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Find video protocols related to scientific articles indexed in Pubmed.
Expression and function of Toll-like receptors in peripheral blood mononuclear cells from patients with ovarian cancer.
Cancer Immunol. Immunother.
PUBLISHED: 03-10-2014
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Inflammation has been implicated in the initiation and progression of ovarian cancer (OC), the underlying mechanisms of which are still unclear. We hypothesized that the abnormal expression of Toll-like receptors (TLRs), which were potential activators of nuclear factor-kappa B p65 (NF-?B p65), could promote inflammation and tumorigenesis in OC. In this study, we characterized the expression of TLRs in peripheral blood mononuclear cells (PBMCs) and found TLR2 and TLR6 mRNAs levels to be higher in PBMCs from OC patients than in those from benign disease (BC) or healthy normal controls (NC). Flow cytometry analysis showed that TLR1, TLR2 and TLR6 were highly expressed in monocytes from OC patients, but not in those from control subjects. Consistently, inflammatory cytokines interleukin (IL)-1? and IL-6 were up-regulated in PBMCs from OC patients upon stimulation with Pam3CSK4 (TLR1 ligand) and HKLM (TLR2 ligand), compared with unstimulated PBMCs. Stimulation of PBMCs with TLR ligands led to activation of downstream signaling molecules in TLRs (MyD88, TRAF6, TANK, NF-?B p65 and p-NF-?B p65). We also discovered that SK-OV-3-secreted factors were potent PBMCs activators, leading to the production of IL-1?, IL-6 and IL-8 through activation of TLRs and downstream signaling molecules in PBMCs. Before coculturing with SK-OV-3, pretreatment of THP-1 cells or PBMCs with monoclonal antibodies against TLR1, TLR2 or TLR6 inhibited the production of IL-1? and IL-6 and activation of MyD88, TRAF6, TANK, NF-?B p65 and p-NF-?B p65. Our results provided new evidence that TLR1, TLR2 and TLR6 signaling was linked with inflammation in OC microenvironment.
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Direct renin inhibition with aliskiren protects against myocardial ischemia/reperfusion injury by activating nitric oxide synthase signaling in spontaneously hypertensive rats.
J Am Heart Assoc
PUBLISHED: 01-30-2014
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We tested the hypothesis that direct renin inhibition with aliskiren protects against myocardial ischemia/reperfusion (I/R) injury in spontaneously hypertensive rats (SHR), and examined the mechanism by which this occurs.
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Emergence of linezolid resistance in a clinical Staphylococcus capitis isolate from Jiangsu Province of China in 2012.
J Thorac Dis
PUBLISHED: 01-19-2014
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Linezolid (LZD) is an important antimicrobial agent for the treatment of infections caused by Gram-positive organisms, including methicillin-resistant Staphylococci. And until now, LZD resistance in clinical is still rare. Here we reported the first case of LZD resistance Staphylococcus capitis in Jiangsu, China. This strain was isolated from a 92-year old female who received long-term and repeatedly antibiotics treatment because of recurrent pulmonary infections in August 2012. Isolated from blood, the Staphylococcus capitis showed a resistance to LZD with a minimal inhibitory concentration (MIC) of 64 µg/mL, and the followed gene detection showed that the isolates existed C2190T and C2561Y point mutations in the 23S rRNA. Moreover, the isolation was also found carrying the cfr gene.
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MALDI-TOF MS versus VITEK 2 ANC card for identification of anaerobic bacteria.
J Thorac Dis
PUBLISHED: 01-18-2014
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Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an accurate, rapid and inexpensive technique that has initiated a revolution in the clinical microbiology laboratory for identification of pathogens. The Vitek 2 anaerobe and Corynebacterium (ANC) identification card is a newly developed method for identification of corynebacteria and anaerobic species. The aim of this study was to evaluate the effectiveness of the ANC card and MALDI-TOF MS techniques for identification of clinical anaerobic isolates.
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Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6 promotes cell proliferation and migration by upregulating DNMT1 via STAT3 activation.
PLoS ONE
PUBLISHED: 01-01-2014
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Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with Kaposi's sarcoma (KS), the most common AIDS-related malignancy. KSHV vIL-6 promotes KS development, but the exact mechanisms remain unclear. Here, we reported that KSHV vIL-6 enhanced the expression of DNA methyltransferase 1 (DNMT1) in endothelial cells,increased the global genomic DNA methylation, and promoted cell proliferation and migration. And this effect could be blocked by the DNA methyltransferase inhibitor, 5-azadeoxycytidine. We also showed that vIL-6 induced up-regulation of DNMT1 was dependent on STAT3 activation. Therefore, the present study suggests that vIL-6 plays a role in KS tumorigenesis partly by activating DNMT1 and inducing aberrant DNA methylation, and it might be a potential target for KS therapy.
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Amylase: sensitive tumor marker for amylase-producing lung adenocarcinoma.
