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Find video protocols related to scientific articles indexed in Pubmed.
Genetic Polymorphism of Interleukin-1A (IL-1A), IL-1B, and IL-1 Receptor Antagonist (IL-1RN) and Prostate Cancer Risk.
Asian Pac. J. Cancer Prev.
PUBLISHED: 11-07-2014
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We aimed to investigate the associations between polymorphisms of interleukin-1A (IL-1A), IL-1B, and IL-1 receptor antagonist (IL-1RN) and prostate cancer (PCa) risk.
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Obesity affects the biopsy-mediated detection of prostate cancer, particularly high-grade prostate cancer: a dose-response meta-analysis of 29,464 patients.
PLoS ONE
PUBLISHED: 09-03-2014
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In previous studies, obesity (measured according to the body mass index) has correlated inconsistently with the risk of biopsy-measured prostate cancer, and specifically high-grade prostate cancer. This meta-analysis aimed to clarify these correlations.
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Performance of serum prostate-specific antigen isoform [-2]proPSA (p2PSA) and the prostate health index (PHI) in a Chinese hospital-based biopsy population.
Prostate
PUBLISHED: 08-31-2014
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The use of serum [-2]proPSA (p2PSA) and its derivative, the prostate health index (PHI), in detecting prostate cancer (PCa) have been consistently shown to have better performance than total prostate-specific antigen (tPSA) in discriminating biopsy outcomes in western countries. However, little is known about their performance in Chinese men. Our objective is to test the performance of p2PSA and PHI and their added value to tPSA in discriminating biopsy outcomes in Chinese men.
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Will metformin postpone high-fat diet promotion of TRAMP mouse prostate cancer development and progression?
Int Urol Nephrol
PUBLISHED: 08-27-2014
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We aimed to examine the effect of high-fat diet (HFD) on prostate cancer (PCa) development and progression and to investigate whether metformin would postpone PCa development and progression promoted by HFD.
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The effect of CXCL9 on the invasion ability of hepatocellular carcinoma through up-regulation of PREX2.
J. Mol. Histol.
PUBLISHED: 08-24-2014
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Elevated expression of CXCL9 has been shown to involve in the infiltration of inflammatory cells and liver damage after Hepatitis B virus (HBV) infection. However, whether and by what underlying mechanism does CXCL9 play a role in HBV infection associated hepatocellular carcinoma (HCC) invasion ability remain unclear. In this study, human HCC as well as adjacent noncancerous tissues, together with three kinds of liver cancer cell lines were investigated to clarify the possible involvement of CXCL9 in the regulation of HCC invasion and metastasis. Invasion ability of liver cancer cells were evaluated by transwell assays and it is enhanced after co-cultured with recombined human CXCL9 (rhCXCL9). As a trigger of Rac GTPase signaling after G protein-coupled receptors (GPCR) activated by CXCL9, Phosphatidylinositol-3, 4, 5-trisphosphate RAC Exchanger 2 (PREX2) mRNA expression of the liver cancer cell lines was elevated after co-cultured with rhCXCL9. Moreover, the mRNA level of PREX2 in HCC tissues was significantly higher than those in adjacent noncancerous tissues. Besides, the mRNA levels of PREX2 were positively correlated with the poor differentiation, portal vein invasion, metastasis and qualitative HbsAg results in 45 pairs of HCC specimens. Similarly, PREX2 mRNA was higher in three liver cancer cell lines when compared with the normal liver cell line whereas knocked down of PREX2 by small interference RNA (PREX2-siRNA) reduced the invasion ability of liver cancer cells in transwell assays. Overall, our results suggested CXCL9 was involved in the invasion ability of HCC possibly through up-regulation of its potential effector PREX2.
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Snail is an independent prognostic indicator for predicting recurrence and progression in non-muscle-invasive bladder cancer.
Int Urol Nephrol
PUBLISHED: 08-22-2014
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Snail, an inducer of the epithelial-to-mesenchymal transition, increases motility and invasiveness of cancer cells by repressing E-cadherin expression. We investigate the relationship between Snail expression and clinicopathological parameters and evaluate its prognostic significance in patients with non-muscle-invasive bladder cancer (NMIBC).
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Risk of breast cancer and family history of other cancers in first-degree relatives in Chinese women: a case control study.
BMC Cancer
PUBLISHED: 08-12-2014
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Few studies have systematically reported the relationship between the risk of breast cancer and family history of other cancers. This study was designed to systematically determine the relationship between breast cancer risk and family history of other cancers in first-degree relatives.
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A mouse line for inducible and reversible silencing of specific neurons.
Mol Brain
PUBLISHED: 07-24-2014
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BackgroundGenetic methods for inducibly and reversibly inhibiting neuronal activity of specific neurons are critical for exploring the functions of neuronal circuits. The engineered human glycine receptor, called ivermectin (IVM)-gated silencing receptor (IVMR), has been shown to possess this ability in vitro.ResultsHere we generated a mouse line, in which the IVMR coding sequence was inserted into the ROSA26 locus downstream of a loxP-flanked STOP cassette. Specific Cre-mediated IVMR expression was revealed by mis-expression of Cre in the striatum and by crossing with several Cre lines. Behavioral alteration was observed in Rosa26-IVMR mice with unilateral striatal Cre expression after systemic administration of IVM, and it could be re-initiated when IVM was applied again. A dramatic reduction in neuron firing was recorded in IVM-treated free moving Rosa26-IVMR;Emx1-Cre mice, and neuronal excitability was reduced within minutes as shown by recording in brain slice.ConclusionThis Rosa26-IVMR mouse line provides a powerful tool for exploring selective circuit functions in freely behaving mice.
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Therapeutic targeting of SRC kinase in myofibroblast differentiation and pulmonary fibrosis.
J. Pharmacol. Exp. Ther.
PUBLISHED: 07-21-2014
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Myofibroblasts are effector cells in fibrotic disorders that synthesize and remodel the extracellular matrix (ECM). This study investigated the role of the Src kinase pathway in myofibroblast activation in vitro and fibrogenesis in vivo. The profibrotic cytokine, transforming growth factor ?1 (TGF-?1), induced rapid activation of Src kinase, which led to myofibroblast differentiation of human lung fibroblasts. The Src kinase inhibitor AZD0530 (saracatinib) blocked TGF-?1-induced Src kinase activation in a dose-dependent manner. Inhibition of Src kinase significantly reduced ?-smooth muscle actin (?-SMA) expression, a marker of myofibroblast differentiation, in TGF-?1-treated lung fibroblasts. In addition, the induced expression of collagen and fibronectin and three-dimensional collagen gel contraction were also significantly inhibited in AZD0530-treated fibroblasts. The therapeutic efficiency of Src kinase inhibition in vivo was tested in the bleomycin murine lung fibrosis model. Src kinase activation and collagen accumulation were significantly reduced in the lungs of AZD0530-treated mice when compared with controls. Furthermore, the total fibrotic area and expression of ?-SMA and ECM proteins were significantly decreased in lungs of AZD0530-treated mice. These results indicate that Src kinase promotes myofibroblast differentiation and activation of lung fibroblasts. Additionally, these studies provide proof-of-concept for targeting the noncanonical TGF-? signaling pathway involving Src kinase as an effective therapeutic strategy for lung fibrosis.
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Kallikreins are involved in an miRNA network that contributes to prostate cancer progression.
Biol. Chem.
PUBLISHED: 05-26-2014
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MicroRNAs (miRNAs) are short RNA nucleotides that negatively regulate their target genes. They are differentially expressed in prostate cancer. Kallikreins are genes that encode serine proteases and are dysregulated in cancer. We elucidated a miRNA-kallikrein network that can be involved in prostate cancer progression. Target prediction identified 23 miRNAs that are dysregulated between high and low risk biochemical failure and are predicted to target five kallikreins linked to prostate cancer; KLK2, KLK3, KLK4, KLK14 and KLK15. We also identified 14 miRNAs that are differentially expressed between Gleason grades and are predicted to target these kallikreins. This demonstrates that kallikreins are downstream effectors through which miRNAs influence tumor progression. We show, through in-silico and experimental analysis, that miR-378/422a and its gene targets PIK3CG, GRB2, AKT3, KLK4 and KLK14 form an integrated circuit in prostate cancer. Our analysis shows that a minisatellite sequence in the kallikrein locus consists of a number of microsatellite repeats that represent predicted miRNA response elements. A number of kallikrein and non-kallikrein prostate cancer-related genes share these microsatellite repeats. We validated some of these interactions in prostate cancer cell lines. Finally, we provide preliminary evidence on the presence of a miRNA-mediated cross-talk between kallikreins, including a kallikrein pseudogene.
