JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Ag-nanoparticle-decorated porous ZnO-nanosheets grafted on a carbon fiber cloth as effective SERS substrates.
Nanoscale
PUBLISHED: 11-10-2014
Show Abstract
Hide Abstract
We report on the large-scale synthesis of Ag-nanoparticle (Ag-NP) decorated ZnO-mesoporous-nanosheets (NSs) grafted on a flexible carbon fiber cloth (CFC), as sensitive and reproducible surface enhanced Raman scattering (SERS) substrates with excellent flexibility. The composite SERS-substrates are achieved by a combination of atomic layer deposition of ZnO-seeds on each fiber of the CFC (denoted as ZnO-seeds@CFC), chemical bath deposition and subsequent pyrolysis for the creation of ZnO-mesoporous-NSs grafted on ZnO-seeds@CFC, and ion-sputtering of Ag-NPs on the ZnO-mesoporous-NSs. As abundant SERS "hot spots" are generated from the electromagnetic coupling of the densely distributed Ag-NPs, and the semiconducting ZnO-mesoporous-NSs also have chemical supporting enhancement and distinct molecule adsorbing abilities, the composite SERS-substrates demonstrate high SERS-sensitivity with good signal reproducibility. As a trial for potential applications, the composite SERS-substrates were used to identify pesticides and highly toxic polychlorinated biphenyls (PCBs), and low concentrations down to 10(-7) M for methyl parathion and 5 × 10(-6) M for PCB-77 were reached, respectively, showing promising potential for the SERS-based rapid detection of toxic organic pollutants in the environment.
Related JoVE Video
Enantioselective Analysis and Dissipation of Triazole Fungicide Penconazole in Vegetables by Liquid Chromatography-Tandem Mass Spectrometry.
J. Agric. Food Chem.
PUBLISHED: 11-07-2014
Show Abstract
Hide Abstract
Penconazole is a typical triazole fungicide, which is commonly used to control powdery mildew in vineyard and vegetable field. In this study, the enantioselective dissipation of penconazole in cucumber, tomato, head cabbage, and pakchoi was investigated by field experiments. A sensitive method for enantiomeric analysis of penconazole was established on the basis of the buffered QuEChERS sample preparation technique followed by reverse-liquid chromatography equipped with a TSQ Discovery triple quadrupole mass spectrometer and a Lux Cellulose-2 chiral column. Methanol and 2 mM ammonium acetate buffer solution containing 0.1% formic acid (70:30, v/v) were used as mobile phase at a 0.2 mL L(-1) flow rate isocratic elution. The linearity, recovery, and precision of this method were also evaluated. Finally, the results of this study demonstrated that enantioselective dissipation occurred in head cabbage and pakchoi, with the preferential degradation of (-)-penconazole, and resulting in an enrichment of the (+)-penconazole residue in the two vegetables. However, the enantioselective behavior was not observed in cucumber and tomato. More importantly, this is the first report of enantioselective behavior of penconazole, and the result may provide useful information for the risk evaluation of penconazole in food and environmental safety.
Related JoVE Video
Are there gender differences in sagittal spinal pelvic inclination before and after the adolescent pubertal growth spurt?
Eur Spine J
PUBLISHED: 09-04-2014
Show Abstract
Hide Abstract
Significant progression of spinal deformity could occur during the peak of pubertal growth in adolescent idiopathic scoliosis (AIS). Gender differences in spinal and vertebral inclination have been reported in asymptomatic young adults and are thought to affect the risk of curve progression in male and female AIS. The present study aimed to investigate whether there were gender differences in the sagittal spinal-pelvic profile and whether any differences occurred before or developed during the normal pubertal growth spurt.
Related JoVE Video
Long-term Survival and Late Effects among 1-year Survivors of Second Allogeneic Hematopoietic Cell Transplantation for Relapsed Acute Leukemia and Myelodysplastic Syndromes.
Biol. Blood Marrow Transplant.
PUBLISHED: 08-19-2014
Show Abstract
Hide Abstract
We analyzed the outcomes of patients who survived disease-free for 1-year or more following second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant following disease relapse; among these 325 survived relapse-free at 1-year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplant in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least one year were 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status prior to second HCT was significantly associated with higher risk for overall mortality (HR 1.71 for patients with disease not in complete remission prior to second HCT, P<0.01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults following second transplant. Chronic GVHD was the leading cause of non-relapse mortality followed by organ failure and infection. The cumulative incidence of developing at least one of the studied late effects at 10-years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence 22%) and cataracts (20%), and in adults were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease-free for at least 1-year, many can be expected to survive long term. However, they continue to be at risk for relapse and non-relapse morbidity and mortality. Novel approaches are needed to minimize relapse risk and long-term transplant morbidity in this population.
Related JoVE Video
Amide alkaloids from Scopolia tangutica.
Planta Med.
PUBLISHED: 08-15-2014
Show Abstract
Hide Abstract
Four new hydroxycinnamic acid amides, scotanamines A-D (1-4), and seven known alkaloids, including N (1),N (10)-di-dihydrocaffeoylspermidine (5), scopolamine (6), anisodamine (7), hyoscyamine (8), anisodine (9), caffeoylputrescine (10), and N (1)-caffeoyl-N (3)-dihydrocaffeoylspermidine (11), were obtained from the roots of Scopolia tangutica. The present study represents the first recognition of hydroxycinnamic acid amides containing putrescine or spermidine in S. tangutica. Compound 1, in particular, contains a moiety resulting from the condensation of nortropinone and putrescine. Compound 2 exhibited moderate agonist activity at the µ-opioid receptor (EC50=7.3 µM). Compound 2 was tested in vivo and induced analgesia in mice. The analgesic effect was recorded using the tail-flick assay and was reversed by naloxone.
Related JoVE Video
Discovery of N-methyltetrahydroprotoberberines with ?-opioid receptor agonists-opioid receptor agonist activities from corydalis yanhusuo W. T. Wang by using two-dimensional liquid chromatography.
J Ethnopharmacol
PUBLISHED: 08-06-2014
Show Abstract
Hide Abstract
The need for an efficacious analgesic without unwanted side effects is urgent. ?-opioid receptor agonists are known to exhibit potent analgesic effects and elicited fewer side effects than other opioid agonists. Thus in this study we chose the ?-opioid receptor as the target to identify the active components from traditional Chinese medicines (TCMs).
Related JoVE Video
[Effect of native aortic valve sparing aortic root reconstruction surgery on short- and long-term prognosis in Marfan syndrome patients:a meta-analysis].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 07-22-2014
Show Abstract
Hide Abstract
This meta-analysis was performed to analyze the effect of preserving the native aortic valve on short- and long-term prognosis post aortic root reconstruction surgery for patients with Marfan syndrome.
Related JoVE Video
Which cannulation (axillary cannulation or femoral cannulation) is better for acute type A aortic dissection repair? A meta-analysis of nine clinical studies.
Eur J Cardiothorac Surg
PUBLISHED: 07-13-2014
Show Abstract
Hide Abstract
There is a trend towards using the axillary artery cannulation (AXC) site for cardiopulmonary bypass surgery in patients requiring acute type A aortic dissection (AAD) repair. However, AXC has not been established as a routine procedure, because there is controversy about its clinical advantage when compared with femoral artery cannulation (FAC). This meta-analysis assesses major short-term outcomes in patients undergoing acute AAD repair with AXC or FAC using non-randomized retrospective studies dating from 1992 to 2011 comparing AXC and FAC for major outcomes. Outcomes of interest were short-term mortality, neurological dysfunction and malperfusion. The fixed-effects model was used. Sensitivity and heterogeneity were analysed. Analysis of nine non-randomized studies comprising 715 patients [AXC, 359 (50.2%) and FAC, 356 (49.8%)] showed a significantly lower incidence of short-term mortality in the AXC group [odds ratio, 0.25, 95% confidence interval (CI) (0.15, 0.42), ?(2) = 7.23, P < 0.01]. The pattern of incidence of neurological dysfunction among the AXC group [odds ratio, 0.46, 95% CI (0.29, 0.72), ?(2) = 9.01, P < 0.01] was similar. The incidence of malperfusion did not differ [odds ratio, 0.84, 95% CI (0.37, 1.90), ?(2) = 2.25, P = 0.67]. Because no study was a randomized trial, our results are more uncertain than indicated by the 95% CI. Nevertheless, AXC seems to give better short-term mortality and neurological dysfunction rates than FAC.
Related JoVE Video
ABO blood group and esophageal carcinoma risk: from a case-control study in Chinese population to meta-analysis.
Cancer Causes Control
PUBLISHED: 07-10-2014
Show Abstract
Hide Abstract
The association between ABO blood group and the risk of esophageal carcinoma (EC) in previously published studies is uncertain and conflicting. The aim of the current study was to determine the correlation of ABO blood group with EC risk via a case-control study and meta-analysis.
Related JoVE Video
Identification of neuropeptide receptors expressed by melanin-concentrating hormone neurons.