J Thorac Dis
PUBLISHED: 07-31-2013
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Hyperamylasemia in patients with lung cancer is rarely, comprising 1% to 3% of all lung cancers. This report describes two cases of lung adenocarcinoma coexisting with hyperamylasemia in two women aged 77 and 57, respectively. In these two cases, CT revealed a normal pancreas. We monitored the serum and urine amylase levels during therapy and found it paralleled tumor response to chemotherapy and metastasis. We suggest that the amylase levels are related to the tumor size and might be a valuable factor in predicting chemotherapy and progression of disease for amylase-producing lung cancer.
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A 4-year surveillance of antimicrobial resistance patterns of Acinetobacter baumanni in a university-affiliated hospital in China.
J Thorac Dis
PUBLISHED: 07-30-2013
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To investigate the changes in resistance of Acinetobacter baumanni (A. baumannii) to different antimicrobial agents and the association of resistance rates with several independent factors: specimen origin, hospital wards, patients gender and age, from 2008 to 2011.
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Comparison of four DNA extraction methods for detecting Mycobacterium tuberculosis by real-time PCR and its clinical application in pulmonary tuberculosis.
J Thorac Dis
PUBLISHED: 04-07-2013
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China is one of the countries with a high burden of Mycobacterium tuberculosis (MTB) infection. One challenge for the earlier diagnosis of tuberculosis is the DNA extraction of MTB. This study was to compare four MTB DNA extraction methods, and use the best one in the diagnosis of pulmonary tuberculosis.
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A new method for the detection of adenosine based on time-resolved fluorescence sensor.
Biosens Bioelectron
PUBLISHED: 03-27-2013
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In this work, we report a thrombin binding aptamer complex based time-resolved fluorescence sensor for small molecule detection. The sensor employs two strands (DNA1 and DNA2) of oligonucleotides. This two strands of oligonucleotides contain two aptamer (?-aptamer and ?-aptamer) respectively. DNA1 and DNA2 were labeled with biotin and DIG at the 3-end, respectively. Binding of the ?-aptamer and ?-aptamer to the thrombin promotes the hybridization between the complementary stem sequences attached to the two oligonucleotide sequences. The hybridization then brings biotin to be hidden in the shield part on DNA1, shielding biotin from being approached by the streptavidin modified on the microplate due to the steric hindrance effect of the shield part of DNA1. Result in the thrombin-aptamer complex cannot be modified on the surface of microplate which further leads to no signal reported. The strategy integrates the distinguishing features of aptamer and fluorescent techniques. As a proof-of-principle, adenosine in serum was detected with a detection limit of 0.5 nM. A nice detection limit and linear relationship were obtained.
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Use of RBC-O and S-MCV parameters of SYSMEX XE-2100 in a patient with RBC cold agglutination.
Clin. Lab.
PUBLISHED: 03-20-2013
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Sometimes EDTA blood of erythrocyte agglutination cannot be well resolved by incubation at 37 degrees C. In this case report, however, such a specimen was detected from a lymphoma patient at room temperature by using RBC-O and S-MCV parameters of the SYSMEX XE-2100 hematology analyzer. The specimen was diluted with 0.9% NaCL solution at 1:1 before measurement. HCT, MCV, and MCHC, corrected by RBC-O, HGB and S-MCV, were all in their normal ranges. This case indicates that RBC-O and S-MCV parameters of XE-2100 can be used in the routine blood examination of erythrocyte agglutination specimen at room temperature.
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Prevalence and trends of aminoglycoside resistance in Shigella worldwide, 1999-2010.
J Biomed Res
PUBLISHED: 01-17-2013
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Shigellosis causes diarrheal disease in humans in both developed and developing countries, and multi-drug resistance in Shigella is an emerging problem. Understanding changing resistance patterns is important in determining appropriate antibiotic treatments. This meta-analysis systematically evaluated aminoglycoside resistance in Shigella. A systematic review was constructed based on MEDLINE and EMBASE databases. Random-effect models or fixed-effect models were used based on P value considering the possibility of heterogeneity between studies for meta-analysis. Data manipulation and statistical analyses were performed using software STATA 11.0. By means of meta-analysis, we found a lower resistance to three kinds of aminoglycosides in the Europe-America areas during the 12 year study period than that of the Asia-Africa areas. Kanamycin resistance was observed to be the most common drug resistance among Shigella isolates with a prevalence of 6.88% (95%CI: 6.36%-7.43%). Comparison of data from Europe-America and Asia-Africa areas revealed that Shigella flexneri resistance was greater than the resistance calculated for Shigella sonnei. Importantly, Shigella sonnei has played a significant role in aminoglycoside-resistance in recent years. Similarly, data showed that resistance to these drugs in children was higher than the corresponding data of adults. In conclusion, aminoglycoside-resistant Shigella is not an unusual phenomenon worldwide. Distribution in Shigella resistance differs sharply based on geographic areas, periods of time and subtypes. The results from the present study highlight the need for continuous surveillance of resistance and control of antibiotic usage.
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The hydrogen sulfide donor, GYY4137, exhibits anti-atherosclerotic activity in high fat fed apolipoprotein E(-/-) mice.
Br. J. Pharmacol.
