OBJECTIVETo predict the function of KIAA0101 gene over-expressed in human non-small cell lung cancer by bioinformatics methods.

METHODSThe gene expression profiles of the lung cancer tissues and the adjacent normal tissues were compared by dChip software analysis, and the differential genes coexpressed with KIAA0101 gene were identified. The biological functions of these genes were analyzed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), Gene Ontology (GO) and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and the common transcription factors of these genes were predicted using Gene Annotation Tool to Help Explain Relationships (GATHER).

RESULTSNine genes were found to have at least two-fold overexpressions in the lung cancer tissues in comparison with the expression level in the adjacent normal tissues, and showed similar pattern of expression variations in the lung cancer tissue. Most of these genes had the E2F1 binding sites in the promoter region.

CONCLUSIONKIAA0101 gene may participate in the cell cycle regulation of the non-small cell lung cancer, and the expression levels of the 9 genes identified may be regulated by the transcription factor E2F1.

Carcinoma, Non-Small-Cell Lung ; genetics ; Carrier Proteins ; genetics ; metabolism ; Gene Expression Profiling ; methods ; Humans ; Lung Neoplasms ; genetics

OBJECTIVETo investigate the correlation of CD80 and CD86 mRNA expression with the expression of transforming growth factor-beta1 mRNA (TGF-beta1) and interleukin-10 mRNA (IL-10) in the esophageal cancer. To explore the reason of impaired immunological function of dentritic cell (DC) and the mechanism of cancer cell escaption from body immunity system in the esophageal cancer patient.

METHODSExpression of CD80, CD86, TGF-beta1 and IL-10R mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR) in specimens of 62 esophageal carcinoma and 16 normal esophageal mucosal tissues used as normal control.

RESULTSExpression of CD80 and CD86 mRNA in the esophageal cancer tissue was significantly lower than that in the normal esophageal mucosal tissue (CD80: P = 0.038; CD86: P = 0.0002). It was significantly higher in stage I or II than that in stage III or IV (CD80: P = 0.029; CD86: P = 0.045); and also higher in paitents with high or moderate differentiation than that with poor differentiation (CD80: P = 0.046; CD86: P = 0.044). Furthermore, it was found to be reversely correlated with expression of TGF-beta1, IL-10 mRNA by multiple regression analysis (P = 0. 0001) respectively, the more TGF-beta1 and IL-10 mRNA expressed in the tumor tissue, the less CD80 and CD86 mRNA expressed by dendritic cells.

CONCLUSIONThe expression of CD80 and CD86 mRNA in the tissues of esophageal cancer are found to be weak, and reversely correlated with the expression of TGF-beta1 and IL-10 mRNA. High level expression of TGF-beta1 and IL-10 mRNA may be an important influential factor to the weak expression of CD80 and CD86 mRNA, which may be one of the reasons leading to impaired function of dendritic cells and immune escape of cancer cells in the esophageal cancer patient.

Adenocarcinoma ; genetics ; pathology ; Adult ; Aged ; B7-1 Antigen ; genetics ; B7-2 Antigen ; genetics ; Carcinoma, Squamous Cell ; genetics ; pathology ; Esophageal Neoplasms ; genetics ; pathology ; Esophagus ; metabolism ; pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Interleukin-10 ; genetics ; Male ; Middle Aged ; Mucous Membrane ; metabolism ; pathology ; Neoplasm Staging ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transforming Growth Factor beta1 ; genetics

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.

Objective To evaluate left ventricular function in patients with hypertensive hypertrophic cardiomyopathy(HHC)using real-time 3-dimensional echocardiography(RT-3DE).Methods Thirty patients with HHC and 32 control subjects were studied.Full-volume RT-3DE data from apical window were acquired,and regional volumetric time curves of 17 segments were obtained by fast 3-dimensional border detection software.Several left ventricular function parameters were calculated semiautomatically,including global left ventricular end-diastolic volume(EDV),end-systolic volume(ESV),left ventricular ejection fraction(LVEF),the ratio of ESV/EDV of 17 segments,the standard deviation(SD)and difference(Dif)(adjusted by the R-R interval) of time to minimum systolic volume(Tmsv)in 16 segments(Tmsv16-SD and Tmsv16-Dif).Results EDV and ESV were significantly larger in patients with HHC than that in control subjects[(88±29)ml vs (72±15) ml,t=-2.680,P=0.008;(28±10)ml vs (22±6 )ml,t=-2.613,P=0.01].HHC had a higher ratio of ESV/EDV at interventricular septum(IVS)compared with control group[mid-segments of anterior IVS:(40.51±20.28)% vs (26.43±10.10)%,t=-3.378,P=0.002;mid-segments of posterior IVS:(41.44±23.55)% vs (24.46±8.12)%,t=-3.688,P=0.001;apical segments of IVS:(30.96±21.31)% vs (19.53±7.33)%,t=-2.745,P=0.01].In patients with HHC,Tmsv16-SD and Tmsv16-Dif were significantly longer[(2.48±1.38)% vs (1.16±0.26)%,t=-5.117,P＜0.001;(7.67±5.07)% vs (3.95±1.48)%,t=-3.865,P＜0.001].And the prevalence of left ventricular dyssynchrony was higher than that in control subjects(43% vs 3%).Conclusions HHC patients may have regional left ventricular systolic dysfunction before global changes,and have a higher prevalence of left ventricular dyssynchrony.RT-3DE is a useful imaging modality for assessing left ventricular systolic function.