J. Comp. Neurol.
PUBLISHED: 06-17-2014
Show Abstract
Hide Abstract
Melanin-concentrating hormone (MCH) is a 19-amino-acid cyclic neuropeptide that acts in rodents via the MCH receptor 1 (MCHR1) to regulate a wide variety of physiological functions. MCH is produced by a distinct population of neurons located in the lateral hypothalamus (LH) and zona incerta (ZI), but MCHR1 mRNA is widely expressed throughout the brain. The physiological responses and behaviors regulated by the MCH system have been investigated, but less is known about how MCH neurons are regulated. The effects of most classical neurotransmitters on MCH neurons have been studied, but those of most neuropeptides are poorly understood. To gain insight into how neuropeptides regulate the MCH system, we investigated which neuropeptide receptors are expressed by MCH neurons by using double in situ hybridization. In all, 20 receptors, selected based on either a suspected interaction with the MCH system or demonstrated high expression levels in the LH and ZI, were tested to determine whether they are expressed by MCH neurons. Overall, 11 neuropeptide receptors were found to exhibit significant colocalization with MCH neurons: nociceptin/orphanin FQ opioid receptor (NOP), MCHR1, both orexin receptors (ORX), somatostatin receptors 1 and 2 (SSTR1, SSTR2), kisspeptin recepotor (KissR1), neurotensin receptor 1 (NTSR1), neuropeptide S receptor (NPSR), cholecystokinin receptor A (CCKAR), and the ?-opioid receptor (KOR). Among these receptors, six have never before been linked to the MCH system. Surprisingly, several receptors thought to regulate MCH neurons displayed minimal colocalization with MCH, suggesting that they may not directly regulate the MCH system.
Related JoVE Video
Phosphorylation of Akt at the C-terminal tail triggers Akt activation.
Cell Cycle
PUBLISHED: 06-16-2014
Show Abstract
Hide Abstract
Aberrant hyper-activation of the protein kinase Akt plays a critical role in promoting tumorigenesis. Mechanistically, previous studies establish that phosphorylation of Akt at S473 and T308 by mTORC2 and PDK1, respectively, is necessary for its full activation, thereby having been used as Akt activation markers. Recently, we report that phosphorylation of S477 and T479 at the extreme C-terminus of Akt1 promotes Akt1 activation. We further demonstrate that Akt1 pS477 and pT479 events are governed by Cdk2/Cyclin A or mTORC2 under distinct cellular contexts such as cell cycle progression or growth stimulation conditions. Here, we summarize our major findings regarding the biological significance for pS477/pT479-mediated activation of Akt and also provide perspectives for future follow-up studies.
Related JoVE Video
Curcumin inhibits cell growth and invasion through up-regulation of miR-7 in pancreatic cancer cells.
Toxicol. Lett.
PUBLISHED: 06-15-2014
Show Abstract
Hide Abstract
Accumulating evidence has revealed that a natural compound curcumin exerts its anti-tumor activity in pancreatic cancer. However, the underlying molecular mechanism remains elusive. Recently, miRNAs have been demonstrated to play a crucial role in tumorigenesis, suggesting that targeting miRNAs could be a promising approach for the treatment of human cancers. In this study, we explored whether curcumin regulates miR-7, leading to the inhibition of cell growth, migration and invasion in pancreatic cancer cells. We observed that curcumin suppressed cell growth, migration and invasion, and induced cell apoptosis, which is associated with increased expression of miR-7 and subsequently decreased expression of SET8, one of the miR-7 targets. These findings demonstrated that targeting miR-7 by curcumin could be a novel strategy for the treatment of pancreatic cancer.
Related JoVE Video
Second solid cancers after allogeneic hematopoietic cell transplantation using reduced-intensity conditioning.
Biol. Blood Marrow Transplant.
PUBLISHED: 06-12-2014
Show Abstract
Hide Abstract
We examined risk of second solid cancers after allogeneic hematopoietic cell transplantation (AHCT) using reduced-intensity/nonmyeloablative conditioning (RIC/NMC). RIC/NMC recipients with leukemia/myelodysplastic syndrome (MDS) (n = 2833) and lymphoma (n = 1436) between 1995 and 2006 were included. In addition, RIC/NMC recipients 40 to 60 years of age (n = 2138) were compared with patients of the same age receiving myeloablative conditioning (MAC, n = 6428). The cumulative incidence of solid cancers was 3.35% at 10 years. There was no increase in overall cancer risk compared with the general population (leukemia/MDS: standardized incidence ratio [SIR] .99, P = 1.00; lymphoma: SIR .92, P = .75). However, risks were significantly increased in leukemia/MDS patients for cancers of lip (SIR 14.28), tonsil (SIR 8.66), oropharynx (SIR 46.70), bone (SIR 23.53), soft tissue (SIR 12.92), and vulva (SIR 18.55) and skin melanoma (SIR 3.04). Lymphoma patients had significantly higher risks of oropharyngeal cancer (SIR 67.35) and skin melanoma (SIR 3.52). Among RIC/NMC recipients, age >50 years was the only independent risk factor for solid cancers (hazard ratio [HR] 3.02, P < .001). Among patients ages 40 to 60 years, when adjusted for other factors, there was no difference in cancer risks between RIC/NMC and MAC in leukemia/MDS patients (HR .98, P = .905). In lymphoma patients, risks were lower after RIC/NMC (HR .51, P = .047). In conclusion, the overall risks of second solid cancers in RIC/NMC recipients are similar to the general population, although there is an increased risk of cancer at some sites. Studies with longer follow-up are needed to realize the complete risks of solid cancers after RIC/NMC AHCT.
Related JoVE Video
Aberrant regulation of FBW7 in cancer.
Oncotarget
PUBLISHED: 06-06-2014
Show Abstract
Hide Abstract
FBW7 (F-box and WD repeat domain-containing 7) or Fbxw7 is a tumor suppressor, which promotes the ubiquitination and subsequent degradation of numerous oncoproteins including Mcl-1, Cyclin E, Notch, c- Jun, and c-Myc. In turn, FBW7 is regulated by multiple upstream factors including p53, C/EBP-?, EBP2, Pin1, Hes-5 and Numb4 as well as by microRNAs such as miR-223, miR-27a, miR-25, and miR-129-5p. Given that the Fbw7 tumor suppressor is frequently inactivated or deleted in various human cancers, targeting FBW7 regulators is a promising anti-cancer therapeutic strategy.
Related JoVE Video
Hospital Length of Stay in the First 100 Days after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia in Remission: Comparison among Alternative Graft Sources.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-27-2014
Show Abstract
Hide Abstract
Several studies have shown comparable survival outcomes with different graft sources, but the relative resource needs of hematopoietic cell transplantation (HCT) by graft source have not been well studied. We compared total hospital length of stay in the first 100 days after HCT in 1577 patients with acute leukemia in remission who underwent HCT with an umbilical cord blood (UCB), matched unrelated donor (MUD), or mismatched unrelated donor (MMUD) graft between 2008 and 2011. To ensure a relatively homogenous study population, the analysis was limited to patients with acute myelogenous leukemia and acute lymphoblastic leukemia in first or second complete remission who underwent HCT in the United States. To account for early deaths, we compared the number of days alive and out of the hospital in the first 100 days post-transplantation. For children who received myeloablative conditioning, the median time alive and out of the hospital in the first 100 days was 50 days for single UCB recipients, 54 days for double UCB recipients, and 60 days for MUD bone marrow (BM) recipients. In multivariate analysis, use of UCB was significantly associated with fewer days alive and out of the hospital compared with MUD BM. For adults who received myeloablative conditioning, the median time alive and out of the hospital in first 100 days was 52 days for single UCB recipients, 55 days for double UCB recipients, 69 days for MUD BM recipients, 75 days for MUD peripheral blood stem cell (PBSC) recipients, 63 days for MMUD BM recipients, and 67 days for MMUD PBSC recipients. In multivariate analysis, UCB and MMUD BM recipients had fewer days alive and out of the hospital compared with recipients of other graft sources. For adults who received a reduced-intensity preparative regimen, the median time alive and out of the hospital during the first 100 days was 65 days for single UCB recipients, 63 days for double UCB recipients, 79 days for MUD PBSC recipients, and 79 days for MMUD PBSC recipients. Similar to the other 2 groups, receipt of UCB was associated with a fewer days alive and out of the hospital. In conclusion, length of stay in the first 100 days post-transplantation varies by graft source and is longer for UCB HCT recipients. These data provide insight into the resource needs of patients who undergo HCT with these various graft sources.
Related JoVE Video
Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation.
Blood
PUBLISHED: 04-17-2014
Show Abstract
Hide Abstract
Because the outcome of allogeneic hematopoietic cell transplantation (HCT) is predominantly influenced by disease type and status, it is essential to be able to stratify patients undergoing HCT by disease risk. The Disease Risk Index (DRI) was developed for this purpose. In this study, we analyzed 13,131 patients reported to the Center for International Blood and Marrow Transplant Research who underwent HCT between 2008 and 2010. The DRI stratified patients into 4 groups with 2-year overall survival (OS) ranging from 64% to 24% and was the strongest prognostic factor, regardless of age, conditioning intensity, graft source, or donor type. A randomly selected training subgroup of 9849 patients was used to refine the DRI, using a multivariable regression model for OS. This refined DRI had improved prediction ability for the remaining 3282 patients compared with the original DRI or other existing schemes. This validated and refined DRI can be used as a 4- or 3-group index, depending on the size of the cohort under study, for prognostication; to facilitate the interpretation of single-center, multicenter, or registry studies; to adjust center outcome data; and to stratify patients entering clinical trials that enroll patients across disease categories.
Related JoVE Video
Decreased expression of P54(nrb) /NonO correlates with collagen deposition and fibrosis in human aortic dissection.
Histopathology
PUBLISHED: 04-09-2014
Show Abstract
Hide Abstract
Aortic dissection (AD) is characterized by changes in the extracellular matrix, including fibrosis with collagen production. P54(nrb) /NonO is known to be involved in collagen formation. In this study, we examined whether AD is associated with abnormal P54(nrb) /NonO expression.