PUBLISHED: 01-11-2013
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Atherosclerosis is associated with reduced vascular hydrogen sulfide (H2 S) biosynthesis. GYY4137 is a novel slow-releasing H2 S compound that may effectively mimic the time course of H2 S release in vivo. However, it is not known whether GYY4137 affects atherosclerosis.
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Characterization of Osterix protein stability and physiological role in osteoblast differentiation.
PLoS ONE
PUBLISHED: 01-09-2013
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Osterix (Osx/SP7) is a C2H2 zinc finger-containing transcription factor of the SP gene family. Osx knockout mice indicate that the gene plays an essential role in osteoblast differentiation and bone formation. However, the mechanisms involved in the regulation of Osx are still poorly understood. Here, we report a novel post-translational mechanism for the regulation of Osx in mammalian cells. We found that the stability of endogenous and exogenous Osx reduced after cycloheximide treatment. In cells treated with the proteasome inhibitors MG-132 or lactacystin, both endogenous and exogenous Osx protein expression increased in a time-dependent manner. Co-immunoprecipitation (Co-IP) assays showed that both endogenous and exogenous Osx were ubiquitinated. Six lysine residues of Osx were identified as candidate ubiquitination sites by construction of point mutant plasmids and luciferase reporter assays. Furthermore, we confirmed that K58 and K230 are the ubiquitination sites of Osx by Co-IP assays and protein stability assays. Moreover, the Osx K58R and K230R mutations promoted the expression of osteoblast differentiation markers (alkaline phosphatase, collagen I and osteocalcin) and enhanced osteogenic differentiation in C2C12 cells. Taken together, our data indicate that Osx is an unstable protein, and that the ubiquitin-proteasome pathway is involved in the regulation of Osx and thereby regulates osteoblast differentiation.
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Downregulation of IFNG in CD4(+) T Cells in Lung Cancer through Hypermethylation: A Possible Mechanism of Tumor-Induced Immunosuppression.
PLoS ONE
PUBLISHED: 01-01-2013
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Tumor survival is significantly correlated with the immune response of patients. IFNG plays an important role in the tumor host response and decreased IFNG expression is often observed in lung cancer. Studies have shown that CpG island hypermethylation plays a critical role in transcriptional silencing of IFNG gene expression. However, there is limited understanding regarding the molecular mechanisms of altered methylation, and whether the tumor microenvironment has any effect on DNA methylation and IFNG production. In the current study, we demonstrate that plasma and intra-cellular IFNG levels are significantly lower in lung cancer patients. Hypermethylation of the IFNG promoter in CD4(+) T cells and plasma IFNG was negatively correlated. CD4(+) T cells from healthy individuals co-cultured with SPC-A1 cells generated lower levels of IFNG after activation, elevated expression of DNA methyltransferases (DNMTs), and exhibited hypermethylation of the IFNG promoter. In conclusion, decreased IFNG expression of CD4(+) T cells co-cultured with lung cancer cell is associated with IFNG promoter hypermethylation. Our study suggests that interaction between lung cancer cells and CD4(+) T cells induces DNMT expression and IFNG promoter hypermethylation in CD4(+) T cell, which may serve as an important mechanism of tumor-induced immunosuppression.
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Early second-trimester serum miRNA profiling predicts gestational diabetes mellitus.
PLoS ONE
PUBLISHED: 07-29-2011
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Gestational diabetes mellitus (GDM) is one type of diabetes that presents during pregnancy and significantly increases the risk of a number of adverse consequences for the fetus and mother. The microRNAs (miRNA) have recently been demonstrated to abundantly and stably exist in serum and to be potentially disease-specific. However, no reported study investigates the associations between serum miRNA and GDM.
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Epidemiology and molecular mechanism of integron-mediated antibiotic resistance in Shigella.
Arch. Microbiol.
PUBLISHED: 05-17-2011
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Integrons are gene capture and expression systems that are characterized by the presence of an integrase gene. This encodes an integrase, a recombined site, and a promoter. They are able to capture gene cassettes from the environment and incorporate them using site-specific recombination. The role of integrons and gene cassettes in the dissemination of multidrug resistance in Gram-negative bacteria is significant. In Shigella species, antimicrobial resistance is often associated with the presence of class 1 and class 2 integrons that contain resistance gene cassettes. Multiple and complex expression regulation mechanisms involving mobile genetic elements in integrons have been developed in the evolution of Shigella strains. Knowledge of the epidemiology and molecular mechanisms of antimicrobial resistance in this important pathogen is essential for the implementation of intervention strategies. This review was conducted to introduce the structures and functions of integrons in Shigella species and mechanisms that control integron-mediated events linked to antibiotic resistance.
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Potentially functional polymorphisms in DNA repair genes and non-small-cell lung cancer survival: a pathway-based analysis.
Mol. Carcinog.
