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.
Polymorphisms in genes involved in the mechanism of action of methotrexate: are they associated with outcome in rheumatoid arthritis patients?
Pharmacogenomics
PUBLISHED: 08-02-2014
Show Abstract
Hide Abstract
Methotrexate (MTX) is the first-line treatment option for newly diagnosed rheumatoid arthritis (RA) patients. However, 50-70% of the patients respond to treatment and 30% suffer toxicity.
Related JoVE Video
Association between methylation of the glucocorticoid receptor gene, childhood maltreatment, and clinical severity in borderline personality disorder.
J Psychiatr Res
PUBLISHED: 06-11-2014
Show Abstract
Hide Abstract
The hypothalamus-pituitary-adrenal axis (HPA) is essential in the regulation of stress responses. Increased methylation of the promoter region of the glucocorticoid receptor gene (NR3C1) has been described both in subjects with history of childhood trauma and in patients with Borderline Personality Disorder (BPD). However, no data on the possible association between a higher methylation of this gene and clinical severity is available. The aim of this study was to evaluate the association between NR3C1 methylation status, the history of childhood trauma, and current clinical severity in subjects with BPD. A sample of 281 subjects with BPD (diagnosed by SCID-II and DIB-R semi-structured diagnostic interviews) was recruited. Clinical variables included previous hospitalizations, self-injurious behavior, and self-reported history of childhood trauma. DNA was extracted from peripheral blood. The results indicated a significant positive correlation between NR3C1 methylation status and childhood maltreatment (specifically physical abuse). In addition, a positive correlation between methylation status and clinical severity (DIB-R total score and hospitalizations) was observed. These findings suggest that NR3C1 methylation in subjects with BPD may be associated not only with childhood trauma but also with clinical severity, adding new evidence to the involvement of gene-environment interactions in this disorder.
Related JoVE Video
Pharmacogenetics of the DNA repair pathways in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy.
Cancer Lett.
PUBLISHED: 03-07-2014
Show Abstract
Hide Abstract
Genetic variants in DNA repair genes may play a role in the effectiveness of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). We analyzed 17 SNPs in eight genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, XPA, XRCC1 and XRCC2) involved in DNA repair mechanisms and its association with outcome in NSCLC. This prospective study included patients with stages III and IV treated with platinum-based chemotherapy. All patients (n?=?161) received cisplatin or carboplatin plus a third-generation drug. Additionally, stage IIIA and IIIB patients (n?=?74) received concomitant or sequential radiotherapy. Germline polymorphisms were analyzed using the BioMark system in blood DNA samples. We found that in stage III patients, response was significantly associated with SNPs in ERCC1 and in ERCC3 genes, while radiotherapy-derived toxicity correlated with SNPs in the ERCC2 gene. In stage IV patients, response was associated with a genetic variant in the ERCC4 gene and survival with a SNP in the XRCC1 gene. The complexity of the DNA repair mechanisms along with the heterogeneity in the treatment of lung cancer could explain the role of multiple genes as putative biomarkers of patient outcome.
Related JoVE Video
IFNL4 ss469415590 variant shows similar performance to rs12979860 as predictor of response to treatment against Hepatitis C Virus genotype 1 or 4 in Caucasians.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
The rs12979860 variant, linked to IL28B gene, predicts sustained viral response (SVR) to pegylated-interferon/ribavirin (pegIFN/RBV) therapy in Hepatitis C Virus genotype 1 or 4 (HCV-1/4)-infected patients. Recently, a functional variant, ss469415590, in linkage disequilibrium (LD) with rs12979860, has been discovered. Our objective was to assess the value of ss469415590 to predict SVR to pegIFN/RBV in Caucasian HCV-1/4-infected individuals and to compare its performance with that of rs12979860.
Related JoVE Video
MTP gene polymorphisms and postprandial lipemia in familial combined hyperlipidemia: Effects of treatment with atorvastatin.
Clin Investig Arterioscler
PUBLISHED: 09-24-2013
Show Abstract
Hide Abstract
The microsomal triglyceride transfer protein (MTP) is involved in hepatic and intestinal apoB secretion. We studied the effect of the functional MTP-493G/T polymorphism on fasting and postprandial lipoproteins in patients with familial combined hyperlipidemia (FCH) before and after treatment with atorvastatin.
Related JoVE Video
Association of thymidylate synthase polymorphisms with acute pancreatitis and/or peripheral neuropathy in HIV-infected patients on stavudine-based therapy.
