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Find video protocols related to scientific articles indexed in Pubmed.
Pharmacogenetics of childhood acute lymphoblastic leukemia.
Pharmacogenomics
PUBLISHED: 08-27-2014
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Acute lymphoblastic leukemia (ALL) is the major pediatric cancer in developed countries. Although treatment outcome has improved owing to advances in chemotherapy, there is still a group of patients for which therapy fails while some patients experience severe toxicity. In the last few years, several pharmacogenetic studies have been performed to search for markers of outcome and toxicity in pediatric ALL. However, to date, TPMT is the only pharmacogenetic marker in ALL with clinical guidelines for drug dosing. In this article, we will provide an overview of the most important findings carried out in pharmacogenetics for pediatric ALL, such as the interest drawn by methotrexate transporters in the context of methotrexate treatment. Even if most of the studies are centered on coding genes, we will also point to new approaches focusing on noncoding regions and epigenetic variation that could be interesting for consideration in the near future.
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Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging.
Age (Dordr)
PUBLISHED: 07-30-2014
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Chromosome translocations are especially frequent in human lymphomas and leukemias but are insufficient to drive carcinogenesis. Indeed, several of the so-called tumor specific translocations have been detected in peripheral blood of healthy individuals, finding a higher frequency of some of them with aging. The inappropriate repair of DNA double strand breaks by the nonhomologous end joining (NHEJ) pathway is one of the reasons for a translocation to occur. Moreover, fidelity of this pathway has been shown to decline with age. Although the mechanism underlying this inefficacy is unknown, other repair pathways are inactivated by methylation with aging. In this study, we analyzed the implication of NHEJ genes methylation in the increase of translocations with the age. To this aim, we determined the relationship between translocations and aging in 565 Spanish healthy individuals and correlated these data with the methylation status of 11 NHEJ genes. We found higher frequency of BCL2-JH and BCR-ABL (major) translocations with aging. In addition, we detected that two NHEJ genes (LIG4 and XRCC6) presented age-dependent promoter methylation changes. However, we did not observe a correlation between the increase of translocations and methylation, indicating that other molecular mechanisms are involved in the loss of NHEJ fidelity with aging.
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Development and evaluation of a canine laparoscopic simulator for veterinary clinical training.
J Vet Med Educ
PUBLISHED: 07-09-2014
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Human laparoscopic simulators have been used in medical education for minimally invasive surgery (MIS) in the past years. Simulator-based laparoscopic training has attracted much interest because unique skills have to be learned not only by surgeons in training but also by surgeons in practice. MIS forces the surgeon to adapt to monocular vision and decreased tactile sensation and entails training and improving hand-eye and hand-hand coordination. Those skills require a learning curve that could be overcome gradually with use of simulators. The Canine Laparoscopic Simulator (CLS) for laparoscopic training was developed based on the working and optical space obtained from computed tomography (CT) scan images of three Beagle dogs. Thirty veterinarians (expert group, n=7; novice group, n=23) performed basic laparoscopic exercises in one training session on the CLS. During the performance of the exercises, an experienced laparoscopic veterinarian assessed all the tasks. Afterwards, participants were asked to complete an anonymous survey describing their experience. Most participants expressed positive opinions about the design and usability of the CLS. There were no significant differences between the two groups' opinions. The CLS showed good preliminary acceptance in the basic laparoscopy tasks by veterinarians. They perceived it to be a good training tool, and these results suggest that CLS is an engaging tool for education but still has some limitations inherent in training boxes. Further studies would be needed to establish the validity of training programs performed in the CLS.
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Comparison of single access devices during cut and suturing tasks on simulator.
J. Surg. Res.
PUBLISHED: 02-26-2014
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Published comparisons of the different available laparoendoscopic single-site surgery (LESS) devices focused on its economic cost and technical aspects. With this study, we aimed to objectively compare the use of three different LESS access devices in controlled experimental tasks.
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A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma.