OBJECTIVETo investigate the possible association between the glutamate-cysteine ligase catalytic subunit gene (GCLC) C-129T and modifier subunit gene (GCLM) G-23T polymorphisms with coronary heart disease (CHD) in Chinese population.

METHODSGCLC C-129T and GCLM G-23T genotypes were determined in 212 CHD patients and 218 healthy individuals using a PCR-based restriction fragment length polymorphism (RFLP) method. Odds ratio (OR) for CHD and 95% confidence interval (CI) from unconditional logistic regression models were used to evaluate relative risks.

RESULTSThe T allele of the GCLC C-129T polymorphism was more frequently found in CHD cases than in controls (P < 0.01) and individuals with GCLC-129T allele had a significantly higher risk for CHD (OR = 2.38, 95% CI: 1.25 - 4.54) as compared to individuals with the -129C allele. When compared with CC homozygote, CT heterozygote had a 2.14-fold higher risk for CHD (95% CI: 1.08 - 4.24, P < 0.05) and carriers of the-129T allele (CT or TT genotype) also had a similarly 2.28-fold higher risk for CHD (95% CI: 1.16 - 4.49, P < 0.05). In contrast, the frequency of T allele of the GCLM G-23T polymorphism was lower in CHD patients than that of controls (0.174 vs. 0.264) and individuals with the GCLM-23T allele had a significantly lower risk for CHD (OR = 0.59, 95% CI: 0.42 - 0.82, P < 0.01) as compared to the -23G allele. When compared with GG homozygote, the OR of CHD for GT heterozygote was 0.71 (95% CI: 0.47 - 1.08, P > 0.05), for TT homozygote was 0.18 (95% CI: 0.06 - 0.55, P < 0.01), and for carriers of the -23T allele (GT or TT genotype) was 0.61 (95% CI: 0.42 - 0.92, P < 0.05).

CONCLUSIONThe GCLC C-129T polymorphism may be one of the genetic risk factor while the GCLM G-23T polymorphism may be one of the genetic protective factors for CHD in this Chinese population.

Aged ; Alleles ; Coronary Disease ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Glutamate-Cysteine Ligase ; genetics ; Humans ; Male ; Polymorphism, Single Nucleotide

Phosphodiesterase 4 (PDE4) is an important member of the phosphodiesterase enzyme family that specifically catalyzes the hydrolysis of cyclic adenosine monophosphate (cAMP), activates the downstream phosphorylation cascade pathway by altering cAMP concentration, and is strongly associated with multiple diseases. Inhibition of PDE4 is clinically investigated as a therapeutic strategy in a broad range of disease areas, including respiratory system diseases, autoimmune disorders, central nervous system diseases, and dermatological conditions. However, the incidence of adverse reactions such as nausea and vomiting is relatively high in the marketed PDE4 inhibitors, which has stalled their clinical development. In this review, we provide an overview of the clinical progression and safety issues of the marketed PDE4 inhibitors. We also review the main causes underlying PDE4-mediated adverse effects by combining the structural analysis of the PDE4 protein, the mechanism of action of PDE4 inhibitors, and the related side effect mechanism research, aiming to provide a reference for the development of safe and effective PDE4 inhibitors.

BACKGROUNDThe purpose of this study was to investigate the feasibility of avoiding axillary lymph node dissection (ALND) for patients with only one sentinel lymph node (SLN) metastasis. The characteristics and predictive factors for non-sentinel lymph node (NSLN) metastasis of patients with single positive SLN were also analyzed.

METHODSPatients with no and only one SLN metastasis (0/n and 1/n group, n ≥ 2) were selected from 1228 cases of invasive breast carcinoma, who underwent axillary dissection in Shandong Cancer Hospital between November 1999 and December 2011, to compare the characteristics of NSLN metastasis between them. For the 1/n group, the factors that influenced the NSLN metastasis were analyzed by univariate and multivariate analysis.

RESULTSDifferences of the NSLN metastasis between the 0/n and the 1/n groups were significant (P < 0.001). There was no significant difference between the axillary lymph node metastasis on level III in 1/n group and 0/n group (P = 0.570). When the total SLN number was ≥ 4 and with one positive case, the NSLN metastasis was not significantly different from that in the 0/n group (P = 0.118). In the 1/n group, clinical tumor size (P = 0.012), over-expression of Her-2 (P = 0.003), tumor grade (P = 0.018) and the total number of SLN (P = 0.047) significantly correlated with non-SLN metastasis. Clinical tumor size (P = 0.015) and the expression of Her-2 (P = 0.01) were independent predictive factors for non-SLN metastasis by the Logistic regression model.

CONCLUSIONUnder certain conditions, breast cancer patients with single SLN metastasis could avoid ALND.