Related JoVE Video
FAM3A activates PI3K p110?/Akt signaling to ameliorate hepatic gluconeogenesis and lipogenesis.
Hepatology
PUBLISHED: 03-27-2014
Show Abstract
Hide Abstract
FAM3A belongs to a novel cytokine-like gene family, and its physiological role remains largely unknown. In our study, we found a marked reduction of FAM3A expression in the livers of db/db and high-fat diet (HFD)-induced diabetic mice. Hepatic overexpression of FAM3A markedly attenuated hyperglycemia, insulin resistance, and fatty liver with increased Akt (pAkt) signaling and repressed gluconeogenesis and lipogenesis in the livers of those mice. In contrast, small interfering RNA (siRNA)-mediated knockdown of hepatic FAM3A resulted in hyperglycemia with reduced pAkt levels and increased gluconeogenesis and lipogenesis in the livers of C57BL/6 mice. In vitro study revealed that FAM3A was mainly localized in the mitochondria, where it increases adenosine triphosphate (ATP) production and secretion in cultured hepatocytes. FAM3A activated Akt through the p110? catalytic subunit of PI3K in an insulin-independent manner. Blockade of P2 ATP receptors or downstream phospholipase C (PLC) and IP3R and removal of medium calcium all significantly reduced FAM3A-induced increase in cytosolic free Ca(2+) levels and attenuated FAM3A-mediated PI3K/Akt activation. Moreover, FAM3A-induced Akt activation was completely abolished by the inhibition of calmodulin (CaM).
Related JoVE Video
Roles of F-box proteins in cancer.
Nat. Rev. Cancer
PUBLISHED: 03-25-2014
Show Abstract
Hide Abstract
F-box proteins, which are the substrate-recognition subunits of SKP1-cullin 1-F-box protein (SCF) E3 ligase complexes, have pivotal roles in multiple cellular processes through ubiquitylation and subsequent degradation of target proteins. Dysregulation of F-box protein-mediated proteolysis leads to human malignancies. Notably, inhibitors that target F-box proteins have shown promising therapeutic potential, urging us to review the current understanding of how F-box proteins contribute to tumorigenesis. As the physiological functions for many of the 69 putative F-box proteins remain elusive, additional genetic and mechanistic studies will help to define the role of each F-box protein in tumorigenesis, thereby paving the road for the rational design of F-box protein-targeted anticancer therapies.
Related JoVE Video
SCF(?-TRCP)-mediated degradation of NEDD4 inhibits tumorigenesis through modulating the PTEN/Akt signaling pathway.
Oncotarget
PUBLISHED: 03-25-2014
Show Abstract
Hide Abstract
The HECT domain-containing ubiquitin E3 ligase NEDD4 is widely expressed in mammalian tissues and plays a crucial role in governing a wide spectrum of cellular processes including cell growth, tissue development and homeostasis. Recent reports have indicated that NEDD4 might facilitate tumorigenesis through targeted degradation of multiple tumor suppressor proteins including PTEN. However, the molecular mechanism by which NEDD4 stability is regulated has not been fully elucidated. Here we report that SCF(?-TRCP) governs NEDD4 protein stability by targeting it for ubiquitination and subsequent degradation in a Casein Kinase-I (CKI) phosphorylation-dependent manner. Specifically, depletion of ?-TRCP, or inactivation of CKI, stabilized NEDD4, leading to down-regulation of its ubiquitin target PTEN and subsequent activation of the mTOR/Akt oncogenic pathway. Furthermore, we found that CKI?-mediated phosphorylation of Ser347 and Ser348 on NEDD4 promoted its interaction with SCF(?-TRCP) for subsequent ubiquitination and degradation. As a result, compared to ectopic expression of wild-type NEDD4, introducing a non-degradable NEDD4 (S347A/S348A-NEDD4) promoted cancer cell growth and migration. Hence, our findings revealed the CKI/SCF(?-TRCP) signaling axis as the upstream negative regulator of NEDD4, and further suggested that enhancing NEDD4 degradation, presumably with CKI or SCF(?-TRCP) agonists, could be a promising strategy for treating human cancers.
Related JoVE Video
Overexpression of Dickkopf-1 predicts poor prognosis for patients with hepatocellular carcinoma after orthotopic liver transplantation by promoting cancer metastasis and recurrence.
Med. Oncol.
PUBLISHED: 03-23-2014
Show Abstract
Hide Abstract
Our previous data had shown that Dickkopf-1 (DKK1) combined with ?-catenin was a novel prognostic predictor for hepatocellular carcinoma (HCC) patients. However, the role and mechanism of DKK1 in HCC recurrence or metastasis remain poorly understand. This study was to assess the role of DKK1 in tumor metastasis for patients with hepatocellular carcinoma after orthotopic liver transplantation (OLT). The expression of DKK1 protein was detected in hepatic cell lines, HCC cell lines, and HCC patients after OLT with different potential of metastasis. After DKK1 expression in the HCCLM3 cells was downregulated by siRNA-mediated approach, the role of DKK1 in cell invasion and metastasis was investigated. cDNA genechip was used to analyze the differential expressed genes related with DKK1 in two pairs of HCC cells. The prognostic significance of DKK1 was further assessed by Kaplan-Meier and Cox regression analyses in 148 HCC patients after OLT. The expression of DKK1 protein was higher in the high-invasive HCC cells and HCC patients of the disease recurrence group. With the downregulation of DKK1, HCCLM3 cells showed decreased aggressiveness in vitro and lower metastatic ability in vivo. DKK1 could regulate many genes involved in biological processes and pathways related with tumor progression. Furthermore, DKK1 overexpression correlated with tumor microvessel density in clinical HCC samples. Multivariate analysis revealed that DKK1 was an independent prognostic indicator for overall survival and cumulative recurrence in this cohort of HCC patients post-OLT. Collectively, overexpression of DKK1 was implicated in invasion/metastasis of HCC after OLT and DKK1 overexpression may be potential molecular therapeutic targets for liver cancer.
Related JoVE Video
Histamine inhibits the melanin-concentrating hormone system: implications for sleep and arousal.
J. Physiol. (Lond.)
PUBLISHED: 03-17-2014
Show Abstract
Hide Abstract
Melanin-concentrating hormone (MCH)-producing neurons are known to regulate a wide variety of physiological functions such as feeding, metabolism, anxiety and depression, and reward. Recent studies have revealed that MCH neurons receive projections from several wake-promoting brain regions and are integral to the regulation of rapid eye movement (REM) sleep. Here, we provide evidence in both rats and mice that MCH neurons express histamine-3 receptors (H3R), but not histamine-1 (H1R) or histamine-2 (H2R) receptors. Electrophysiological recordings in brain slices from a novel line of transgenic mice that specifically express the reporter ZsGreen in MCH neurons show that histamine strongly inhibits MCH neurons, an effect which is TTX insensitive, and blocked by the intracellular presence of GDP-?-S. A specific H3R agonist, ?-methylhistamine, mimicks the inhibitory effects of histamine, and a specific neutral H3R antagonist, VUF 5681, blocks this effect. Tertiapin Q (TPQ), a G protein-dependent inwardly rectifying potassium (GIRK) channel inhibitor, abolishes histaminergic inhibition of MCH neurons. These results indicate that histamine directly inhibits MCH neurons through H3R by activating GIRK channels and suggest that that inhibition of the MCH system by wake-active histaminergic neurons may be responsible for silencing MCH neurons during wakefulness and thus may be directly involved in the regulation of sleep and arousal.
Related JoVE Video
NEDD4: a promising target for cancer therapy.
Curr Cancer Drug Targets
PUBLISHED: 03-14-2014
Show Abstract
Hide Abstract
The Neuronally expressed developmentally downregulated 4 (NEDD4), functioning largely as an E3 ubiquitin ligase, has been demonstrated to play a critical role in the development and progression of human cancers. In this review, to understand the regulatory mechanism(s) of NEDD4 as well as the signaling pathways controlled by NEDD4, we briefly describe the NEDD4 upstream regulators and its downstream ubiquitin substrates. Moreover, we further discuss its oncogenic roles in human malignancies. Therefore, targeting NEDD4 could be a potential therapeutic strategy for treatment of human cancers.
Related JoVE Video
Direct C-H arylation of thiophenes at low catalyst loading of a phosphine-free bis(alkoxo)palladium complex.
J. Org. Chem.
PUBLISHED: 03-14-2014
Show Abstract
Hide Abstract
An efficient phosphine-free direct C-H arylation of thiophenes at the ?-position has been developed at low catalyst loading of bis(alkoxo)palladium complex (Cat.I, 0.1-0.2 mol %). The developed synthetic method can be applied to the synthesis of ?-aryl/heteroaryl thiophenes from aryl or heteroaryl bromides in good to excellent yields and is compatible with the substrates bearing electron-donating or electron-withdrawing groups. The reactivities of the 2- and 5-positions of thiophenes are equivalent and not dependent on steric hindrance under optimal conditions. This condition can also be applied to other heterocyclic moieties such as benzothiophene, benzofuran, and pyrrole with high conversion yields.
Related JoVE Video
Survival improvements in adolescents and young adults after myeloablative allogeneic transplantation for acute lymphoblastic leukemia.
Biol. Blood Marrow Transplant.