PLoS ONE
PUBLISHED: 01-21-2013
Show Abstract
Hide Abstract
Low expression thymidylate synthase (TS) polymorphism has been associated with increased stavudine triphosphate intracellular (d4T-TP) levels and the lipodystrophy syndrome. The use of d4T has been associated with acute pancreatitis and peripheral neuropathy. However, no relationship has ever been proved between TS polymorphisms and pancreatitis and/or peripheral neuropathy.
Related JoVE Video
The LCS6 polymorphism in the binding site of let-7 microRNA to the KRAS 3-untranslated region: its role in the efficacy of anti-EGFR-based therapy in metastatic colorectal cancer patients.
Pharmacogenet. Genomics
PUBLISHED: 01-18-2013
Show Abstract
Hide Abstract
Although KRAS mutation status has been identified as a strong predictor of response to anti-epidermal growth factor receptor (EGFR) therapies, not all wild-type patients respond. The lethal-7 (let-7) family of microRNAs regulates KRAS activity. A functional polymorphism (rs61764370) has been described in the let-7 complementary site (LCS6). We hypothesized a possible association between this KRAS let-7 LCS6 polymorphism and the response to anti-EGFR treatments in KRAS and BRAF wild-type metastatic colorectal cancer patients (mCRC).
Related JoVE Video
Multiple breath nitrogen washout: a feasible alternative to mass spectrometry.
PLoS ONE
PUBLISHED: 01-15-2013
Show Abstract
Hide Abstract
The lung clearance index (LCI), measured by multiple breath washout (MBW), reflects global ventilation inhomogeneity and is a sensitive marker of early cystic fibrosis (CF) lung disease. Current evidence is based on a customized mass spectrometry system that uses sulfur hexafluoride (SF6) as a tracer gas, which is not widely available. Nitrogen (N2) washout may be better suited for clinical use and multi-center trials.
Related JoVE Video
Polymorphisms of Pyrimidine Pathway Enzymes Encoding Genes and HLA-B*40?01 Carriage in Stavudine-Associated Lipodystrophy in HIV-Infected Patients.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
To assess in a cohort of Caucasian patients exposed to stavudine (d4T) the association of polymorphisms in pyrimidine pathway enzymes and HLA-B*40?01 carriage with HIV/Highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS).
Related JoVE Video
Chronic Stenotrophomonas maltophilia infection and exacerbation outcomes in cystic fibrosis.
J. Cyst. Fibros.
PUBLISHED: 05-30-2011
Show Abstract
Hide Abstract
Chronic Stenotrophomonas maltophilia infection is a risk factor for pulmonary exacerbation in cystic fibrosis (CF) but its impact on subsequent clinical outcomes is unknown. The aim of this study was to determine the effect of chronic S. maltophilia infection and associated antimicrobial therapy on the recovery of forced expiratory lung volume in 1s (FEV(1)) following pulmonary exacerbation.
Related JoVE Video
Association of thymidylate synthase gene polymorphisms with stavudine triphosphate intracellular levels and lipodystrophy.
Antimicrob. Agents Chemother.
PUBLISHED: 01-31-2011
Show Abstract
Hide Abstract
The antiviral activity and toxicity of stavudine (d4T) depend on its triphosphate metabolite, stavudine triphosphate (d4T-TP). Therefore, modifications in intracellular levels of d4T-TP may change the toxicity profile of stavudine. d4T-TP intracellular levels in peripheral blood mononuclear cells were determined with a prominence liquid chromatograph connected to a triple-quadruple mass spectrometer. Polymorphisms in the thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), dihydrofolate reductase (DHFR), reduced folate carrier 1 (RFC1; SLC19A1), and cyclin D1 (CCND1) genes were determined by direct sequencing using an ABI Prism 3100 genetic analyzer or Fluidigms Biomark system. The Mann-Whitney test, rank analysis of variance (with Bonferronis adjusted post hoc comparisons), and logistic regression were used for the inferential analyses. Thirty-three stavudine-treated patients were enrolled in this cross-sectional study. d4T-TP intracellular levels were 11.50 fmol/10(6) cells (interquartile range [IQR] = 8.12 to 13.87 fmol/10(6) cells) in patients with a high-expression TS genotype (2/3G, 3C/3G, and 3G/3G), whereas in those with a low-expression TS genotype (2/2, 2/3C, and 3C/3C), they were 21.40 fmol/10(6) cells (IQR = 18.90 to 27.0 fmol/10(6) cells) (P < 0.0001). Polymorphisms in the MTHFR, DHFR, RFC1, and CCND1 genes did not influence the intracellular concentration of d4T-TP. d4T-TP levels were independently associated with the TS genotype (low versus high expression; odds ratio [OR] = 86.22; 95% confidence interval [CI] = 8.48 to nonestimable; P = 0.0023). The low-expression TS genotype was associated with the development of HIV/highly active antiretroviral therapy-associated lypodystrophy syndrome (HALS) (OR = 14.0; 95% CI = 2.09 to 108.0; P = 0.0032). Our preliminary data show that polymorphisms in the thymidylate synthase gene are strongly associated with d4T-TP intracellular levels and with development of HALS.
