JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Clinical cancer research: the past, present and the future.
Nat Rev Clin Oncol
PUBLISHED: 09-23-2014
Show Abstract
Hide Abstract
In the past decade, we have witnessed unprecedented changes and some remarkable advances that have enabled true personalized medicine. Nevertheless, many challenges in clinical cancer research remain and need to be overcome if we are to witness similar progress in the next decade. Such hurdles include, but are not limited to, clinical development and testing of multiple agents in combination, design of clinical trials to best accommodate the ever increasing knowledge of heterogeneity of the disease, regulatory challenges relating to drug development and trial design, and funding for basic research. With this in mind, we asked four leading cancer researchers from around the world, and who have been associated with the journal since its launch in November 2004 what, in their opinion, we have learnt over the past 10 years and how we should progress in the next 10 years.
Related JoVE Video
Policy: EU data protection regulation--harming cancer research.
Nat Rev Clin Oncol
PUBLISHED: 09-02-2014
Show Abstract
Hide Abstract
The cancer community is deeply concerned about the unintended consequences of the current wording of the European Union (EU) draft Regulation on Data Protection, which may challenge the survival of retrospective clinical research, biobanking, and population-based cancer registries in the EU. This directive could negatively affect Europe's competitiveness in cancer research.
Related JoVE Video
Health diplomacy: a new approach to the Muslim world?
Global Health
PUBLISHED: 05-30-2014
Show Abstract
Hide Abstract
Three years ago, the Lancet's frontispiece stated "Health is now the most important foreign policy issue of our time" and last year, the Director-General of WHO, Margaret Chan, in her opening address, to the Executive Board at its 132nd Session said "health diplomacy works". The nascent field of health diplomacy provides a political framework which aims to deliver the dual goals of improved health in target populations and enhanced governmental relations between collaborating countries. Any government that offered tangible health improvement as a component of aid to a nation with whom they wished to develop stronger diplomatic links would have an advantage in developing a deeper relationship with its citizens.Here we suggest several different mechanisms through which such links could be developed or enhanced, including: provision of relevant health solutions, applied research, cultural alignment and the development of collaborative networks. The Islamic tradition promotes the practice of medicine as a service to humanity. Physical and spiritual wellbeing are intimately related in popular Muslim consciousness. Thoughtful Health Diplomacy therefore has the potential to bridge the perceived divides between Western and predominantly Muslim nations.
Related JoVE Video
Recovery of hypoglycemia awareness in long-standing type 1 diabetes: a multicenter 2 × 2 factorial randomized controlled trial comparing insulin pump with multiple daily injections and continuous with conventional glucose self-monitoring (HypoCOMPaSS).
Diabetes Care
PUBLISHED: 05-22-2014
Show Abstract
Hide Abstract
To determine whether impaired awareness of hypoglycemia (IAH) can be improved and severe hypoglycemia (SH) prevented in type 1 diabetes, we compared an insulin pump (continuous subcutaneous insulin infusion [CSII]) with multiple daily injections (MDIs) and adjuvant real-time continuous glucose monitoring (RT) with conventional self-monitoring of blood glucose (SMBG).
Related JoVE Video
'Toxgnostics': an unmet need in cancer medicine.
Nat. Rev. Cancer
PUBLISHED: 05-15-2014
Show Abstract
Hide Abstract
If we were to summarize the rationale that underpins medical oncology in a Latin aphorism, it might be 'veneno ergo sum'; that is, I poison, therefore I am. The burden of chemotherapy-associated toxicity is well recognized, but we have relatively few tools that increase the precision of anticancer drug prescribing. We propose a shift in emphasis from the focussed study of polymorphisms in drug metabolic pathways in small sets of patients to broader agnostic analyses to systematically correlate germline genetic variants with adverse events in large, well-defined cancer populations. Thus, we propose the new science of 'toxgnostics' (that is, the systematic, agnostic study of genetic predictors of toxicity from anticancer therapy).