PUBLISHED: 03-08-2011
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To assess systematically whether potentially functional polymorphisms in DNA repair genes influence the clinical behavior of non-small-cell lung cancer (NSCLC), we examined the impact of a comprehensive panel of 218 signal nucleotide polymorphisms (SNP) in 50 candidate DNA repair genes on overall survival of NSCLC in a case-cohort of 568 lung cancer patients. SNPs associated with lung cancer prognosis primarily mapped to 14 genes in different repair pathways, and 6 SNPs were remained in the final model after multivariate stepwise Cox regression analysis: ATM rs189037; MRE11A rs11020802; ERCC2 rs1799793; MBD4 rs140693; XRCC1 rs25487, and PMS1 rs5742933. In the combined analysis of these 6 SNPs, an increasing number of unfavorable loci was associated with a poorer prognosis (P for trend: <0.0001) and patients having 2-4 unfavorable loci had a 1.99-fold elevated risk of death 95% confidence interval (CI)?= 1.58-2.50, compared with those carrying 0-1 unfavorable loci, and this elevated risk was more evident among stages I-II patients (hazard ratio = 3.04, 95% CI = 1.86-4.98, P for heterogeneity: 0.07). Furthermore, a significant effect of SNPs in nucleotide excision repair pathway on lung cancer survival was observed among 185 stages III-IV patients treated with platinum-based chemotherapy without surgical operation: XPC rs2228000 (Ala499Val; P = 0.002) and ERCC1 rs11615 (Asn118Asn; P = 0.012). Our data indicate that potentially functional polymorphisms in DNA repair genes may serve as candidate prognostic markers of clinical outcome of NSCLC.
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Host immune gene polymorphisms were associated with the prognosis of non-small-cell lung cancer in Chinese.
Int. J. Cancer
PUBLISHED: 03-02-2011
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Laboratory-based studies showed that host immune genes could influence the prognosis of non-small-cell lung cancer (NSCLC). Therefore, genetic polymorphisms in host immune genes may serve as predictors for NSCLC clinical outcome. To test the hypothesis that functional single nucleotide polymorphisms (SNPs) in host immune genes are associated with the prognosis of NSCLC, we systematically performed a genotyping analysis for a total of 178 SNPs from 52 immune genes in a prospective case cohort of 568 NSCLC patients. Among the 178 SNPs, 24 were significantly associated with NSCLC prognosis in different genetic models and four of them were remained in the final predictive model after multivariate stepwise Cox regression, including IL-5R rs11713419 (5-untranslated region, 5-UTR) (P = 0.001), IL23R rs6682925 (5-flanking region, 5-FR) (P = 0.017), TLR1 rs5743551 (5-FR) (P = 0.02) and TLR3 rs3775291 (Leu412Phe) (P = 0.01). We then put the above four SNPs together, and found that the risk of death was significantly increased by 124% (HR = 2.24, 95% CI: 1.33-3.75) for the patients carrying "1" unfavorable locus and by 175% (HR = 2.75, 95% CI: 1.67-4.51) for those carrying "2-4" unfavorable loci. The risk score model and time-dependent ROC analyses further support the four SNPs and clinical risk score model. The area under curve (AUC) at year 5 increased from 0.484 to 0.831 after combining the four SNPs risk score with clinical risk score. These findings indicate that potentially functional polymorphisms in immune genes may serve as prognostic markers of clinical outcome of NSCLC.
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Polymorphisms of key chemokine genes and survival of non-small cell lung cancer in Chinese.
Lung Cancer
PUBLISHED: 01-09-2011
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Chemokines play an important role in the pathogenesis of non-small cell lung cancer (NSCLC). Although the deregulations of chemokines have been reported to be associated with the development and progression of many human cancers including lung cancer, polymorphisms of chemokine genes have not been examined with the survival of NSCLC. We systematically investigated associations of 23 common potentially functional SNPs in the key chemokine genes (CCL2, CCL5, CCL8, CCL20, CCL22, CXCL1, CXCL6, CXCL9 and CXCL12) with the survival of NSCLC in a case cohort of 568 NSCLC patients in a Chinese population. The results showed that variant genotypes of CCL2 rs3760396 and CCL8 rs3138035 were associated with a significantly decreased risk of death for NSCLC (dominant model: adjusted HR=0.65, 95% CI=0.48-0.89 for rs3760396; dominant model: adjusted HR=0.65, 95% CI=0.49-0.86 for rs3138035), while CXCL12 rs1804429 was associated with an increased risk of death for NSCLC (CC vs AA: adjusted HR=6.03, 95% CI=1.44-25.24). Further stepwise regression analysis suggested that only rs3138035, a SNP located at 5-flanking region of CCL8, was an independently favorable factor for the prognosis of NSCLC and the protective effect was more evident in smokers (adjusted HR=0.61, 95% CI=0.42-0.87), patients with squamous cell cancer (adjusted HR=0.58, 95% CI=0.35-0.96), patients with early stage (adjusted HR=0.32, 95% CI=0.15-0.67) and patients treated with surgical operation (adjusted HR=0.47, 95% CI=0.31-0.71). In addition, the interaction analysis demonstrated that stage and surgical operation interacted with the genetic effect of rs3138035 in relation to NSCLC survival (adjusted P(interaction)=0.02 and 0.01, respectively). These findings suggest that CCL8 rs3138035 may be one of the candidate biomarkers for NSCLC survival and may modify death risk associated with stage and surgical operation. Larger studies incorporating functional evaluations are warranted to validate our findings.