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ZBTB20 regulates nociception and pain sensation by modulating TRP channel expression in nociceptive sensory neurons.
Nat Commun
PUBLISHED: 05-19-2014
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In mammals, pain sensation is initiated by the detection of noxious stimuli through specialized transduction ion channels and receptors in nociceptive sensory neurons. Transient receptor potential (TRP) channels are the key sensory transducers that confer nociceptors distinct sensory modalities. However, the regulatory mechanisms about their expression are poorly defined. Here we show that the zinc-finger protein ZBTB20 regulates TRP channels expression in nociceptors. ZBTB20 is highly expressed in nociceptive sensory neurons of dorsal root ganglia. Disruption of ZBTB20 in nociceptors led to a marked decrease in the expression levels of TRPV1, TRPA1 and TRPM8 and the response of calcium flux and whole-cell currents evoked by their respective specific agonists. Phenotypically, the mice lacking ZBTB20 specifically in nociceptors showed a defect in nociception and pain sensation in response to thermal, mechanical and inflammatory stimulation. Our findings point to ZBTB20 as a critical regulator of nociception and pain sensation by modulating TRP channels expression in nociceptors.
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Negative regulation of NADPH oxidase 4 by hydrogen peroxide-inducible clone 5 (Hic-5) protein.
J. Biol. Chem.
PUBLISHED: 05-15-2014
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Hydrogen peroxide-inducible clone 5 (Hic-5) is a focal adhesion adaptor protein induced by the profibrotic cytokine TGF-?1. We have demonstrated previously that TGF-?1 induces myofibroblast differentiation and lung fibrosis by activation of the reactive oxygen species-generating enzyme NADPH oxidase 4 (Nox4). Here we investigated a potential role for Hic-5 in regulating Nox4, myofibroblast differentiation, and senescence. In normal human diploid fibroblasts, TGF-?1 induces Hic-5 expression in a delayed manner relative to the induction of Nox4 and myofibroblast differentiation. Hic-5 silencing induced constitutive Nox4 expression and enhanced TGF-?1-inducible Nox4 levels. The induction of constitutive Nox4 protein in Hic-5-silenced cells was independent of transcription and translation and controlled by the ubiquitin-proteasomal system. Hic-5 associates with the ubiquitin ligase Cbl-c and the ubiquitin-binding protein heat shock protein 27 (HSP27). The interaction of these proteins is required for the ubiquitination of Nox4 and for maintaining low basal levels of this reactive oxygen species-generating enzyme. Our model suggests that TGF-?1-induced Hic-5 functions as a negative feedback mechanism to limit myofibroblast differentiation and senescence by promoting the ubiquitin-proteasomal system-mediated degradation of Nox4. Together, these studies indicate that endogenous Hic-5 suppresses senescence and profibrotic activities of myofibroblasts by down-regulating Nox4 protein expression. Additionally, these are the first studies, to our knowledge, to demonstrate posttranslational regulation of Nox4.
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Up-regulation of S100A16 expression promotes epithelial-mesenchymal transition via Notch1 pathway in breast cancer.
J. Biomed. Sci.
PUBLISHED: 05-10-2014
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BackgroundOur previous studies demonstrated that S100A16 promotes adipogenesis and is involved in weight gain attenuation induced by dietary calcium. Till now, the function of S100A16 in the breast cancer remains to be elucidated.ResultsIn this study, we observed that S100A16 was expressed in higher levels in human breast cancer tissues compared with paired adjacent non-cancerous tissues. Further examination showed that overexpression of S100A16 in MCF-7 cells could increase cell proliferation and colony formation. One major mechanistic change was that S100A16 was able to up-regulate the transcription factors Notch1, ZEB1, and ZEB2, which had the capacities to directly repress the expression of epithelial markers E-cadherin and ß-catenin but increase mesenchymal markers N-cadherin and vimentin, a characterized phenotype of epithelial-mensenchymal transition (EMT). In addition to display with morphologic change, migration and invasion were increased in S100A16 over-expressed MCF-7 cells. Importantly, knockdown of Notch1 by specific siRNA could reverse the EMT induced by S100A16 overexpression, which confirmed that Notch1 played a critical role in the process of EMT induced by S100A16.ConclusionsAll together, our data indicated that S100A16 had a potential function to regulate some embryonic transcription factors to promote EMT in breast cancer cells which may be an important target site for the therapy of breast cancer.
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Lysophosphatidic acid increases SLC26A3 expression in inflamed intestine and reduces diarrheal severity in C57BL/6 mice with dextran-sodium-sulfate-induced colitis.
Chin. Med. J.
PUBLISHED: 05-06-2014
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Diarrhea is a common clinical feature of ulcerative colitis resulting from unbalanced intestinal fluid and salt absorption and secretion. The Cl(-)/HCO3(-) exchanger SLC26A3 is strongly expressed in the mid-distal colon and plays an essential role in colonic Cl(-) absorption and HCO3(-) secretion. Slc26a3 expression is up-regulated by lysophosphatidic acid (LPA) in vitro. Our study was designed to investigate the effects of LPA on SLC26A3 expression and the diarrheal phenotype in a mouse colitis model.
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RNA-binding protein RNPC1: acting as a tumor suppressor in breast cancer.
BMC Cancer
PUBLISHED: 04-29-2014
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RNA binding proteins (RBPs) play a fundamental role in posttranscriptional control of gene expression. Different RBPs have oncogenic or tumor-suppressive functions on human cancers. RNPC1 belongs to the RNA recognition motif (RRM) family of RBPs, which could regulate expression of diverse targets by mRNA stability in human cancer cells. Several studies reported that RNPC1 played an important role in cancer, mostly acting as an oncogene or up-regulating in tumors. However, its role in human breast cancer remains unclear.
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Image and pathological changes after microwave ablation of breast cancer: a pilot study.
Eur J Radiol
PUBLISHED: 04-24-2014
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To prospectively assess MR imaging evaluation of the ablation zone and pathological changes after microwave ablation (MWA) in breast cancer.
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Effects of continuous passage on immunomodulatory properties of human adipose-derived stem cells.
Cell Tissue Bank
PUBLISHED: 04-22-2014
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Human adipose-derived stem cells (hADSCs) have the ability to influence immune response, and hence are key cell sources for tissue repair and regeneration. In this study we explored the effect of continuous passage on the immunomodulatory properties of hADSCs to provide some advises for large-scale production of hADSCs for clinical applications. We found that after continuous passage, the specific surface markers expression levels as well as the adipogenic and osteogenic differentiation capacities of hADSCs had no obvious changes. However, the secretion levels of IL-10 and HGF reduced dramatically along with passage numbers. Furthermore, the INF-? level was found higher in which medium peripheral blood mononuclear cells were co-cultured with hADSCs with higher passage numbers. Also, the in vivo experiments showed that the peritonitis model mice, which were injected with higher passage numbers of hADSCs, tended to have higher levels of inflammation. All these together indicated that continuous passage has only minor effect on the cell phenotypes but will impair the immunomodulatory properties of hADSCs. This suggests that hADSCs could be prepared by continuous passage, but only those cells of lower passage numbers would be ideal therapeutic tools.
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Fewer complications after laparoscopic nephrectomy as compared to the open procedure with the modified Clavien classification system--a retrospective analysis from southern China.
World J Surg Oncol
PUBLISHED: 04-12-2014
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The objective of the study is to compare complication rates of laparoscopic nephrectomy and open nephrectomy using a standardized classification method.
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Estrogen preserves split renal function in a chronic complete unilateral ureteral obstruction animal model.
Exp Ther Med
PUBLISHED: 03-25-2014
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Estrogen may help to preserve renal function in chronic kidney disease. This study examined whether estrogen administration or deprivation affected the split renal function in rats subjected to chronic unilateral ureteral obstruction (UUO). Fifteen adult female Sprague-Dawley rats were randomly divided into three groups. Low- and high-estrogen groups were modeled by female castration or estrogen intraperitoneal injection, respectively, and the rats in the normal-estrogen group were untreated. Intermittent split renal function [glomerular filtration rate (GFR)] examination was performed on rats on days 2, 6 and 16 after UUO surgery via single-photon emission computed tomography (SPECT/CT). Routine hematoxylin and eosin (H&E) staining, immunohistochemistry, pathology examination and electron microscopy were performed to compare the histological differences. Low-, normal- and high-estrogen groups were successfully established (P<0.001). In the acute stage, the GFR of the contralateral healthy kidney showed a greater compensatory rise in the normal- and high-estrogen groups than in the low-estrogen group (P<0.05). In the chronic stage, the GFR of the obstructed kidney continued to decrease with the GFR of the high-estrogen group being significantly better preserved than that of the low-estrogen group (P<0.05). The GFR of the contralateral kidney compensated to the greatest extent in the high-estrogen group (P=0.01), and the total GFR was significantly superior (P<0.05). Routine H&E examination showed significant histological changes following surgery. The low-estrogen group had significant renal interstitial fibrosis compared with the normal- and high-estrogen groups (P<0.05), as observed by immunohistochemical (IHC) examination of transforming growth factor-? (TGF-?) and ?-smooth muscle actin (?-SMA). Electron-microscopic (EM) examination also differentiated between groups. In conclusion, estrogen administration and deprivation significantly affected renal function. Estrogen may preserve the split renal function (GFR) in rats with chronic UUO.