Related JoVE Video
Alternative splicing of TIA-1 in human colon cancer regulates VEGF isoform expression, angiogenesis, tumour growth and bevacizumab resistance.
Mol Oncol
PUBLISHED: 04-22-2014
Show Abstract
Hide Abstract
The angiogenic capability of colorectal carcinomas (CRC), and their susceptibility to anti-angiogenic therapy, is determined by expression of vascular endothelial growth factor (VEGF) isoforms. The intracellular protein T-cell Intracellular Antigen (TIA-1) alters post-transcriptional RNA processing and binds VEGF-A mRNA. We therefore tested the hypothesis that TIA-1 could regulate VEGF-A isoform expression in colorectal cancers. TIA-1 and VEGF-A isoform expression was measured in colorectal cancers and cell lines. We discovered that an endogenous splice variant of TIA-1 encoding a truncated protein, short TIA-1 (sTIA-1) was expressed in CRC tissues and invasive K-Ras mutant colon cancer cells and tissues but not in adenoma cell lines. sTIA-1 was more highly expressed in CRC than in normal tissues and increased with tumour stage. Knockdown of sTIA-1 or over-expression of full length TIA-1 (flTIA-1) induced expression of the anti-angiogenic VEGF isoform VEGF-A165b. Whereas flTIA-1 selectively bound VEGF-A165 mRNA and increased translation of VEGF-A165b, sTIA-1 prevented this binding. In nude mice, xenografted colon cancer cells over-expressing flTIA-1 formed smaller, less vascular tumours than those expressing sTIA-1, but flTIA-1 expression inhibited the effect of anti-VEGF antibodies. These results indicate that alternative splicing of an RNA binding protein can regulate isoform specific expression of VEGF providing an added layer of complexity to the angiogenic profile of colorectal cancer and their resistance to anti-angiogenic therapy.
Related JoVE Video
Juvenile justice girls' depressive symptoms and suicidal ideation 9 years after Multidimensional Treatment Foster Care.
J Consult Clin Psychol
PUBLISHED: 04-14-2014
Show Abstract
Hide Abstract
Multidimensional Treatment Foster Care (MTFC) has been found to reduce delinquency among girls in juvenile justice through 2-year follow-up. Given that such girls are at elevated risk for suicide and depression into adulthood, we tested MTFC effects on long-term trajectories of suicidal ideation and depressive symptoms.
Related JoVE Video
A candidate gene study of capecitabine-related toxicity in colorectal cancer identifies new toxicity variants at DPYD and a putative role for ENOSF1 rather than TYMS.
Gut
PUBLISHED: 03-21-2014
Show Abstract
Hide Abstract
Capecitabine is an oral 5-fluorouracil (5-FU) pro-drug commonly used to treat colorectal carcinoma and other tumours. About 35% of patients experience dose-limiting toxicity. The few proven genetic biomarkers of 5-FU toxicity are rare variants and polymorphisms, respectively, at candidate loci dihydropyrimidine dehydrogenase (DPYD) and thymidylate synthase (TYMS).
Related JoVE Video
Parental monitoring of children's media consumption: the long-term influences on body mass index in children.
JAMA Pediatr
PUBLISHED: 03-19-2014
Show Abstract
Hide Abstract
Although children's media consumption has been one of the most robust risk factors for childhood obesity, effects of specific parenting influences, such as parental media monitoring, have not been effectively investigated.
Related JoVE Video
Building capacity for sustainable research programmes for cancer in Africa.
Nat Rev Clin Oncol
PUBLISHED: 03-11-2014
Show Abstract
Hide Abstract
Cancer research in Africa will have a pivotal role in cancer control planning in this continent. However, environments (such as those in academic or clinical settings) with limited research infrastructure (laboratories, biorespositories, databases) coupled with inadequate funding and other resources have hampered African scientists from carrying out rigorous research. In September 2012, over 100 scientists with expertise in cancer research in Africa met in London to discuss the challenges in performing high-quality research, and to formulate the next steps for building sustainable, comprehensive and multi-disciplinary programmes relevant to Africa. This was the first meeting among five major organizations: the African Organisation for Research and Training in Africa (AORTIC), the Africa Oxford Cancer Foundation (AfrOx), and the National Cancer Institutes (NCI) of Brazil, France and the USA. This article summarizes the discussions and recommendations of this meeting, including the next steps required to create sustainable and impactful research programmes that will enable evidenced-based cancer control approaches and planning at the local, regional and national levels.
