OBJECTIVETo investigate the relationship between apolipoprotein E (ApoE) gene polymorphism and serum lipid profile.

METHODSPolymerase chain reaction-restricted fragments length polymorphism (PCR-RFLP) was used to determine ApoE genotype on 1452 subjects including 1101 cases with cardio cerebrovascular disease including 379 cases with cerebral infarction, 313 cases with cerebral hemorrhage, 257 cases with coronary heart disease, and 152 cases with other types and on 351 healthy controls.

RESULTSAfter adjusting for age, sex and BMI, the subjects with ApoE4 carriers had significantly higher levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and ApoB than those with ApoE2 carriers and ApoE3/3 (P < 0.05), and higher level of triglyceride(TG) than those with ApoE3/3 (P < 0.05), while the subjects with ApoE2 carriers had significantly higher levels of high density lipoprotein-cholesterol (HDL-C) than those with ApoE4 (P < 0.05). The effects of ApoE polymorphism exhibited similarity in different sex and age of subjects. Linear regression analysis showed that unlike ApoE3/3, the HDL-C level in ApoE2 carriers tend upward with age (beta = 0.178, P = 0.015), significantly higher than ApoE4 carriers and ApoE3/3 in the cohort of 65-74 years (P < 0.05). The level of TC and TG in ApoE4 carriers had a tendency of downward with age (p = -0.179, P = 0.009; beta = -0.147, P = 0.032).

CONCLUSIONApoE gene polymorphism affected profile of blood lipids and the effects were found in different sex and age. The degrees of effects related to ApoE2 carriers and ApoE4 carriers to blood lipid level seemed to be related to age.

Adult ; Age Factors ; Aged ; Aged, 80 and over ; Apolipoproteins E ; genetics ; Case-Control Studies ; Female ; Genotype ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Polymorphism, Genetic ; Sex Factors ; Young Adult

OBJECTIVENimotuzumab is a humanized monoclonal antibody targeted against epidermal growth factor receptor (EGFR). Recent clinical studies show that patients with malignant gliomas could benefit from nimotuzumab treatment. The aim of the present study was to evaluate the efficacy and side effects of nimotuzumab in combination with chemotherapy for patients with malignant gliomas.

METHODSThe patients received 200 mg of nimotuzumab infusion intravenously over 60 minutes once weekly for the first eight weeks and then once every two weeks until unacceptable toxicity or tumor progression occurred. Individualized chemotherapy was administered based on O(6)-methylguanine-DNA methyltransferase (MGMT) expression and previous chemotherapy responses in combined with nimotuzumab.

RESULTSFourteen patients received a total of 122 times of nimotuzumab ranging from 2 to 20 (median 7.5 times). Combined chemotherapy regimens included: continuous 21-day temozolomide (10 cases), standard 5-day temozolomide (2 cases), teniposide plus cisplatin (1 case), and teniposide plus nimustine (1 case). Partial response (PR) and stable disease (SD) were found in 3 patients (21.4%)and 6 patients (42.9%), respectively. Disease control rate (PR + SD) was 64.3%. The median progression-free survival (PFS) was 4 months (95%CI: 0.7 - 7.3) and PFS at 6 months was 30.6%. The most common toxicities include grade I-II neutropenia (2 cases), thrombocytopenia (2 cases), lymphopenia (1 case), nausea and vomitting (3 case) and asymptomatic transaminase increase (1 case). One patient developed grade IV neutropenia and thrombocytopenia. One patient developed nimotuzumab-related acneiform rash.

CONCLUSIONSNimotuzumab in combination with chemotherapy has moderate activity in patients with malignant gliomas and the toxicities are well tolerable, therefore, worth further investigation.

Adolescent ; Adult ; Antibodies, Monoclonal, Humanized ; administration & dosage ; adverse effects ; therapeutic use ; Antineoplastic Agents, Alkylating ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Astrocytoma ; drug therapy ; Child ; Cisplatin ; administration & dosage ; adverse effects ; Dacarbazine ; adverse effects ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Female ; Glioblastoma ; drug therapy ; Glioma ; drug therapy ; Humans ; Infusions, Intravenous ; Male ; Nausea ; chemically induced ; Neutropenia ; chemically induced ; Nimustine ; administration & dosage ; adverse effects ; Teniposide ; administration & dosage ; adverse effects ; Thrombocytopenia ; chemically induced ; Young Adult

