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.
Pregnane X receptor activation and silencing promote steatosis of human hepatic cells by distinct lipogenic mechanisms.
Arch. Toxicol.
PUBLISHED: 09-03-2014
Show Abstract
Hide Abstract
In addition to its well-characterized role in the regulation of drug metabolism and transport by xenobiotics, pregnane X receptor (PXR) critically impacts on lipid homeostasis. In mice, both ligand-dependent activation and knockout of PXR were previously shown to promote hepatic steatosis. To elucidate the respective pathways in human liver, we generated clones of human hepatoma HepG2 cells exhibiting different PXR protein levels, and analyzed effects of PXR activation and knockdown on steatosis and expression of lipogenic genes. Ligand-dependent activation as well as knockdown of PXR resulted in increased steatosis in HepG2 cells. Activation of PXR induced the sterol regulatory element-binding protein (SREBP) 1-dependent lipogenic pathway via PXR-dependent induction of SREBP1a, which was confirmed in primary human hepatocytes. Inhibiting SREBP1 activity by blocking the cleavage-dependent maturation of SREBP1 protein impaired the induction of lipogenic SREBP1 target genes and triglyceride accumulation by PXR activation. On the other hand, PXR knockdown resulted in up-regulation of aldo-keto reductase (AKR) 1B10, which enhanced the acetyl-CoA carboxylase (ACC)-catalyzed reaction step of de novo lipogenesis. In a cohort of human liver samples histologically classified for non-alcoholic fatty liver disease, AKR1B10, SREBP1a and SREBP1 lipogenic target genes proved to be up-regulated in steatohepatitis, while PXR protein was reduced. In summary, our data suggest that activation and knockdown of PXR in human hepatic cells promote de novo lipogenesis and steatosis by induction of the SREBP1 pathway and AKR1B10-mediated increase of ACC activity, respectively, thus providing mechanistic explanations for a putative dual role of PXR in the pathogenesis of steatohepatitis.
Related JoVE Video
Experimental heart failure induces alterations of the lung proteome - insight into molecular mechanisms.
Cell. Physiol. Biochem.
PUBLISHED: 01-22-2014
Show Abstract
Hide Abstract
Background: Heart failure (CHF) is characterized by dyspnea and pulmonary changes. The underlying molecular adaptations are unclear, but might provide targets for therapeutic interventions. We therefore conceived a study to determine molecular changes of early pulmonary stress failure in a model of tachycardia-induced heart failure. Methods: CHF was induced in rabbits by progessive right ventricular pacing (n=6). Invasive blood pressure measurements and echocardiography were repeatedly performed. Untreated animals served as controls (n=6). Pulmonary tissue specimens were subjected to two-dimensional gel electrophoresis, and differentially expressed proteins were identified by mass spectrometry. Selected proteins were validated by Western Blot analysis and localized by immunohistochemical staining. Results: CHF animals were characterized by significantly altered functional, morphological, and hemodynamic parameters. Upon proteomic profiling, a total of 33 proteins was found to be differentially expressed in pulmonary tissue of CHF animals (18 up-regulated, and 15 down-regulated) belonging to 4 functional groups: 1. proteins involved in maintaining cytoarchitectural integrity, 2. plasma proteins indicating impaired alveolar-capillary permeability, 3. proteins with antioxidative properties, and 4. proteins participating in the metabolism of selenium compounds Conclusion: Experimental heart failure profoundly alters the pulmonary proteome. Our results supplement the current knowledge of pulmonary stress failure by specifying its molecular fundament. © 2014 S. Karger AG, Basel.
Related JoVE Video
STAG2 is a clinically relevant tumor suppressor in pancreatic ductal adenocarcinoma.
Genome Med
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer characterized by complex aberrant genomes. A fundamental goal of current studies is to identify those somatic events arising in the variable landscape of PDA genomes that can be exploited for improved clinical outcomes.
Related JoVE Video
Gene expression profiling of ampullary carcinomas classifies ampullary carcinomas into biliary-like and intestinal-like subtypes that are prognostic of outcome.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Adenocarcinomas of the ampulla of Vater are classified as biliary cancers, though the exact epithelium of origin for these cancers is not known. We sought to molecularly classify ampullary adenocarcinomas in comparison to known adenocarcinomas of the pancreas, bile duct, and duodenum by gene expression analysis.
