Actins ; metabolism ; Adult ; Breast ; pathology ; Breast Neoplasms ; metabolism ; pathology ; surgery ; Female ; Humans ; Mammography ; Neoplasms, Muscle Tissue ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

Objective To study expression differences of the ataxia telangiectasia mutated (ATM ) protein in early esophageal squamous cell carcinoma tissues and adjacent normal tissues in order to explore its diagnostic significance for early esophageal squa-mous cell carcinoma .Methods ATM protein expression was detected in early esophageal squamous cell carcinoma tissues and adja-cent normal tissues by immunohistochemical SP method and the differential expression was calculated by using statistical methods . Results The positive positive expression rate of ATM protein in the early esophageal squamous cell carcinoma tissue and adjacent normal tissue were 65% and 95% respectively ,which were statistically different (P= 0 .044) .Conclusion The ATM protein ex-pression in esophageal squamous cell carcinoma tissue declined .The detection of ATM protein in esophageal squamous cell carcino-ma tissue could become a reliable method for early diagnose of esophageal squamous cell carcinoma .

Adult ; CD56 Antigen ; metabolism ; Carcinoma, Papillary ; diagnosis ; metabolism ; pathology ; surgery ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; methods ; Female ; Humans ; Male ; Neprilysin ; metabolism ; Pancreatic Neoplasms ; diagnosis ; metabolism ; pathology ; surgery ; Receptors, Progesterone ; metabolism ; Vimentin ; metabolism ; Young Adult ; beta Catenin ; metabolism

Biopsy, Fine-Needle ; methods ; Breast ; pathology ; Breast Neoplasms ; pathology ; Carcinoma, Ductal, Breast ; pathology ; Female ; Humans ; Immunohistochemistry ; methods ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Paraffin Embedding ; methods ; Receptor, ErbB-2 ; metabolism

Objective To study the value of DSA for hepatic vascular anatomy,and to evaluate the efficacy of portal vein occlusion in rabbits with hepatic VX2 tumor.Methods Twenty New Zealand white rabbits were randomly divided into two groups with 10 in each group,including test group A and positive control group B of ham operation.For the test group A,portal branch ligation(PBL)was performed for the left external branch after 3 weeks of the tumor implantation to the left external lobe.Two weeks later,the DSA of hepatic artery and portal vein were performed in all of the rabbits.Results The total displaying effectiveness of the branches of hepatic artery by DSA was better than that by vascular perfusion.There was hypovascular blood supply to hepatic artery implantation of the tumor in the test group A,comparing with that of the group B.Conclusion DSA can clearly display spacial details of the hepatic vascular anatomy in rabbits,and play an important role in post-procedual evaluation of the portal vein occlusion in rabbits.

Hypoxia is a general characteristic of most solid malignancies and intimately related to cancer progression. Homeostatic response to hypoxia is primarily mediated by hypoxia inducible factor-1alpha (HIF-1alpha) that elicits transcriptional activity through recruitment P300 coactivator. Targeting the interaction of HIF- alpha and P300 would thus constitute a novel approach for cancer treatment by suppressing tumor angiogenesis and metastasis. Here, a screening assay was developed for inhibitors targeting the interaction between HIF-1alpha and P300. The nucleotide sequence of human HIF-1alpha and P300 were cloned into pBIND and pACT vectors, named pBIND-HIF1alpha and pACT-P300. The interaction of HIF-1alpha and P300 was identified in HEK293 cell using mammalian two-hybrid system. And compound chetomin decreased their interaction in this mammalian two-hybrid system. We further verified HIF-1 inhibition effect of chetomin in U251-HRE cells. Therefore, we established a screening assay combined HIF-1alpha and P300 mammalian two-hybrid system and U251-HRE reporter assay for HIF-1 selective inhibitors.
Cell Hypoxia ; Disulfides ; pharmacology ; Drug Screening Assays, Antitumor ; E1A-Associated p300 Protein ; antagonists & inhibitors ; HEK293 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; antagonists & inhibitors ; Indole Alkaloids ; pharmacology ; Two-Hybrid System Techniques

OBJECTIVETo investigate the effect of miRNA-101 on the expression of the enhancer of zeste homolog 2 (EXH2) in human androgen-independent prostated cancer LNCaP cells.

METHODSWe divided LNCaP cells into a blank control, a negative control, and a miRNA-l01 transfection group, constructed the vector by transfecting synthetic miRNA-101 mimics into the LNCaP cells, and evaluated the efficiency of transfection by fluorescence microscopy. Then we determined the expression level of EZH2 mRNA by qRT-PCR in the three groups of cells and that of the EZH2 protein in the negative control and transfection groups by Western blot.

RESULTSGreen fluorescence signals were observed in over 70% of the LNCaP cells in the transfection group after 24 hours of transfection. At 72 hours, the expression of miRNA-101 was significantly upregulated in the transfected cells (P < 0.01), that of EZH2 mRNA was remarkably lower in the transfection group (0.01 ± 0.10) than in the blank control (0.95 ± 0.40) and negative control (0.86 ± 0.30) groups (both P < 0.01), and that of the EZH2 protein was increased in the negative control but decreased in the transfection group with the extension of culture time.