Blood
PUBLISHED: 01-07-2014
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The genetic hallmark of Burkitt lymphoma (BL) is the t(8;14)(q24;q32) and its variants leading to activation of the MYC oncogene. It is a matter of debate whether true BL without MYC translocation exists. Here, we identified 59 lymphomas concordantly called BL by 2 gene expression classifiers among 753 B-cell lymphomas. Only 2 (3%) of these 59 molecular BL lacked a MYC translocation, which both shared a peculiar pattern of chromosome 11q aberration characterized by interstitial gains including 11q23.2-q23.3 and telomeric losses of 11q24.1-qter. We extended our analysis to 17 MYC-negative high-grade B-cell lymphomas with a similar 11q aberration and showed this aberration to be recurrently associated with morphologic and clinical features of BL. The minimal region of gain was defined by high-level amplifications in 11q23.3 and associated with overexpression of genes including PAFAH1B2 on a transcriptional and protein level. The recurrent region of loss contained a focal homozygous deletion in 11q24.2-q24.3 including the ETS1 gene, which was shown to be mutated in 4 of 16 investigated cases. These findings indicate the existence of a molecularly distinct subset of B-cell lymphomas reminiscent of BL, which is characterized by deregulation of genes in 11q.
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Noncoding RNA-related polymorphisms in pediatric acute lymphoblastic leukemia susceptibility.
Pediatr. Res.
PUBLISHED: 01-01-2014
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Evidence for an inherited genetic risk for pediatric acute lymphoblastic leukemia has been provided in several studies. Most of them focused on coding regions. However, those regions represent only 1.5% of the entire genome. In acute lymphoblastic leukemia (ALL), it has been suggested that the expression of microRNAs (miRNAs) is dysregulated, which suggests that they may have a role in ALL risk. Changes in miRNA function may occur through single-nucleotide polymorphisms (SNPs). Therefore, the aim of this study was to evaluate whether polymorphisms in pre-miRNAs, and/or miRNA-processing genes, contribute to a predisposition for childhood ALL.
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Performance analysis on physical simulator of four different instrument setups in laparo-endoscopic single-site (LESS) surgery.
Surg Endosc
PUBLISHED: 08-14-2013
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Over the past decades, minimally invasive surgery has undergone continuous development due to the demand for scarless results, with laparo-endoscopic single-site (LESS) surgery constituting one of todays most favored alternatives. In this study, we aim to assess the relative technical difficulty and performance benefits of dynamic articulating and pre-bent instruments, either combined with conventional laparoscopic tools or not, during the completion of two basic tasks hands-on simulator.
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Intron 3 of the ARID5B gene: a hot spot for acute lymphoblastic leukemia susceptibility.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 08-05-2013
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Single-nucleotide polymorphisms (SNPs) in AT-rich interactive domain 5B (ARID5B) have been associated with risk for pediatric acute lymphoblastic leukemia (ALL). After reviewing previous studies, we realized that the most significant associations were restricted to intron 3, but the mechanism(s) by which those SNPs affect ALL risk remain to be elucidated. Therefore, the aim of this study was to analyze the association between genetic variants of the intron 3 region of ARID5B and the incidence of B-ALL in a Spanish population. We also aimed to find a functional explanation for the association, searching for copy number variations (CNVs), and changes in ARID5B expression associated with the genotypes of the SNPs.
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Ergonomic analysis of muscle activity in the forearm and back muscles during laparoscopic surgery: influence of previous experience and performed task.
Surg Laparosc Endosc Percutan Tech
PUBLISHED: 04-13-2013
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The first aim of this study is to analyze the muscle activity in back and forearm muscles in surgeons during laparoscopic dissection and suturing maneuvers. The second aim is to determine the influence of the surgeons previous experience in laparoscopic surgery.
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Recurrent loss of heterozygosity in 1p36 associated with TNFRSF14 mutations in IRF4 translocation negative pediatric follicular lymphomas.
Haematologica
PUBLISHED: 02-26-2013
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Pediatric follicular lymphoma is a rare disease that differs genetically and clinically from its adult counterpart. With the exception of pediatric follicular lymphoma with IRF4-translocation, the genetic events associated with these lymphomas have not yet been defined. We applied array-comparative genomic hybridization and molecular inversion probe assay analyses to formalin-fixed paraffin-embedded tissues from 18 patients aged 18 years and under with IRF4 translocation negative follicular lymphoma. All evaluable cases lacked t(14;18). Only 6 of 16 evaluable cases displayed chromosomal imbalances with gains or amplifications of 6pter-p24.3 (including IRF4) and deletion and copy number neutral-loss of heterozygosity in 1p36 (including TNFRSF14) being most frequent. Sequencing of TNFRSF14 located in the minimal region of loss in 1p36.32 showed nine mutations in 7 cases from our series. Two subsets of pediatric follicular lymphoma were delineated according to the presence of molecular alterations, one with genomic aberrations associated with higher grade and/or diffuse large B-cell lymphoma component and more widespread disease, and another one lacking genetic alterations associated with more limited disease.