Objective To investigate the role of liver X receptors (LXRs) on endothelin-1 ( ET-1 )induced murine HL-1 cardiomyocytes hypertrophy.Methods Cutured murine HL-1 cardiomyocytes were divided into four experiment groups:①Control group:treated with DMSO ; ②T0901317 group:treated with LXRs agonist T0901317( 1 μmol/L) ; ③ET-1 group:treated with ET-1 ( 1 nmoL/L) ; ④T0901317 + ET-1 group:treated with T0901317 ( 1 μmol/L) for 8 hours,then treated with ET-1 ( 1 nmol/L).Twenty-four hours later,immunofluorescent staining was performed on HL-1 cells,the surface area of HL-1 cells was analyzed with NIH Image J software,and the synthetic rate of protein in HL-1 cells was detected by 3 H-leucine incorporation.The mRNA level of atrial natriuretic peptide (ANP) and β-myosin heavy chain (β-MyHC ) was measured by quantitative realtime PCR.The effect of T0901317 on mRNA expression of ANP was also detected after LXRs gene silencing.Results The surface area of HL-1 cells,mRNA expression of ANP and β-MyHC,and 3H-leucine incorporation in ET-1 group were 2.00 ± 0.29,1.98 ± 0.47,2.13 ±0.39 and 1.79 ±0.17,respectively,which were singnficantly higher than those of control group ( 1.00 ±0.26,1.00 ±0.21,1.00 ±0.31 and 1.00 ±0.03,respectively,all P ＜0.05).Compared with ET-1 group,the surface area of HL-1 cells,mRNA expression of ANP and β-MyHC,and 3H-leucine incorporation were significantly decreased in T0901317 + ET-1 group ( 1.24 ± 0.25,1.19 ± 0.21,1.48 ± 0.27 and 1.15 ±0.11,respectively,all P ＜ 0.05 ).After inhibition of LXRo/β expression in HL-1 cardiomyocytes using the specific siRNAs,the mRNA expression of ANP in T0901317 + ET-1 group was 1.78 ± 0.05,which was similar as that in ET-1 group ( 1.94 ± 0.17,P ＞ 0.05).Conclusion T0901317,an agonist of LXRs,could inhibit ET-1 induced cardiac hypertrophy in vitro,and LXR Iigand-mediated inhibition on ANP mRNA expression by T0901317 is receptor dependent.

OBJECTIVETo study whether antisense oligonucleotides and ultrasonic microbubble intensifier transfection combined with ultrasound irradiation is an effective and directional way in reversing multidrug resistance (MDR) in tumors.

METHODSMdr1, mrp, and lrp genes antisense oligonucleotides on the ultrasound microbubble intensifier were transfected for the human HepG2/ADM cell lines and then the cells were radiated with low intensity ultrasound. The effects of the reversion of carcinoma cells' MDR and the reduction of their malignancy and growth capability in vitro and in vivo were assessed using RT-PCR, Western blot and MTT.

RESULTSThe treatment restrained the multiplication of the human HepG2/AMD cell lines. The levels of their mRNA and protein of cells' mdr1 and mrp genes dropped significantly. Growth of the subcutaneous transplanted tumors in the nude mice decreased.

CONCLUSIONSTransfection of MDR genes antisense oligonucleotides on the ultrasonic microbubble intensifier combined with low intensity ultrasound radiation may serve as a new treatment method for hepatocellular carcinoma.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Animals ; Carcinoma, Hepatocellular ; pathology ; Cell Line, Tumor ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Humans ; Liver Neoplasms ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Microbubbles ; Oligonucleotides, Antisense ; genetics ; Transfection ; Ultrasonics

Herein, solid lipid nanoparticles (SLN) were proposed as a new drug delivery system for adefovir dipivoxil (ADV). The octadecylamine-fluorescein isothiocynate (ODA-FITC) was synthesized and used as a fluorescence maker to be incorporated into SLN to investigate the time-dependent cellular uptake of SLN by HepG2.2.15. The SLN of monostearin with ODA-FITC or ADV were prepared by solvent diffusion method in an aqueous system. About 15 wt% drug entrapment efficiency (EE) and 3 wt% drug loading (DL) could be reached in SLN loading ADV. Comparing with free ADV, the inhibitory effects of ADV loaded in SLN on hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels in vitro were significantly enhanced.
Adenine ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Amines ; Antiviral Agents ; administration & dosage ; pharmacokinetics ; Cell Line ; Drug Delivery Systems ; Fluorescein-5-isothiocyanate ; Fluorescent Dyes ; Glycerides ; Hepatitis B virus ; drug effects ; Humans ; Nanoparticles ; Nanotechnology ; Organophosphonates ; administration & dosage ; pharmacokinetics