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Extracellular signal-regulated kinase (ERK) activation is required for itch sensation in the spinal cord.
Mol Brain
PUBLISHED: 03-23-2014
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Itch, chronic itch in particular, can have a significant negative impact on an individual's quality of life. However, the molecular mechanisms underlying itch processing in the central nervous system remain largely unknown.
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Urokinase-type plasminogen activator receptor (uPAR) ligation induces a raft-localized integrin signaling switch that mediates the hypermotile phenotype of fibrotic fibroblasts.
J. Biol. Chem.
PUBLISHED: 03-18-2014
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The urokinase-type plasminogen activator receptor (uPAR) is a glycosylphosphatidylinositol-linked membrane protein with no cytosolic domain that localizes to lipid raft microdomains. Our laboratory and others have documented that lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) exhibit a hypermotile phenotype. This study was undertaken to elucidate the molecular mechanism whereby uPAR ligation with its cognate ligand, urokinase, induces a motile phenotype in human lung fibroblasts. We found that uPAR ligation with the urokinase receptor binding domain (amino-terminal fragment) leads to enhanced migration of fibroblasts on fibronectin in a protease-independent, lipid raft-dependent manner. Ligation of uPAR with the amino-terminal fragment recruited ?5?1 integrin and the acylated form of the Src family kinase, Fyn, to lipid rafts. The biological consequences of this translocation were an increase in fibroblast motility and a switch of the integrin-initiated signal pathway for migration away from the lipid raft-independent focal adhesion kinase pathway and toward a lipid raft-dependent caveolin-Fyn-Shc pathway. Furthermore, an integrin homologous peptide as well as an antibody that competes with ?1 for uPAR binding have the ability to block this effect. In addition, its relative insensitivity to cholesterol depletion suggests that the interactions of ?5?1 integrin and uPAR drive the translocation of ?5?1 integrin-acylated Fyn signaling complexes into lipid rafts upon uPAR ligation through protein-protein interactions. This signal switch is a novel pathway leading to the hypermotile phenotype of IPF patient-derived fibroblasts, seen with uPAR ligation. This uPAR dependent, fibrotic matrix-selective, and profibrotic fibroblast phenotype may be amenable to targeted therapeutics designed to ameliorate IPF.
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The influence of prostate volume on cancer detection in the Chinese population.
Asian J. Androl.
PUBLISHED: 03-15-2014
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In western populations, prostate volume (PV) has been proven to be one of the strongest predictors of detecting prostate cancer (PCa) in biopsies. We performed this study in a biopsy cohort, to evaluate associations among the prostate volume, prostate-specific antigen (PSA) and PCa detection in the Chinese population. Between the years, 2007-13, 1486 men underwent prostate biopsy at Huashan Hospital, Fudan University, Shanghai, China. The study population was divided into two groups for analysis according to total PSA (tPSA) range (4 ng ml-1 < tPSA ? 20 ng ml-1 and tPSA > 20 ng ml-1 ). PV, age, tPSA, digital rectal examination (DRE) and transrectal ultrasound (TRUS) results were also included in the analysis. Although the positive biopsy rates decreased in both tPSA range groups, the downtrend was more pronounced in the 4 ng ml-1 < tPSA ? 20 ng ml-1 group; therefore, we focused on 853 men in this group with increasing PV. In multivariate logistic regression analysis, only DRE was found to be associated with PCa in four PV groups (P < 0.05) and tPSA did not show a good predictive ability when PV exceeded 50 ml (P > 0.05). Further, it may suggest that with increasing PV, the cancer detection rate decreased in men with different tPSA, DRE and TRUS nodule statuses (all P values for trends were <0.001). Our study indicates that in tPSA ranging from 4 to 20 ng ml-1 , the use of PV ranges of 0-35 ml, 35-50 ml and > 50 ml might be taken into consideration for the biopsy decision-making in the Chinese population.
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Visualizing hepatitis C virus infection in humanized mice.
J. Immunol. Methods
PUBLISHED: 03-05-2014
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Hepatitis C virus (HCV) establishes frequently persistent infections. Chronic carriers can develop severe liver disease. HCV has been intensely studied in a variety of cell culture systems. However, commonly used cell lines and primary hepatocyte cultures do not or only in part recapitulate the intricate host environment HCV faces in the liver. HCV infects readily only humans and chimpanzees, which poses challenges in studying HCV infection in vivo. Consequently, tractable small animal models are needed that are not only suitable for analyzing HCV infection but also for testing novel therapeutics. Here, we will focus our discussion on humanized mice, i.e. mice engrafted with human tissues or expressing human genes, which support HCV infection. We will further highlight novel methods that can be used to unambiguously detect HCV infected cells in situ, thereby facilitating a spatio-temporal dissection of HCV infection in the three dimensional context of the liver.
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Depletion of canonical Wnt signaling components has a neuroprotective effect on midbrain dopaminergic neurons in an MPTP-induced mouse model of Parkinson's disease.
Exp Ther Med
PUBLISHED: 03-04-2014
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The canonical Wnt signaling pathway is critical for the development of midbrain dopaminergic (DA) neurons, and recent studies have suggested that disruption of this signaling cascade may underlie the pathogenesis of Parkinson's disease (PD). However, the exact role of the canonical Wnt signaling pathway, including low-density lipoprotein receptor-related protein 5 and 6 (LRP5/6) and ?-catenin components, in a mouse model of PD remains unclear. In the present study, the tyrosine hydroxylase (TH)-Cre transgenic mouse line was used to generate mice with the specific knockout of LRP5, LRP6 or ?-catenin in DA neurons. Following inactivation of LRP5, LRP6 or ?-catenin, TH-immunohistochemical staining was performed. The results indicated that ?-catenin is required for the development or maintenance of these neurons; however, LRP5 and LRP6 were found to be dispensable. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, the depletion of LRP5, LRP6 or ?-catenin was found to be protective for the midbrain DA neurons to a certain extent. These in vivo results provide a novel perspective for the function of the canonical Wnt signaling pathway in a mouse model of PD.
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Expression of PRMT5 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth in vitro.
J. Neurooncol.
PUBLISHED: 02-28-2014
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Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of ?-NG,N'G-symmetric dimethylarginine residues on histones as well as other proteins. These modifications play an important role in cell differentiation and tumor cell growth. However, the role of PRMT5 in human glioma cells has not been characterized. In this study, we assessed protein expression profiles of PRMT5 in control brain, WHO grade II astrocytomas, anaplastic astrocytomas, and glioblastoma multiforme (GBM) by immunohistochemistry. PRMT5 was low in glial cells in control brain tissues and low grade astrocytomas. Its expression increased in parallel with malignant progression, and was highly expressed in GBM. Knockdown of PRMT5 by small hairpin RNA caused alterations of p-ERK1/2 and significantly repressed the clonogenic potential and viability of glioma cells. These findings indicate that PRMT5 is a marker of malignant progression in glioma tumors and plays a pivotal role in tumor growth.
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Targeting stem cell signaling pathways for drug discovery: advances in the Notch and Wnt pathways.
Sci China Life Sci
PUBLISHED: 02-15-2014
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Signaling pathways transduce extracellular stimuli into cells through molecular cascades to regulate cellular functions. In stem cells, a small number of pathways, notably those of TGF-?/BMP, Hedgehog, Notch, and Wnt, are responsible for the regulation of pluripotency and differentiation. During embryonic development, these pathways govern cell fate specifications as well as the formation of tissues and organs. In adulthood, their normal functions are important for tissue homeostasis and regeneration, whereas aberrations result in diseases, such as cancer and degenerative disorders. In complex biological systems, stem cell signaling pathways work in concert as a network and exhibit crosstalk, such as the negative crosstalk between Wnt and Notch. Over the past decade, genetic and genomic studies have identified a number of potential drug targets that are involved in stem cell signaling pathways. Indeed, discovery of new targets and drugs for these pathways has become one of the most active areas in both the research community and pharmaceutical industry. Remarkable progress has been made and several promising drug candidates have entered into clinical trials. This review focuses on recent advances in the discovery of novel drugs which target the Notch and Wnt pathways.