PUBLISHED: 02-25-2014
Show Abstract
Hide Abstract
Adolescents and young adults (AYAs, ages 15 to 40 years) with cancer have not experienced survival improvements to the same extent as younger and older patients. We compared changes in survival after myeloablative allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) among children (n = 981), AYAs (n = 1218), and older adults (n = 469) who underwent transplantation over 3 time periods: 1990 to 1995, 1996 to 2001, and 2002 to 2007. Five-year survival varied inversely with age group. Survival improved over time in AYAs and paralleled that seen in children; however, overall survival did not change over time for older adults. Survival improvements were primarily related to lower rates of early treatment-related mortality in the most recent era. For all cohorts, relapse rates did not change over time. A subset of 222 AYAs between the ages of 15 and 25 at 46 pediatric or 49 adult centers were also analyzed to describe differences by center type. In this subgroup, there were differences in transplantation practices among pediatric and adult centers, although HCT outcomes did not differ by center type. Survival for AYAs undergoing myeloablative allogeneic HCT for ALL improved at a similar rate as survival for children.
Related JoVE Video
Numerical Simulation of Bubble Cluster Induced Flow by Three-Dimensional Vortex-in-Cell Method.
J Fluids Eng
PUBLISHED: 02-24-2014
Show Abstract
Hide Abstract
The behavior of air bubble clusters rising in water and the induced flow field are numerically studied using a three-dimensional two-way coupling algorithm based on a vortex-in-cell (VIC) method. In this method, vortex elements are convected in the Lagrangian frame and the liquid velocity field is solved from the Poisson equation of potential on the Eulerian grid. Two-way coupling is implemented by introducing a vorticity source term induced by the gradient of void fraction. Present simulation results are favorably compared with the measured results of bubble plume, which verifies the validity of the proposed VIC method. The rising of a single bubble cluster as well as two tandem bubble clusters are simulated. The mechanism of the aggregation effect in the rising process of bubble cluster is revealed and the transient processes of the generation, rising, strengthening, and separation of a vortex ring structure with bubble clusters are illustrated and analyzed in detail. Due to the aggregation, the average rising velocity increases with void fraction and is larger than the terminal rising velocity of single bubble. For the two tandem bubble cluster cases, the aggregation effect is stronger for smaller initial cluster distance, and both the strength of the induced vortex structure and the average bubble rising velocity are larger. For the 20?mm cluster distance case, the peak velocity of the lower cluster is about 2.7 times that of the terminal velocity of the single bubble and the peak average velocity of two clusters is about 2 times larger. While for the 30?mm cluster distance case, both the peak velocity of the lower cluster and two clusters are about 1.7 times that of the terminal velocity of the single bubble.
Related JoVE Video
Differentiation of iPSCs into insulin-producing cells via adenoviral transfection of PDX-1, NeuroD1 and MafA.
Diabetes Res. Clin. Pract.
PUBLISHED: 02-24-2014
Show Abstract
Hide Abstract
The aim of this study was to evaluate the effect of PDX-1 (pancreatic and duodenal homeobox-1), NeuroD1 (neurogenic differentiation-1) and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homolog A) in the differentiation of induced pluripotent stem cells (iPSCs) into insulin-producing cells and to explore this new approach of cell transplantation therapy for type 1 diabetes in mice.
Related JoVE Video
An anaerobic dynamic membrane bioreactor (AnDMBR) for landfill leachate treatment: performance and microbial community identification.
Bioresour. Technol.
PUBLISHED: 02-24-2014
Show Abstract
Hide Abstract
In this study, a pilot-scale anaerobic dynamic membrane bioreactor was operated for 142days for treating landfill leachate. Under stable operation, average COD removal efficiency of 62.2% was achieved when the reactor was fed with the raw leachate containing total ammonium concentration above 3000mg/L and COD above 13,000mg/L. The methane content in the biogas was in the range of 70-90%, and the average methane yield was 0.34L/g CODremoved at the organic loading rate of 4.87kg COD/(m(3)d). Pyrosequencing analyses indicated that during the operation the archaeal community was relatively stable while obvious changes took place in the bacterial community. Alkaliphilus, Petrimonas, Fastidiosipila and vadinBC27 were the abundant fermentation bacteria in bacterial communities. Moreover, phylum TM6 gradually became the most dominant bacterial community and reached the highest relative abundance of 32.9% as the operation elapsed. In archaeal communities, genus Methanosarcina was identified as the dominant methanogen.
Related JoVE Video
Strong coupling of the iron-quadrupole and anion-dipole polarizations in Ba(Fe(1-x)Co(x))2As2.
Phys. Rev. Lett.
PUBLISHED: 02-20-2014
Show Abstract
Hide Abstract
We use a quantitative convergent beam electron diffraction based method to image the valence electron density distribution in Ba(Fe1-xCox)2As2. We show a remarkable increase in both the charge quadrupole of the Fe cations and the charge dipole of the arsenic anions upon Co doping from x=0 (Tc=0??K) to x=0.1 (Tc=22.5??K). Our data suggest that an unexpected electronic correlation effect, namely strong coupling of Fe orbital fluctuation and anion electronic polarization, is present in iron-based superconductors.
Related JoVE Video
Highly expressed S100A12 in aortic wall of patients with DeBakey type I aortic dissection could be a promising marker to predict perioperative complications.
Ann Vasc Surg
PUBLISHED: 02-12-2014
Show Abstract
Hide Abstract
Thoracic aortic dissection (TAD) is a catastrophic acute disease with a high postoperative mortality and few biochemical factors are known to predict outcomes. This study evaluated whether S100A12 could be a promising marker for TAD.
Related JoVE Video
Gemcitabine resistance is associated with epithelial-mesenchymal transition and induction of HIF-1? in pancreatic cancer cells.
Curr Cancer Drug Targets
PUBLISHED: 02-08-2014
Show Abstract
Hide Abstract
Pancreatic cancer is one of the highly aggressive malignant diseases worldwide. To achieve better treatment outcome of pancreatic cancer, in the current study we explore the underlying molecular mechanism of drug resistance in pancreatic cancer cells. We found that resistance to gemcitabine is associated with epithelial-mesenchymal transition (EMT) phenotype in a panel of pancreatic cancer cell lines. Notably, gemcitabine-resistant pancreatic cancer cells acquire EMT phenotype. Moreover, gemcitabine-resistant cells have increased migration and invasion activities. Furthermore, we observed the high expression of HIF-1? in gemcitabine-resistant cells. More importantly, inhibition of HIF-1? in gemcitabine-resistant cells caused partial reversal of EMT phenotype, suggesting that HIF-1? was critically involved in gemcitabine-resistant-mediated EMT. Therefore, targeting HIF-1? could be an effective strategy for the treatment of pancreatic cancer.
Related JoVE Video
Arsenic trioxide targets miR-125b in glioma cells.
Curr. Pharm. Des.
PUBLISHED: 01-28-2014
Show Abstract
Hide Abstract
Arsenic trioxide (As2O3) has been demonstrated to suppress tumorigenesis in human glioma. However, the exact molecular mechanisms by which As2O3 exerts its tumor suppressor functions are elusive. Therefore, it is warranted to explore the underlying mechanism of As2O3-mediated anti-tumor activity in glioma.
Related JoVE Video
Genistein inhibits cell growth and invasion through regulation of miR-27a in pancreatic cancer cells.
Curr. Pharm. Des.
PUBLISHED: 01-28-2014
Show Abstract
Hide Abstract
Although genistein has been reported to exert its anti-tumor activity, the exact mechanism of its action is poorly elucidated. Recently, it has been found that genistein could regulate the expression of microRNAs. Therefore, our aim in the present study was to find whether genistein regulates specific miR-27a in pancreatic cancer cells.
Related JoVE Video
MiR-200a inhibits epithelial-mesenchymal transition of pancreatic cancer stem cell.
BMC Cancer
PUBLISHED: 01-27-2014
Show Abstract
Hide Abstract
Pancreatic cancer is one of the most aggressive cancers, and the aggressiveness of pancreatic cancer is in part due to its intrinsic and extrinsic drug resistance characteristics, which are also associated with the acquisition of epithelial-to-mesenchymal transition (EMT). Increasing evidence suggests that EMT-type cells share many biological characteristics with cancer stem-like cells. And miR-200 has been identified as a powerful regulator of EMT.
Related JoVE Video
Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus.
Nature
PUBLISHED: 01-23-2014
Show Abstract
Hide Abstract
Akt, also known as protein kinase B, plays key roles in cell proliferation, survival and metabolism. Akt hyperactivation contributes to many pathophysiological conditions, including human cancers, and is closely associated with poor prognosis and chemo- or radiotherapeutic resistance. Phosphorylation of Akt at S473 (ref. 5) and T308 (ref. 6) activates Akt. However, it remains unclear whether further mechanisms account for full Akt activation, and whether Akt hyperactivation is linked to misregulated cell cycle progression, another cancer hallmark. Here we report that Akt activity fluctuates across the cell cycle, mirroring cyclin A expression. Mechanistically, phosphorylation of S477 and T479 at the Akt extreme carboxy terminus by cyclin-dependent kinase 2 (Cdk2)/cyclin A or mTORC2, under distinct physiological conditions, promotes Akt activation through facilitating, or functionally compensating for, S473 phosphorylation. Furthermore, deletion of the cyclin A2 allele in the mouse olfactory bulb leads to reduced S477/T479 phosphorylation and elevated cellular apoptosis. Notably, cyclin A2-deletion-induced cellular apoptosis in mouse embryonic stem cells is partly rescued by S477D/T479E-Akt1, supporting a physiological role for cyclin A2 in governing Akt activation. Together, the results of our study show Akt S477/T479 phosphorylation to be an essential layer of the Akt activation mechanism to regulate its physiological functions, thereby providing a new mechanistic link between aberrant cell cycle progression and Akt hyperactivation in cancer.