Liver cancer is one of the most common neoplastic diseases with high mortality in China. Currently, antimicrotubule drugs such as paclitaxel (PTX) and vincristine (VCR), are used as the common agents in the clinical chemotherapy for liver cancer. However, the responses of patients to these drugs vary markedly. Successful identification of intracellular factors influencing liver cancer's sensitivity to antimicrotubule drugs would be of great clinical importance. In this study, by engineering human hepatoma cell HepG2 to overexpress synuclein-gamma (SNCG), we investigated if SNCG is a molecular factor associated with the sensitivity to antimicrotubule drug treatment. Real-time RT-PCR and Western blotting assays showed SNCG was successfully overexpressed in HepG2/ SNCG cells compared with HepG2/Neo cells. The overexpressed SNCG altered the proliferation activity in HepG2 cells, which was 66% higher than that of HepG2/Neo cells through MTT method. The overexpressed SNCG also reduced sensitivity of HepG2 cells to antimicrotubule drugs: after PTX or VCR treatment, the proportion of HepG2/SNCG cells in G2/M arrest was significantly lower than that in HepG2/Neo cells. Correspondingly, HepG2/SNCG cells showed significantly lower mitotic index than HepG2/Neo cells. Meanwhile, HepG2/SNCG cells showed higher resistance to PTX and VCR than HepG2/Neo cells, with resistance index 21 and 15 respectively. Our studies suggested that the overexpression of SNCG could confer resistance to antimicrotubule drugs in hepatoma cells; and it indicated that SNCG may be as a potential response marker for antimicrotubule drugs in liver cancer chemotherapy.
Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Cycle ; Cell Proliferation ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic ; Genetic Vectors ; Hep G2 Cells ; drug effects ; metabolism ; Humans ; Microtubules ; drug effects ; Mitosis ; drug effects ; Mitotic Index ; Paclitaxel ; pharmacology ; Plasmids ; RNA, Messenger ; metabolism ; Transfection ; Vincristine ; pharmacology ; gamma-Synuclein ; biosynthesis ; genetics ; physiology

OBJECTIVETo investigate the effect of interaction between paranoxonase 1 (PON1)gene polymorphism and ATP-binding cassette transporter 1 (ABCA1) genetic variation on serum lipid level.

METHODSPolymerase chain reaction-restricted fragments length polymorphism was used to determine PON1 A/B192 and ABCA1R219K genotype of 1019 subjects, including 680 patients with strokes and 339 healthy individuals as controls.

RESULTSNo significant association between A/B192 genotype and any of the lipid measurements was detected. The levels of HDL-C in the subjects with RR, RK and KK genotypes showed a significant upward tendency respectively (P < 0.05); the levels of their triglyceride (TG) tended downward respectively, but there were no significant differences between them. The relationship between R219K genotype and serum lipid level was modified by A/B192 genotype. The levels of HDL-C in the subjects with AA/RR genotype and BB/KK genotype [(1.41 +/- 0.40) mmol/L, (1.41 +/- 0.39) mmol/L] were significantly different from that in the subjects with BB/RR genotype [(1.28 +/- 0.36) mmol/L] (P < 0.05).

CONCLUSIONThe result exhibited an interaction of PON1 A/B192 and ABCA1 R219K on serum lipid level.

ATP-Binding Cassette Transporters ; genetics ; Aged ; Aryldialkylphosphatase ; genetics ; Base Sequence ; Female ; Genotype ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Sequence Analysis, DNA

OBJECTIVETo investigate whether the titrate-resistant acid phosphatase 5 (ACP5) gene polymorphisms were associated with the occurrence or curve severity of adolescent idiopathic scoliosis (AIS).

METHODSThere were 372 AIS patients from January 2006 to December 2008 and 239 normal controls from March 2005 to August 2006 were recruited. The Cobb angles were ≥ 10° in all AIS patients. Using the haplotype data of Han population from the Hapmap Project, two tag SNPs (rs2229531, rs2071484) were defined for ACP5 gene. PCR-restriction fragment length polymorphism was used for the genotyping.