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The anticancer effect and mechanism of ?-hederin on breast cancer cells.
Int. J. Oncol.
PUBLISHED: 02-14-2014
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Natural plant products occupy a very important position in the area of cancer chemotherapy. Many triterpenoid saponins have been proved as potential agents for chemoprevention and therapy of breast cancer. ?-hederin, a monodesmosidic triterpenoid saponin distributed in Hedera or Nigella species, displays many biological activities. It is increasingly investigated for its promising anticancer potential since it has been shown to have cytotoxicity against several types of cancer cells. However, studies of ?-hederin on breast cancer are limited, most of which focus on biological activity, while the mechanisms have not been widely reported yet. Previously, we purified and identified ?-hederin from Clematis ganpiniana, a herb used in traditional Chinese medicine with antitumor action. In the present study, ?-hederin showed strong inhibitory activity on the growth of breast cancer cells and induced apoptosis in these cells. ?-hederin induced depolarization of mitochondrial membrane potential which released Apaf-1 and cytochrome c from the intermembrane space into the cytosol, where they promoted caspase-3 and caspase-9 activation. This is the first report on the growth inhibition and pro-apoptotic effects of ?-hederin on breast cancer cells and the relative apoptosis pathways. It implied that triterpenoid saponin ?-hederin could be a promising candidate for chemotherapy of breast cancer.
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The role of Src family kinases in growth and migration of glioma stem cells.
Int. J. Oncol.
PUBLISHED: 02-13-2014
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Src family kinases (SFKs) are highly expressed and active in clinical glioblastoma multiforme (GBM) specimens. SFKs inhibitors have been demonstrated to inhibit proliferation and migration of glioma cells. However, the role of SFKs in glioma stem cells (GSCs), which are important for treatment resistance and recurrence, has not been reported. Here, we examined the expression pattern of individual members of SFKs and their functional role in CD133? GSCs in comparison to primary glioma cells. We found that Fyn, c-Src and Yes were robustly expressed in GSCs while Lck was absent. Knockdown of c-Src, Yes or treatment with the SFK inhibitor dasatinib inhibited the migration of GSCs, but had no impact on their growth or self-renewal. These results suggest that SFKs represent an effective target for GSC migration but not for their growth.
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Are EORTC risk tables suitable for Chinese patients with non-muscle-invasive bladder cancer?
Cancer Epidemiol
PUBLISHED: 01-27-2014
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To evaluate the applicability of using EORTC risk tables in Chinese patients with non-muscle-invasive bladder cancer.
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Upregulated PD-1 Expression Is Associated with the Development of Systemic Lupus Erythematosus, but Not the PD-1.1 Allele of the PDCD1 Gene.
Int J Genomics
PUBLISHED: 01-21-2014
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Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complicated genetic inheritance. Programmed death 1 (PD-1), a negative T cell regulator to maintain peripheral tolerance, induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of SLE. In order to examine whether expression levels of PD-1 contribute to the pathogenesis of SLE, 30 patients with SLE and 30 controls were recruited and their PD-1 expression levels in peripheral blood mononuclear cells (PBMCs) were measured via flow cytometry and quantitative real-time-reverse transcription polymerase chain reaction (RT-PCR). Also, whether PD-1 expression levels are associated with the variant of the SNP rs36084323 and the SLE Disease Activity Index (SLEDAI) was studied in this work. The PD-1 expression levels of SLE patients were significantly increased compared with those of the healthy controls. The upregulated PD-1 expression levels in SLE patients were greatly associated with SLEDAI scores. No significant difference was found between PD-1 expression levels and SNP rs36084323. The results suggest that increased expression of PD-1 may correlate with the pathogenesis of SLE, upregulated PD-1 expression may be a biomarker for SLE diagnosis, and PD-1 inhibitor may be useful to SLE treatment.
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CD133 facilitates epithelial-mesenchymal transition through interaction with the ERK pathway in pancreatic cancer metastasis.
Mol. Cancer
PUBLISHED: 01-21-2014
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Pancreatic cancer is a lethal disease due to the high incidence of metastasis at the time of detection. CD133 expression in clinical pancreatic cancer correlates with poor prognosis and metastasis. However, the molecular mechanism of CD133-regulated metastasis remains unclear. In recent years, epithelial-mesenchymal transition (EMT) has been linked to cancer invasion and metastasis. In the present study we investigated the role of CD133 in pancreatic cancer metastasis and its potential regulatory network.
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Predictive value of clinicopathological markers for the metachronous bladder cancer and prognosis of upper tract urothelial carcinoma.
Sci Rep
PUBLISHED: 01-20-2014
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Upper tract urothelial carcinoma (UTUC) is rare but aggressive with poor prognosis. We aimed to find effective predictive markers for recurrence and prognosis in UTUC patients. In this retrospective study, we included 88 UTUC patients treated with radical neprhoureterectomy (RNU) and analyzed their clinicopathological parameters. For study of incidence of metachronous bladder tumor, models were adjusted with inclusion of prophylactic intravesical instillation chemotherapy. The mean follow-up was 28.59 months (2 to 82 mo). Lack of gross hematuria (RR 0.060, 95%CI 0.008-0.468), tumor located at ureter (RR 0.037, 95%CI 0.004-0.378), advanced stage and higher p53 expression were independent factors for worse survival. Recurrence of bladder cancer occurred 20% of patients at median follow-up of 37.65 months (5 to 82 mo). Higher tumor grade (RR 5.998, 95%CI 1.359-26.479) and presence of ipsilateral non-functioning kidney at diagnosis (RR 5.982, 95%CI 1.338-26.750) were predictors for recurrence. The present study identified several parameters with predictive value in the prognosis and intravesicle recurrence in UTUCand shed light on the better monitoring and management of the disease.
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Neonatal intrahippocampal injection of lipopolysaccharide induces deficits in social behavior and prepulse inhibition and microglial activation in rats: Implication for a new schizophrenia animal model.
Brain Behav. Immun.
PUBLISHED: 01-18-2014
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Several lines of evidence have suggested that the dysregulation of immune system is involved in the pathogenesis of schizophrenia. Microglia are the resident macrophage of the brain and the major player in innate immunity in the brain. We hypothesized that microglia activation may be closely associated with the neuropathology of schizophrenia. Neonatal intrahippocampal injection of lipopolysaccharide (LPS), an activator of microglia, was performed in rats at postnatal day 7 (PD7), and they were separately treated with saline or minocycline for consecutive 3days. Behavioral changes (locomotor activity, social interaction and prepulse inhibition) were examined in adulthood, and the number of microglia was assessed using immunohistochemistry at PD9, PD21 and PD67. The adult rats in LPS-injected group showed obvious behavioral alterations (deficits in social behavior and prepulse inhibition) and a persistently dramatic increase of number of activated microglial cells in the hippocampus, cerebral cortex and thalamus compared to those in saline-injected group. Interestingly, pretreatment with minocycline could significantly rescue the behavioral deficits and prevent microglia activation. Our results suggest that neonatal intrahippocampal LPS injection may serve as a potential schizophrenia animal model, and inhibition of microglia activation may be a potential treatment strategy for schizophrenia.
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Evolving renorrhaphy technique for retroperitoneal laparoscopic partial nephrectomy: single-surgeon series.
Int. J. Urol.
PUBLISHED: 01-08-2014
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To evaluate renorrhaphy techniques and to analyze surgical outcomes in retroperitoneal laparoscopic partial nephrectomy.
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Obesity has multifaceted impact on biochemical recurrence of prostate cancer: a dose-response meta-analysis of 36,927 patients.
Med. Oncol.
PUBLISHED: 01-05-2014
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Obesity is inconsistently related to biochemical recurrence (BCR) of prostate cancer (PCa) in different epidemiological studies. We conducted a systematic review and dose-response meta-analysis of published studies from MEDLINE and EMBASE in order to determine the relationship between body mass index (BMI) and BCR of PCa. We identified a total of 26 studies including 36,927 individuals. Pooled estimates of relative risk (RR) and confidence interval (CI) were computed, and dose-response meta-analysis was subsequently performed. Based on the random-effects approach, a 5 kg/m(2) increase in BMI was associated with 16 % (RR 1.16, 95 % CI 1.08-1.24) higher risk of BCR for entire set of 26 studies. Significantly higher rates of BCR were also observed in radical prostatectomy series (RR 1.17, 95 % CI 1.07-1.28) and external beam radiation therapy series (RR 1.19, 95 % CI 1.10-1.28), while no significant correlation was observed in brachytherapy series (RR 0.91, 95 % CI 0.64-1.28). Different BCR outcomes came out for studies held in USA (RR 1.18, 95 % CI 1.10-1.28), Europe (RR 1.04 95 % CI 0.91-1.17) and Asia (RR 1.83 95 % CI 0.85-3.97), respectively. There was limited evidence of a nonlinear association between BMI and BCR, which showed a critical point of 33 in BMI. The findings from meta-analysis showed that excess BMI was positively correlated with BCR of PCa multifacetedly, indicating good weight control and detailed attention to treating obese patients might improve the prognosis of PCa.