Related JoVE Video
Integrity of the LXXLL motif in Stat6 is required for the inhibition of breast cancer cell growth and enhancement of differentiation in the context of progesterone.
BMC Cancer
PUBLISHED: 01-08-2014
Show Abstract
Hide Abstract
Progesterone is essential for the proliferation and differentiation of mammary gland epithelium. Studies of breast cancer cells have demonstrated a biphasic progesterone response consisting of an initial proliferative burst followed by sustained growth arrest. However, the transcriptional factors acting with the progesterone receptor (PR) to mediate the effects of progesterone on mammary cell growth and differentiation remain to be determined. Recently, it was demonstrated that signal transducer and activator of transcription 6 (Stat6) is a cell growth suppressor. Similar to progesterone-bound PR, Stat6 acts by inducing the expression of the G1 cyclin-dependent kinase inhibitors p21 and p27. The possible interaction between Stat6 and progesterone pathways in mammary cells was therefore investigated in the present study.
Related JoVE Video
Enantioselective degradation of (2RS,3RS)-paclobutrazol in peach and mandarin under field conditions.
Chirality
PUBLISHED: 01-06-2014
Show Abstract
Hide Abstract
In this study we investigated the enantioselective degradation of (2RS,3RS)-paclobutrazol in peach and mandarin fruits under field conditions after foliar treatment at 500 mg active ingredient/L using a Lux Cellulose-1 chiral column on a reverse-phase liquid chromatography-tandem mass spectrometry system. Degradations of paclobutrazol in both fruits followed first-order kinetics, with half-lives of about 9 days. Initial deposits were 1.63 mg/kg on peach and 1.99 mg/kg on mandarin; terminal concentrations were lower than 0.05 mg/kg, which was acceptable in most cases. As anticipated, paclobutrazol levels in peels of mature mandarin were about 6.3 times higher than in pulp, indicating the potential risk of peel consumption. We also observed that paclobutrazol degradation in mature mandarin was relatively slow, indicating it might not be efficient enough to hold mandarin fruits on trees for lowering paclobutrazol concentrations. Significant enantioselectivity was observed: the (2R,3R)-enantiomer was preferentially degraded in mandarin (whole fruit, peels, and pulp) but enriched in peach. Because of its more rapid degradation in mandarin and the lower levels observed in pulp compared with peels, potential endocrine-related side effects due to the (2R,3R)-enantiomer pose less of a risk in mandarin than in peach.
Related JoVE Video
A novel analgesic isolated from a traditional Chinese medicine.
Curr. Biol.
PUBLISHED: 01-02-2014
Show Abstract
Hide Abstract
Current pain management is limited, in particular, with regard to chronic pain. In an attempt to discover novel analgesics, we combined the approach developed to characterize traditional Chinese medicine (TCM), as part of the "herbalome" project, with the reverse pharmacology approach aimed at discovering new endogenous transmitters and hormones.
Related JoVE Video
Avascular necrosis of bone after allogeneic hematopoietic cell transplantation in children and adolescents.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-02-2014
Show Abstract
Hide Abstract
We conducted a nested case-control study within a cohort of 6244 patients to assess risk factors for avascular necrosis (AVN) of bone in children and adolescents after allogeneic transplantation. Eligible patients were ?21 years of age, received their first allogeneic transplant between 1990 and 2008 in the United States, and had survived ? 6 months from transplantation. Overall, 160 patients with AVN and 478 control subjects matched by year of transplant, length of follow-up and transplant center were identified. Patients and control subjects were confirmed via central review of radiology, pathology, and/or surgical procedure reports. Median time from transplant to diagnosis of AVN was 14 months. On conditional logistic regression, increasing age at transplant (?5 years), female gender, and chronic graft-versus-host disease (GVHD) were significantly associated with increased risks of AVN. Compared with patients receiving myeloablative regimens for malignant diseases, lower risks of AVN were seen in patients with nonmalignant diseases and those who had received reduced-intensity conditioning regimens for malignant diseases. Children at high risk for AVN include those within the age group where rapid bone growth occurs as well as those who experience exposure to myeloablative conditioning regimens and immunosuppression after hematopoietic cell transplantation for the treatment of GVHD. More research is needed to determine whether screening strategies specifically for patients at high risk for developing AVN with early interventions may mitigate the morbidity associated with this complication.
Related JoVE Video
MicroRNA expression profile of gastric cancer stem cells in the MKN-45 cancer cell line.
Acta Biochim. Biophys. Sin. (Shanghai)
PUBLISHED: 01-02-2014
Show Abstract
Hide Abstract
MicroRNAs (miRNAs) play important roles in post-transcriptional gene silencing of target messenger RNAs, which are involved in virtually all biological processes. Previously, we have demonstrated that spheroid body-forming cells from the MKN-45 cancer cell line possessed gastric cancer stem cell (CSC) properties. In this study, we aimed to determine the miRNA profile of the gastric CSCs and to explore the role of miRNAs in gastric CSCs. Human miRNA microarrays, which contain probes specific for 1887 human miRNAs were used to determine the expression profiles of the gastric CSCs. A total of 182 miRNAs with a more than 2-fold change were identified to be differentially expressed between the spheroid body-forming cells and the parental cells. Of these miRNAs, 9 miRNAs were over-expressed in the spheroid body-forming cells, while the other 173 miRNAs were all under-expressed, indicating that the role of most miRNAs in human gastric CSCs may be tumor suppressors. The results of microarray analysis were validated by quantitative real-time polymerase chain reaction, and the consistence rate is 70% (7 out of 10). The target genes for the validated miRNAs were predicted by using three online software programs, miRanda, PicTar, and TargetScan. Most of the potential targets of the miRNAs were relevant to the regulation of actin cytoskeleton, focal adhesion, extracellular matrix-receptor interaction, and the pathways in cancer. Especially, several genes are associated with some pivotal signaling pathways of the 'stem cell genes'. Evaluating the characteristic miRNAs of the gastric CSCs may be a new method for studying gastric cancer and developing therapeutic strategies, which aimed at eradicating the subpopulation of CSCs in gastric cancer.
Related JoVE Video
Identification of microbial communities in open and closed circuit bioelectrochemical MBRs by high-throughput 454 pyrosequencing.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Two bioelectrochemical membrane bioreactors (MBRs) developed by integrating microbial fuel cell and MBR technology were operated under closed-circuit and open-circuit modes, and high-throughput 454 pyrosequencing was used to investigate the effects of the power generation on the microbial community of bio-anode and bio-cathode. Microbes on the anode under open-circuit operation (AO) were enriched and highly diverse when compared to those on the anode under closed-circuit operation (AC). However, among the cathodes the closed-circuit mode (CC) had richer and more diverse microbial community compared to the cathode under open-circuit mode (CO). On the anodes AO and AC, Proteobacteria and Bacteroidetes were the dominant phyla, while Firmicutes was enriched only on AC. Deltaproteobacteria affiliated to Proteobacteria were also more abundant on AC than AO. Furthermore, the relative abundance of Desulfuromonas, which are well-known electrogenic bacteria, were much higher on AC (10.2%) when compared to AO (0.11%), indicating that closed-circuit operation was more conducive for the growth of electrogenic bacteria on the anodes. On the cathodes, Protebacteria was robust on CC while Bacteroidetes was more abundant on CO. Rhodobacter and Hydrogenophaga were also enriched on CC than CO, suggesting that these genera play a role in electron transfer from the cathode surface to the terminal electron acceptors in the bioelectrochemical MBR under closed-circuit operation.
Related JoVE Video
Start-up of an anaerobic dynamic membrane digester for waste activated sludge digestion: temporal variations in microbial communities.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
An anaerobic dynamic membrane digester (ADMD) was developed to digest waste sludge, and pyrosequencing was used to analyze the variations of the bacterial and archaeal communities during the start-up. Results showed that bacterial community richness decreased and then increased over time, while bacterial diversity remained almost the same during the start-up. Proteobacteria and Bacteroidetes were the major phyla. At the class level, Betaproteobacteria was the most abundant at the end of start-up, followed by Sphingobacteria. In the archaeal community, richness and diversity peaked at the end of the start-up stage. Principle component and cluster analyses demonstrated that archaeal consortia experienced a distinct shift and became stable after day 38. Methanomicrobiales and Methanosarcinales were the two predominant orders. Further investigations indicated that Methanolinea and Methanosaeta were responsible for methane production in the ADMD system. Hydrogenotrophic pathways might prevail over acetoclastic means for methanogenesis during the start-up, supported by specific methanogenic activity tests.
Related JoVE Video
Feasibility of low-dose contrast medium high pitch CT angiography for the combined evaluation of coronary, head and neck arteries.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
To evaluate the image quality and radiation dose of combined heart, head, and neck CT angiography (CTA) using prospectively electrocardiography (ECG)-triggered high-pitch spiral scan protocol, compared with single coronary CTA.
Related JoVE Video
SCF?-TRCP targets MTSS1 for ubiquitination-mediated destruction to regulate cancer cell proliferation and migration.
