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Find video protocols related to scientific articles indexed in Pubmed.
Relationship Between Tumor Necrosis Factor-? (TNFA) Gene Polymorphisms and Cardiac Sarcoidosis.
In Vivo
PUBLISHED: 11-16-2014
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Identification of genetic predisposition to cardiac sarcoidosis could play a critical role in the detection of sub-clinical forms of the disease. The aim of this study was to investigate the possible correlations between the emergence of cardiac sarcoidosis and the -1.031T/C, -857C/T, -308G/A, and -238G/A Tumor Necrosis Factor-? (TNFA) polymorphisms in a well-defined Greek cohort. One-hundred and seventy-three patients of Greek origin with sarcoidosis were recruited in the present study. Cardiac sarcoidosis was determined according to established criteria. Blood samples were collected and the TNFA polymorphisms were genotyped. No significant difference was noted between the patients with cardiac involvement and those without, concerning the -1.031T/C and -238G/A TNFA polymorphisms. Regarding the -857C/T polymorphism, the TT genotype and the T allele were found to be over-represented in patients with cardiac involvement (p=0.02 and 0.012, respectively). AA genotype of the -308G/A as well as the A allele were also found significantly more frequently in patients with cardiac sarcoidosis (p=0.014 and 0.012 respectively). From the investigated TNFA promoter polymorphisms, we were able to deduce nine main haplotypes. Haplotypes 3 and 5, including A nucleotide at position -308, and T nucleotide at position -857 respectively, were significantly over-represented in the group with cardiac involvement. We detected an increased presence of genetic polymorphisms in the TNFA gene of patients with cardiac involvement. However, the role and the clinical application of these findings need further exploration.
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Quantum Dots-Bevacizumab Complexes for In Vivo Imaging of Tumors.
In Vivo
PUBLISHED: 11-16-2014
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Background/Aim: The basic role of vascular endothelial growth factor (VEGF) in cancer is underscored by the approval of bevacizumab for first-line treatment of cancer patients. Recent anticancer therapeutics based on active tumor targeting by conjugating tumor-specific antibodies has become of great interest in oncology. Current progress in nanomedicine has exploited the possibility of designing tumor-targeted nanocarriers able to deliver specific molecule payloads in a selective manner to improve the efficacy and safety of cancer imaging and therapy. We herein aimed to determine the targeting ability of bevacizumab-conjugated quantum dots (QDs) in vitro and in vivo. Materials and Methods: We used QDs labeled with bevacizumab, in various in vitro experiments using cell lines derived from colorectal cancer (CRC) and breast cancer (BC). For a competition study of QD-bevacizumab complex and bevacizumab, the cells were pre-treated with bevacizumab (100 nmol/L) for 24 h before exposure to the QD-bevacizumab complex. The breast cancer cells (MDA-MB-231) were injected to 9 nude mice to make the xenograft tumor model. The QD-bevacizumab complex was injected into the tumor model and fluorescence measurements were performed at 1, 12, and 24 h post-injection. Results: Immunocytochemical data confirmed strong and specific binding of the QD-bevacizumab complex to the cell lines. The cells pre-treated with an excess of bevacizumab showed absence of QD binding. The in vivo fluorescence image disclosed that there was an increased signal of tumor after the injection of QDs. Ex vivo analysis showed 3.1±0.8%, 28.6±5.4% and 30.8±4.2% injected dose/g accumulated in the tumors at 1, 12 and 24 h respectively. Tumor uptake was significantly decreased in the animals pretreated with excess of bevacizumab (p=0.001). Conclusion: In conclusion, we could successfully detect the VEGF-expressing tumors using QDs-bevacizumab nanoprobes in vitro and in vivo, opening new perspectives for VEGF-targeted non-invasive imaging in clinical practice.
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Serum Protein Profiling of Adults And Children With Crohn's Disease.
J. Pediatr. Gastroenterol. Nutr.
PUBLISHED: 09-25-2014
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Crohn's disease (CD) and ulcerative colitis (UC), known collectively as inflammatory bowel disease (IBD), are chronic immuno-inflammatory pathologies of unknown etiology. Despite the frequent utilization of biomarkers in medical practice, there is a relative lack of information regarding validated paediatric biomarkers for IBD. Further, biomarkers proved to be efficacious in adults are frequently extrapolated to the paediatric clinical setting without considering that the pathogenesis of many diseases is distinctly different in children. In the current study, proteomics technology was employed in order to monitor differences in protein expression among adult and children CD patients, in order to identify a panel of candidate protein biomarkers that might be used to improve prognostic-diagnostic accuracy and to advance paediatric medical care.
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Genetic polymorphisms of inflammatory response gene TNF-? and its influence on sporadic pancreatic neuroendocrine tumors predisposition risk.
Med. Oncol.
PUBLISHED: 09-01-2014
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The diagnosed incidence of pancreatic neuroendocrine tumors (pNETs) is increasing; however, their etiology remains poorly understood. PNETs are a rare, heterogeneous group of tumors arising from the endocrine cells of the pancreas, and genetic risk factors for sporadic pNETs are inadequately understood. It is known that pNETs secrete biogenic amines, hormones and growth factors, tumor necrosis factor-a (TNF-?) being one of them. Furthermore, cytokines and other proinflammatory mediators have been implicated in inflammatory pancreatic diseases including pancreatitis and cancer. The aim of our study was to analyze TNF-? promoter gene polymorphisms as risk factors for pNETs using germline DNA collected in a population-based case-control study of pancreatic cancer [42 pNET cases, 78 pancreatic ductal adenocarcinoma (PDAC) cases, 17 intraductal papillary mucinous neoplasm (IPMN) and 98 healthy controls] conducted in the Athens, Greece and Izmir, Turkey areas. For subsequent analysis, we excluded cases and controls with known genetic syndromes. The CC genotype at the -1031 position was more frequent in pNET and IPMN patients (p=0.0002 and p=0.009, respectively), suggesting its possible role in pNET development. Furthermore, the AA genotype at the -308 position was overrepresented in IPMN cases (p=0.03), and AA genotype at the -238 position was more frequent in PDAC cases (p=0.03) compared to healthy individuals. With regard to tumor characteristics, no statistically significant association was detected. Our findings suggest the putative role of TNF-? -1031 polymorphism in the development of pNET and IPMN, whereas the -308 polymorphism seems to be overrepresented among IPMN cases and -238 polymorphism among PDAC cases.
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Polymorphism Analysis of COL4A3 and COL4A4 Genes in Greek Patients with Keratoconus.
Ophthalmic Genet.
PUBLISHED: 08-01-2014
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Abstract Background: In this study, we conducted the genotyping of D326Y in COL4A3 and M1327V, as well as F1644F in COL4A4 polymorphisms, in a case-control sample panel of Greek origin population.
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Pancreatic neuroendocrine tumors: current opinions on a rare, but potentially curable neoplasm.
Eur J Gastroenterol Hepatol
PUBLISHED: 07-03-2014
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Pancreatic neuroendocrine tumors (PNETs) share a unique genetic identity, functional behavior, and clinical course. Compared with tumors of the exocrine pancreas, they are rare and show a different biologic behavior and prognosis. On the basis of data from recent studies, all PNETs, outside of small insulinomas, should be considered potentially malignant and treated accordingly. Untreated tumors have a high possibility to grow locally into adjacent structures or spread to distant organs. Although surgical excision irrespective of tumor functioning or nonfunctioning state remains the cornerstone of therapy, providing the best disease-free and survival rates to date, the understanding of the genetic nature of the disease yields new 'targets' to consider in drug development. The aim of this review is to summarize all recent advances of genetic research and new drug development in terms of PNETs, especially their genetic identity and subsequent alterations leading to the development of near or total malignant activity, and the new medical treatment strategies of this potentially curable disease on the basis of therapeutical agents acting, where possible, at the genetic level.
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Effect of infliximab on the healing of intestinal anastomosis. An experimental study in rats.
Int J Surg
PUBLISHED: 05-18-2014
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Infliximab is effective in the induction and maintenance of remission in Crohn's disease. Whether, the perioperative administration of anti-TNF-a compromises intestinal healing leading to anastomotic failure and increased risk of postoperative complications, remains controversial. The aim of the study was to evaluate the effect of Infliximab on intestinal anastomosis healing.
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The economic considerations and implications of the stratification of future oncology therapeutics.