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[Training and research in urologic laparoscopic surgery. Design of training programs and experimental models of renal tumor].
Arch. Esp. Urol.
PUBLISHED: 02-15-2013
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We present our experience with surgical training programs development for basic and advanced laparoscopic urological surgery. Both training programs consist of 21 and 28 hours respectively. Basic surgical programs start with general knowledge of ergonomics and instrumentation, there after, attendants acquire basic skills on physical simulator. Posteriorly, techniques on animal model are undertaken, always assisted by an expert. Advanced activities start with surgical tasks on physical simulator. Posteriorly, reconstructive urological surgical techniques are undertaken on animal model, focused on partial nephrectomy, and always assisted by an expert tutor. We present our results on exophytic renal tumour model creation based chromatic Alginate.
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Ureteral obstruction swine model through laparoscopy and single port for training on laparoscopic pyeloplasty.
Int J Med Sci
PUBLISHED: 01-01-2013
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This study aims firstly to assess the most adequate surgical approach for the creation of an ureteropelvic juntion obstruction (UPJO) animal model, and secondly to validate this model for laparoscopic pyeloplasty training among urologists. Thirty six Large White pigs (28.29±5.48 Kg) were used. The left ureteropelvic junction was occluded by means of an endoclip. According to the surgical approach for model creation, pigs were randomized into: laparoscopic conventional surgery (LAP) or single port surgery (LSP). Each group was further divided into transperitoneal (+T) or retroperitoneal (+R) approach. Time needed for access, surgical field preparation, wound closure, and total surgical times were registered. Social behavior, tenderness to the touch and wound inflammation were evaluated in the early postoperative period. After ten days, all animals underwent an Anderson-Hynes pyeloplasty carried out by 9 urologists, who subsequently assessed the model by means of a subjective validation questionnaire. Total operative time was significantly greater in LSP+R (p=0.001). Tenderness to the touch was significantly increased in both retroperitoneal approaches, (p=0.0001). Surgeons rated the UPJO porcine model for training on laparoscopic pyeloplasty with high or very high scores, all above 4 on a 1-5 point Likert scale. Our UPJO animal model is useful for laparoscopic pyeloplasty training. The model created by retroperitoneal single port approach presented the best score in the subjective evaluation, whereas, as a whole, transabdominal laparoscopic approach was preferred.
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[Preliminary validation of the Simulap(®) physical simulator and its assessment system for laparoscopic surgery].
Cir Esp
PUBLISHED: 05-05-2011
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Our aim is to assess the face and content validities of the physical simulator Simulap(®), as well as the construct validity of its assessment method.
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Epigenetic activation of SOX11 in lymphoid neoplasms by histone modifications.
PLoS ONE
PUBLISHED: 04-28-2011
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Recent studies have shown aberrant expression of SOX11 in various types of aggressive B-cell neoplasms. To elucidate the molecular mechanisms leading to such deregulation, we performed a comprehensive SOX11 gene expression and epigenetic study in stem cells, normal hematopoietic cells and different lymphoid neoplasms. We observed that SOX11 expression is associated with unmethylated DNA and presence of activating histone marks (H3K9/14Ac and H3K4me3) in embryonic stem cells and some aggressive B-cell neoplasms. In contrast, adult stem cells, normal hematopoietic cells and other lymphoid neoplasms do not express SOX11. Such repression was associated with silencing histone marks H3K9me2 and H3K27me3. The SOX11 promoter of non-malignant cells was consistently unmethylated whereas lymphoid neoplasms with silenced SOX11 tended to acquire DNA hypermethylation. SOX11 silencing in cell lines was reversed by the histone deacetylase inhibitor SAHA but not by the DNA methyltransferase inhibitor AZA. These data indicate that, although DNA hypermethylation of SOX11 is frequent in lymphoid neoplasms, it seems to be functionally inert, as SOX11 is already silenced in the hematopoietic system. In contrast, the pathogenic role of SOX11 is associated with its de novo expression in some aggressive lymphoid malignancies, which is mediated by a shift from inactivating to activating histone modifications.