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Genetic polymorphisms in the precursor MicroRNA flanking region and non-small cell lung cancer survival.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 10-01-2010
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Previously, we reported that common variants in precursor microRNA (pre-miRNA) sequences played a role in the prediction of non-small cell lung cancer (NSCLC) survival.
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Activation of calcium-sensing receptors is associated with apoptosis in a model of simulated cardiomyocytes ischemia/reperfusion.
J Biomed Res
PUBLISHED: 07-01-2010
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Calcium-sensing receptors (CaSRs) are G-protein coupled receptors which maintain systemic calcium homeostasis and participate in hormone secretion, activation of ion channels, cell apoptosis, proliferation, and differentiation. Previous studies have shown that CaSRs induce apoptosis in isolated adult rat heart and in normal neonatal rat cardiomyocytes by G-protein-PLC-IP3 signaling transduction. However, little knowledge is presently available concerning the role of CaSRs in the apoptosis induced by ischemia and reperfusion in neonatal cardiomyocytes.
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Double recognition of oligonucleotide and protein in the detection of DNA methylation with surface plasmon resonance biosensors.
Biosens Bioelectron
PUBLISHED: 05-26-2010
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DNA methylation plays an essential role in maintenance of cellular function. A growing number of human diseases have been found to be associated with aberrant DNA methylation, especially cancer. However, current technologies used in DNA methylation detection are complicated and time consuming. A promotor of the Adenomatous polyposis coli (APC) gene, a well-studied tumor suppressor gene, was used as the detection target DNA sequence. The double recognition mechanism was realized with oligonucleotide probe hybridization and specific protein binding. First, complementary target DNA was captured by the probe immobilized onto a surface plasmon resonance (SPR) sensor chip. Then, the recombinant methyl-CpG binding domain (MBD) protein was passed over the surface to recognize and bind to methylated CpG sites. Binding resulted in an increase in the refractive index, and a detectable optical signal was generated. Five picomoles of methylated APC promotor DNA could be easily detected with this method. The entire detection could be completed within 1h. This work represents the first SPR based biosensor technology, which achieves simple and specific DNA methylation detection and avoids complicated bisulfite treatment and methylation-sensitive restriction digestion. It will improve our ability to detect DNA methylation specifically and rapidly, and promote our understanding of the role of DNA methylation in gene regulation and diseases.
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[Research and development of medical case database: a novel medical case information system integrating with biospecimen management].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 05-21-2010
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To meet the needs of management of medical case information and biospecimen simultaneously, we developed a novel medical case information system integrating with biospecimen management. The database established by MS SQL Server 2000 covered, basic information, clinical diagnosis, imaging diagnosis, pathological diagnosis and clinical treatment of patient; physicochemical property, inventory management and laboratory analysis of biospecimen; users log and data maintenance. The client application developed by Visual C++ 6.0 was used to implement medical case and biospecimen management, which was based on Client/Server model. This system can perform input, browse, inquest, summary of case and related biospecimen information, and can automatically synthesize case-records based on the database. Management of not only a long-term follow-up on individual, but also of grouped cases organized according to the aim of research can be achieved by the system. This system can improve the efficiency and quality of clinical researches while biospecimens are used coordinately. It realizes synthesized and dynamic management of medical case and biospecimen, which may be considered as a new management platform.
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Polymorphisms in EGFR and VEGF contribute to non-small-cell lung cancer survival in a Chinese population.
Carcinogenesis
PUBLISHED: 04-16-2010
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Over the last decades, combined chemotherapies that inhibit different signalling pathways together have been demonstrated to be more effective to treat the non-small-cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) and the vascular endothelium growth factor (VEGF) are two key targets. Polymorphisms in EGFR and VEGF genes have been identified to be associated with therapy-response and cancer survival. In this study, we hypothesized that single-nucleotide polymorphisms (SNPs) of EGFR and VEGF genes are associated with NSCLC patients survival in Chinese. Therefore, we screened and genotyped 54 potentially functional SNPs as well as tagging SNPs in these two genes using Illumina Golden Gate platform in 568 NSCLC patients. We found that subjects carrying EGFR rs3735061AA and rs6958497AG/GG genotypes survived significantly shorter time [median survival time (MST): 22.2 and 19.4 months, respectively] than those carrying rs3735061AG/GG (MST: 25.1 months) and rs6958497AA (MST: 25.9 months) (log-rank P = 0.015 for rs3735061 and log-rank P = 0.028 for rs6958497). However, subjects carrying EGFR rs759165AG/AA genotypes survived significantly longer (MST: 38.7 months) than those carrying rs759165GG genotype (MST: 24.7 months) (log-rank P = 0.024). Multivariate Cox regression analyses showed that the genotypes of rs3735061AA and rs6958497AG/GG were associated with a significantly increased risk of death for NSCLC [hazard ratio (HR) = 2.82, 95% confidence interval (CI) = 1.66-4.78 for rs3735061AA and HR = 1.69, 95% CI = 1.26-2.28 for rs6958497AG/GG], whereas the rs759165AG/AA were associated with a 44% significantly decreased risk of death of NSCLC (HR = 0.56, 95% CI = 0.39-0.83). Stepwise COX regression analyses suggested that EGFR rs373506, rs759165 and rs6958497 may be independent candidate biomarkers to predict NSCLC survival in this population.