Oncotarget
PUBLISHED: 12-10-2013
Show Abstract
Hide Abstract
Metastasis suppressor 1 (MTSS1) is an important tumor suppressor protein, and loss of MTSS1 expression has been observed in several types of human cancers. Importantly, decreased MTSS1 expression is associated with more aggressive forms of breast and prostate cancers, and with poor survival rate. Currently, it remains unclear how MTSS1 is regulated in cancer cells, and whether reduced MTSS1 expression contributes to elevated cancer cell proliferation and migration. Here we report that the SCF?-TRCP regulates MTSS1 protein stability by targeting it for ubiquitination and subsequent destruction via the 26S proteasome. Notably, depletion of either Cullin 1 or ?-TRCP1 led to increased levels of MTSS1. We further demonstrated a crucial role for Ser322 in the DSGXXS degron of MTSS1 in governing SCF?-TRCP-mediated MTSS1 degradation. Mechanistically, we defined that Casein Kinase I? (CKI?) phosphorylates Ser322 to trigger MTSS1s interaction with ?-TRCP for subsequent ubiquitination and degradation. Importantly, introducing wild-type MTSS1 or a non-degradable MTSS1 (S322A) into breast or prostate cancer cells with low MTSS1 expression significantly inhibited cellular proliferation and migration. Moreover, S322A-MTSS1 exhibited stronger effects in inhibiting cell proliferation and migration when compared to ectopic expression of wild-type MTSS1. Therefore, our study provides a novel molecular mechanism for the negative regulation of MTSS1 by ?-TRCP in cancer cells. It further suggests that preventing MTSS1 degradation could be a possible novel strategy for clinical treatment of more aggressive breast and prostate cancers.
Related JoVE Video
Chemoresistance to gemcitabine in hepatoma cells induces epithelial-mesenchymal transition and involves activation of PDGF-D pathway.
Oncotarget
PUBLISHED: 10-26-2013
Show Abstract
Hide Abstract
Hepatocellular carcinoma (HCC) is one of the common malignances in the world and has high mortality in part due to development of acquired drug resistance. Therefore, it is urgent to investigate the molecular mechanism of drug resistance in HCC. To explore the underlying mechanism of drug resistance in HCC, we developed gemcitabine-resistant (GR) HCC cells. We used multiple methods to achieve our goal including RT-PCR, Western blotting analysis, transfection, Wound-healing assay, migration and invasion assay. We observed that gemcitabine-resistant cells acquired epithelial-mesenchymal transition (EMT) phenotype. Moreover, we found that PDGF-D is highly expressed in GR cells. Furthermore, down-regulation of PDGF-D in GR cells led to partial reversal of the EMT phenotype. Our findings demonstrated that targeting PDGF-D could be a novel strategy to overcome gemcitabine resistance in HCC.
Related JoVE Video
Bioinspired in situ growth of conversion films with underwater superoleophobicity and excellent self-cleaning performance.
ACS Appl Mater Interfaces
PUBLISHED: 10-16-2013
Show Abstract
Hide Abstract
Wax deposition during the production and transportation of crude oil is a global problem in oil industries. Fabrication of underwater self-cleaning materials can provide a new strategy to prohibit wax deposition. In this paper, conversion films on carbon steel with hierarchical micro/nanostructure are fabricated through a novel in situ alternating-current deposition method. The flower-like conversion films are composed of amorphous iron phosphate and present superhydrophilicity in air and superoleophobicity underwater. The conversion films can efficiently prevent the deposition of wax in water-contained crude oil, showing excellent self-cleaning performance. This facile and low-cost fabrication of a self-cleaning film provides a good strategy for underwater-oil prevention.
Related JoVE Video
Total hip arthroplasty using a combined anterior and posterior approach via a lateral incision in patients with ankylosed hips.
Can J Surg
PUBLISHED: 09-27-2013
Show Abstract
Hide Abstract
For most patients with severely ankylosed hips, traditional surgical approaches do not provide sufficient exposure during THAs. We report our experience with a combined anterior and posterior approach using a lateral incision for total hip arthroplasty (THA) in patients with severe, spontaneous bony hip ankylosis.
Related JoVE Video
Angiotensin-II induces phosphorylation of ERK1/2 and promotes aortic adventitial fibroblasts differentiating into myofibroblasts during aortic dissection formation.
J. Mol. Histol.
PUBLISHED: 09-16-2013
Show Abstract
Hide Abstract
The development of acute aortic dissection (AD) is attributed to unbearable wall tension superimposed on disordered of cells and extracellular matrix (ECM) in the aortic wall. Adventitial fibroblasts (AFs) phenotypic differentiation response to stress exhibits essential function to regulate the remolding of vascular. Little is known about the AFs phenotypic differentiation and its possible mechanism in patients with AD. In this study, we examined their roles in AD. Surgical specimens of the aorta from AD patients (n = 10) and controls (n = 10) were tested for ?-smooth muscle actin (?-SMA), extracellular signal-regulated kinase 1,2 (ERK1/2) and phospho-ERK1/2 expression, respectively by western blot. When compared with controls, protein levels of ?-SMA was significantly decreased and levels of phospho-ERK1/2 was increased significantly in the aortic wall from patients with AD. Immunohistochemistry results showed elevated staining of both ?-SMA and phospho-ERK1/2 in the adventitia of the aortic wall from patients with AD, on the contrary, staining of ?-SMA in the media was decreased compared with controls. In vitro, the Raf/MEK/ERK pathway was involved in Ang-II-induced phenotypic differentiation and matrix metalloproteinase-2 (MMP-2) mRNA expression in AFs. This study provides a new insight into the biological action of AFs and phospho-ERK1/2 promoting phenotypic differentiation and MMP-2 expression, suggesting an important role of AFs in leading to disorder the delicate balance of ECM metabolism in the aortic wall, so that AFs may be an essential participant during AD formation.
Related JoVE Video
Sodium tanshinone IIA sulfonate inhibits porcine reproductive and respiratory syndrome virus via suppressing N gene expression and blocking virus induced apoptosis.
Antivir. Ther. (Lond.)
PUBLISHED: 09-13-2013
Show Abstract
Hide Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) causes huge economic loss in the swine industry. Currently, there is no effective way to prevent PRRSV infection. Sodium tanshinone IIA sulfonate (STS), a natural compound derived from salvia miltiorrhiza, was shown to possess the anti-PRRSV activity, but the underlying mechanisms remain unclear. The objective of this study was to investigate the effect of STS on PRRSV-induced cell apoptosis and PRRSV N protein expression pattern.
Related JoVE Video
Microstructure and physical properties of two charge density wave states in NbSe3 nanowires.
J Nanosci Nanotechnol
PUBLISHED: 07-19-2013
Show Abstract
Hide Abstract
The whisker-like niobium triselenide (NbSe3) nanowires were synthesized using the traditional solid state reaction. X-ray diffraction experiment suggested the monoclinic structure (P2(1)/m), and crystal morphology analysis indicated that the band-like shape is the stable morphology. Two charge density wave (CDW) states were observed at around 140 K and 50 K, respectively, and the nonlinear effect was detected in the CDW states from the R-T and I-V measurements. The doped Fe atoms, as pinning centers, play an important role in the nonlinear properties of the CDW state. Electron diffraction and HRTEM experiments were carried out at different temperatures in order to investigate the structural features and their evolution. The sets of incommensurate modulation spots with modulation vector q1 - (h, k +/- 0.243, l) appeared below 145 K, and other sets of complex superstructure spots with modulation vector q2 - (h, k + 0.3, l + 1.3424), q3 - (h, k - 0.3137, 1.5685), q4 = (1/3, k, 1) and q5 = (0.5, 0.25, 0.5) were observed at [1 0 0] and [3 0 1] zone axis at about 20 K, respectively, suggesting the complex incommensurately modulated structures in this material.
Related JoVE Video
The siRNA cocktail targeting VEGF and HER2 inhibition on the proliferation and induced apoptosis of gastric cancer cell.
Mol. Cell. Biochem.
PUBLISHED: 07-18-2013
Show Abstract
Hide Abstract
The aim of this study was to investigate the inhibitory effect of a siRNA cocktail targeting Vascular endothelial growth factor (VEGF) and Human epidermal growth factor receptor 2 (HER2) on cell proliferation, induced apoptosis and the expression of VEGF and HER2 in human gastric carcinoma cell. The silencing rate of pre-designed siRNAs that targeted VEGF and HER2 was detected by Real-time Quantitative PCR (RT-QPCR) analysis. Furthermore, the best silencing siRNA that targeted VEGF and HER2 was prepared as a cocktail to co-knockdown VEGF and HER2 expression at both mRNA and protein levels which were detected by RT-QPCR and Western blot analysis. Cell proliferation inhibition rates were determined by CCK8 assay. The effect of siRNA cocktail on cell apoptosis was determined by flow cytometry. The migration inhibition of siRNA cocktail was analyzed by wound-healing assay. The ability of VEGF to induce endothelial cells to proliferate was examined in HUVECs by the method of tube formation assay. The pre-designed siRNAs could inhibit VEGF and HER2 mRNA level. siRNA cocktail, and co-downregulation of VEGF and HER2 result in significant inhibition of gastric cancer growth and migration in vitro. The inhibition of VEGF and HER2 expressions can induce apoptosis of SGC-7901 cells.
Related JoVE Video
Genistein down-regulates miR-223 expression in pancreatic cancer cells.
Curr Drug Targets
PUBLISHED: 06-28-2013
Show Abstract
Hide Abstract
Although genistein has been shown to inhibit tumorigenesis in a variety of human cancers including pancreatic cancer (PC), the exact molecular mechanism of its anti-cancer effects has not yet been fully elucidated. Recently, microRNAs (miRNAs) have been reported to regulate multiple aspects of tumor development and progression, indicating that targeting miRNAs could be a novel strategy to treat human cancers. In the current study, we investigated whether a natural compound genistein could down-regulate onco-miR-223, resulting in the inhibition of cell growth and invasion, and induction of apoptosis in PC cells. We found that genistein treatment significantly inhibited miR-223 expression and up-regulated Fbw7, one of the targets of miR-223. Moreover, down-regulation of miR-223 inhibited cell growth and induced apoptosis in PC cells. These findings suggest that genistein exerts its anti-tumor activity partly through downregulation of miR-223 in PC cells.