Mol Diagn Ther
PUBLISHED: 05-15-2014
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Cancer accounts for approximately 13 % of all deaths worldwide. Development of stratification biomarkers, for cancer screening, diagnosis, monitoring, and treatment optimization, is a vital concept to facilitate disease prevention and drug development. The advent of stratified medicine should result in the safer, more effective use of therapeutic drugs to treat cancer, and in reducing the cost associated with inappropriate therapeutic regimens; however, many barriers delay the use of biomarkers in drug development and clinical practice. Since the incorporation of biomarkers in clinical practice might have additional initial costs, the question arises regarding whether the improvement in outcomes is reached at a realistic additional cost. This review presents an overview of economic issues surrounding biomarkers in cancer treatment optimization.
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DNA methylation changes in inflammatory bowel disease.
Ann Gastroenterol
PUBLISHED: 04-16-2014
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The cause of inflammatory bowel disease, encompassing Crohn's disease and ulcerative colitis, remains a mystery but evidence is accumulating that complex interactions between the genetic background and the gut microbiota of the host and environmental factors associated with rapid industrialization and westernized life styles may underlie its pathogenesis. Recent epigenetic studies have suggested that interactions between environment and host DNA may play a leading role in the phenotypical expression of both diseases, explaining amongst others the differences in disease expression in monozygotic twins. DNA methylation is the most studied epigenetic modification and during the last decade its correlation to IBD pathogenesis has been well established. Genes from different molecular pathways have been studied but till now there is no standardized database of methylated genes in IBD. Thus, a thorough and in depth study of DNA methylation, its potential relation to IBD and its interaction with the available pharmaceutical armamentarium is of great interest.
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Kallikrein-related peptidases in cancers of gastrointestinal tract: an inside view of their role and clinical significance.
J BUON
PUBLISHED: 03-25-2014
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Human tissue kallikrein (KLK1) and is related peptidases (KLK2-KLK15) are a family of 15 homologous serine proteases, participating in numerous processes of normal physiology. Considering the irreversible impact of proteases on substrates, the tissue-dependent regulation of KLKs activity becomes crucial for their beneficial role in normal homeostasis. Moreover, KLKs expression is strongly regulated at the transcriptional and post-transcriptional level by steroid hormones and miRNAs, respectively. Deregulation of KLKs expression, secretion and/or activation has been observed in most human malignancies and there is a trend to identify their role in the multi-complex process of cancer development. The identification of extracellular matrix (ECM) proteins, cell-surface receptors, cell-surface adhesion molecules and growth factors among substrates, clearly support the driving role of KLK abnormal expression and function during tumorigenesis and cancer progression. KLKs have also clinical utility in cancer diagnosis and monitoring like KLK 3 (PSA) in prostate cancer. In this review, we tried to summarize the existing literature about the role of KLKs in gastrointestinal cancers as well as to emphasize their clinical significance for patients' prognosis.
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Molecular basis of the irritable bowel syndrome.
World J. Gastroenterol.
PUBLISHED: 02-28-2014
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Irritable bowel syndrome (IBS) is a functional disorder characterized by abdominal pain, discomfort and bloating. The pathophysiology of IBS is poorly understood, but the presence of psychosocial basis is now known. There is an increasing number of publications supporting the role of genetics in IBS. Most of the variations are found in genes associated with the brain-gut axis, revealing the strong correlation of brain-gut axis and IBS. miRNAs, which play critical roles in physiological processes, are not well studied in IBS. However, so far there is found an involvement of alterations in miRNA expression or sequence, in IBS symptoms. IBS phenotype is affected by epigenetic alteration and environment. Changes in DNA and histone methylation are observed in patients who suffered childhood trauma or abuse, resulting in altered gene expression, such as the glucocorticoid receptor gene. Finally, diet is another factor associated with IBS, which may contribute to symptom onset. Certain foods may affect on bacterial metabolism and epigenetic modifications, predisposing to IBS.
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Stem cells as potential targeted therapy for inflammatory bowel disease.
Inflamm. Bowel Dis.
PUBLISHED: 02-28-2014
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The incidence and prevalence of inflammatory bowel disease is increasing in Western countries. Current therapies, ranging from anti-inflammatory drugs, immunosuppressive regimens to new biological therapies, remain inadequate. Advances in our understanding of the pathophysiological mechanisms underlying the pathogenetic disease process and the recent findings on the regenerative and immunoregulatory potential of stem cells open new opportunities in the therapy of inflammatory bowel disease. Therapeutic modalities, including hematopoietic stem cells, adult mesenchymal stem/stromal cells, and the recently identified amniotic origin stem cells, attracted much attention in the recent years. The current review highlights the recent pivotal findings for stem cell-based approaches to inflammatory bowel disease therapy.
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The impact of peri-operative anti-TNF treatment on anastomosis-related complications in Crohn's disease patients. A critical review.
J. Gastrointest. Surg.
PUBLISHED: 02-13-2014
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Tumor necrosis factor (TNF)? is a cytokine exerting pleiotropic effects on critical cell functions and, most importantly, is the main regulator of pro-inflammatory cytokine production and a key player in the pathophysiology of numerous autoimmune diseases, including Crohn's disease.
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Evaluation of the microbial safety of child food of animal origin in Greece.
J. Food Sci.
PUBLISHED: 02-07-2014
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Foodborne illness is a major cause of morbidity and mortality especially for children, even in the developed world. The aim of this study was to assess the microbial safety of food of animal origin intended for consumption by children in Greece. Sampling involved 8 categories of retail products and was completed with a collection of 850 samples. These were tested by PCR and/or culture for Listeria monocytogenes, Campylobacter spp., Escherichia coli O157, Salmonella spp., Cronobacter sakazakii, Brucella spp., and Mycobacterium avium subsp paratuberculosis (MAP). The number of positive results recorded collectively for the pathogens under investigation over the total number of samples tested was 3.52% and 0.12% by PCR and culture, respectively. The most frequently detected pathogen was enterohemorrhagic E. coli (1.29%) followed by Brucella (0.82%) and Listeria (0.82%). DNA belonging to MAP was detected in 0.35% of samples, which was also the percentage of positivity recorded for Campylobacter. The percentage for Salmonella was 0.12%. It can be concluded from the results that there is no indication of noncompliance for the tested food samples. However, detection of DNA belonging to pathogens that are transmissible to humans through food is indicative that constant vigilance regarding food safety is an absolute necessity.
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Loss-of-function of the voltage-gated sodium channel NaV1.5 (channelopathies) in patients with irritable bowel syndrome.
Gastroenterology
PUBLISHED: 02-06-2014
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SCN5A encodes the ?-subunit of the voltage-gated sodium channel NaV1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of NaV1.5.
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Association of rs1568885, rs1813443 and rs4411591 polymorphisms with anti-TNF medication response in Greek patients with Crohn's disease.
World J. Gastroenterol.
PUBLISHED: 01-20-2014
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To investigate the correlation between rs1568885, rs1813443 and rs4411591 polymorphisms and response to infliximab in a cohort of Greek patients with Crohn's disease (CD).
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Clock genes: their role in colorectal cancer.
World J. Gastroenterol.
PUBLISHED: 01-06-2014
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Clock genes create a complicated molecular time-keeping system consisting of multiple positive and negative feedback loops at transcriptional and translational levels. This circadian system coordinates and regulates multiple cellular procedures implicated in cancer development such as metabolism, cell cycle and DNA damage response. Recent data support that molecules such as CLOCK1, BMAL1 and PER and CRY proteins have various effects on c-Myc/p21 and Wnt/?-catenin pathways and influence multiple steps of DNA damage response playing a critical role in the preservation of genomic integrity in normal and cancer cells. Notably, all these events have already been related to the development and progression of colorectal cancer (CRC). Recent data highlight critical correlations between clock genes' expression and pathogenesis, progression, aggressiveness and prognosis of CRC. Increased expression of positive regulators of this circadian system such as BMAL1 has been related to decrease overall survival while decreased expression of negative regulators such as PER2 and PER3 is connected with poorer differentiation, increased aggressiveness and worse prognosis. The implications of these molecules in DNA repair systems explain their involvement in the development of CRC but at the same time provide us with novel targets for modern therapeutic approaches for patients with advanced CRC.
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Comparative assessment of lymph node micrometastasis in cervical, endometrial and vulvar cancer: insights on the real time qRT-PCR approach versus immunohistochemistry, employing dual molecular markers.