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Potentially functional polymorphisms in cell cycle genes and the survival of non-small cell lung cancer in a Chinese population.
Lung Cancer
PUBLISHED: 04-02-2010
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The cell cycle governs the proliferation and growth of cells and is strictly controlled by some regulators including cyclins, CDKs and CKIs. Germ-line and somatic mutations in cell cycle genes were frequently observed in a subset of cancers including non-small cell lung cancer (NSCLC). In this study, we hypothesized that potentially functional single nucleotide polymorphisms (SNPs) in cell cycle genes may contribute to the prognosis of NSCLC in China. 54 potentially functional polymorphisms in key cell cycle genes (CDK1, CDK2, CDK4, CDK6, CDK7, CCND1, CCND2, CCND3, CCNE1, CCNA1, CCNA2, CCNB1, CCNH, p15, p16, p18, p19, p21, p27, Cdc25A and Cdc25B) were genotyped by using Illumina SNP genotyping platform to evaluate their associations with survival of NSCLC in a clinical cohort of 568 patients. We found that p18 rs3176447 variant genotypes were significantly associated with the decreased risk of death of NSCLC patients (adjusted HR=0.74, 95% CI=0.57-0.97 in an additive model; adjusted HR=0.76, 95% CI=0.55-0.97 in a dominant model); however, p21 rs2395655 variant genotypes were significantly associated with the increased risk of death (adjusted HR=1.21, 95% CI=1.02-1.42 in an additive model; adjusted HR=1.38, 95% CI=1.07-1.78 in a recessive model). Furthermore, the combined effect of unfavorable genotypes for these two SNPs was more prominent in patients with squamous cell carcinoma, late stage and without chemo- or radio-therapy. Although the exact biological function remains to be explored, our findings suggest possible association of polymorphisms of p18 and p21 with the prognosis of NSCLC in a Chinese population. Further large and functional studies are needed to confirm our findings.
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Deregulated expression of miR-21, miR-143 and miR-181a in non small cell lung cancer is related to clinicopathologic characteristics or patient prognosis.
Biomed. Pharmacother.
PUBLISHED: 01-29-2010
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MicroRNAs (miRNAs) represent a class of small non-coding RNAs that regulate the gene expressions at the posttranscriptional level, subsequently control crucial physiological processes. Recent evidence demonstrates that some miRNAs have the functions similar to oncogene or tumor suppressors, it may play important roles in tumorigenesis. MiRNA expression profiles may become useful biomarkers for cancer diagnostics, prognosis and prediction of response to treatment, and it could be a powerful tool for cancer prevention and therapeutics.
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The property of methylated APC gene promotor and its influence on lung cancer cell line.
Biomed. Pharmacother.
PUBLISHED: 12-16-2009
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Previous findings have suggested that methylation of the APC gene may be associated with some tumors including lung cancer. To explore the pattern of APC methylation and the effect of APC gene methylation on its protein expression in lung cancer cell lines, we investigated APC promotor methylation by methylation specific PCR (MSP) and bisulfite sequencing and analyzed the APC protein levels by western blot in three lung cancer cell lines. Monoallelic methylation and 20 methylated CpGs in CpG island near the open reading frame (ORF) of the APC gene were found in the NCI-H460 cell line, and were stablely inherited within 10 generations of the cell line in culture. Our results showed that two special CpG sites (794, 797) might be binding sites for proteins that regulate APC expression. Protein expression of the APC gene in the NCI-H460 cell line declined, but was enhanced after the treatment with 5-aza-2-deoxycytidine (5-aza-dC). Inherited monoallelic methylation of the APC gene may play an important role in lung cancer. Demethylation of the APC gene by 5-aza-dC may be useful for the treatment of lung cancer.
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[Clinical significance of peripheral blood circular DNA level measurements in patients with acute myocardial infarction].
Zhongguo Yi Liao Qi Xie Za Zhi
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To explore clinical value of circular DNA in acute myocardial infarction.
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Genetic variants at 6p21.1 and 7p15.3 are associated with risk of multiple cancers in Han Chinese.
Am. J. Hum. Genet.
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Cancer susceptibility loci identified in reported genome-wide association studies (GWAS) are often tumor-specific; however, evidence of pleiotropy of some genes/loci has also been observed and biologically plausible. We hypothesized that there are important regions in the genome harboring genetic variants associated with risk of multiple types of cancer. In the current study, we attempted to map genetic variants that have consistent effects on risk of multiple cancers using our existing genome-wide scan data of lung cancer, noncardia gastric cancer, and esophageal squamous-cell carcinoma with overall 5,368 cases and 4,006 controls (GWAS stage), followed by a further evaluation in additional 9,001 cases with one of these cancer types and 11,436 controls (replication stage). Five variants satisfying the criteria of pleiotropy with p values from 1.10 × 10(-8) to 8.96 × 10(-6) for genome-wide scans of three cancer types were further evaluated in the replication stage. We found consistent associations of rs2494938 at 6p21.1 and rs2285947 at 7p15.3 with these three cancers in both GWAS and replication stages. In combined samples of GWAS and replication stages, the minor alleles of rs2494938 and rs2285947 were significantly associated with an increased risk of the cancers (odds ratio [OR] = 1.15, 95% confidence interval [CI], 1.10-1.19 and OR = 1.17, 95% CI, 1.12-1.21), with the p values being 1.20 × 10(-12) and 1.26 × 10(-16), respectively, which are at a genome-wide significance level. Our findings highlight the potential importance of variants at 6p21.1 and 7p15.3 in the susceptibility to multiple cancers.