Related JoVE Video
Functional role of miR-34 family in human cancer.
Curr Drug Targets
PUBLISHED: 06-28-2013
Show Abstract
Hide Abstract
Recently, microRNAs (miRNAs) including miR-34 family have been found to play a critical role in tumorigenesis through regulating the expression of its target genes, which are involved in many cellular processes such as cell proliferation, survival, apoptosis, migration, invasion and angiogenesis. Thus, this review described the role of miR-34 family and how its deregulation is involved in the development and progression of human malignances. Moreover, we described the potential role of miR-34 as a novel biomarker for tumor diagnosis. Furthermore, we summarized that miR-34 family could be up-regulated by natural compounds in human cancers. Therefore, targeting miR-34 family could be a novel strategy for achieving better treatment outcome of cancer patients in the future.
Related JoVE Video
Strategy for market expansion: medical services of Traditional Chinese Medicine.
J Tradit Chin Med
PUBLISHED: 06-25-2013
Show Abstract
Hide Abstract
To explore a possible strategy of market expansion for Traditional Chinese Medicine (TCM) medical services
Related JoVE Video
Tumor cell-mediated neovascularization and lymphangiogenesis contrive tumor progression and cancer metastasis.
Biochim. Biophys. Acta
PUBLISHED: 06-04-2013
Show Abstract
Hide Abstract
Robust neovascularization and lymphangiogenesis have been found in a variety of aggressive and metastatic tumors. Endothelial sprouting angiogenesis is generally considered to be the major mechanism by which new vasculature forms in tumors. However, increasing evidence shows that tumor vasculature is not solely composed of endothelial cells (ECs). Some tumor cells acquire processes similar to embryonic vasculogenesis and produce new vasculature through vasculogenic mimicry, trans-differentiation of tumor cells into tumor ECs, and tumor cell-EC vascular co-option. In addition, tumor cells secrete various vasculogenic factors that induce sprouting angiogenesis and lymphangiogenesis. Vasculogenic tumor cells actively participate in the formation of vascular cancer stem cell niche and a premetastatic niche. Therefore, tumor cell-mediated neovascularization and lymphangiogenesis are closely associated with tumor progression, cancer metastasis, and poor prognosis. Vasculogenic tumor cells have emerged as key players in tumor neovascularization and lymphangiogenesis and play pivotal roles in tumor progression and cancer metastasis. However, the mechanisms underlying tumor cell-mediated vascularity as they relate to tumor progression and cancer metastasis remain unclear. Increasing data have shown that various intrinsic and extrinsic factors activate oncogenes and vasculogenic genes, enhance vasculogenic signaling pathways, and trigger tumor neovascularization and lymphangiogenesis. Collectively, tumor cells are the instigators of neovascularization. Therefore, targeting vasculogenic tumor cells, genes, and signaling pathways will open new avenues for anti-tumor vasculogenic and metastatic drug discovery. Dual targeting of endothelial sprouting angiogenesis and tumor cell-mediated neovascularization and lymphangiogenesis may overcome current clinical problems with anti-angiogenic therapy, resulting in significantly improved anti-angiogenesis and anti-cancer therapies.
Related JoVE Video
Rapid reversible superhydrophobicity-to-superhydrophilicity transition on alternating current etched brass.
ACS Appl Mater Interfaces
PUBLISHED: 05-28-2013
Show Abstract
Hide Abstract
Reversible surface wetting behavior is a hot topic of research because of the potential engineering applications. In the present work, a hierarchical micro/nanostructure is fabricated on brass by alternate current (AC) etching. The superhydrophilic as-prepared etched brass (EB) turns into superhydrophobic after the modification of stearic acid for 1 min. After annealing at 350 °C for 5 min, the superhydrophobic modified EB surface becomes superhydrophilic again. Furthermore, the annealed EB can restore the superhydrophobicity with the remodification of stearic acid. The wetting transition is realized by stearic acid modification and annealing rapidly in 6 min. The wetting transition mechanism is discussed based on the surface chemical analysis. This method is facile and suitable for the construction of large-scale and complex brass surfaces with tunable wetting behaviors.
Related JoVE Video
Effect of VEGF and CX43 on the promotion of neurological recovery by hyperbaric oxygen treatment in spinal cord-injured rats.
Spine J
PUBLISHED: 05-13-2013
Show Abstract
Hide Abstract
Spinal cord injury (SCI) is a serious health issue that may result in high health care costs, with additional social and psychological burdens. Hyperbaric oxygen (HBO) treatment has been found to be beneficial for neurological recovery; however, the underlying mechanisms are yet to be characterized.
Related JoVE Video
Regulation of EMT by Notch Signaling Pathway in Tumor Progression.
Curr Cancer Drug Targets
PUBLISHED: 05-10-2013
Show Abstract
Hide Abstract
Notch signaling pathway has been reported to play critical roles in the development and progression of human cancers because Notch signaling pathway is critically involved in many cellular processes including cell proliferation, survival, apoptosis, migration, invasion, angiogenesis, and metastasis. Emerging evidence suggests that Notch regulates EMT (Epithelial-to-Mesenchymal Transition), leading to tumor invasion and metastasis. Thus, this mini-review is focused on discussing the novel role of Notch signaling pathway in the regulation of EMT. Moreover, we summarized that Notch signaling pathway could be down-regulated by its inhibitors or natural compounds, resulting in the reversal of EMT to MET (Mesenchymal-to-Epithelial Transition), which could be a promising strategy for achieving better treatment outcome in patients diagnosed with cancer.
Related JoVE Video
Knockdown of Oct4 and Nanog expression inhibits the stemness of pancreatic cancer cells.
Cancer Lett.
PUBLISHED: 05-06-2013
Show Abstract
Hide Abstract
Pancreatic cancer is notorious for its difficult diagnosis at early stage and poor recurrence-free prognosis. This study aimed to investigate the possible involvement of Oct4 and Nanog in pancreatic cancer. The high expressions of Oct4 and Nanog in human pancreatic cancer tissues were found to indicate a worse prognostic value of patients. The pancreatic cancer stem cells (PCSCs) that isolated from PANC-1 cell line by flow cytometry exhibited high expressions of Oct4 and Nanog. To investigate whether Oct4 and Nanog play crucial role in maintaining the stemness of PCSCs, double knockdown of Oct4 and Nanog demonstrated that Oct4 and Nanog significantly reduced proliferation, migration, invasion, chemoresistance, and tumorigenesis of PCSCs in vitro and in vivo. The altered expression of the genes related to pancreatic carcinogenesis, metastasis, drug resistance and epithelial-mesenchymal transdifferentiation (EMT) might affect the biological characteristics of PCSCs. Our results suggest that Oct4 and Nanog may serve as a potential marker of prognosis and a novel target of therapy for pancreatic cancer.
Related JoVE Video
Similar cerebral protective effectiveness of antegrade and retrograde cerebral perfusion combined with deep hypothermia circulatory arrest in aortic arch surgery: A meta-analysis and systematic review of 5060 patients.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 05-02-2013
Show Abstract
Hide Abstract
Our objective was to determine if antegrade cerebral perfusion (ACP) and retrograde cerebral perfusion (RCP) combined with deep hypothermia circulatory arrest in aortic arch surgery results in different mortality and neurologic outcomes.
Related JoVE Video
Inactivation of tumor suppressor gene HIC1 in gastric cancer is reversed via small activating RNAs.
Gene
PUBLISHED: 04-23-2013
Show Abstract
Hide Abstract
HIC1 is a tumor suppressor gene that is down-expressed in different malignancies, in part, because of promoter hypermethylation. However, the biological function of HIC1 in gastric cancer remains unclear. It is known that small double-stranded RNAs can induce gene expression by targeting promoter sequences. In the present study, we examined the expression levels of HIC1 in gastric cancer tissue. Several pieces of small double-stranded RNAs were used for the activation of HIC1. Tissue microarray analysis of gastric cancer indicated that down-regulation of HIC1 in gastric cancer tissue was dramatic compared with the adjacent gastric mucosa. Gastric cancer cell lines also showed down-regulated HIC1 expression compared with a human immortalized gastric mucosa cell line. One out of four dsRNAs produced activation of HIC1 as assessed by real-time PCR and Western blotting. Use of a cell counting kit 8 and clonogenicity assays indicated that dsRNA-mediated re-expression of HIC1 inhibited cell proliferation and clonogenicity in gastric cancer. Reactivation of HIC1 suppressed cell migration and induced cell cycle arrest in the G0/G1 phase, as well as induced apoptosis. These results suggest that HIC1 is a potential target of gene therapy against gastric cancer, and that dsRNAs could function as a therapeutic option for up-regulating tumor suppressor genes in gastric cancer and other malignancies.
Related JoVE Video
Tumour vasculogenic mimicry is associated with poor prognosis of human cancer patients: a systemic review and meta-analysis.
Eur. J. Cancer
PUBLISHED: 04-22-2013
Show Abstract
Hide Abstract
Vasculogenic mimicry (VM) has been reported in various malignant tumours and is known to play an important role in cancer progression and metastasis. However, the impact of VM on the overall survival of human cancer patients remains controversial. The goal of this study was to evaluate whether VM is associated with 5-year survival of human cancer patients.
Related JoVE Video
CD59 is overexpressed in human lung cancer and regulates apoptosis of human lung cancer cells.
Int. J. Oncol.