Biomed Res Int
PUBLISHED: 01-02-2014
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To address the value of qRT-PCR and IHC in accurately detecting lymph node micrometastasis in gynecological cancer, we performed a systematic approach, using a set of dual molecular tumor-specific markers such as cytokeratin 19 (CK19) and carbonic anhydrase 9 (CA9), in a series of 46 patients (19 with cervical cancer, 18 with endometrial cancer, and 9 with vulvar cancer). A total of 1281 lymph nodes were analyzed and 28 were found positive by histopathology. Following this documentation, 82 lymph nodes, 11 positive and 71 negative, were randomly selected and further analyzed both by IHC and qRT-PCR for CK19 and CA9 expression. All 11 (100%) expressed CK19 by IHC, while only 6 (54.5%) expressed CA9. On the contrary, all the histologically negative for micrometastases lymph nodes were also negative by IHC analysis for both markers. The comparative diagnostic efficacy of the two markers using qRT-PCR, however, disclosed that the analysis of the same aliquots of the 82 lymph nodes led to 100% specificity for the CK19 biomarker, while, in contrast, CA9 failed to recapitulate a similar pattern. These data suggest that qRT-PCR exhibits a better diagnostic accuracy compared to IHC, while CK19 displays a consistent pattern of detection compared to CA9.
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Association of the miR-146aC>G, miR-149T>C, and miR-196a2T>C polymorphisms with gastric cancer risk and survival in the Greek population.
Mol. Biol. Rep.
PUBLISHED: 01-01-2014
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MicroRNAs (miRNAs) play an important role in regulating gene expression at the post-transcriptional level and are involved in numerous physiological processes. Accumulating evidence suggests that single-nucleotide polymorphisms (SNPs) in human miRNA genes may affect miRNA biogenesis pathway and influence the susceptibility to several diseases such as cancer. The aim of the study was to investigated whether three common miRNA polymorphisms [miR-146a C>G (rs2910164), miR-149 T>C (rs2292832), and miR-196a2 T>C (rs11614913)] are associated with the susceptibility and prognosis of gastric cancer (GC) in the Greek population. The three mRNA SNPs were identified in a case-control study (163 patients; 480 controls) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. We found that the risk for GC was significantly higher for the carriers of miR-149 rs2292832CC (p = 0.009) and miR-196a2 rs11614913CC (p < 0.0001) genotypes, as well as for the carriers of the rs2910164/rs2292832/rs11614913 CCC and GTC haplotype (p < 0.0001 and p = 0.03, respectively). The rs2910164/rs2292832/rs11614913 CTT and CCT haplotypes seems to have a protective role against GC (p = 0.002 and p = 0.001, respectively). Our data demonstrate that specific miRNA SNPs are associated with GC susceptibility in the Greek population.
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Polymorphism Analysis of VSX1 and SOD1 Genes in Greek Patients with Keratoconus.
Ophthalmic Genet.
PUBLISHED: 10-09-2013
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Abstract Background: A number of mutations in the VSX1 and SOD1 genes have been reported to be associated with keratoconus (KC), however the results from different studies are controversial. In this study, we conducted the genotyping of common polymorphisms [VSX1: D144E, H244R, R166W, G160D; SOD1: intronic 7-base deletion (c.169?+?50delTAAACAG)], in a case-control sample panel of the Greek population. Materials and methods: A case-control panel, with 33 KC patients and 78 healthy controls, were surveyed. DNA from each individual was tested for the VSX1: D144E, H244R, R166W, G160D and SOD1: intronic 7-base deletion (c.169?+?50delTAAACAG) polymorphisms by direct sequencing. Results: We observed no polymorphisms of the VSX1 gene in the case-control panel. Concerning the SOD1 intronic 7-base deletion (c.169?+?50delTAAACAG), our findings suggest that heterozygous carriers are over-represented among KC cases compared to healthy controls (p?=?0.002). Conclusions: We cannot confirm the previously reported association of the polymorphism in the VSX1 gene with KC. Our results suggest a possible causative role of SOD1 in the pathogenesis of KC. Further studies are required to identify other important genetic factors involved in the pathogenesis and progression of KC.
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A novel non-amplification assay for the detection of Leishmania spp. in clinical samples using gold nanoparticles.
J. Microbiol. Methods
PUBLISHED: 07-30-2013
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Leishmaniosis is a zoonose caused by protozoans of the genus Leishmania. The need for accurate diagnostic investigation of cases of leishmaniosis has rendered today the use of molecular biology techniques broadly applicable. However, the reliable application of these methods requires highly-specialised personnel, dedicated equipment and space. The aim of this study was the design and construction of functionalized gold nanoparticles (AuNPs) that would be incorporated into an easily applicable DNA detection methodology for the identification of Leishmania spp. in clinical samples. AuNPs 20nm in diameter were conjugated with four oligonucleotide probes, targeting kinetoplastid minicircle DNA of Leishmania spp. In the absence of complimentary DNA, AuNPs-probes precipitate under acid environment causing a change of color from red to purple, which can be detected by visual observation. In the presence of target DNA the color of the solution remains red. The specific methodology was applied to positive and negative control samples and whole blood collected from dogs with suspected canine leishmaniosis. The methods minimum detection limit was defined to 11.5ng of target DNA per ?l of sample. Repeatability and reproducibility were 100%. Relative sensitivity and specificity referenced to PCR were calculated to 92% and 100% regarding collectively control and clinical samples. The proposed approach can be considered an appealing diagnostic solution especially for screening purposes in enzootic areas, where detection of very small amounts of the targeted analyte is not top priority.
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Association of the clock genes polymorphisms with colorectal cancer susceptibility.
J Surg Oncol
PUBLISHED: 06-20-2013
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The circadian rhythm regulates the cell cycle progression and DNA damage response. The aim of our study was to investigate the association between polymorphisms in the CLOCK1, PER2, and PER3 genes with the colorectal cancer (CRC) susceptibility and clinicopathological variables.
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Expression of microRNAs in patients with pancreatic cancer and its prognostic significance.
Pancreas
PUBLISHED: 05-31-2013
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Investigation of expression profile of well-established microRNAs in pancreatic adenocarcinoma, and its correlation with clinicopathological factors.
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Expression of clock genes in patients with colorectal cancer.
Int. J. Biol. Markers
PUBLISHED: 05-27-2013
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Recent studies have demonstrated the influence of clock genes in cell cycle regulation, cell proliferation, apoptosis and DNA damage recognition and repair. There is evidence suggesting the implication of clock genes in colorectal cancer (CRC) development and progression. The aim of this study is to evaluate the expression levels of clock genes in CRC and correlate them with patients prognosis. Forty-two CRC samples (from 24 males and 18 females), their paired noncancerous tissues and 8 biopsies from healthy individuals were included. Quantitative real-time PCR was used to examine the expression levels of CLOCK1, BMAL1, PER1, PER2 and PER3 genes in all the samples. In the cancerous tissues CLOCK1 (p<0.0001) and BMAL1 (p<0.0001) expression levels were higher, while PER1 (p<0.0024) and PER3 (p<0.0001) expression levels were lower compared to matched healthy tissues. No difference was observed in the expression levels of PER2 (p=0.99). No correlation was found between clock gene expression and patients clinicopathological characteristics or prognosis. The results suggest abnormal expression of CLOCK1, BMAL1, PER1 and PER3 genes in CRC but no correlation with patients prognosis.
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PON1-108 TT and PON1-192 RR genotypes are more frequently encountered in Greek PCOS than non-PCOS women, and are associated with hyperandrogenaemia.
Clin. Endocrinol. (Oxf)
PUBLISHED: 05-11-2013
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To investigate the frequencies of three paraoxonase (PON)1 polymorphisms in Greek polycystic ovary syndrome (PCOS) and non-PCOS women, and their genotypes association with hyperandrogenaemia and insulin resistance.
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Association study of genetic variants in miRNAs in patients with inflammatory bowel disease: preliminary results.
Dig. Dis. Sci.
PUBLISHED: 03-11-2013
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Aberrant expression and structural alteration of miRNAs are considered to participate in inflammation and cancer development. It has been suggested that common single-nucleotide polymorphisms (SNPs) in miRNAs are associated with susceptibility to several human diseases.
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The role of variations within microRNA in inflammatory bowel disease.