Related JoVE Video
Chronic psychosocial stress increases the risk for inflammation-related colon carcinogenesis in male mice.
Stress
PUBLISHED: 12-20-2011
Show Abstract
Hide Abstract
Patients with inflammatory bowel diseases (IBDs) have a higher risk of developing colorectal cancer (CRC) than the general population. Furthermore, chronic psychosocial stress increases the likelihood of developing IBD and multiple types of malignant neoplasms, including CRC. Here, for the first time, we investigate the effects of chronic psychosocial stress in male mice on an artificially induced CRC, by employing the chronic subordinate colony (CSC) housing paradigm in combination with the reliable azoxymethane (AOM)/dextran sodium sulfate (DSS) CRC model. Colonoscopy revealed that CSC mice showed accelerated macroscopic suspect lesions. In addition, more CSC mice developed low-grade dysplasia (LGD) and/or high-grade dysplasia (HGD) in the colonic tissue compared to the single-housed control mice (SHC). CSC mice showed an increased number of Ki67+ and a decreased number of terminal deoxynucleotidyl transferase dUTP nick end labeling epithelial cells in colonic tissue. Colonic liver receptor homolog-1 (LRH-1), cyclooxygenase II (COXII), tumor necrosis factor, forkhead box P3 (FoxP3) mRNA as well as colonic ß-catenin, COXII, and LRH-1 protein expression were also increased in CSC compared with SHC mice. Although the number of CD4+ Th cells was increased, a tendency toward a decreased colonic interferon-? (IFN-?) mRNA expression was observed. Furthermore, despite an increased percentage of CD3+ cells and CD3+/FoxP3+ double-positive cells within mesenteric lymph node cells of CSC mice, IFN-? secretion from these cells was unaffected. Altogether, our results suggest that chronic psychosocial stress increases the risk for AOM/DSS-induced and, thus, inflammation-related CRC. Finally, assessment of additional time points may test whether the shift from tumor-protective Th1 cell to regulatory T-cell immunity represents a consequence of increased carcinogenesis or a causal factor involved in its development.
Related JoVE Video
Effect of EpCAM, CD44, CD133 and CD166 expression on patient survival in tumours of the ampulla of Vater.
J. Clin. Pathol.
PUBLISHED: 11-30-2011
Show Abstract
Hide Abstract
Carcinomas of the Vaterian system are rare and presumably arise from pre-existing adenomas. According to the cancer stem cell (CSC) hypothesis, only a small subset of tumor cells has the ability to initiate and develop tumor growth. In colorectal cancer, CD44, CD133, CD166 and EpCAM have been proposed to represent CSC marker proteins and their expression has been shown to correlate with patient survival.
Related JoVE Video
Impact of Toll-like receptor 2 expression in renal allograft rejection.
Nephrol. Dial. Transplant.
PUBLISHED: 07-13-2010
Show Abstract
Hide Abstract
An important role of TLR2 has been shown in various experimental models of renal ischaemia/reperfusion injury. To study the expression of TLR2 in renal allograft rejection systematically, we established an experimental rat transplantation model.
Related JoVE Video
Impact of chemokine receptor CX3CR1 in human renal allograft rejection.
Transpl. Immunol.
PUBLISHED: 03-22-2010
Show Abstract
Hide Abstract
Chemokine receptors play pivotal roles for leukocyte recruitment in acute and chronic inflammatory processes. This study was performed to analyze the expression, distribution and cellular localization of CX3CR1 in human renal transplant biopsies and to assess its role as potential diagnostic and prognostic marker. CX3CR1 was prospectively analyzed in 174 renal graft biopsies from patients with normal morphology (n=76), antibody-mediated acute rejection (n=6), acute tubulointerstitial rejection (n=27), acute vascular rejection (n=31), and with acute tubulus necrosis (n=34). Double immunofluorescence was additionally performed for CX3CR1 and CD4, CD8, CD20, CD68, and CD209/DC-SIGN. The number of CX3CR1 positive interstitial cells was significantly higher in the biopsies with acute tubulointerstitial and acute vascular rejection as compared to normal renal allograft biopsies. CX3CR1 positive cells were mainly CD68 positive monocytes/macrophages and CD209/DC-SIGN positive dendritic cells. The percentage of the CX3CR1 positive staining area was a predictor for steroid responsiveness and for worse clinical outcome 3 and 12 months after transplantation. CX3CR1 positive macrophages and/or dendritic cells are significantly elevated in acute renal allograft rejection. As CX3CR1 was associated with outcome parameters, it has to be further evaluated as a prognostic marker in human renal transplantation.