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The single nucleotide polymorphism and haplotype analysis of MDR1 in Jiangsu Han population of China.
Biomed. Pharmacother.
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The aim of this study was to perform the frequency distribution of MDR1 gene SNPs and haplotypes of Jiangsu Han population in China. A total of 225 Jiangsu Han unrelated volunteers were enrolled and genotyped by PCR-ASP method at three loci: C1236T (rs1128503), G2677T/A (rs2032582) and C3435T (rs1045642). In total, C and T were found at locus 1236, with the frequency of 35% and 65%, respectively. The most frequent allele at locus 2677 was G with the frequency of 44%, followed by T (41%) and A (15%). At locus 3435, C was more common (60%) than T (40%). The most common haplotype at loci 1236-2677-3435 was T-T-T (31.84%), at loci 1236-2677 was T-T (37.68%), at loci 2677-3435 was G-C (39.06%), and at loci 1236-3435 was T-T (34.28%). The haplotype linkage disequilibrium study found that all three loci were in linkage disequilibrium, such as T-T at loci 1236-2677, T-T at loci 2677-3435 and C-C at loci 1236-3435 (P<0.01). The dendrogram study indicated that the distribution of MDR1 SNPs in Jiangsu Han population were close to Japan and Malay populations and far away from European countries. These findings could shade new lights in population genetics and anthropology studies of Han-Chinese. It also provides basic data for research on MDR1 gene polymorphism, disease association and drug resistance study.
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EDTA-temperature-Induced pseudohematocytopenia in a patient with multiple myeloma.
Clin. Lab.
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Platelet clumping caused by ethylenediamine tetraacetic acid (EDTA) and erythrocyte agglutination caused by cold agglutinins are often found in clinical findings. However, erythrocyte agglutination induced by EDTA has not been reported as yet.
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Changing trend of antimicrobial resistance among pathogens isolated from lower respiratory tract at a university-affiliated hospital of China, 2006-2010.
J Thorac Dis
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To investigate the distribution and the antimicrobial resistance of pathogens in lower respiratory tract infection from 2006 to 2010.
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l-Tetrahydropalmatine, an active component of Corydalis yanhusuo W.T. Wang, protects against myocardial ischaemia-reperfusion injury in rats.
PLoS ONE
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l-Tetrahydropalmatine (l-THP) is an active ingredients of Corydalis yanhusuo W.T. Wang, which protects against acute global cerebral ischaemia-reperfusion injury. In this study, we show that l-THP is cardioprotective in myocardial ischaemia-reperfusion injury and examined the mechanism. Rats were treated with l-THP (0, 10, 20, 40 mg/kg b.w.) for 20 min before occlusion of the left anterior descending coronary artery and subjected to myocardial ischaemia-reperfusion (30 min/6 h). Compared with vehicle-treated animals, the infarct area/risk area (IA/RA) of l-THP (20, 40 mg/kg b.w.) treated rats was reduced, whilst l-THP (10 mg/kg b.w.) had no significant effect. Cardiac function was improved in l-THP-treated rats whilst plasma creatine kinase activity declined. Following treatment with l-THP (20 mg/kg b.w.), subunit of phosphatidylinositol 3-kinase p85, serine(473) phosphorylation of Akt and serine(1177) phosphorylation of endothelial NO synthase (eNOS) increased in myocardium, whilst expression of inducible NO synthase (iNOS) decreased. However, the expression of HIF-1? and VEGF were increased in I(30 min)R(6 h), but decreased to normal level in I(30 min)R(24 h), while treatment with l-THP (20 mg/kg b.w.) enhanced the levels of these two genes in I(30 min)R(24 h). Production of NO in myocardium and plasma, activity of myeloperoxidase (MPO) in plasma and the expression of tumour necrosis factor-? (TNF-?) in myocardium were decreased by l-THP. TUNEL assay revealed that l-THP (20 mg/kg b.w.) reduced apoptosis in myocardium. Thus, we show that l-THP activates the PI3K/Akt/eNOS/NO pathway and increases expression of HIF-1? and VEGF, whilst depressing iNOS-derived NO production in myocardium. This effect may decrease the accumulation of inflammatory factors, including TNF-? and MPO, and lessen the extent of apoptosis, therefore contributing to the cardioprotective effects of l-THP in myocardial ischaemia-reperfusion injury.