Eur J Gastroenterol Hepatol
PUBLISHED: 03-08-2013
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MicroRNAs (miRNAs) are small noncoding RNAs that are implicated in gene expression regulation at both a transcriptional and at a translational level. Single-nucleotide polymorphisms may occur in miRNA biogenesis pathway genes, primary miRNA, pre-miRNA, or a mature miRNA sequence. Such polymorphisms may be functional with respect to biogenesis and actions of mature miRNA. These single-nucleotide polymorphisms may have a potential to affect the efficiency of miRNA binding to the target sites or can create or disrupt binding sites. The resulting gene dysregulation may involve changes in phenotype and may eventually prove critical for the susceptibility to inflammatory bowel disease and its onset. In this review, we summarize their importance as candidate inflammatory bowel disease biomarkers.
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E-Selectin S128R gene polymorphism in gastric cancer.
Int. J. Biol. Markers
PUBLISHED: 03-08-2013
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E-selectin is an adhesion molecule expressed on activated endothelial cells. E-selectin plays an important role in the process of inflammation and is also involved in the mechanism of cancer metastasis regulating the adhesion of circulating cancer cells to the blood vessels. The aim of our study was to determine whether an association exists between its most common gene polymorphism, S128R, and gastric cancer (GC).?
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MMP-2 -1306C>T polymorphism in breast cancer: a case-control study in a South European population.
Mol. Biol. Rep.
PUBLISHED: 01-29-2013
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This case control study aims to investigate the role of MMP-2 -1306C>T polymorphism as a potential risk factor and possible prognostic marker for breast cancer in a South European population. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy controls were recruited. MMP-2 -1306C>T polymorphism was genotyped; multivariate logistic regression as well as Cox regression analysis were performed. MMP-2 -1306C>T status was not associated with breast cancer risk either at the total sample or at the subanalyses on premenopausal and postmenopausal women. At the survival analysis, a trend towards a favorable association between MMP-2 -1306C>T allele and disease-free survival as well as overall survival was observed. Regarding subanalyses on ER-negative and ER-positive cases, the favorable association implicating MMP-2 -1306C>T allele was particularly evident among ER-positive cases; no significant associations emerged among ER-negative cases. MMP-2 -1306C>T polymorphism does not seem to be a risk factor for breast cancer in South European population; however, a trend towards a favorable association with survival has been observed.
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Circadian clock gene expression is impaired in gestational diabetes mellitus.
Gynecol. Endocrinol.
PUBLISHED: 01-17-2013
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Dysfunction of the circadian clock genes is involved in the development of obesity and type 2 diabetes (T2D). Since gestational diabetes mellitus (GDM) and T2D share common genetic and phenotypic features, in the present study, we investigated the status of the circadian clock in a cohort of 40 Greek pregnant women with GDM, four with T2D and 20 normal controls. Peripheral blood mRNA transcript levels of 10 clock genes (CLOCK1, BMAL1, PER1, PER2, PER3, PPAR?, PPARD, PPARG, CRY1 and CRY2) were determined by real-time quantitative PCR. GDM patients expressed significantly lower transcript levels of BMAL1, PER3, PPARD and CRY2 compared to control women (p < 0.05). No significant difference was documented between GDM women maintained either under insulin treatment or diet. A positive correlation was found between the expression of BMAL1 versus CRY2 (r = 0.45, p = 0.003) and BMAL1 versus PPARD (r = 0.43, p = 0.004). Further investigation on the functional relevance of these clock genes, disclosed that expression of PER3 correlated negatively with HbA1C levels (r = -0.36, p = 0.022). These data document for the first time that the expression of BMAL1, PER3, PPARD and CRY2 genes is altered in GDM compared to normal pregnant women and support the notion that deranged expression of clock genes may play a pathogenic role in GDM.
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MicroRNA gene polymorphisms in pancreatic cancer.
Pancreatology
PUBLISHED: 01-11-2013
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MicroRNAs (miRNAs) act as regulators of gene expression via translational repression. Single nucleotide polymorphisms (SNPs) in miRNAs have been shown to affect the regulatory capacity of miRNAs by influencing miRNA processing and/or miRNA-mRNA interactions. The purpose of this study was to investigate the association between 2 SNPs commonly found in precursor miRNA and the susceptibility and clinicopathological characteristics of pancreatic cancer. The rs11614913/miR-196a2, rs2910164/miR-146a SNPs were genotyped in 93 patients with pancreatic cancer and in 122 healthy controls. No significant differences in genotype distributions between controls and PC patients were observed. However, rs2910164 GG and rs11614913 CC genotypes and the rs2910164C/rs11614913C and rs2910164G/rs11614913C haplotypes were significantly overrepresented in PC patients with T1 and T2 tumor status than in those with T3 and T4. Our findings suggested that the rs2910164 and rs11614913 SNPs might play a role in pancreatic tumorigenesis, but the molecular mechanism underlying the particular sequence variations in miRNA that can cause aberrant expression remains to be determined.
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Expression of microRNAs, miR-21, miR-31, miR-122, miR-145, miR-146a, miR-200c, miR-221, miR-222, and miR-223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance.
Mol. Carcinog.
PUBLISHED: 07-15-2011
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MicroRNAs are a class of non-coding molecules found to regulate a variety of cellular functions in health and disease. Dysregulation of microRNAs is involved in liver disease, especially hepatocarcinogenesis. Since primary hepatic malignancies are typically characterized by late diagnosis, frequent recurrence, and poor response to adjuvant therapy, there is a need for the discovery of novel biomarkers in order to achieve earlier diagnosis, predict tumor aggressiveness and response to adjuvant therapy. The purpose of this study is to evaluate the expression of certain microRNAs (miR-21, -31, -122, -145, -146a, - 200c, -221, -222 and -223) in patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), as well as to assess their prognostic significance. Micro-RNA expression was assessed by reverse transcription and real-time PCR (RT-PCR). Clinicopathological data and survival rates were retrieved and analyzed. According to our results, miR-21, miR-31, miR-122, miR-221, miR-222 were significantly up-regulated in HCC tissues, whereas miR-145, miR-146a, miR-200c, and miR-223 were found to be down-regulated. Concerning ICC samples, miR-21, miR-31, and miR-223 were found to be over-expressed, whereas miR-122, miR-145, miR-200c, miR-221, and miR-222 were down-regulated. Additionally, expression of miR-21, miR-31, miR-122, and miR-221 in HCC correlated with cirrhosis, while miR-21 and miR-221 associated with tumor stage and poor prognosis. In ICC tissues, miR-21, miR-31, and miR-223 were found to be over-expressed, but no correlation with clinicopathological features was found.
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Long-term plasma ghrelin and leptin modulation after sleeve gastrectomy in Wistar rats in comparison with gastric tissue ghrelin expression.
Obes Surg
PUBLISHED: 05-26-2011
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Sleeve gastrectomy (SG) is a gaining ground operation amongst the ones applied for treatment of morbid obesity. Though SG is a food limiting operation, the removal of the gastric fundus where ghrelin is mainly produced may indicate a hormonal impact of the procedure. The purpose of this experiment is to study how SG affects the levels of ghrelin and leptin.
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Polymorphisms of caspase 8 and caspase 9 gene and colorectal cancer susceptibility and prognosis.
Int J Colorectal Dis
PUBLISHED: 04-14-2011
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Caspase-8 (CASP8) and caspase-9 (CASP9) play crucial roles in regulating apoptosis, and their functional polymorphisms may alter cancer risk. Our aim was to investigate the association between CASP8 and CASP9 gene polymorphisms and colorectal cancer (CRC) susceptibility.
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Caspase 8 and caspase 9 gene polymorphisms and susceptibility to gastric cancer.
Gastric Cancer
PUBLISHED: 03-07-2011
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Caspase-8 (CASP8) and caspase-9 (CASP9) play crucial roles in regulating apoptosis, and their functional polymorphisms may alter cancer risk. Our aim was to investigate the association of CASP8 and CASP9 gene polymorphisms with gastric cancer (GC) susceptibility.
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Detection of pathogenic mycobacteria based on functionalized quantum dots coupled with immunomagnetic separation.