Related JoVE Video
Transcranial electro-hyperthermia combined with alkylating chemotherapy in patients with relapsed high-grade gliomas: phase I clinical results.
J. Neurooncol.
PUBLISHED: 06-14-2009
Show Abstract
Hide Abstract
Non-invasive loco-regional electro-hyperthermia (EHT) plus alkylating chemotherapy is occasionally used as salvage treatment in the relapse of patients with high-grade gliomas. Experimental data and retrospective studies suggest potential effects. However, no prospective clinical results are available. We performed a single-center prospective non-controlled single-arm Phase I trial. Main inclusion criteria were recurrent high-grade glioma WHO Grade III or IV, age 18-70, and Karnofsky performance score > or = 70. Primary endpoints were dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) with the combined regimen. Groups of 3 or 4 patients were treated 2-5 times a week in a dose-escalation scheme with EHT. Alkylating chemotherapy (ACNU, nimustin) was administered at a dose of 90 mg/m(2) on day 1 of 42 days for up to six cycles or until tumor progression (PD) or DLT occurred. Fifteen patients with high-grade gliomas were included. Relevant toxicities were local pain and increased focal neurological signs or intracranial pressure. No DLT occurred. In some patients, the administration of mannitol during EHT or long-term use of corticosteroids was necessary to resolve symptoms. Although some patients showed responses in their primarily treated sites, the pattern of response was not well defined. EHT plus alkylating chemotherapy is tolerable in patients with relapse of high-grade gliomas. Episodes of intracranial pressure were, at least, possibly attributed to EHT but did not cause DLTs. A Phase II trial targeting treatment effects is warranted on the basis of the results raised in this trial.
Related JoVE Video
Comprehensive morphometric analysis of mononuclear cell infiltration during experimental renal allograft rejection.
Transpl. Immunol.
Show Abstract
Hide Abstract
The role of specific subtypes of infiltrating cells in acute kidney allograft rejection is still not clear and was so far not examined by different analyzing methods under standardized conditions of an experimental kidney transplantation model. Immunohistochemical staining of CD3, CD20 and CD68 was performed in rat allografts, in syngeneically transplanted rats and in control rats with a test duration of 6 and 28 days. The detailed expression and localization of infiltrating cells were analyzed manually in different kidney compartments under light microscope and by the two different morphometric software programs. Data were correlated with the corresponding kidney function as well as with histopathological classification. The information provided by the morphometric software programs on the infiltration of the specific cell types after renal transplantation was in accordance with the manual analysis. Morphometric methods were solid to analyze reliably the induction of cellular infiltrates after renal transplantation. By manual analysis we could clearly demonstrate the detailed localization of the specific cell infiltrates in the different kidney compartments. Besides infiltration of CD3 and CD68 infiltrating cells, a robust infiltration of CD20 B-cells in allogeneically transplanted rats, even at early time points after transplantation was detected. Additionally an MHC class I expression could reliable be seen in allogeneically transplanted rats. The infiltration of B-cells and the reliable antigen presentation might act as a silent subclinical trigger for subsequent chronic rejection and premature graft loss.
Related JoVE Video
The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma.
Nature
Show Abstract
Hide Abstract
Pancreatic ductal adenocarcinoma (PDA) remains a lethal malignancy despite much progress concerning its molecular characterization. PDA tumours harbour four signature somatic mutations in addition to numerous lower frequency genetic events of uncertain significance. Here we use Sleeping Beauty (SB) transposon-mediated insertional mutagenesis in a mouse model of pancreatic ductal preneoplasia to identify genes that cooperate with oncogenic Kras(G12D) to accelerate tumorigenesis and promote progression. Our screen revealed new candidate genes for PDA and confirmed the importance of many genes and pathways previously implicated in human PDA. The most commonly mutated gene was the X-linked deubiquitinase Usp9x, which was inactivated in over 50% of the tumours. Although previous work had attributed a pro-survival role to USP9X in human neoplasia, we found instead that loss of Usp9x enhances transformation and protects pancreatic cancer cells from anoikis. Clinically, low USP9X protein and messenger RNA expression in PDA correlates with poor survival after surgery, and USP9X levels are inversely associated with metastatic burden in advanced disease. Furthermore, chromatin modulation with trichostatin A or 5-aza-2-deoxycytidine elevates USP9X expression in human PDA cell lines, indicating a clinical approach for certain patients. The conditional deletion of Usp9x cooperated with Kras(G12D) to accelerate pancreatic tumorigenesis in mice, validating their genetic interaction. We propose that USP9X is a major tumour suppressor gene with prognostic and therapeutic relevance in PDA.