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Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults.
Blood
PUBLISHED: 04-12-2011
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The prognosis of germinal center-derived B-cell (GCB) lymphomas, including follicular lymphoma and diffuse large-B-cell lymphoma (DLBCL), strongly depends on age. Children have a more favorable outcome than adults. It is not known whether this is because of differences in host characteristics, treatment protocols, or tumor biology, including the presence of chromosomal alterations. By screening for novel IGH translocation partners in pediatric and adult lymphomas, we identified chromosomal translocations juxtaposing the IRF4 oncogene next to one of the immunoglobulin (IG) loci as a novel recurrent aberration in mature B-cell lymphoma. FISH revealed 20 of 427 lymphomas to carry an IG/IRF4-fusion. Those were predominantly GCB-type DLBCL or follicular lymphoma grade 3, shared strong expression of IRF4/MUM1 and BCL6, and lacked PRDM1/BLIMP1 expression and t(14;18)/BCL2 breaks. BCL6 aberrations were common. The gene expression profile of IG/IRF4-positive lymphomas differed from other subtypes of DLBCL. A classifier for IG/IRF4 positivity containing 27 genes allowed accurate prediction. IG/IRF4 positivity was associated with young age and a favorable outcome. Our results suggest IRF4 translocations to be primary alterations in a molecularly defined subset of GCB-derived lymphomas. The probability for this subtype of lymphoma significantly decreases with age, suggesting that diversity in tumor biology might contribute to the age-dependent differences in prognosis of lymphoma.
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[Ergonomics in laparoscopic surgery and its importance in surgical training].
Cir Esp
PUBLISHED: 03-03-2011
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Despite the many advantages that laparoscopic surgery has for patients, it involves a series of risks for the surgeon. These are related to the reduced freedom of movement and forced postures which lead to greater muscle fatigue than with conventional surgery. In laparoscopic surgery there are few references on the introduction of training programs in ergonomics, despite the numerous advantages demonstrated in other disciplines. The application of ergonomic criteria in the surgical field could have great benefits, both for surgeons and patients. In this work we attempt to review the existing literature and our experience to provide the surgeon with some ergonomic guidelines for body stance and positioning of equipment. We also present a training model based on ergonomics which we have introduced into the training activities carried out in our Centre.
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A putative "hepitype" in the ATM gene associated with chronic lymphocytic leukemia risk.
Genes Chromosomes Cancer
PUBLISHED: 02-28-2011
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Chronic lymphocytic leukemia (CLL) cells are characterized by several chromosomal lesions. Some of these aberrations imply chromosome breaks as a result of unrepaired double strand breaks (DSBs) in the DNA. The ATM (ataxia telangiectasia-mutated) protein is the principal integrator of cellular responses to DSBs. ATM deletion is also an adverse prognostic factor in CLL. Taking this into account, we evaluated if genetic and/or epigenetic variation in the ATM gene may modulate the individual susceptibility to develop CLL. Our case-control association study was performed in a large Spanish population of 1,503 individuals, including 742 patients with CLL and 761 controls. We identified one haplotype within the ATM gene that confers an increased risk of CLL development (OR = 1.33; 95% CI: 1.10-1.60). Two polymorphisms of this ATM haplotype eliminated one CpG site each in Introns 15 and 61, causing changes in DNA methylation pattern. These data provide the first evidence for the existence of a putative "hepitype" in the ATM gene associated with CLL risk.
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Pipeline for large-scale microdroplet bisulfite PCR-based sequencing allows the tracking of hepitype evolution in tumors.
PLoS ONE
PUBLISHED: 01-13-2011
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Cytosine methylation provides an epigenetic level of cellular plasticity that is important for development, differentiation and cancerogenesis. We adopted microdroplet PCR to bisulfite treated target DNA in combination with second generation sequencing to simultaneously assess DNA sequence and methylation. We show measurement of methylation status in a wide range of target sequences (total 34 kb) with an average coverage of 95% (median 100%) and good correlation to the opposite strand (rho?=?0.96) and to pyrosequencing (rho?=?0.87). Data from lymphoma and colorectal cancer samples for SNRPN (imprinted gene), FGF6 (demethylated in the cancer samples) and HS3ST2 (methylated in the cancer samples) serve as a proof of principle showing the integration of SNP data and phased DNA-methylation information into "hepitypes" and thus the analysis of DNA methylation phylogeny in the somatic evolution of cancer.