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Abnormal anxiety- and depression-like behaviors in mice lacking both central serotonergic neurons and pancreatic islet cells.
Front Behav Neurosci
PUBLISHED: 01-01-2014
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Dysfunction of central serotonin (5-HT) system has been proposed to be one of the underlying mechanisms for anxiety and depression, and the association of diabetes mellitus and psychiatric disorders has been noticed by the high prevalence of anxiety/depression in patients with diabetes mellitus. This promoted us to examine these behaviors in central 5-HT-deficient mice and those also suffering with diabetes mellitus. Mice lacking either 5-HT or central serotonergic neurons were generated by conditional deletion of Tph2 or Lmx1b respectively. Simultaneous depletion of both central serotonergic neurons and pancreatic islet cells was achieved by administration of diphtheria toxin (DT) in Pet1-Cre;Rosa26-DT receptor (DTR) mice. The central 5-HT-deficient mice showed reduced anxiety-like behaviors as they spent more time in and entered more often into the light box in the light/dark box test compared with controls; similar results were observed in the elevated plus maze test. However, they displayed no differences in the immobility time of the forced swimming and tail suspension tests suggesting normal depression-like behaviors in central 5-HT-deficient mice. As expected, DT-treated Pet1-Cre;Rosa26-DTR mice lacking both central serotonergic neurons and pancreatic islet endocrine cells exhibited several classic diabetic symptoms. Interestingly, they displayed increased anxiety-like behaviors but reduced immobility time in the forced swimming and tail suspension tests. Furthermore, the hippocampal neurogenesis was dramatically enhanced in these mice. These results suggest that the deficiency of central 5-HT may not be sufficient to induce anxiety/depression-like behaviors in mice, and the enhanced hippocampal neurogenesis may contribute to the altered depression-like behaviors in the 5-HT-deficient mice with diabetes. Our current investigation provides understanding the relationship between diabetes mellitus and psychiatric disorders.
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Minocycline and risperidone prevent microglia activation and rescue behavioral deficits induced by neonatal intrahippocampal injection of lipopolysaccharide in rats.
PLoS ONE
PUBLISHED: 01-01-2014
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Various signs of activation of microglia have been reported in schizophrenia, and it is hypothesized that microglia activation is closely associated with the neuropathology of schizophrenia.
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A small peptide with potential ability to promote wound healing.
PLoS ONE
PUBLISHED: 01-01-2014
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Wound-healing represents a major health burden, such as diabetes-induced skin ulcers and burning. Many works are being tried to find ideal clinical wound-healing biomaterials. Especially, small molecules with low cost and function to promote production of endogenous wound healing agents (i.e. transforming growth factor beta, TGF-?) are excellent candidates. In this study, a small peptide (tiger17, c[WCKPKPKPRCH-NH2]) containing only 11 amino acid residues was designed and proved to be a potent wound healer. It showed strong wound healing-promoting activity in a murine model of full thickness dermal wound. Tiger17 exerted significant effects on three stages of wound healing progresses including (1) the induction of macrophages recruitment to wound site at inflammatory reaction stage; (2) the promotion of the migration and proliferation both keratinocytes and fibroblasts, leading to reepithelialization and granulation tissue formation; and (3) tissue remodeling phase, by promoting the release of transforming TGF-?1 and interleukin 6 (IL-6) in murine macrophages and activating mitogen-activated protein kinases (MAPK) signaling pathways. Considering its easy production, store and transfer and function to promote production of endogenous wound healing agents (TGF-?), tiger17 might be an exciting biomaterial or template for the development of novel wound-healing agents.
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The apoptotic effect of D Rhamnose ?-Hederin, a novel oleanane-type triterpenoid saponin on breast cancer cells.
PLoS ONE
PUBLISHED: 01-01-2014
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There is growing interest in development of natural products as anti-cancer and chemopreventive agents. Many triterpenoids have been proved as potential agents for chemoprevention and therapy of breast cancer. Ginsenosides from ginseng, which mostly belong to dammarane-type triterpenoids, have gained great attention for their anti-breast cancer activity with diverse mechanisms. However, studies of other kinds of triterpenoid saponins on breast cancer are limited. Previously, we purified and identified a novel oleanane-type triterpene saponin named D Rhamnose ?-hederin (DR?-H) from Clematis ganpiniana, a Chinese traditional anti-tumor herb. In the present study, DR?-H showed strong inhibitory activity on the growth of various breast cancer cells and induced apoptosis in these cells. DR?-H inhibited PI3K/AKT and activated ERK signaling pathway. PI3K inhibitor LY294002 synergistically enhanced DR?-H-induced apoptosis whereas MEK inhibitor U0126 reduced the apoptosis rate. Moreover, DR?-H regulated the ratio of pro-apoptotic and anti-apoptotic Bcl-2 family proteins. Furthermore, DR?-H induced depolarization of mitochondrial membrane potential which released Apaf-1 and Cytochrome C from the inter membrane space into the cytosol, where they promoted caspase-9 and caspase-3 activation. This is the first report on the pro-apoptotic effects of DR?-H, a novel oleanane-type triterpenoid saponin, on breast cancer cells and its comprehensive apoptosis pathways. It implied that oleanane-type triterpenoid saponin DR?-H could be a promising candidate for chemotherapy of breast cancer.
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Sensory input is required for callosal axon targeting in the somatosensory cortex.
Mol Brain
PUBLISHED: 11-24-2013
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Sensory input is generally thought to be necessary for refining and consolidating neuronal connections during brain development. We here report that cortical callosal axons in somatosensory cortex require sensory input for their target selection in contralateral cortex.
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Ki67 and TP53 expressions predict recurrence of non-muscle-invasive bladder cancer.
Tumour Biol.
PUBLISHED: 09-04-2013
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Tumor markers Ki67, TP53, and TP63 are common labels in the diagnosis of bladder cancer (BCa) around the world. The combination of those biomarkers may have advantages in predicting BCa prognosis and non-muscle-invasive bladder cancer (NMIBC) postoperative recurrence. We investigated the immunohistochemical profiles of 313 bladder cancer samples classified under the WHO/ISUP (2004) grading scale and the UICC-TNM (2002) classification. Then we investigated their predictive value in the tumor recurrence of 270 NMIBC patients after TURBT. Expression of Ki67 correlates with grade, stage, tumor size, and tumor numbers. Semiquantitative evaluation of TP53 correlates with grade and invasive conditions. The positive expression rate of TP63 correlated with tumor grade and stage. The combined effect of TP53 and Ki67 revealed a predictive value in NMIBC recurrence. However, the positive TP63 expression did not show any protective effect in NMIBC recurrence. The expression of TP53 and Ki67 could be used to predict the risk of NMIBC recurrence postoperatively.
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5-Aminolevulinic acid combined with ferrous iron induces carbon monoxide generation in mouse kidneys and protects from renal ischemia-reperfusion injury.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 07-31-2013
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Renal ischemia reperfusion injury (IRI) is a major factor responsible for acute renal failure. An intermediate in heme synthesis, 5-aminolevulinic acid (5-ALA) is fundamental in aerobic energy metabolism. Heme oxygenase (HO)-1 cleaves heme to form biliverdin, carbon monoxide (CO), and iron (Fe(2+)), which is used with 5-ALA. In the present study, we investigated the role of 5-ALA in the attenuation of acute renal IRI using a mouse model. Male Balb/c mice received 30 mg/kg 5-ALA with Fe(2+) 48, 24, and 2 h before IRI and were subsequently subjected to bilateral renal pedicle occlusion for 45 min. The endogenous CO concentration of the kidneys from the mice administered 5-ALA/Fe(2+) increased significantly, and the peak concentrations of serum creatinine and blood urea nitrogen decreased. 5-ALA/Fe(2+) treatments significantly decreased the tubular damage and number of apoptotic cells. IRI-induced renal thiobarbituric acid-reactive substance levels were also significantly decreased in the 5-ALA/Fe(2+) group. Furthermore, mRNA expression of HO-1, TNF-?, and interferon-? was significantly increased after IRI. Levels of HO-1 were increased and levels of TNF-? and interferon-? were decreased in the 5-ALA/Fe(2+)-pretreated renal parenchyma after IRI. F4/80 staining showed reduced macrophage infiltration, and TUNEL staining revealed that there were fewer interstitial apoptotic cells. These findings suggest that 5-ALA/Fe(2+) can protect the kidneys against IRI by reducing macrophage infiltration and decreasing renal cell apoptosis via the generation of CO.