CONCLUSIONmiRNA-101, with its inhibitory effect on the expression of EZH2 in LNCaP cells, is a potential biotherapeutic for prostate cancer.

Androgens ; Cell Line, Tumor ; Enhancer of Zeste Homolog 2 Protein ; Genetic Vectors ; Humans ; Male ; MicroRNAs ; physiology ; Polycomb Repressive Complex 2 ; genetics ; metabolism ; Prostatic Neoplasms ; metabolism ; RNA, Messenger ; metabolism ; Transfection

In the heart, stimulation of beta-adrenergic receptors (betaAR) serves as the most powerful means to increase cardiac contractility and relaxation in response to stress or a "fight-or-flight" situation. However, sustained beta-adrenergic stimulation promotes pathological cardiac remodeling such as myocyte hypertrophy, apoptosis and necrosis, thus contributing to the pathogenesis of chronic heart failure. Over the past decade, compelling evidence has demonstrated that coexisting cardiac betaAR subtypes, mainly beta(1)AR and beta (2)AR, activate markedly different signaling cascades. As a result, acute beta(1)AR stimulation activates the G(s) -adenylyl cyclase-cAMP-PKA signaling that can broadcast throughout the cell, whereas beta(2)AR-evoked cAMP signaling is spatially and functionally compartmentalized, due to concurrent G(i) activation. Chronic stimulation of beta(1)AR and beta(2)AR elicits opposing effects on the fate of cardiomyocytes: beta(1)AR induces hypertrophy and apoptosis; but beta(2)AR promotes cell survival. The cardiac protective effect of beta(2)AR is mediated by a signaling pathway sequentially involving G(i), G(betagamma), PI3K and Akt. Unexpectedly, beta(1)AR-induced myocyte hypertrophy and apoptosis are independent of the classic cAMP/PKA pathway, but require activation of Ca(2+)/calmodulin-dependent kinase II (CaMK II). The outcomes of cardiac-specific transgenic overexpression of either beta AR subtype in mice have reinforced the fundamentally different functional roles of these betaAR subtypes in governing cardiac remodeling and performance. These new insights regarding betaAR subtype stimulation not only provide clues as to cellular and molecular mechanisms underlying the beneficial effects of beta AR blockers in patients with chronic heart failure, but also delineate rationale for combining selective beta(1)AR blockade with moderate beta(2)AR activation as a potential novel therapy for the treatment of chronic heart failure.
Adenylyl Cyclases ; metabolism ; Animals ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; GTP-Binding Proteins ; metabolism ; Heart ; physiology ; Heart Failure ; physiopathology ; Humans ; Myocardium ; metabolism ; Receptors, Adrenergic, beta ; classification ; physiology ; Receptors, Adrenergic, beta-1 ; physiology ; Receptors, Adrenergic, beta-2 ; physiology ; Signal Transduction

Animals ; Cochlea ; pathology ; Gene Deletion ; Hearing Loss ; etiology ; pathology ; KCNQ1 Potassium Channel ; genetics ; Mice

Objective To investigate association between gene mutations of surfactant protein C (SP-C) exon Ⅱ and neonatal respiratory distress syndrome(NRDS).Methods From January 2013 to December 2014 in Neonatal Intensive Care Unit of Bayi Children's Hospital Affiliated to Beijing Military General Hospital,a total of 90 cases with NRDS were selected as NRDS group,and they were grouped into 3 subgroups,30 cases in each subgroup.Clinical data were collected by observation figures.A total of 90 cases without NRDS as control group were matched with NRDS group as for the gestational age (GA),gender and birth weight(BW).The study samples were from the clinically diagnosed venous sampling 1 mL,and genomic DNA was extracted with routine technique.After the polymerase chain reaction (PCR) amplification of sequencing was performed.Chromas software and Vector NTI Advanc software were used for analysis,the results were compared with the normal SP-C sequence of GenBank.Results Heterozygous missense mutations included c.115G ＞ T and c.139G ＞ C existed in exon Ⅱ of SP-C gene,which changed protein sequence.GT genotype frequency(0.067) of c.115G ＞T mutation in NRDS group was higher than that(0) in control group (x2 =7.283,P ＜ 0.05).With c.115 G ＞ T gene mutations in patients with NRDS,Ⅲ-Ⅳ grade chest changed and mortality was higher than that of control group.GC genotype frequency (0.067) of c.139G ＞ C mutation in NRDS group was higher than that(0) in control group (x2 =6.207,P ＜ 0.05).Among NRDS group,64 cases of cesarean section patients,GC genotype frequencies were lower than GG genotype frequency (x2 =9.276,P ＜ 0.01),55 cases of patients needed 3-4 PS pulmonary surfactant treatment,GC genotype frequencies were lower than GG genotype frequency (x2 =5.343,P ＜ 0.05).Conclusions Two heterozygous mutations were located in SP-C gene of exon Ⅱ in Chinese Han population of this study.These mutations have never been reported before.c.115G ＞ T of SP-C gene mutation is associated with pathogenesis and severity of NRDS and increases the risk of death in NRDS;while c.139G ＞ C of SP-C gene mutation is associated with pathogenesis of NRDS,but it does not increase the risk of severity and death in NRDS.