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Polymorphisms of the SLCO1B1 gene predict methotrexate-related toxicity in childhood acute lymphoblastic leukemia.
Pediatr Blood Cancer
PUBLISHED: 01-13-2011
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Methotrexate (MTX) is an important component of the therapy for childhood acute lymphoblastic leukemia. Treatment with high-dose MTX often causes toxicity, recommending a dose reduction and/or cessation of treatment. Polymorphisms in genes involved in the MTX metabolism have been associated with toxicity with controversial results. The discrepancies could be due to differences in treatment protocols among studies, small, or non-homogeneous populations or the use of different toxicity criteria. The aim of the present study was to analyze the possible correlation of polymorphisms of genes involved in the MTX metabolism with the toxicity during therapy with the well-established LAL/SHOP protocol.
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Cytomegalovirus promoter up-regulation is the major cause of increased protein levels of unstable reporter proteins after treatment of living cells with proteasome inhibitors.
J. Biol. Chem.
PUBLISHED: 08-13-2009
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Fluorescent unstable proteins obtained by the fusion of a fluorescent protein coding sequence with specific amino acid sequences that promote its fast degradation have become popular to gauge the activity of the ubiquitin/proteasome system in living cells. The steady-state levels of expression of these unstable proteins is low in agreement with their short half-lives, and they accumulate in the cell upon treatment with proteasome inhibitors. We show here that this accumulation is mainly due to transcriptional up-regulation of the cytomegalovirus promoter by proteasome inhibitors and mediated, at least in part, by AP1 transactivation. These simple facts put under quarantine conclusions reached about the activity of the ubiquitin/proteasome pathway in animal cells in culture or in transgenic mice, where popular cytomegalovirus-driven constructs are used, as transcriptional regulation of the expression of the reporter protein construct and not degradation of the unstable protein by the ubiquitin/proteasome system may contribute significantly to the interpretation of the results observed.
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High mitochondrial DNA stability in B-cell chronic lymphocytic leukemia.
PLoS ONE
PUBLISHED: 07-31-2009
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Chronic Lymphocytic Leukemia (CLL) leads to progressive accumulation of lymphocytes in the blood, bone marrow, and lymphatic tissues. Previous findings have suggested that the mtDNA could play an important role in CLL.
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Chromosome instability in lymphocytes of children with coeliac disease.
J. Pediatr. Gastroenterol. Nutr.
PUBLISHED: 06-12-2009
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Undiagnosed individuals with celiac disease (CD) or those who do not comply with gluten-free diet (GFD) are at a higher risk of developing malignancies. A possible origin of chromosomal alteration in autoimmune reaction could be mistakes in the rearrangement of V(D)J of the IgH gene. Our aim was to verify whether higher genomic instability was found in coeliac individuals and whether GFD reduced it. As marker of genomic instability we analysed the frequency of 2 translocations, t(14;18) and t(11;14), in peripheral blood by nested PCR, in 37 patients with CD at diagnosis, 27 patients with CD after 2 years on GFD, and 36 control individuals. No significant differences were found.
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High resolution copy number analysis of IRF4 translocation-positive diffuse large B-cell and follicular lymphomas.
Genes Chromosomes Cancer
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Translocations affecting chromosome subband 6p25.3 containing the IRF4 gene have been recently described as characteristic alterations in a molecularly distinct subset of germinal center B-cell-derived lymphomas. Secondary changes have yet only been described in few of these lymphomas. Here, we performed array-comparative genomic hybridization and molecular inversion probe microarray analyses on DNA from 12 formalin-fixed paraffin-embedded and two fresh-frozen IRF4 translocation-positive lymphomas, which together with the previously published data on nine cases allowed the extension of copy number analyses to a total of 23 of these lymphomas. All except one case carried chromosomal imbalances, most frequently gains in Xq28, 11q22.3-qter, and 7q32.1-qter and losses in 6q13-16.1, 15q14-22.31, and 17p. No recurrent copy-neutral losses of heterozygosity were observed. TP53 point mutations were detected in three of six cases with loss of 17p. Overall this study unravels a recurrent pattern of secondary genetic alterations in IRF4 translocation-positive lymphomas.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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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.