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Reproductive factors and breast cancer risk among BRCA1 or BRCA2 mutation carriers: Results from ten studies.
Cancer Epidemiol
PUBLISHED: 07-09-2013
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Although reproductive factors are among the most well-established risk factors for breast cancer in the general population, it is still a matter for debate whether these factors act as risk modifiers among BRCA1 or BRCA2 mutation carriers. This meta-analysis is the first to be performed to determine the relationship between reproductive factors and breast cancer risk among BRCA1 and BRCA2 mutation carriers. We searched the PubMed database up to February 2013. A total of ten studies met the inclusion criteria. The results showed that the reproductive factors may be associated with breast cancer risk only among BRCA1 mutation carriers. No association was found between parity and breast cancer risk. Compared with women at the youngest age in the first-birth category, women in the oldest age category were at a 38% lower risk of breast cancer (RR=0.62, 95%CI=0.45-0.85). Breastfeeding for at least 1 or 2 years was associated with a 37% reduction in breast cancer risk (RR=0.63, 95%CI=0.46-0.86). Women at the oldest age in the menarche category were at a 34% lower risk of breast cancer (RR=0.66, 95%CI=0.53-0.81) than women in the youngest age category. However, none of the reproductive factors were associated with breast cancer risk among BRCA2 mutation carriers. In conclusion, late age at first birth, breastfeeding, and late age at menarche protect against breast cancer in BRCA1 mutation carriers only. Further studies are needed to explore the mechanisms.
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The prognostic value of C-reactive protein in renal cell carcinoma: A systematic review and meta-analysis.
Urol. Oncol.
PUBLISHED: 06-21-2013
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C-reactive protein (CRP) has been reported to be associated with poorer prognosis in patients with renal cell carcinoma (RCC); however, conflicting results exist. We conducted a systematic review to evaluate the prognostic value, and a meta-analysis was done if the extracted data could be merged.
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Hypoxia inducible factor-1 alpha plays a pivotal role in hepatic metastasis of pancreatic cancer: an immunohistochemical study.
J Hepatobiliary Pancreat Sci
PUBLISHED: 06-20-2013
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Hypoxia is an important condition to promote angiogenesis that is essential to tumor progression, including pancreatic ductal adenocarcinoma (PDAC). We evaluated whether the immunohistochemistry for hypoxia inducible factor-1? (HIF-1?) was correlated with hepatic metastases in PDAC.
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Plateau effect of prostate cancer risk-associated SNPs in discriminating prostate biopsy outcomes.
Prostate
PUBLISHED: 06-18-2013
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Additional prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) continue to be identified. It is unclear whether addition of newly identified SNPs improves the discriminative performance of biopsy outcomes over previously established SNPs.
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mTOR plays critical roles in pancreatic cancer stem cells through specific and stemness-related functions.
Sci Rep
PUBLISHED: 06-17-2013
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Pancreatic cancer is characterized by near-universal mutations in KRAS. The mammalian target of rapamycin (mTOR), which functions downstream of RAS, has divergent effects on stem cells. In the present study, we investigated the significance of the mTOR pathway in maintaining the properties of pancreatic cancer stem cells. The mTOR inhibitor, rapamycin, reduced the viability of CD133(+) pancreatic cancer cells and sphere formation which is an index of self-renewal of stem-like cells, indicating that the mTOR pathway functions to maintain cancer stem-like cells. Further, rapamycin had different effects on CD133(+) cells compared to cyclopamine which is an inhibitor of the Hedgehog pathway. Thus, the mTOR pathway has a distinct role although both pathways maintain pancreatic cancer stem cells. Therefore, mTOR might be a promising target to eliminate pancreatic cancer stem cells.
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Activation of postsynaptic 5-HT1A receptors improve stress adaptation.
Psychopharmacology (Berl.)
PUBLISHED: 06-12-2013
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Serotonin-1A (5-HT1A) receptors modulate the stress response and have been implicated in the etiology and treatment of depression and anxiety disorders. A reduction in postsynaptic 5-HT1A receptor function in limbic areas has consistently been observed following exposure to chronic stress.
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Prostate-specific antigen kinetics under androgen deprivation therapy and prostate cancer prognosis.
Urol. Int.
PUBLISHED: 06-11-2013
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To compare the difference in characteristics of post-treatment prostate-specific antigen (PSA) kinetics among respective patients and their influence on disease prognosis.
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Lysophosphatidic acid accelerates lung fibrosis by inducing differentiation of mesenchymal stem cells into myofibroblasts.
J. Cell. Mol. Med.
PUBLISHED: 06-08-2013
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Lung fibrosis is characterized by vascular leakage and myofibroblast recruitment, and both phenomena are mediated by lysophosphatidic acid (LPA) via its type-1 receptor (LPA1). Following lung damage, the accumulated myofibroblasts activate and secrete excessive extracellular matrix (ECM), and form fibrotic foci. Studies have shown that bone marrow-derived cells are an important source of myofibroblasts in the fibrotic organ. However, the type of cells in the bone marrow contributing predominantly to the myofibroblasts and the involvement of LPA-LPA1 signalling in this is yet unclear. Using a bleomycin-induced mouse lung-fibrosis model with an enhanced green fluorescent protein (EGFP) transgenic mouse bone marrow replacement, we first demonstrated that bone marrow derived-mesenchymal stem cells (BMSCs) migrated markedly to the bleomycin-injured lung. The migrated BMSC contributed significantly to ?-smooth muscle actin (?-SMA)-positive myofibroblasts. By transplantation of GFP-labelled human BMSC (hBMSC) or EGFP transgenic mouse BMSC (mBMSC), we further showed that BMSC might be involved in lung fibrosis in severe combined immune deficiency (SCID)/Beige mice induced by bleomycin. In addition, using quantitative-RT-PCR, western blot, Sircol collagen assay and migration assay, we determined the underlying mechanism was LPA-induced BMSC differentiation into myofibroblast and the secretion of ECM via LPA1. By employing a novel LPA1 antagonist, Antalpa1, we then showed that Antalpa1 could attenuate lung fibrosis by inhibiting both BMSC differentiation into myofibroblast and the secretion of ECM. Collectively, the above findings not only further validate LPA1 as a drug target in the treatment of pulmonary fibrosis but also elucidate a novel pathway in which BMSCs contribute to the pathologic process.
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Paraneoplastic hormones: parathyroid hormone-related protein (PTHrP) and erythropoietin (EPO) are related to vascular endothelial growth factor (VEGF) expression in clear cell renal cell carcinoma.
Tumour Biol.
PUBLISHED: 05-23-2013
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To investigate the correlation between parathyroid hormone-related protein (PTHrP), erythropoietin (EPO), and vascular endothelial growth factor (VEGF) expression in clear cell renal cell carcinoma (ccRCC). Immunohistochemical studies on PTHrP, EPO and VEGF were performed in 249 patients with ccRCC. Serum calcium level and haematocrit were analyzed. The expression of the factors and clinicopathological parameters were studied statistically for possible correlations. The incidence for hypercalcaemia and polycythaemia were 15.3 % and 2.0 % respectively. Expression of PTHrP, EPO, and VEGF were respectively related to advanced stage (P?
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Distribution of transglutaminase 6 in the central nervous system of adult mice.
Anat Rec (Hoboken)
PUBLISHED: 05-18-2013
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Our previous study identified a new form of spinocerebellar ataxia (SCA), in which mutations in the gene coding for transglutaminase 6 (TG6) were suggested to be causative. However, the data concerning cellular distribution of TG6 in the brain is still fragmentary. Therefore, we now report a comprehensive immunohistochemical examination of the expression profile of TG6 in adult mouse brain. TG6 was abundantly expressed in the septal region, basal ganglia, hypothalamus and brainstem. Notably, numerous TG6-positive neurons were found in the key brain regions involved in regulating locomotion activity, including the globus pallidus, subthalamic nucleus, substantia nigra, cerebellum, some precerebellar nuclei, and spinal motor neurons. Double immunostaining showed that the vast majority of TG6-positive neurons in the reticular nigra were GABAergic and those in the compact nigra were not dopaminergic. In addition, double staining for TG6 with either anti-NeuN or glial fibrillary acidic protein (GFAP) antibodies demonstrated exclusive NeuN-TG6 co-localization. This study presents a comprehensive overview of TG6 expression in the mouse brain, and provides insight for investigating the role of TG6 in the development of SCA.