PLoS ONE
PUBLISHED: 02-23-2011
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Mycobacteria have always proven difficult to identify due to their low growth rate and fastidious nature. Therefore molecular biology and more recently nanotechnology, have been exploited from early on for the detection of these pathogens. Here we present the first stage of development of an assay incorporating cadmium selenide quantum dots (QDs) for the detection of mycobacterial surface antigens. The principle of the assay is the separation of bacterial cells using magnetic beads coupled with genus-specific polyclonal antibodies and monoclonal antibodies for heparin-binding hemagglutinin. These complexes are then tagged with anti-mouse biotinylated antibody and finally streptavidin-conjugated QDs which leads to the detection of a fluorescent signal. For the evaluation of performance, the method under study was applied on Mycobacterium bovis BCG and Mycobacterium tuberculosis (positive controls), as well as E. coli and Salmonella spp. that constituted the negative controls. The direct observation of the latter category of samples did not reveal fluorescence as opposed to the mycobacteria mentioned above. The minimum detection limit of the assay was defined to 10(4) bacteria/ml, which could be further decreased by a 1 log when fluorescence was measured with a spectrofluorometer. The method described here can be easily adjusted for any other protein target of either the pathogen or the host, and once fully developed it will be directly applicable on clinical samples.
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5-HT2A receptor gene polymorphisms and irritable bowel syndrome.
J. Clin. Gastroenterol.
PUBLISHED: 02-18-2011
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The aim of the study was to investigate the potential association between single nucleotide polymorphisms of the 5-HT2A receptor gene and susceptibility to irritable bowel syndrome (IBS) in the Greek population.
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OCT4 spliced variant OCT4B1 is expressed in human colorectal cancer.
Mol. Carcinog.
PUBLISHED: 02-11-2011
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OCT4, a POU-domain transcription factor is considered to be a key factor in maintaining the pluripotency of stem cells. Several OCT4 isoforms are differentially expressed in human pluripotent and non-pluripotent cells. Reactivation of OCT4 expression is postulated to occur in differentiated cells that have undergone tumorigenesis. To examine OCT4 expression in colorectal cancer (CRC) tissues, and to assess the efficacy of OCT4 as a potential biomarker for CRC, in this study, we investigated its expression in CRC tissues, evaluated its relationship to various clinicopathological parameters and defined the isoform of OCT4 that was found to be expressed in CRC cases. Primary tumor tissues and matching adjacent non-cancerous tissues were obtained from 84 CRC patients. OCT4 expression and isoform determination were documented by reverse transcription-PCR and real-time PCR. OCT4, Sox-2, and NANOG localization were performed using immunohistochemistry. The isoforms expressed in the studied cases were confirmed by sequencing. Twenty biopsy specimens representing healthy tissues, retrieved from colonoscopy were studied in parallel as controls. OCT4 expression levels were higher in CRC tissues compared to matching, adjacent non-cancerous tissues, and healthy controls. Additionally, the levels of OCT4 expression in CRC tissues correlated with tumor stage. OCT4 and Sox-2 were localized in the nuclei and the cytoplasm of CRC cells. In all CRC cases, we found that the OCT4B1 isoform is expressed. Over-expression of OCT4B1 was found in poorly and moderately differentiated CRC tissues. In conclusion, the data imply that OCT4B1 isoform may represent a potential biomarker for the initiation, progression, and differentiation of CRC.
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Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
Carl A Anderson, Gabrielle Boucher, Charlie W Lees, Andre Franke, Mauro D'Amato, Kent D Taylor, James C Lee, Philippe Goyette, Marcin Imielinski, Anna Latiano, Caroline Lagacé, Regan Scott, Leila Amininejad, Suzannah Bumpstead, Leonard Baidoo, Robert N Baldassano, Murray Barclay, Theodore M Bayless, Stephan Brand, Carsten Büning, Jean-Frédéric Colombel, Lee A Denson, Martine De Vos, Marla Dubinsky, Cathryn Edwards, David Ellinghaus, Rudolf S N Fehrmann, James A B Floyd, Timothy Florin, Denis Franchimont, Lude Franke, Michel Georges, Jürgen Glas, Nicole L Glazer, Stephen L Guthery, Talin Haritunians, Nicholas K Hayward, Jean-Pierre Hugot, Gilles Jobin, Debby Laukens, Ian Lawrance, Marc Lémann, Arie Levine, Cécile Libioulle, Edouard Louis, Dermot P McGovern, Monica Milla, Grant W Montgomery, Katherine I Morley, Craig Mowat, Aylwin Ng, William Newman, Roel A Ophoff, Laura Papi, Orazio Palmieri, Laurent Peyrin-Biroulet, Julian Panés, Anne Phillips, Natalie J Prescott, Deborah D Proctor, Rebecca Roberts, Richard Russell, Paul Rutgeerts, Jeremy Sanderson, Miquel Sans, Philip Schumm, Frank Seibold, Yashoda Sharma, Lisa A Simms, Mark Seielstad, A Hillary Steinhart, Stephan R Targan, Leonard H van den Berg, Morten Vatn, Hein Verspaget, Thomas Walters, Cisca Wijmenga, David C Wilson, Harm-Jan Westra, Ramnik J Xavier, Zhen Z Zhao, Cyriel Y Ponsioen, Vibeke Andersen, Leif Törkvist, Maria Gazouli, Nicholas P Anagnou, Tom H Karlsen, Limas Kupcinskas, Jurgita Šventoraitytė, John C Mansfield, Subra Kugathasan, Mark S Silverberg, Jonas Halfvarson, Jerome I Rotter, Christopher G Mathew, Anne M Griffiths, Richard Gearry, Tariq Ahmad, Steven R Brant, Mathias Chamaillard, Jack Satsangi, Judy H Cho, Stefan Schreiber, Mark J Daly, Jeffrey C Barrett, Miles Parkes, Vito Annese, Hakon Hakonarson, Graham Radford-Smith, Richard H Duerr, Séverine Vermeire, Rinse K Weersma, John D Rioux.
Nat. Genet.
PUBLISHED: 01-14-2011
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Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohns disease and ulcerative colitis.
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Development and characterization of oligonucleotide-tagged dye-encapsulating EPC/DPPG liposomes.
J Nanosci Nanotechnol
PUBLISHED: 12-08-2010
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Liposomes applications in health care include meanly their ability to carry drugs and genes inside the human body for therapeutic purposes. Nevertheless their applicability can extend far beyond and could be used as analytical tools in order to perform rapid, low-cost, sensitive and specific analyses. Their physical characteristics, such as large internal volume and extended surface area, render them ideal for these applications and specifically for improving the specificity and sensitivity of the analytical assay. The purpose of this study was to develop a simple, stable and low-cost oligonucleotide-tagged liposomal formulation consisting of EggPC and DPPG with a simple to synthesize thiol-reactive conjugate (Mal-SA) incorporated into the lipid bilayer of liposomes. The prepared liposomes, having also the water soluble dye Sulforhodamine B encapsulated in their inner cavity, were characterized in terms of their physicochemical (size, size distribution, zeta-potential, lipid content) and mechanical (morphology, rigidity) properties. The results showed that the final liposomal formulation could be used in the future as analytical tool for detecting pathogen strains of microorganism in biological milieu.
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Stem cells in colon cancer. A new era in cancer theory begins.
Int J Colorectal Dis
PUBLISHED: 07-14-2010
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Despite the various therapeutic combinations and the emergence of new targeted therapies, there is still no curative treatment for all stages of colorectal cancer. Through the query for the best possible combination and solution, a new theory approaching colorectal cancer as a stem cell disease appeared, with a continuously growing body of evidence supporting this idea. The inability to directly recognize cancer stem cells has led researchers to an attempt of distinguishing those using indirect markers.
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Analysis of E-Selectin S128R gene polymorphism in pancreatic cancer.
J Surg Oncol
PUBLISHED: 07-08-2010
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E-selectin, an intercellular adhesion molecule that plays important roles in metastasis of tumor cells, has a polymorphism in exon 4 that results in the substitution of a serine by an arginine within the extracellular domain of the receptor, which increases its affinity for ligands. No evidence exist on the role of E-selectin polymorphism in pancreatic cancer.
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Gestational diabetes mellitus shares polymorphisms of genes associated with insulin resistance and type 2 diabetes in the Greek population.
Gynecol. Endocrinol.