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Comparison of the prevalence and changing resistance to nalidixic acid and ciprofloxacin of Shigella between Europe-America and Asia-Africa from 1998 to 2009.
Int. J. Antimicrob. Agents
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Shigella is becoming an increasing public health problem due to development of multiple antimicrobial resistance, frequently resulting in treatment failure. A systematic review was conducted based on a literature search of computerised databases. Random or fixed-effects models were used, based on the P-value considering the possibility of heterogeneity between studies, for meta-analysis. Statistical analyses were performed using STATA 10.0. In the area of Asia-Africa, resistance rates to nalidixic acid and ciprofloxacin were 33.6% [95% confidence interval (CI) 21.8-46.6%] and 5.0% (95% CI 2.8-7.8%), respectively, 10.5 and 16.7 times those of Europe-America. Moreover, resistance to nalidixic acid and ciprofloxacin in Asia-Africa progressively increased each year, reaching 64.5% (95% CI 13.8-99.3%) and 29.1% (95% CI 0.9-74.8%), respectively, in 2007-2009, whilst isolates in Europe-America remained at low levels of resistance (<5.0% and <1.0%, respectively). All Shigella flexneri strains showed higher resistance than Shigella sonnei in Europe-America: overall, 3.5% (95% CI 1.4-6.4%) vs. 2.6% (95% CI 1.0-5.0%) resistant to nalidixic acid and 1.0% (95% CI 0.3-2.2%) vs. 0.1% (95% CI 0.0-0.3%) resistant to ciprofloxacin. In Asia-Africa, a similar trend was found for ciprofloxacin [3.0% (95% CI 1.4-5.3%) vs. 0.5% (95% CI 0.2-0.8%)], whereas the trend was reversed for nalidixic acid [32.6% (95% CI 14.5-53.9%) vs. 44.3% (95% CI 26.9-62.5%). In conclusion, quinolone resistance in Shigella has increased at an alarming speed, reinforcing the importance of continuous monitoring of antimicrobial resistance in Shigella.
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The study on newly developed McAb NJ001 specific to non-small cell lung cancer and its biological characteristics.
PLoS ONE
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Monoclonal antibody (McAb) is the key tool for cancer immunodiagnosis and immunotherapy. McAb-based immunotherapy that targets tumor antigens has had great achivement. In this study, a cell clone which kept secreting high-titer IgG1-type McAb named NJ001 against human non-small cell lung cancer (NSCLC) cells was obtained. The titer of purified NJ001 was 2×10(6). The antigen named SP70 of NSCLC specifically identified by NJ001 was proved to be a protein with the relative molecular mass (Mr) of 70 kDa. The results of immunohistochemical staining indicated that NJ001 could positively react to NSCLC, but weak positively or negatively react to human small-cell lung cancer (SCLC), pulmonary pseudotumor and other epithelial tumors. In soft agar assay, the colony formation efficiency in NJ001 groups decreased in a dose-dependent manner. For the concentration of 100 µg/ml, 200 µg/ml and 400 µg/ml, the inhibition ratio of colony formation was 23.4%, 62.5% and 100% respectively. Meanwhile, NJ001 caused significant reduction in tumor volume and tumor weight compared to control mice in lung cancer xenograft model. The tumor growth inhibition ratio in 200 µg, 400 µg and 800 µg NJ001 groups was 10.44%, 37.29% and 44.04%, respectively. NJ001 also led to cytomorphological changes and induced the apoptosis of human lung adenocarcinoma cell line SPC-A1 significantly. The newly developed NJ001 selectively reacted to NSCLC and exhibited anti-tumor activity both in vitro and in vivo. NJ001 is of great value concerning immunodiagnostics and immunotherapy for NSCLC and holds promise for further research regarding the mechanism underlying tumor progression of NSCLC.
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Can plasma DNA monitoring be employed in personalized chemotherapy for patients with advanced lung cancer?
Biomed. Pharmacother.
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Personalized chemotherapy is the ideal treatment usually chosen to help improve the survival chances of patients with advanced lung cancer. However, there is no short-term evaluation protocol for predicting the efficacy of the therapy. The aim of this study was to determine the value of using plasma DNA to monitor chemotherapeutic efficacy and to select most appropriate chemotherapeutic regimen for patients with advanced lung cancer. Eighty-eight lung cancer patients and 200 healthy controls were included in this study. Plasma DNA was extracted from plasma samples with internal controls by using the BILATEST DNA Kit. The quantity of plasma DNA was determined by using duplex real-time quantitative PCR. After first-line chemotherapy, plasma DNA levels of partial response patients were significantly different from those of stable disease patients or progressive disease patients, but with no statistical difference from healthy controls (P=0.014, P<0.001 and P=0.418, respectively). Survival analysis showed a statistically better survival time in patients who had lower levels of plasma DNA after the third cycle chemotherapy (P=0.031). In this study, the correlation of the kinetics of DNA concentrations with chemotherapeutic efficacy during the whole therapy was also observed. The quantification of plasma DNA is a sensitive indicator of chemotherapeutic efficacy in advanced lung cancer patients, and it can be useful in predicting response to therapy and guiding medication.
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