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Mesenchymal stem cells in prostate cancer have higher expressions of SDF-1, CXCR4 and VEGF.
Gen. Physiol. Biophys.
PUBLISHED: 05-15-2013
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Our previous study found that the activity of PCa-MSCs, which could stimulate the cell proliferation of RM-1, was significantly different compared to BMMSCs. Our results indicated that it could be mediated in part by growth factors/chemokines, which were involved in the different activity between two kinds of MSCs (PCa-MSCs and BMMSCs). Normal MSCs (BMMSCs) were isolated from the femur, tibia of the normal mice; prostate tumor MSCs (PCa-MSCs) were obtained from the mice implanted with prostate tumor. Analysis of the expression of SDF-1, CXCR4, VEGF?bFGF and vWF of two kinds of MSCs were examined by ELISA, Realtime-PCR and Western blotting. The expressions of SDF-1 and CXCR4 in PCa-MSCs were higher compared to BMMSCs. Expressions of bFGF and vWF were higher in PCa-MSCs yet the difference did not reach statistical significance. The expression of VEGF was significantly higher in PCa-MSCs. Our data showed that activity of PCa-MSCs was significantly improved compared with BMMSCs, which seemed to have an intrinsic, cell-specific capacity localized to PCa. It could be induced by some factors or chemokines such as SDF-1, CXCR4, and VEGF. The possible role of PCa-MSCs in the process of PCa development needed further clarification.
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Tubulin cofactor A functions as a novel positive regulator of ccRCC progression, invasion and metastasis.
Int. J. Cancer
PUBLISHED: 05-10-2013
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Microtubules (Mts), which consist of ?/?-tubulin heterodimers, are involved in cancer development and metastasis. Tubulin cofactor A (TBCA) plays crucial roles in modulating tubulin folding and ?/?-tubulin heterodimer polymerization. Here, we identified the aberrant expression of TBCA in clear cell renal cell carcinoma (ccRCC) specimens as well as cell lines and revealed the function of TBCA as a novel positive regulator in ccRCC progression, invasion and metastasis. qRT-PCR, Western blot and immunohistochemistry assays confirmed that TBCA was significantly highly expressed in ccRCC specimens and cell lines compared to their corresponding normal kidney tissues and HKC. Accordingly, the influence of TBCA on cell proliferation, apoptosis and invasion/migration was detected through overexpression and knockdown of endogenous TBCA protein level in ccRCC cells via plasmids. Silencing of TBCA expression inhibited the proliferation of 786-O cells and Caki-1 cells and promoted the apoptosis of 786-O cells. Down-regulation of TBCA expression also reduced the invasion and migration ability of 786-O cells. Interestingly, overexpression of TBCA did not induce biocharacteristics that directly contrasted to those of TBCA knockdown. Importantly, exploration of the mechanism showed that TBCA could function via modulating cytoskeleton integration and influencing cell cycle progress. Furthermore, down-regulation of TBCA expression in 786-O and Caki-1 cells affected cytoskeleton integration and cell size, induced S/G2 cell cycle arrest and led to cyclineA/E and CDK2 aberrant expression. By investigating novel roles of TBCA in regulation of ccRCC cell progression, invasion and metastasis, our study identified that TBCA may be a potential molecular target for ccRCC therapy.
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Digital three-dimensional model of lumbar region 4-5 and its adjacent structures based on a virtual Chinese human.
Orthop Surg
PUBLISHED: 05-10-2013
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To study the methods for constructing a digitized three-dimensional (3D) model of a virtual lumbar region and its adjacent structures in order to assist anatomical study and virtual surgery.
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Synthesis and characterization of superparamagnetic CoFe2O4/MWCNT hybrids for tumor-targeted therapy.
J Nanosci Nanotechnol
PUBLISHED: 05-08-2013
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Owing to their great potentialities of carbon nanotubes (CNTs)-based magnetic nano-composites, numerous applications of them have been found in nanotechnology, integrated functional system, and in medicine. Herein, nearly monodisperse CoFe2O4 nanoparticles have been deposited on multi-walled carbon nanotubes (MWCNTs) by high-temperature hydrolysis and inorganic polymerization of ionic Co(II) and Fe(III) salts and MWCNTs in a polyol solution. X-ray diffraction, energy-dispersive X-ray spectrometry and transmission electron microscopy were used to characterize the final products. The average size of CoFe2O4 nanoparticles and their coverage density on MWCNTs can be adjusted to some extent by altering the reaction parameters. A proposed formation mechanism of the magnetic hybrids is presented. Magnetic measurements showed that the hybrids were superparamagnetic at room temperature and their saturation magnetization could be fine tuned by changing the loading of CoFe2O4 nanoparticles on the MWCNTs.
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A systematic review and meta-analysis of current evidence comparing laparoendoscopic single-site adrenalectomy and conventional laparoscopic adrenalectomy.
J. Endourol.
PUBLISHED: 04-03-2013
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To assess the efficacy and safety of laparoendoscopic single-site adrenalectomy (LESS-A) and conventional laparoscopic adrenalectomy (LA) as a systematic review and meta-analysis of current evidence.
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Tet1 regulates adult hippocampal neurogenesis and cognition.
Cell Stem Cell
PUBLISHED: 04-02-2013
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DNA hydroxylation catalyzed by Tet dioxygenases occurs abundantly in embryonic stem cells and neurons in mammals. However, its biological function in vivo is largely unknown. Here, we demonstrate that Tet1 plays an important role in regulating neural progenitor cell proliferation in adult mouse brain. Mice lacking Tet1 exhibit impaired hippocampal neurogenesis accompanied by poor learning and memory. In adult neural progenitor cells deficient in Tet1, a cohort of genes involved in progenitor proliferation were hypermethylated and downregulated. Our results indicate that Tet1 is positively involved in the epigenetic regulation of neural progenitor cell proliferation in the adult brain.
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Diabetes mellitus reduces prostate cancer risk - no function of age at diagnosis or duration of disease.
Asian Pac. J. Cancer Prev.
PUBLISHED: 03-29-2013
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Prior studies examining the relation between diabetes mellitus (DM) and prostate cancer risk have reported controversial findings. We examined this association by conducting a detailed meta-analysis of the peer-reviewed literature.
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Family history and risk of ductal carcinoma in situ and triple negative breast cancer in a Han Chinese population: a case-control study.
World J Surg Oncol
PUBLISHED: 03-13-2013
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The association between family history and risk of triple negative breast cancer and ductal carcinoma in situ (DCIS) has not been well investigated, especially in Asian populations. We investigated the association between family history and risk of DCIS or triple negative breast cancer in a Han Chinese population.
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Effect of amitriptyline in treatment interstitial cystitis or bladder pain syndrome according to two criteria: Does ESSIC criteria change the response rate?
Neurourol. Urodyn.
PUBLISHED: 03-06-2013
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AIMS: The European Society for the Study of Interstitial Cystitis (ESSIC) recommended that interstitial cystitis (IC) should be replaced by bladder pain syndrome (BPS), which focused more attention on the painful or discomfort feeling related to bladder and weakened the importance of cystoscopy in diagnosis process. Our study aimed to explore whether this alteration changed the treatment outcomes of amitriptyline and whether cystoscopy was meaningful for the treatment of this disease. METHODS: We conducted a retrospective study including 25 IC patients fulfilled the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) criteria and 42 BPS patients diagnosed according to ESSIC criteria. All the patients received amitriptyline with a self-uptitration protocol. We compared the response rates of two groups by a patient reported global response assessment after 3 months and reclassified all the 67 patients according to ESSIC criteria, the response rates of different BPS types were also assessed. RESULTS: There was no significant difference of response rate between IC patients (12/25, 48%) and BPS patients (19/42, 45.2%) according to different criteria (P?=?0.337). The response rate of BPS type 1 (13/30, 43.3%) was similar to that of type 2 or 3 (18/37, 48.6%) (P?=?0.664). CONCLUSIONS: ESSIC criteria did not decrease the response rate of amitriptyline treatment for BPS patients compared to IC patients with complaint of bladder pain or discomfort. Cystoscopy showed no predictive effect for the treatment outcome of amitriptyline. Neurourol. Urodynam. 9999:XX-XX, 2013. © 2013 Wiley Periodicals, Inc.