Related JoVE Video
Pharmacogenetic study in rectal cancer patients treated with preoperative chemoradiotherapy: polymorphisms in thymidylate synthase, epidermal growth factor receptor, GSTP1, and DNA repair genes.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 01-18-2011
Show Abstract
Hide Abstract
Several studies have been performed to evaluate the usefulness of neoadjuvant treatment using oxaliplatin and fluoropyrimidines for locally advanced rectal cancer. However, preoperative biomarkers of outcome are lacking. We studied the polymorphisms in thymidylate synthase, epidermal growth factor receptor, glutathione S-transferase pi 1 (GSTP1), and several DNA repair genes to evaluate their usefulness as pharmacogenetic markers in a cohort of 128 rectal cancer patients treated with preoperative chemoradiotherapy.
Related JoVE Video
Absence of large intragenic rearrangements in the DPYD gene in a large cohort of colorectal cancer patients treated with 5-FU-based chemotherapy.
Br J Clin Pharmacol
PUBLISHED: 07-27-2010
Show Abstract
Hide Abstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Dihydropyrimidine dehydrogenase (DPD) is the enzyme responsible for the elimination of approximately 80% of the administered dose of 5-fluorouracil (5-FU). * Mutations in the DPD-coding gene have been shown to increase the risk of severe toxicity in 5-FU treated patients. * The IVS14+1G>A is the most common DPYD mutation. WHAT THIS STUDY ADDS * The intragenic rearrangements of DPYD using multiplex ligation-dependent probe amplification (MLPA) were studied for the first time in a large series of 234 colorectal cancer patients treated with 5-FU-containing chemotherapy. * No deletions or duplications of one or more DPYD exons were detected. The presence of the IVS14+1G>A mutation was also excluded. * These data show that neither the large genomic rearrangements in the DPYD gene nor the IVS14+1G>A mutation are responsible for the serious toxicity associated with a 5-FU containing regimen in this cohort of Spanish patients. AIMS To study the relationship between the toxicity associated with a 5-FU-based therapy and the presence of (i) the large intragenic rearrangements in the DPYD gene and (ii) the IVS14+1G>A mutation. METHODS We used the multiplex ligation-dependent probe amplification technique (MLPA) to study genomic DNA from 234 colorectal cancer patients treated with 5-FU-based chemotherapy. RESULTS We did not detect any deletion/duplication in the DPYD gene. The presence of the IVS14+1G>A mutation was also excluded. CONCLUSIONS Neither the large genomic rearrangements in the DPYD gene nor the IVS14+1G>A mutation play a significant role in the development of serious toxicity associated with a 5-FU containing regimen.
Related JoVE Video
Immunoglobulin G fragment C receptor polymorphisms and KRAS mutations: are they useful biomarkers of clinical outcome in advanced colorectal cancer treated with anti-EGFR-based therapy?
Cancer Sci.