PUBLISHED: 03-21-2013
Show Abstract
Hide Abstract
CD59, belonging to membrane complement regulatory proteins (mCRPs), inhibits the cytolytic activity of complement and is overexpressed in many types of solid cancers. The aim of the present study was to detect the expression of CD59 in non-small cell lung cancer (NSCLC) and to investigate the relationship between decreased CD59 expression and tumorigenesis of NSCLC by transfecting recombinant retrovirus encoding shRNA targeting human CD59 into the human NSCLC cell line NCI-H157. CD59 expression in NSCLC was detected by immunocytochemistry (IHC). In the human NSCLC cell line NCI-H157, CD59 mRNA and protein expression suppressed with lentivirus-mediated RNAi was confirmed by using RT-PCR and western blotting, respectively. The proliferation and apoptosis of NCI-H157 cells was measured by using MTT assay and FACS. The resistance to complement cracking ability was detected by LDH assay. Caspase-3 expression in cells was assessed by IHC. Bcl-2 and Fas protein was determined by western blotting both in vitro and in vivo. CD59 is overexpressed in human NLCLC cancer. In NCI-H157 cells, lentivirus-mediated RNAi significantly reduced both CD59 mRNA and protein expression, which resulted in suppressing cell proliferation and increasing cell apoptosis. When incubated with fresh normal human serum (8%, v/v) for 1 h at 37?C, the cell viability was decreased and cell apoptosis was increased in siCD59-infected NCI-H157 cells compared to siCD59-C-infected cells. Reduced CD59 expression led to increased expression of caspase-3 and Fas and decreased expression of Bcl-2. Furthermore, the nude mouse tumor graft weight was significantly decreased and survival rate was significantly increased in the siCD59 group. CD59 is overexpressed in human NLCLC. CD59 silencing in NSCLC cancer cells via retrovirus-mediated RNAi can enhance complement-mediated cell apoptosis, inhibiting the growth of NSCLC. CD59 may serve as a potential target for gene therapy in NSCLC.
Related JoVE Video
Effectiveness of dishwashing liquids in removing chlorothalonil and chlorpyrifos residues from cherry tomatoes.
Chemosphere
PUBLISHED: 03-10-2013
Show Abstract
Hide Abstract
Washing is the most practical way to remove pesticide residues in fruits and vegetables. Two commonly used kitchen dishwashing liquids (detergents) in Chinese market were tested for enhanced removal of chlorpyrifos (CHP) and chlorothalonil (CHT) in cherry tomatoes by soaking the cherry tomatoes in the detergent solutions. The critical micelle concentrations of detergent A and detergent B were about 250 mg L(-1) and 444 mg L(-1), respectively. Detergent A had a higher solubilizing ability for pesticides and hence washing effectiveness than detergent B. The apparent solubility of CHP increased with increasing detergent concentration, while that of CHT remained comparatively invariant independent of detergent concentration within the tested range. The apparent solubility of CHP was also consistently higher in solutions of both detergents as compared to CHT. Due probably to its lower logKow value, CHT was more readily washed off cherry tomatoes than CHP. In terms of washing, a duration of 10-20 min was sufficient for removal of pesticides on cherry tomatoes in distilled water and detergent solutions. The effectiveness of removing pesticides increased with increasing detergent concentration from 50 mg L(-1) to 5 g L(-1), with up to 80% CHT and 42% CHP removed. Multiple washing further increased pesticide removal. Adding 10% acetic acid to lower pH or increasing washing temperature favored pesticide removal, but 10% NaCl produced the shielding effect and substantially reduced the effectiveness of detergent A for pesticide removal.
Related JoVE Video
Autologous haematopoietic cell transplantation for non-Hodgkin lymphoma with secondary CNS involvement.
Br. J. Haematol.
PUBLISHED: 03-04-2013
Show Abstract
Hide Abstract
Pre-existing central nervous system (CNS) involvement may influence referral for autologous haematopoietic cell transplantation (AHCT) for patients with non-Hodgkin lymphoma (NHL). The outcomes of 151 adult patients with NHL with prior secondary CNS involvement (CNS(+) ) receiving an AHCT were compared to 4688 patients without prior CNS lymphoma (CNS(-) ). There were significant baseline differences between the cohorts. CNS(+) patients were more likely to be younger, have lower performance scores, higher age-adjusted international prognostic index scores, more advanced disease stage at diagnosis, more aggressive histology, more sites of extranodal disease, and a shorter interval between diagnosis and AHCT. However, no statistically significant differences were identified between the two groups by analysis of progression-free survival (PFS) and overall survival (OS) at 5 years. A matched pair comparison of the CNS(+) group with a subset of CNS(-) patients matched on propensity score also showed no differences in outcomes. Patients with active CNS lymphoma at the time of AHCT (n = 55) had a higher relapse rate and diminished PFS and OS compared with patients whose CNS lymphoma was in remission (n = 96) at the time of AHCT. CNS(+) patients can achieve excellent long-term outcomes with AHCT. Active CNS lymphoma at transplant confers a worse prognosis.
Related JoVE Video
MicroRNA-133a, downregulated in osteosarcoma, suppresses proliferation and promotes apoptosis by targeting Bcl-xL and Mcl-1.
Bone
PUBLISHED: 02-11-2013
Show Abstract
Hide Abstract
Deregulated microRNAs and their roles in cancer development have attracted much attention. Although miR-133a has been shown to be important in osteogenesis, its roles in osteosarcoma carcinogenesis and progression remain unknown. Hence, we focused on the expression and mechanisms of miR-133a in osteosarcoma development in this study. We found that miR-133a was downregulated in osteosarcoma cell lines and primary human osteosarcoma tissues, and its decrease was significantly correlated with tumor progression and prognosis of the patients. Functional studies revealed that restoration of miR-133a could reduce cell proliferation, promote cell apoptosis, and suppress tumorigenicity in osteosarcoma cell lines. Furthermore, bioinformatic prediction and experimental validation were applied to identify target genes of miR-133a, and the results revealed that the anti-tumor effect of miR-133a was probably due to targeting and repressing of Bcl-xL and Mcl-1 expression. Taken together, our data elucidate the roles of miR-133a in osteosarcoma pathogenesis and implicate its potential in cancer therapy.
Related JoVE Video
Unraveling the mystery of cancer metabolism in the genesis of tumor-initiating cells and development of cancer.
Biochim. Biophys. Acta
PUBLISHED: 01-06-2013
Show Abstract
Hide Abstract
Robust anaerobic metabolism plays a causative role in the origin of cancer cells; however, the oncogenic metabolic genes, factors, pathways, and networks in genesis of tumor-initiating cells (TICs) have not yet been systematically summarized. In addition, the mechanisms of oncogenic metabolism in the genesis of TICs are enigmatic. In this review, we discussed multiple cancer metabolism-related genes (MRGs) that are overexpressed in TICs and are responsible for inducing pluripotent stem cells. Moreover, we summarized that oncogenic metabolic genes and onco-metabolites induce metabolic reprogramming, which switches normal mitochondrial oxidative phosphorylation to cancer anaerobic metabolism, triggers epigenetic, genetic, and environmental alterations, drives the generation of TICs, and boosts the development of cancer. Importantly, cancer metabolism is controlled by positive and negative metabolic regulators. Positive oncogenic metabolic regulators, including key oncogenic metabolic genes, onco-metabolites, hypoxia, and an acidic environment, promote oncogenic metabolic reprogramming and anaerobic metabolism. However, dysfunction of negative metabolic regulators, including defects in p53, PTEN, and LKB1-AMPK-mTOR pathways, enhances cancer metabolism. Loss of the metabolic balance results in oncogenic metabolic reprogramming, genesis of TICs, and tumorigenesis. Collectively, this review provides new insight into the role and mechanism of these oncogenic metabolisms in the genesis of TICs and tumorigenesis. Accordingly, targeting key oncogenic genes, onco-metabolites, pathways, networks, and the acidic cancer microenvironment appears to be an attractive strategy for novel anti-tumor treatment.
Related JoVE Video
Ang II enhances noradrenaline release from sympathetic nerve endings thus contributing to the up-regulation of metalloprotease-2 in aortic dissection patients aorta wall.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
To test the hypothesis that angiotensin II (Ang II) could enhance noradrenaline (NA) release from sympathetic nerve endings of the aorta thus contributing to the up-regulation of matrix metalloproteinase 2 (MMP-2) during the formation of aortic dissection (AD).
Related JoVE Video
Mitochondrial dysfunction promotes breast cancer cell migration and invasion through HIF1? accumulation via increased production of reactive oxygen species.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Although mitochondrial dysfunction has been observed in various types of human cancer cells, the molecular mechanism underlying mitochondrial dysfunction mediated tumorigenesis remains largely elusive. To further explore the function of mitochondria and their involvement in the pathogenic mechanisms of cancer development, mitochondrial dysfunction clones of breast cancer cells were generated by rotenone treatment, a specific inhibitor of mitochondrial electron transport complex I. These clones were verified by mitochondrial respiratory defect measurement. Moreover, those clones exhibited increased reactive oxygen species (ROS), and showed higher migration and invasive behaviors compared with their parental cells. Furthermore, antioxidant N-acetyl cysteine, PEG-catalase, and mito-TEMPO effectively inhibited cell migration and invasion in these clones. Notably, ROS regulated malignant cellular behavior was in part mediated through upregulation of hypoxia-inducible factor-1 ? and vascular endothelial growth factor. Our results suggest that mitochondrial dysfunction promotes cancer cell motility partly through HIF1? accumulation mediated via increased production of reactive oxygen species.
Related JoVE Video

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.