PUBLISHED: 06-14-2010
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Gestational diabetes mellitus (GDM) and type 2 diabetes (T2D) share common pathophysiological features, including ?-cell dysfunction and insulin resistance. In this study, we investigated the association between GDM and five recently identified T2D susceptibility loci, in a Greek population. We studied 148 women with GDM and 107 non-diabetic unrelated pregnant Greek women, for polymorphisms in the TCF7L2 gene (rs7903146 C/T), the PPARG gene (Pro12Ala), the KCNJ11 gene (E23K), the IRS1 gene (G972R) and in the FOXC2 gene (-512C>T). The T-allele of the TCF7L2 rs7903146 (C/T) polymorphism was found to be significantly associated with an increased risk of GDM [p = 0.0003; odds ratio (OR) 2.04 (95%CI 1.38-3.00)]. Additionally, CT and TT genotypes were significantly overrepresented in women with GDM compared to controls (p = 0.0003 and p = 0.0148, respectively). Analysis of the IRS1 G972R polymorphism showed that the R-allele frequency was increased in women with GDM [(p = 0.009; OR 1.67 (95%CI 1.14-2.47)]. The genotypes and allele frequencies of the other polymorphisms studied did not statistically differ between the GDM and the control women. Thus, our data suggest that the common T2D susceptibility polymorphism of TCF7L2 (rs7903146 C/T) gene, and the G972R polymorphism of the IRS1 gene, seem to predispose to GDM in Greek women.
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Current insights in to the pathophysiology of Irritable Bowel Syndrome.
Gut Pathog
PUBLISHED: 04-28-2010
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Irritable Bowel Syndrome (IBS) represents a functional disorder of gastrointestinal tract without the presence of an anatomic defect, in which abdominal pain is relieved with defecation and is associated with altered bowel habits.IBS includes a wide range of symptoms while its pathophysiology is very complicated. Recent studies indicate that the most important mechanisms include visceral sensitivity, abnormal gut motility and autonomous nervous system dysfunction. The interactions between these three mechanisms make bowels function susceptible to many exogenous and endogenous factors like gastrointestinal flora, feeding and psychosocial factors. Recent data indicate that according to the above mechanisms, the influence of genetic factors and polymorphisms of human DNA in the development of IBS is equally important.
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NOD2/CARD15, ATG16L1 and IL23R gene polymorphisms and childhood-onset of Crohns disease.
World J. Gastroenterol.
PUBLISHED: 04-10-2010
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To assess whether the polymorphisms of NOD2/CARD15, autophagy-related 16-like 1 (ATG16L1), and interleukin-23 receptor (IL23R) genes play a more critical role in the susceptibility of childhood-onset than in adult-onset Crohns disease (CD).
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Effects of caspase-9 and survivin gene polymorphisms in pancreatic cancer risk and tumor characteristics.
Pancreas
PUBLISHED: 04-02-2010
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This case-control study was performed to evaluate the association between a specific caspase-9 polymorphism as well as the genetic polymorphism -31G/C located in the cycle-dependent elements/cell cycle homology regions repressor element of the human survivin promoter and the risk of pancreatic cancer.
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Study of association of IRS-1 and IRS-2 genes polymorphisms with clinical and metabolic features in women with polycystic ovary syndrome. Is there an impact?
Gynecol. Endocrinol.
PUBLISHED: 03-10-2010
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Insulin receptor substrate (IRS) proteins are critical to signal transduction in insulin target tissues. The present study was undertaken to determine whether IRS-1 Gly972Arg and IRS-2 Gly1057Asp influence hormonal and metabolic characteristics in Greek patients with polycystic ovary syndrome (PCOS) and controls.
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Analysis of the stromal cell-derived factor 1-3A gene polymorphism in pancreatic cancer.
Mol Med Rep
PUBLISHED: 03-09-2010
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Stromal cell derived factor-1 (SDF-1), a CXC chemokine that plays an important role in the tumor growth, angiogenesis and metastasis of tumor cells, has a polymorphism at position 801 of its 3-untranslated region, known as SDF1-3A. The SDF1-3A polymorphism has been investigated in various types of cancer, but no information is currently available on its role in pancreatic cancer. In this study, 80 pancreatic cancer patients and 160 normal healthy control subjects were investigated for the genotype and allelic frequencies of the SDF-1 gene using PCR-RFLP. The genotype frequencies for GG, GA and AA were 21.25, 77.5 and 1.25% in patients, and 42.5, 55 and 2.5% in healthy subjects, respectively. The A carrier group (GA+AA genotype) and the A allele were overrepresented among the patients with pancreatic cancer (p=0.015 and p=0.031, respectively). The GA+AA genotype was statistically correlated with an advanced T stage and the presence of lymph node metastasis, and displayed a clear trend towards significance in relation to the presence of distant metastatic disease (p=0.061). Only T stage was significantly related to A allele frequency (p=0.004). SDF1-3 A allele carriers were more prevalent among cancer patients than among normal subjects. SDF1-3 A allele carrier status may imply a higher risk of pancreatic cancer, while the presence of the A allele in pancreatic cancer patients may be related to aggressive features of this malignancy.
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Genome-wide association study for ulcerative colitis identifies risk loci at 7q22 and 22q13 (IL17REL).
Nat. Genet.
PUBLISHED: 02-19-2010
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We performed a genome-wide association analysis of 1,897,764 SNPs in 1,043 German ulcerative colitis (UC) cases and 1,703 controls. We discovered new associations at chromosome 7q22 (rs7809799) and at chromosome 22q13 in IL17REL (rs5771069) and confirmed these associations in six replication panels (2,539 UC cases and 5,428 controls) from different regions of Europe (overall study sample P(rs7809799) = 8.81 x 10(-11) and P(rs5771069) = 4.21 x 10(-8), respectively).
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Investigation of the association of the SLC11A1 gene with resistance/sensitivity of goats (Capra hircus) to paratuberculosis.
Vet. Microbiol.
PUBLISHED: 01-14-2010
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SLC11A1 (solute carrier family 11 member A1) protein is located on the phagolysosome membrane of macrophages and participates in bacterial killing. Here we have extended our previous work on the investigation of the potential association of polymorphisms of the 3untranslated region (UTR) of SLC11A1 gene with test-positivity of goats to Mycobacterium avium subsp. paratuberculosis (MAP). Blood, serum and faeces were collected from 223 adult goats, from nine goat farms from Greece with a long-term record of paratuberculosis but no vaccination or tuberculin testing. The samples were subjected to sequence and structure analysis of the SLC11A1 gene and were evaluated by ELISA, culture and real time polymerase chain reaction. The 3UTR region of the targeted gene revealed 2 microsatellites consisting of a variable number of guanine-thymine repeats named regions A and B. Statistically significant association was recorded between genotypes of region B and ELISA results, whereas the presence of B(7) allele was found to contribute to ELISA negativity. The comparison of the SLC11A1 mRNA level pre- and post-exposure to MAP shows elevated gene expression especially at the 3-h time point, in all macrophages tested regardless of their genotype. Unfortunately the latter could not be linked at a statistically significant level with any of the targeted genetic polymorphisms separately. In conclusion it can be stated that the evidence reported here provide the first indications on the association of B genotypes of the SLC11A1 gene and the detection of MAP-specific antibody by ELISA in goats.
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The role of genes in the development of Mullerian anomalies: where are we today?
Obstet Gynecol Surv
PUBLISHED: 10-24-2009
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Recent studies claim that researchers are challenged to find out the pathogenesis of the congenital anomalies of the female reproductive tract. Their frequency is estimated to be between 0.1% and 3% of live births in humans. During the experiments a number of genes were detected to contribute to the formation and development of the female reproductive tract. This review article aims to report these genes, as they probably play a significant role in the pathology of the reproductive tract in females.
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Linking chronic infection and autoimmune diseases: Mycobacterium avium subspecies paratuberculosis, SLC11A1 polymorphisms and type-1 diabetes mellitus.
PLoS ONE
PUBLISHED: 08-13-2009
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The etiology of type 1 diabetes mellitus (T1DM) is still unknown; numerous studies are performed to unravel the environmental factors involved in triggering the disease. SLC11A1 is a membrane transporter that is expressed in late endosomes of antigen presenting cells involved in the immunopathogenic events leading to T1DM. Mycobacterium avium subsp. paratuberculosis (MAP) has been reported to be a possible trigger in the development of T1DM.
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Common polymorphisms in the vascular endothelial growth factor gene and colorectal cancer development, prognosis, and survival.
Mol. Carcinog.
