribution and elimination of (59)Fe-CPIC.

RESULTSThe standard curve was linear within the range of 0.14-141 µg/ml (r=0.9999, n=5). The average recovery was 95% with a relative standard deviation no more than 15%. The pharmacokinetic parameters at 3 doses obtained, namely t1/2 and AUC (0-), were 214∓104, 231∓110, and 181∓81 min, and 1986.3∓513.3, 737.0∓467.0, and 315.1∓226.1 mg·min-1·L(-)1, respectively. (59)Fe-CPIC were detected in all the 13 tissues types examined and high radioactivity intensity was found in the gastrointestinal tract, hematogenic organs and other organs rich in blood. (59)Fe-CPIC was eliminated after intragastric administration primarily via the feces in rats.

CONCLUSIONThe method we established is easy and specific, and the pharmacokinetic parameters of (59)Fe-CPIC fit the two- compartment open model.

Administration, Oral ; Animals ; Area Under Curve ; Coordination Complexes ; administration & dosage ; pharmacokinetics ; urine ; Feces ; chemistry ; Female ; Intestinal Absorption ; Iron ; administration & dosage ; pharmacokinetics ; urine ; Iron Radioisotopes ; Male ; Polysaccharides ; administration & dosage ; isolation & purification ; pharmacokinetics ; urine ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution ; Zea mays ; chemistry

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Expressions of CD133 and CD44 in gastric adenocarcinoma and their relationship with E-cadherin expression.

Guoyu LU ; Xiaofei WU ; Lei ZHOU ; Lan YU ; Shiwu WU

Journal of Southern Medical University.2013;33(11):1632-1637.

OBJECTIVETo explore the expression of CD133 and CD44 in the primary gastric adenocarcinoma (GAC) and their relationship with the expression of E-cadherin.

METHODSThe expressions of CD133, CD44, and E-cadherin was examined by immunohistochemistry in 145 specimens of GAC tissues and 30 specimens of normal gastric tissues.

RESULTSThe positivity rates of CD133, CD44, and E-cadherin in normal gastric tissues were 10.0%, 0%, and 100%, respectively, showing significant differences from the rates in GAC tissues (46.9%, 47.6%, and 42.8%, respectively) (P<0.05). The expressions of CD133, CD44, and E-cadherin were significantly related with the tumor volume, differentiation, lymph node metastasis, invasive depth, pathologic-tumor-node-metastasis (pTNM) stages, and postoperative-survival time (all P<0.05); a positive correlation was found between the expression of CD133 and CD44, and they were both negatively correlated with E-cadherin expression (P<0.005). Kaplan-Meier analysis showed a significant difference in the survival rate between CD133-positive and CD133-negative patients (P<0.001) and between CD44-positive and CD44-negative patients; the patients with positive expression of E-cadherin had a significantly longer survival than those negative for E-cadherin. Cox regression analysis indicated that CD133, CD44, and E-cadherin expressions were all independent prognostic factors of GAC (all P<0.05).

CONCLUSIONThe expressions of CD133, CD44, and E-cadherin are related to the tumor volume, differentiation, pTNM stages, invasive depth, lymph node metastasis, and prognosis of GAC, and their combined detection can be of important value in predicting the prognosis of GAC.

AC133 Antigen ; Adenocarcinoma ; metabolism ; pathology ; Antigens, CD ; metabolism ; Cadherins ; metabolism ; Cell Differentiation ; Female ; Glycoproteins ; metabolism ; Humans ; Hyaluronan Receptors ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Peptides ; metabolism ; Proportional Hazards Models ; Retrospective Studies ; Stomach Neoplasms ; metabolism ; pathology ; Survival Rate ; Tumor Burden

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Influence of electroporation on immunogenicity of the DNA vaccine pVAX-tG250FcGB.

Yi XIAO ; Kun GAO ; Yong YANG ; Jinqi YAN ; Liang ZHANG ; Yu WANG ; Yuanji XU ; Renli TIAN ; Zhiyan DU ; Jiyun YU

Journal of Southern Medical University.2013;33(11):1628-1631.

OBJECTIVETo investigate the influence of electroporation on the immunogenicity of the DNA vaccine pVAX- tG250FcGB.

METHODSThe DNA vaccine pVAX-tG250FcGB was constructed by inserting the coding gene of tG250 fusion genes into the expression vector pVAX. The DNA vaccine was delivered in BALB/c mouse by electroporation or intramuscular injection, and the induced antigen specific immune responses were compared.

RESULTSThe vaccine delivered by electroporation and intramuscular injection both induced immune responses in BALB/c mouse, but electroporation produced an obviously stronger effect than intramuscular injection.

CONCLUSIONElectroporation-mediated DNA vaccine delivery can produce strong immune response in mice and is an effective means for studying the immunogenic effect of DNA vaccine pVAX-tG250FcGB.

Animals ; Antibody Formation ; Antibody Specificity ; Antigens, Neoplasm ; genetics ; immunology ; Electroporation ; Gene Fusion ; Granulocyte-Macrophage Colony-Stimulating Factor ; genetics ; immunology ; HEK293 Cells ; Humans ; Injections, Intramuscular ; Male ; Mice ; Mice, Inbred BALB C ; Plasmids ; Random Allocation ; Recombinant Fusion Proteins ; genetics ; immunology ; Transfection ; Vaccines, DNA ; genetics ; immunology

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Carvacrol pretreatment attenuates myocardial oxidative stress and apoptosis following myocardial ischemia-reperfusion in mice.

Xudong SONG ; Aihua CHEN ; Yingfeng LIU ; Xian-Bao WANG ; Yijun ZHOU ; Lei LIU ; Xiuli ZHANG ; Lizi WANG ; Pingzhen YANG

Journal of Southern Medical University.2013;33(11):1624-1627.

OBJECTIVETo investigate the effect of carvacrol pretreatment on myocardial ischemia-reperfusion (I/R) injury and its underlying mechanisms.

METHODSWild-type male C57 BL/6 mice were randomized into 5 groups (n=13), namely the sham-operated group, vehicle (DMSO in saline)+ I/R group, carvacrol (20 mg/kg) + I/R group, carvacrol (40 mg/kg) + I/R group, and carvacrol (60 mg/kg) + I/R group. The mouse models of myocardial I/R injury were established by a 45-min occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion for 2 h. Carvacrol or vehicle was administered intravenously 15 min before LAD occlusion. After reperfusion, the mice were examined for myocardial oxidative stress level and apoptosis rate.

RESULTSCompared with the vehicle group, the 3 carvacrol-pretreated groups showed significantly reduced myocardial infarct size, oxidative stress level and cardiac myocyte apoptosis rate (P<0.01).

CONCLUSIONCarvacrol can protect against myocardial I/R injury by inhibiting myocardial oxidative stress and apoptosis in mice.

Animals ; Antioxidants ; pharmacology ; Apoptosis ; drug effects ; Cardiotonic Agents ; pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Monoterpenes ; pharmacology ; Myocardial Infarction ; pathology ; Myocardial Reperfusion Injury ; metabolism ; pathology ; Myocytes, Cardiac ; cytology ; drug effects ; Oxidative Stress ; drug effects ; Random Allocation

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