PUBLISHED: 06-17-2010
Show Abstract
Hide Abstract
KRAS mutations have been identified as a strong predictor of resistance to anti-epidermal growth factor receptor (EGFR) therapies. Besides inhibiting the EGFR pathway, anti-EGFR monoclonal antibodies may exert antitumor effects through antibody-dependent cell-mediated cytotoxicity (ADCC). Through this mechanism, the antibody fragment C portion (Fc?) interacts with Fc receptors (Fc?Rs) expressed by immune effectors cells. We investigated the association of Fc?R polymorphisms and KRAS mutation with the clinical outcome of 104 refractory metastatic colorectal cancer (mCRC) patients treated with anti-EGFR antibodies. Fc?RIIa-H131R and Fc?RIIIa-V158F polymorphisms were analyzed in genomic DNA using a 48.48 dynamic array on the BioMark system (Fluidigm, South Sanfrancisco, CA, USA). Tumor tissues from 96 cases were screened for KRAS mutations. KRAS mutation was associated with a lower response rate (RR) (P = 0.035) and a shorter progression-free survival (PFS) (3 vs 7 months; P = 0.36). Fc?RIIa-H131R and Fc?RIIIa-V158F polymorphisms did not show statistically significant associations with response, PFS, or KRAS status. In the logistic regression analysis, KRAS status (P = 0.04) and skin toxicity (P = 0.03) were associated with RR. By multivariate analysis, the clinical risk classification (P?= 0.006) and skin toxicity (P < 0.0001) were found to be independent risk factors for PFS. In conclusion, the Fc?RIIa and Fc?RIIIa polymorphisms are not useful as molecular markers for clinical outcome in mCRC patients. To date, the EORTC (European Organization for Research and Treatment of Cancer Classification), skin toxicity, and KRAS status are the only reliable biomarkers to identify patients that would benefit from anti-EGFR therapy.
Related JoVE Video
Relationship between HIV/Highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome and stavudine-triphosphate intracellular levels in patients with stavudine-based antiretroviral regimens.
Clin. Infect. Dis.
PUBLISHED: 03-03-2010
Show Abstract
Hide Abstract
The link between human immunodeficiency virus/highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS) and the use of thymidine analogues has been well established. However, to our knowledge, no relationship has been proven between intracellular levels of stavudine (d4T) and HALS.
Related JoVE Video
Thymidylate synthase germline polymorphisms in rectal cancer patients treated with neoadjuvant chemoradiotherapy based on 5-fluorouracil.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 02-05-2010
Show Abstract
Hide Abstract
Chemoradiotherapy using 5-fluorouracil has shown to be effective treatment for rectal cancer. Thymidylate synthase (TS) is an important target enzyme for the fluoropyrimidines. However, the predictive role of TS levels in early stage rectal cancer is not yet well understood. We analyzed the value of TS gene polymorphisms as a predictive marker in patients with stage II and III rectal cancer treated with preoperative concomitant radiotherapy and fluoropyrimidine-based chemotherapy.
Related JoVE Video
Association of ITPA gene polymorphisms and the risk of ribavirin-induced anemia in HIV/hepatitis C virus (HCV)-coinfected patients receiving HCV combination therapy.
Antimicrob. Agents Chemother.
Show Abstract
Hide Abstract
Polymorphisms of the ITPA gene have been associated with anemia during combination therapy in hepatitis C virus (HCV)-monoinfected patients. Our aim was to confirm this association in HIV/HCV-coinfected patients. In this prospective, observational study, 73 HIV/HCV-coinfected patients treated with pegylated interferon plus ribavirin (RBV) were enrolled. Two single nucleotide polymorphisms within or adjacent to the ITPA gene (rs1127354 and rs7270101) were genotyped. The associations between the ITPA genotype and anemia or treatment outcome were examined. Fifty-nine patients (80.8%) had CC at rs1127354, whereas 14 (19.2%) had a CA/AA ITPA genotype. Percent decreases from baseline hemoglobin level were significantly greater in patients with the CC genotype than in those with the CA/AA genotype at week 4 (P = 0.0003), week 12 (P < 0.0001), and week 36 (P = 0.0102) but not at the end of treatment. RBV dose reduction was more often needed in patients with the CC genotype than in those with the CA/AA genotype (odds ratio [OR] = 11.81; 95% confidence interval [CI] = 1.45 to 256.17; P = 0.0039), as was erythropoietin therapy (OR = 8.28; 95% CI = 1.04 to 371.12; P = 0.0057). Risk factors independently associated with percent hemoglobin nadir decrease were RBV dose reduction (OR = 11.72; 95% CI = 6.82 to 16.63; P < 0.001), baseline hemoglobin (OR = 1.69; 95% CI = 0.23 to 3.15; P = 0.024), and body mass index (OR = -0.7; 95% CI = -1.43 to 0.03; P = 0.061). ITPA polymorphism was not an independent predictor of sustained virological response. Polymorphisms at rs1127354 in the ITPA gene influence hemoglobin levels during combination HCV therapy and the need for RBV dose reduction and erythropoietin use in HIV/HCV-coinfected patients.
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.