PUBLISHED: 06-13-2009
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Angiogenesis plays an important role in growth, progression, and metastasis of tumors. The most important regulator of angiogenesis is vascular endothelial growth factor (VEGF). VEGF expression has been associated with advance stage and poor survival of several cancers. In the present study we evaluated the association of functional polymorphisms in the VEGF gene with colorectal cancer development, prognosis, and survival. Three hundred twelve consecutive patients with surgically treated colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and five VEGF (-2578C>A, -1154G>A, -634G>C, -460T>C, and +936C>T) gene polymorphisms were determined using a polymerase chain reaction-restriction fragment length polymorphism assay. VEGF -2578C>A, -1154G>A, -634G>C, -460T>C, and +936C>T genotype and allele frequencies were similar among patients and controls. There was a trend showing carriers of the -2578A and +936T alleles more frequent among patients with CRC, but these differences did not reach statistical significance. Furthermore, no correlation was found between all these variants and tumor characteristics like size, histological grading, positive regional lymph node metastases or tumor stage. However, the -2578AA, -634CC, and +936TT genotypes found to be related with a significantly lower overall survival in our study. In conclusion, VEGF gene polymorphisms were found to be an independent prognostic marker for Greek CRC patients.
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Survivin -31G/C promoter polymorphism and sporadic colorectal cancer.
Int J Colorectal Dis
PUBLISHED: 05-19-2009
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Survivin is an apoptotic inhibitor, plays an important role in cell cycle regulation, and may be involved in the development and progression of cancer. A common polymorphism at the survivin gene promoter (-31 G/C) has been shown to influence survivin expression and the risk for cancer.
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Vascular endothelial growth factor and endoglin expression in colorectal cancer.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 03-13-2009
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Vascular endothelial growth factor (VEGF) overexpression has been associated with advanced stage and poor survival in several cancers. Additionally, endoglin was proposed as a marker of neovascularization in solid malignancies. The aim of this study was to evaluate the association between the VEGF and endoglin expression in colorectal carcinoma patients, as well as to correlate the VEGF and endoglin expression with standard parameters, to define their potential prognostic role. VEGF and endoglin expression were evaluated in 99 unrelated patients with colorectal cancer using immunohistochemistry.
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Direct detection of unamplified DNA from pathogenic mycobacteria using DNA-derivatized gold nanoparticles.
J. Microbiol. Methods
PUBLISHED: 02-24-2009
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Mycobacterial infections have a high economic, human and animal health impact. Herein, we present the development of a colorimetric method that relies on the use of gold nanoparticles for fast and specific detection of Mycobacterium spp. dispensing with the need for DNA amplification. The result can be recorded by visual and/or spectrophotometric comparison of solutions before and after acid induced AuNP-probe aggregation. The presence of a complementary target prevents aggregation and the solution remains pink, whereas in the opposite event it turns to purple. The application of the proposed method on isolated bacteria produced positive results with the mycobacterial isolates and negative with the controls. The minimum detection limit of the assay was defined at 18.75 ng of mycobacterial DNA diluted in a sample-volume of 10 microl. In order to obtain an indication of the methods performance on clinical samples we applied the optimized assay to the detection of Mycobacterium avium subsp. paratuberculosis DNA in faeces, in comparison with real-time PCR. The concordance of the two methods with connection to real-time PCR positive and negative sample was defined respectively as 87.5% and 100%. The proposed method could be used as a highly specific and sensitive screening tool for the detection of mycobacteria directly from clinical samples in a very simple manner, without the need of high-cost dedicated equipment. The technology described here, may develop into a platform that could accommodate detection of many bacterial species and could be easily adapted for high throughput and expedite screening of samples.
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Undefined familial colorectal cancer.
World J Gastrointest Oncol
PUBLISHED: 02-16-2009
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Colorectal cancer (CRC), one of the most common cancers of the world, is actually a spectrum of several subtypes, with different molecular profiles, clinico-pathological characteristics and possibly separate pathways of progression. It is estimated that in approximately 25%-35% of cases, a familial component exists, so they are classified as familial CRC (fCRC). However the known hereditary CRC syndromes justify only up to 5%. The rest are attributed to some inherited genetic predisposition passed to offspring through low-penetrance genes, which in the proper environmental setting can bring on tumorigenesis. Furthermore, part of the familial clustering may be attributed to chance. Because of the complexity regarding the etiology of CRC, the clinician is sometimes faced with obscure patient data, and cannot be sure if they are dealing with fCRC or sporadic CRC. The elucidation of what is going on with the as yet "undefined" portion of CRC will aid not only in the diagnosis, classification and treatment of CRC, but more importantly in the proper adjustment of the screening guidelines and in genetic counselling of patients.
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Persistent fetal gamma-globin expression in adult transgenic mice following deletion of two silencer elements located 3 to the human Agamma-globin gene.
Mol. Med.
PUBLISHED: 02-09-2009
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Natural deletions of the human gamma-globin gene cluster lead to specific syndromes characterized by increased production of fetal hemoglobin in adult life and provide a useful model to delineate novel cis-acting elements involved in the developmental control of hemoglobin switching. A hypothesis accounting for these phenotypic features assumes that silencers located within the Agamma-to delta-gene region are deleted in hereditary persistence of fetal hemoglobin (HPFH) and deltabeta-thalassemias, leading to failure of switching. In the present study, we sought to clarify the in vivo role of two elements, termed Enh and F, located 3 to the Agamma-globin, in silencing the fetal genes. To this end, we generated three transgenic lines using cosmid constructs containing the full length of the globin locus control region (LCR) linked to the 3.3-kb Agamma-gene lacking both the Enh and F elements. The Enh/F deletion resulted in high levels of Agamma-globin gene expression in adult mice in all single copy lines, whereas, the LCR-Agamma single copy lines which retain the Enh and F elements exhibited complete normal switching of the fetal Agamma-gene. Our study documents directly for the first time the in vivo role of these two gene-proximal negative regulatory elements in silencing the fetal globin gene in the perinatal period, and thus these data may permit their eventual exploitation in therapeutic approaches for thalassemias.
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Effects of stromal cell-derived factor-1 and survivin gene polymorphisms on gastric cancer risk.
Mol Med Rep
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Stromal-cell derived factor-1 (SDF-1), a CXC chemokine, is important for growth, angiogenesis and metastasis of tumor cells. The SDF1-3A polymorphism has been investigated in various types of cancer; however, no information is currently available on its role in gastric cancer. Survivin is a member of the inhibitor of apoptosis family of proteins and has a genetic polymorphism (-31G/C) located in the CDE/CHR repressor element of its promoter. In this study, 88 gastric cancer patients and 480 normal healthy control subjects were investigated for the genotype and allelic SDF1-3A and survivin -31G/C frequencies using polymerase chain reaction?restriction fragment length polymorphism. The SDF1-3A genotype frequencies for GG, GA and AA were 44.32, 48.86 and 6.92% in patients and 42.71, 47.71 and 9.58% in healthy subjects, respectively. GA+AA genotype frequency and A allele distribution were not identified as significantly different between gastric cancer cases and controls. The survivin frequencies for GG, GC and CC were 20.45, 50 and 29.54% in patients and 33.96, 45 and 21.04% in healthy subjects, respectively. The C carriers (GC+CC genotype) and the C allele were over-represented among the gastric cancer cases (P=0.013 and P=0.0083, respectively). Overall, no statistically significant association was identified for SDF-1 and survivin gene examined alleles and genotypes and any parameter investigated, (e.g., stage, differentiation status and survival). The survivin promoter -31G/C polymorphism may confer an increased susceptibility to gastric cancer, while the SDF1-3A polymorphism may not be a candidate genetic variant to select individuals at higher risk of developing gastric cancer.
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Genetic susceptibility to pancreatic cancer and its functional characterisation: the PANcreatic Disease ReseArch (PANDoRA) consortium.
Dig Liver Dis
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Pancreatic cancer is the fourth leading cause of cancer deaths in the European Union and in the USA, but little is known about its genetic susceptibility. The PANcreatic Disease ReseArch (PANDoRA) consortium was established to unite the efforts of different research groups; its aim is to create a large bio-database to uncover new genetic factors for pancreatic cancer risk, response to treatment, and patient survival. So far 2220 cases of pancreatic adenocarcinoma, a smaller number of cases of endocrine pancreatic tumours (n=86), chronic pancreatitis (n=272) and 3847 healthy controls have been collected. As a collective effort of the consortium, SNPs associated with pancreatic adenocarcinoma risk from a genome-wide association study performed in Caucasians were replicated. The possibility that the same genetic polymorphisms may influence patient survival as well was also addressed. This collective effort is particularly important for pancreatic cancer because it is a relatively rare disease for which little is known about aetiopathogenesis and risk factors. The recruitment of additional collaborators and partner institutions is continuously on-going.