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In vitro tumor cytotoxic activities of extracts from three Liriodendron plants.
Pak J Pharm Sci
PUBLISHED: 03-05-2013
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The extracts prepared from Liriodendron tulipifera Linn., L. chinense (Hemsl.) Sarg., and their hybrid L. chinense x L. tulipifera, were investigated for their cytotoxic abilities in vitro against five human cancer cell lines: MDA-MB-231 and MCF-7 breast cancer cells, SGC-7901 gastric cancer cells, HuH-7 hepatocarcinoma cells, and HCT-15 colon carcinoma cells, and then measured their phenols and alkaloids contents. Of these plant extracts, some of them, especially the lower polar extracts from barks, exhibited potent cytotoxic effects on five tested tumor cell lines.
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Hepatitis C virus NS4B blocks the interaction of STING and TBK1 to evade host innate immunity.
J. Hepatol.
PUBLISHED: 03-03-2013
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Hepatitis C virus (HCV) is a major human viral pathogen that causes chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. In most cases, acute HCV infection becomes persistent, at least in part due to viral evasion of host innate immune response. Although HCV genomic RNA contains pathogen-associated molecular pattern (PAMP) that is able to induce host interferon responses, HCV can shut down the responses by using the viral NS3/4A protease to cleave MAVS/VISA and TRIF, two key adaptor molecules essential for the interferon signaling activation. The aim of this study was to explore a novel NS3/4A-independent mechanism HCV utilizes to evade host innate immune responses.
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Downregulation of miR-106b induced breast cancer cell invasion and motility in association with overexpression of matrix metalloproteinase 2.
Cancer Sci.
PUBLISHED: 03-01-2013
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Breast cancer (BC) is one of the most common cancers in women, and it can often metastasize to the bone. The mechanism of BC bone metastasis remains unclear and requires in-depth investigation. In a previous study, we found the expression of matrix metalloproteinase 2 (MMP2) to be significantly more pronounced at metastatic bone sites than at orthotopic sites. MicroRNA expression profiling showed miR-106b to be markedly downregulated during BC bone metastasis. However, the specific manner in which MMP2 and miR-106b are involved in the BC bone metastasis is still unclear. In the present study, we found MMP2 expression in orthotopic tumor tissue to be related to the risk of bone metastasis in BC patients. MiR-106b levels in orthotopic tumor tissue showed a negative correlation with MMP2 expression and breast cancer bone metastasis. MMP2 was shown to be a direct target of miR-106b. Both gain- and loss-of-function studies showed that MMP2 could promote the migration and invasion of BC cells and that miR-106b could suppress both. The blockage of MMP2 by RNA interference mimicked the anti-migration and anti-invasion effects of miR-106b, and introduction of MMP2 antagonized the function of miR-106b. MMP2 was also found to regulate the ERK signaling cascade and so adjust the bone microenvironment to favor osteoclastogenesis and bone metastasis. These results suggest that MMP2 upregulation plays an important role in BC bone metastasis through ERK pathways, and miR-106b directly regulates MMP2 expression. The miR-106b/MMP2/ERK pathway may be a promising therapeutic target for inhibiting BC bone metastasis.
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Hypoxia-induced factor-1 alpha upregulates vascular endothelial growth factor C to promote lymphangiogenesis and angiogenesis in breast cancer patients.
J Biomed Res
PUBLISHED: 02-22-2013
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Hypoxia-induced factor-1 alpha (HIF-1?) affects many effector molecules and regulates tumor lymphangiogenesis and angiogenesis during hypoxia. The aim of this study was to investigate the role of HIF-1? in the regulation of vascular endothelial growth factor C (VEGF-C) expression and its effect on lymphangiogenesis and angiogenesis in breast cancer. Lymphatic vessel density (LVD), microvessel density (MVD) and the expressions of HIF-1? and VEGF-C proteins were evaluated by immunohistochemistry in 75 breast cancer samples. There was a significant correlation between HIF-1? and VEGF-C (P = 0.014, r = 0.273, Spearmans coefficient of correlation). HIF-1? and VEGF-C overexpression was significantly correlated with higher LVD (P = 0.003 and P = 0.017, respectively), regional lymph nodal involvement (P = 0.002 and P = 0.004, respectively) and advanced tumor, node, metastasis (TNM) classification (P = 0.001 and P = 0.01, respectively). Higher MVD was observed in the group expressing higher levels of HIF-1? and VEGF-C (P = 0.033 and P = 0.037, respectively). Univariate analysis showed shorter survival time in patients expressing higher levels of HIF-1? and VEGF-C. HIF-1? was also found to be an independent prognostic factor of overall survival in multivariate analysis. The results suggest that HIF-1? may affect VEGF-C expression, thus acting as a crucial regulator of lymphangiogenesis and angiogenesis in breast cancer. This study highlights promising potential of HIF-1? as a therapeutic target against tumor lymph node metastasis.
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The association between overall survival of prostate cancer patients and hypertension, hyperglycemia, and overweight in Southern China: a prospective cohort study.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 02-18-2013
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Hypertension, hyperglycemia, and overweight are considered associated with the development and prognosis of prostate cancer (PCa). This study is aimed at investigating the association between pre-existing hypertension, hyperglycemia, and overweight and the overall survival (OS) of PCa patients receiving androgen deprivation therapy (ADT).
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Prediction of prostate cancer from prostate biopsy in Chinese men using a genetic score derived from 24 prostate cancer risk-associated SNPs.
Prostate
PUBLISHED: 02-15-2013
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Twenty-four prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) in Chinese men have been cataloged. We evaluated whether these SNPs can independently predict outcomes of prostate biopsy, and improve the predictive performance of existing clinical variables.
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Pleural mesothelial cell differentiation and invasion in fibrogenic lung injury.
Am. J. Pathol.
PUBLISHED: 02-09-2013
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The origin of the myofibroblast in fibrotic lung disease is uncertain, and no effective medical therapy for fibrosis exists. We have previously demonstrated that transforming growth factor-?1 (TGF-?1) induces pleural mesothelial cell (PMC) transformation into myofibroblasts and haptotactic migration in vitro. Whether PMC differentiation and migration occurs in vivo, and whether this response can be modulated for therapeutic benefit, is unknown. Here, using mice recombinant for green fluorescent protein (GFP) driven by the Wilms tumor-1 (WT-1) promoter, we demonstrate PMC trafficking into the lung and differentiation into myofibroblasts. Carbon monoxide or the induction of heme oxygenase-1 (HO-1) inhibited the expression of myofibroblast markers, contractility, and haptotaxis in PMCs treated with TGF-?1. Intrapleural HO-1 induction inhibited PMC migration after intratracheal fibrogenic injury. PMCs from patients with idiopathic pulmonary fibrosis (IPF) exhibited increased expression of myofibroblast markers and enhanced contractility and haptotaxis, compared with normal PMCs. Carbon monoxide reversed this IPF PMC profibrotic phenotype. WT-1-expressing cells were present within fibrotic regions of the lungs in IPF subjects, supporting a role for PMC differentiation and trafficking as contributors to the myofibroblast population in lung fibrosis. Our findings also support a potential role for pleural-based therapies to modulate pleural mesothelial activation and parenchymal fibrosis progression.
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Adrenal myelolipoma: a mingle of progenitor cells?
Med. Hypotheses
PUBLISHED: 02-08-2013
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Adrenal myelolipoma (AML) is a rare benign tumour composed or mature haematopoietic tissue and fat. The tumour is functionally inert and is usually detected incidentally. Mainly introduced in case reports, the tumourigenesis of AML is poorly understood with 3 historical hypotheses seemingly unrelated to each other. Here we propose the tumourigenic pathway based on the novel findings on stem/progenitor cell and our preliminary data. We hypothesize the tumourigenesis as follows: the fat components are derived by the mesenchymal stem cells of stromal fat of adrenal cortex under certain stimuli. Mature adipocytes begin to accumulate and become inflammatory stimulating neighbouring adrenal cortex tissue to release possibly G-CSF to recruit circulating haematopoietic progenitors. During the tumour growth, haematopoietic cell in the central part acquire energy from burning the surrounding fat until they are fully differentiated and division stops. Lacking the ability to further grow, the central part undergoes necrosis and calcification whilst the peripheral part continues to slowly pile up newly derived adipocytes and haematopoietic progenitor cells. The necrosis or calcification of the tumour the inflammation persists and the tumour generates a self-growing signalling loop, entailing a continuous growth even without further stimuli. Our theory offers a logical explanation to the diverse phenomena identified on AML and unifies the historical theories. Future studies may focus on the stem/progenitor cell profiles of AML to confirm and supplement our hypothesis.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.