RESULTSNo polymorphism in rs2229531 was found in this study. The genotype and allele frequency distribution in rs2071484 were similar between AIS patients and normal controls (χ(2) = 3.336 and 1.438, P > 0.05). The mean maximum Cobb angles of different genotypes of rs2071484 in ACP5 gene were 38° ± 19° in AA, 34° ± 14° in AG and 38° ± 21° in GG, which were similar with each other among AIS patients who reached skeletal maturity or received surgery treatment (P = 0.157).

CONCLUSIONThe ACP5 gene is neither associated with the occurrence nor the curve severity of AIS.

Acid Phosphatase ; genetics ; Adolescent ; Child ; Female ; Humans ; Isoenzymes ; genetics ; Male ; Polymorphism, Genetic ; Scoliosis ; genetics ; Tartrate-Resistant Acid Phosphatase

OBJECTIVESTo compare the sagittal profiles between thoracic idiopathic scoliosis (IS) patients with different curve progression and to determine the risk factors associated with curve progression.

METHODSA total of 83 thoracic IS patients from September 2009 to May 2010 were included in this study and were divided into 3 groups according to different curve progression. All the patients did not receive any previous treatments. There were 26 skeletally mature patients whose Risser sign were 5 degree with Cobb angle < 40° in non-curve progression group (NCP group), 29 mature patients whose Risser sign were 5 degree with Cobb angle ≥ 40° in moderate curve progression group (MCP group) and 28 immature patients whose Risser sign ≤ 3 degree with Cobb angle ≥ 40° in severe curve progression group (SCP group). Five sagittal parameters, including thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic incidence (PI) and pelvic tilt (PT) were measured on the lateral X-ray films. Analysis of variance was used to compare these parameters among the 3 groups.

RESULTSThe average thoracic Cobb angle was significantly smaller in NCP group when compared with MCP group (P < 0.01) or SCP group (P < 0.01), but not significantly different between the 2 latter groups (P = 0.619). The average TK was 19° ± 7° in NCP group, 13° ± 6° in MCP group and 8° ± 5° in SCP group. The average TK was significantly smaller in SCP group when compared with MCP group (P = 0.011) or NCP group (P < 0.01), while the average TK was significantly smaller in MCP group when compared with NCP group (P < 0.01). None of the other 4 parameters showed any significant difference between the 3 groups (P > 0.05).

CONCLUSIONSThoracic hypokyphosis is strongly associated with curve progression in thoracic IS patients. Pelvic sagittal profile may not be involved in the underlying mechanism of curve progression in thoracic IS patients.

Adolescent ; Adult ; Female ; Humans ; Male ; Radiography ; Scoliosis ; diagnostic imaging ; pathology ; Thoracic Vertebrae ; diagnostic imaging ; pathology ; Young Adult

OBJECTIVETo investigate the association between the tissue inhibitor of metalloproteinase-2 (TIMP-2) gene polymorphisms with the predisposition and disease severity of thoracic adolescent idiopathic scoliosis (AIS).

METHODSThree hundred and fifty-four female thoracic AIS patients treated from January 2007 to March 2009 and 210 healthy female who underwent health examination during March 2005 to June 2006 as normal controls were recruited in this study. One SNP-418G/C (rs8179090) in the promoter region were selected for TIMP-2 gene. PCR- RFLP was used for genotyping.

RESULTSNo significant differences of genotype and allele frequency distribution were found between AIS patients and normal controls (P > 0.05). In AIS patients, the frequency of C allele of the patients with the body mass index (BMI) < 17 kg/m(2) was significantly higher than those with the BMI > or = 17 kg/m(2) (P < 0.05), and the frequency of C allele of cases with the major Cobb angle > or = 40 degrees was significantly higher than that with Cobb angle < 40 degrees (P < 0.05). Among the patients who reached skeletal maturity without any interference of natural history, significantly higher average maximum Cobb angle was found in patients with GC and CC genotype compare with those with GG genotype.

CONCLUSIONSThe SNP-418G/C (rs8179090) in the promoter region of TIMP-2 gene may be associated with abnormal growth pattern and curve progression of thoracic AIS. TIMP-2 gene is a disease-modifier gene of thoracic AIS.

Adolescent ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Scoliosis ; genetics ; Tissue Inhibitor of Metalloproteinase-2 ; genetics