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The major circadian pacemaker ARNT-like protein-1 (BMAL1) is associated with susceptibility to gestational diabetes mellitus.
Diabetes Res. Clin. Pract.
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Recently a relationship between circadian clock function and the risk for type 2 diabetes (T2D) has been shown. BMAL1 is a key component of the mammalian molecular clock. Two SNPs in the BMAL1 gene have been identified to confer T2D susceptibility. In the present study we investigated for the first time the association between the BMAL1 gene and the risk for GDM, in a Greek population.
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Transcription factor ATF-3 regulates allele variation phenotypes of the human SLC11A1 gene.
Mol. Biol. Rep.
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Genetic polymorphisms in the human solute carrier family 11 member 1 (SLC11A1) gene predispose to susceptibility to infectious/inflammatory diseases and cancer. Human susceptibility to these diseases exhibits allelic association with a polymorphic regulatory Z-DNA-forming microsatellite of a (GT/AC)n repeat. The carriage of different alleles may influence chromatin remodeling and accessibility by transcription factors. Of particular importance is the binding site for the Activating Protein 1 (AP-1) elements, (ATF-3 and c-Jun), adjacent to the 5 sequence of the Z-DNA-forming polymorphism. The aim of the study was to characterize the transcriptional mechanisms controlling different alleles of SLC11A1 expression by ATF-3 and c-Jun. Allele 2, [T(GT)5AC(GT)5AC(GT)10GGCAGA(G)6], and Allele 3, [T(GT)5AC(GT)5AC(GT)9GGCAGA(G)6], were subcloned into the PGL2Basic vector. Transient transfections of THP-1 cells with the constructs, in the presence or absence of pATF-3 were preformed. Luciferase expression was determined. To document the recruitment of ATF-3 and c-Jun, to the polymorphic promoter alleles in vivo, we performed ChIP assays with transient transfected THP-1 cells treated with or without lipopolyssacharides. Our data documented that ATF-3 suppresses the transcriptional activation of Allele-3, and this suppression is enhanced in the presence of lipopolyssacharides. Our findings suggest that ATF-3 and c-Jun may influence heritable variation in SLC11A1-dependent innate resistance to infection and inflammation both within and between populations.
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The impact of the stromal cell-derived factor-1-3A and E-selectin S128R polymorphisms on breast cancer.
Mol. Biol. Rep.
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Breast cancer is prone to metastasis even in early stage disease. Stromal cell-derived factor-1 (SDF-1) is a chemokine that has been associated with the egress of cancer cells from the primary focus and homing to distant sites, while E-selectin has been implicated in their trans-endothelial migration. This study was performed to evaluate the association between SDF-1-3A and E-selectin S128R-two polymorphisms associated with enhanced function-and the risk of breast cancer, as well as their influence on breast cancer outcome. A retrospective analysis was conducted on 261 patients and 480 healthy controls using PCR-RFLP. The frequencies for the wild-type (GG), GA and AA genotypes of SDF-1 were 43.7, 45.2, and 11.1 % in patients, and 51.5, 41.3, and 7.3 % in healthy controls, respectively, while the SDF-1-3A allelic frequency was 33.7 % at patients and 27.9 % at controls. The SDF-1-3A carrier group of patients and the A allele of SDF-1 were overrepresented among the breast cancer cases (p = 0.04 and 0.02, respectively). For the E-selectin S128R polymorphism, the frequencies for the wild-type (AA), AC and CC genotypes were 58.6, 38.3, and 3.1 % in patients and 63.8, 31.4, and 3.8 % in controls, respectively, while the C allelic frequency was 22.2 % for patients and 19.5 % for controls. The CC genotype was associated with poorer survival. Otherwise, no significant association was detected between examined genotypes and tumor characteristics. Overall, our findings support that the SDF-1-3A confers increased susceptibility to breast cancer and that the E-selectin S128R CC genotype may be related to poorer prognosis. Investigation in bigger cohorts of patients is warranted.
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HSP90, HSPA8, HIF-1 alpha and HSP70-2 polymorphisms in breast cancer: a case-control study.
Mol. Biol. Rep.
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This case control study aims to investigate the role of HSP90 Gln488His (C > G), HSP70-2 P1/P2, HIF-1 alpha C1772T and HSPA8 intronic 1541-1542delGT polymorphisms as potential risk factors and/or prognostic markers for breast cancer. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy cases were recruited. The above mentioned polymorphisms were genotyped; multivariate logistic regression was performed. HSP90 GG (His/His) genotype was associated with elevated breast cancer risk. Similarly, the allele dose-response model pointed to increase in breast cancer risk per G allele. HSP70-2 P1/P2, HSPA8 intronic 1541-1542delGT and HIF-1 alpha polymorphisms were not associated with breast cancer risk, as evidenced by the dose-response allele models. The positive association between HSP90 G allele and breast cancer risk seemed to pertain to both premenopausal and postmenopausal women. With respect to survival analysis, none of the aforementioned polymorphisms was associated with either disease-free survival or overall survival. HSP90? Gln488His polymorphism seems to be a risk factor for breast cancer. On the other hand, our study did not point to excess risk conferred by HSPA8 1541-1542delGT, Hsp70-2 P1/P2 and HIF-1? C1772T.
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HTERT MNS16A polymorphism in breast cancer: a case-control study.
Mol. Biol. Rep.
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This case-control study aims to investigate the role of HTERT MNS16A polymorphism as a potential risk factors and/or a prognostic marker for breast cancer. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy controls were recruited. HTERT MNS16A polymorphism was genotyped (L: long allele, S: short allele); multivariate logistic regression was performed. No significant association was noted either at the overall analysis (OR = 1.57, 95 % CI 0.84-2.93 for heterozygous LS carriers; OR = 1.02, 95 % CI 0.54-1.95 for homozygous SS carriers) or at the subanalyses in premenopausal and postmenopausal women. With respect to survival analysis, HTERT MNS16A polymorphism was not associated with either disease-free survival or overall survival. HTERT MNS16A polymorphism does not seem to be a risk factor for breast cancer in the Caucasian Greek population. Further, larger studies from other countries and subjects seem to be needed as this novel polymorphism is being examined in depth.
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Polymorphisms of the CD14 genes are associated with susceptibility to alcoholic liver disease in Greek patients.
Alcohol. Clin. Exp. Res.
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The incidence and severity of alcoholic liver disease (ALD) in chronic drinkers has been found to correlate with some environmental factors and especially with the dose of alcohol consumption, but it is obvious that other parameters clearly contribute to individual alcohol susceptibility. Chronic ethanol exposure leads to continuous endotoxin-mediated Toll-like receptor-4 (TLR-4) and CD14 activation and subsequent cytokine release resulting in chronic inflammation with continued hepatocellular damage. Therefore, genetic studies of polymorphism in TLR-4 and CD14 genes seem to be appropriate in determining genetic susceptibility to ALD. Our aim is to evaluate in a series of Greek drinkers, the possible association of polymorphisms in the TLR-4 and CD14 genes with ALD.
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Caspase 9 promoter polymorphisms confer increased susceptibility to breast cancer.
Cancer Genet
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Caspases (CASPs), play a crucial role in the development and progression of cancer. We evaluated the association between two polymorphisms (rs4645978 and rs4645981) of the CASP9 gene and the risk of breast cancer (BC). Genotypes and allelic frequencies for the two polymorphisms were determined in 261 patients with breast cancer and 480 healthy controls. Polymerase chain reaction-restriction fragment length polymorphisms were used, and statistical significance was determined by the ?(2) test. Carriers of the rs4645978G allele (AG and GG genotypes) were at higher risk for BC than individuals with other genotypes (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.07-2.37, P = 0.022). The rs4645978GG genotype, in particular, was associated with the highest risk for BC development (OR 2.25, 95% CI 1.45-3.49, P = 0.0003). Similarly, individuals with at least one rs4645981T allele were at a significantly increased risk of developing BC compared with those harboring the CC genotype (OR 2.75, 95% CI 1.99-3.78, P < 0.0001), and the risk of BC increased with increasing numbers of rs4645981T alleles (OR 2.66, 95% CI 1.91-3.69, P < 0.0001 for the CT genotype; OR 3.95, 95% CI 1.58-9.88, P = 0.004 for the TT genotype). The CASP9 promoter polymorphisms rs4645978 and rs4645981 are associated with BC susceptibility and suggest that CASP9 transcriptional regulation is an important factor during BC development.
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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.