Related JoVE Video
The cancer stem cell subtype determines immune infiltration of glioblastoma.
Stem Cells Dev.
Show Abstract
Hide Abstract
Immune cell infiltration varies widely between different glioblastomas (GBMs). The underlying mechanism, however, remains unknown. Here we show that TGF-beta regulates proliferation, migration, and tumorigenicity of mesenchymal GBM cancer stem cells (CSCs) in vivo and in vitro. In contrast, proneural GBM CSCs resisted TGF-beta due to TGFR2 deficiency. In vivo, a substantially increased infiltration of immune cells was observed in mesenchymal GBMs, while immune infiltrates were rare in proneural GBMs. On a functional level, proneural CSC lines caused a significantly stronger TGF-beta-dependent suppression of NKG2D expression on CD8(+) T and NK cells in vitro providing a mechanistic explanation for the reduced immune infiltration of proneural GBMs. Thus, the molecular subtype of CSCs TGF-beta-dependently contributes to the degree of immune infiltration.
Related JoVE Video
Google goes cancer: improving outcome prediction for cancer patients by network-based ranking of marker genes.
PLoS Comput. Biol.
Show Abstract
Hide Abstract
Predicting the clinical outcome of cancer patients based on the expression of marker genes in their tumors has received increasing interest in the past decade. Accurate predictors of outcome and response to therapy could be used to personalize and thereby improve therapy. However, state of the art methods used so far often found marker genes with limited prediction accuracy, limited reproducibility, and unclear biological relevance. To address this problem, we developed a novel computational approach to identify genes prognostic for outcome that couples gene expression measurements from primary tumor samples with a network of known relationships between the genes. Our approach ranks genes according to their prognostic relevance using both expression and network information in a manner similar to Googles PageRank. We applied this method to gene expression profiles which we obtained from 30 patients with pancreatic cancer, and identified seven candidate marker genes prognostic for outcome. Compared to genes found with state of the art methods, such as Pearson correlation of gene expression with survival time, we improve the prediction accuracy by up to 7%. Accuracies were assessed using support vector machine classifiers and Monte Carlo cross-validation. We then validated the prognostic value of our seven candidate markers using immunohistochemistry on an independent set of 412 pancreatic cancer samples. Notably, signatures derived from our candidate markers were independently predictive of outcome and superior to established clinical prognostic factors such as grade, tumor size, and nodal status. As the amount of genomic data of individual tumors grows rapidly, our algorithm meets the need for powerful computational approaches that are key to exploit these data for personalized cancer therapies in clinical practice.
Related JoVE Video
Nucleosome remodeler SNF2L suppresses cell proliferation and migration and attenuates Wnt signaling.
Mol. Cell. Biol.
Show Abstract
Hide Abstract
ISWI is an evolutionarily conserved ATPase that catalyzes nucleosome remodeling in different macromolecular complexes. Two mammalian ISWI orthologs, SNF2H and SNF2L, are thought to have specialized functions despite their high sequence similarity. To date, the function of SNF2L in human cells has not been a focus of research. Newly established specific monoclonal antibodies and selective RNA interference protocols have now enabled a comprehensive characterization of loss-of-function phenotypes in human cells. In contrast to earlier results, we found SNF2L to be broadly expressed in primary human tissues. Depletion of SNF2L in HeLa cells led to enhanced proliferation and increased migration. These phenomena were explained by transcriptome profiling, which identified SNF2L as a modulator of the Wnt signaling network. The cumulative effects of SNF2L depletion on gene expression portray the cell in a state of activated Wnt signaling characterized by increased proliferation and chemotactic locomotion. Accordingly, high levels of SNF2L expression in normal melanocytes contrast with undetectable expression in malignant melanoma. In summary, our data document an inverse relationship between SNF2L expression and features characteristic of malignant cells.
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.