Adult ; Aged ; Breast Neoplasms ; complications ; pathology ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; pathology ; Middle Aged ; Sentinel Lymph Node Biopsy

Objective To investigate the efficacy of CD151 gene delivery in promoting blood perfusion in swines after myocardial infarction.Metheds Swines received coronary artery ligation and intramyocardial iniection with rAAV-CD151,rAAV-anti-CD151 or rAAV-GFP.Eight weeks after vector injection,Western blot,immunostaining and 13N-labeled NH3 PET were performed to detect gene expression and biological effects of various treatments.Results High level of CD151 protein expression was detected in the rAAV-CD151 group.The capillary density in the rAAV-CD151 group[(83.8±6.7)n/mm2]was significantly higher than that in the control group[(33.2±4.5)n/mm2]and rAAV-GFP group[(41.6±5.6)n/mm2](all P＜0.05);the arteriole density in the rAAV-CD151 group[(16.4±2.5)n/mm2]was also higher than that in the control group[(6.6±2.3)n/mm2]and the rAAV-GFP group[(8.4±1.6)n/mm2](all P＜0.05).However,the lowest capillary density and arteriole density were evldanced in rAAV-anti-CD151 group.Myocardial blood perfusion was significantly increased in rAAV-CD151 group and significantly reduced in rAAV-anti-CD151 group(a11 P＜0.05 vs.control).Conclusion Intramyocardial injection of rAAV-CD151 could enhance the myoeardial express of CD151 protein,increase capillary and arteriole densities and improve blood perfusion in swine with myoeardial infarction.

OBJECTIVEThe purpose of this study was to investigate the clinicopathologic factors associated with false-negative rate of sentinel lymph node biopsy (SLNB) in breast cancer, and to explore how to reduce the false-negative rate of SLNB.

METHODSThe clinicopathological data of 2265 patients with invasive breast carcinoma who underwent sentinel lymph nodes biopsy (SLNB) in Shandong Cancer Hospital between November 1999 and December 2011 were retrospectively analyzed. We screened 1228 patients who received axillary lymph node dissection after SLNB, and studied the clinicopathological factors that could be associated with false-negative rate of SLNB.

RESULTSThe false negative rate of this group was 10.7% (73/683), accuracy rate was 94.1% (1155/1228), and negative predictive value was 88.2% (545/618). Clinical tumor size (all P < 0.05), calendar year of surgery (all P < 0.05) and numbers of detected SLNs (all P < 0.05) were significantly related with false negative rate and accuracy rate of SLNB, determined by single factor analysis. Logistic regression model analysis showed that calendar year of surgery (P = 0.034) and numbers of detected SLNs (P = 0.012) were independent predictive factors for the false negative rate of SLNB.

CONCLUSIONSFalse negative rate and accuracy rate of SLNB are significantly related to the calendar year of surgery and number of detected SLNs. Strict case selection, standard operation procedure, increaseing numbers of detected SLNs, and improvement of the skill of operators are effective measures to reduce the false negative rate of SLNB.

Adult ; Aged ; Axilla ; Breast Neoplasms ; pathology ; surgery ; Carcinoma, Ductal, Breast ; pathology ; surgery ; Carcinoma, Lobular ; pathology ; surgery ; Carcinoma, Medullary ; pathology ; surgery ; False Negative Reactions ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; surgery ; Lymphatic Metastasis ; Middle Aged ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; Young Adult

BACKGROUNDOsteopontin (OPN) is a secreted phosphoglycoprotein (SSP) that is overexpressed in a variety of tumors and was regarded as a molecular marker of tumors. In this study, we intended to demonstrate the role of OPN in human breast cancer cell line MDA-MB-231.

METHODSRecombinant plasmid expressing small interfering RNA (siRNA) specific to OPN mRNA was transfected into MDA-MB-231 cells to generate the stable transfected cell line MDA-MB-343, and the empty plasmid tansfected cells (MDA-MB-neg) or wildtype MDA-MB-231 cells were used as control cells respectively. Expression of OPN, hypoxia inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) proteins was analyzed by Western blotting analysis. The radiosensitivity of cells was determined by detecting cell apoptosis, cell proliferation and cell senescence.

RESULTSHIF-1 and VEGF proteins in MDA-MB-343 cells were significantly downregulated upon the efficient knockdown of OPN expression under either hypoxia or normoxia environment. Moreover, expression of OPN protein was upregualted upon hypoxic culture. Stable OPN-silencing also decreased cell invasion, increased cell apoptosis and cell senescence, as well as reduced clonogenic survival, resulting in increase radiation tolerance.

CONCLUSIONSSuppression of OPN gene expression can enhance radiosensitivity and affect cell apoptosis in breast cancer cells. OPN seems to be an attractive target for the improvement of radiotherapy.

Breast Neoplasms ; genetics ; metabolism ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; drug effects ; genetics ; Humans ; Hypoxia-Inducible Factor 1 ; genetics ; metabolism ; Osteopontin ; genetics ; metabolism ; RNA, Small Interfering ; Radiation Tolerance ; genetics ; physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; genetics ; metabolism