Related JoVE Video
Suicidal Behavior Outcomes of Childhood Sexual Abuse: Longitudinal Study of Adjudicated Girls.
Suicide Life Threat Behav
PUBLISHED: 02-23-2014
Show Abstract
Hide Abstract
Childhood sexual abuse (CSA) histories are prevalent among adolescent girls in the juvenile justice system (JJS) and may contribute to their high rates of suicidal behavior. Among 166 JJS girls who participated in an intervention trial, baseline CSA and covariates were examined as predictors of suicide attempt and nonsuicidal self-injury (NSSI) reported at long-term follow-up (7-12 years later). Early forced CSA was related to lifetime suicide attempt and NSSI history and (marginally) to postbaseline attempt; effects were not mediated by anxiety or depressive symptoms. Findings suggest that earlier victimization and younger entry into JJS are linked with suicide attempt and NSSI.
Related JoVE Video
Young adult follow-up of adolescent girls in juvenile justice using the Columbia suicide severity rating scale.
Suicide Life Threat Behav
PUBLISHED: 01-22-2014
Show Abstract
Hide Abstract
This study focused on the reliability and validity of the Columbia Suicide Severity Scale (C-SSRS). Severely delinquent adolescent girls (n = 166) participated in a treatment trial and repeated assessments over time. Lifetime suicide attempt history was measured using the C-SSRS in early adulthood (n = 144; 7-12 years postbaseline). Nonclinician raters showed strong interrater reliability using the C-SSRS. Self-reports, caseworker reports, and caregiver reports of girls' suicide attempt histories collected at baseline correlated with adult participants' recollections of their baseline attempt histories. Suicidal ideation measured prospectively across a 7- to -12-year period was associated with retrospectively reported suicide attempt across the same period.
Related JoVE Video
Stability and performance of rapid-acting insulin analogs used for continuous subcutaneous insulin infusion: a systematic review.
J Diabetes Sci Technol
PUBLISHED: 12-20-2013
Show Abstract
Hide Abstract
We review and summarize the literature on the safety and stability of rapid-acting insulin analogs used for continuous subcutaneous insulin infusion (CSII) in patients with diabetes.
Related JoVE Video
Evaluation of PIK3CA Mutation As a Predictor of Benefit From Nonsteroidal Anti-Inflammatory Drug Therapy in Colorectal Cancer.
J. Clin. Oncol.
PUBLISHED: 09-23-2013
Show Abstract
Hide Abstract
Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) protect against colorectal cancer (CRC) and are associated with reduced disease recurrence and improved outcome after primary treatment. However, toxicities of NSAIDs have limited their use as antineoplastic therapy. Recent data have suggested that the benefit of aspirin after CRC diagnosis is limited to patients with PIK3CA-mutant cancers. We sought to determine the predictive utility of PIK3CA mutation for benefit from both cyclooxygenase-2 inhibition and aspirin.
Related JoVE Video
Comparative validation study to demonstrate the equivalence of a minor modification to AOAC Official Method 2005.05 Assurance GDS shiga Toxin Genes (O157) method to the reference culture method: 375 gram sample size.
J AOAC Int
PUBLISHED: 09-05-2013
Show Abstract
Hide Abstract
The Assurance GDS Shiga Toxin Genes (0157), AOAC Official MethodsM 2005.05, has been modified to include a larger sample size of 375 g. A methods comparison study was conducted to demonstrate the equivalence of this modification to the reference culture method. Ninety samples and controls, representing three foods, were analyzed. Results show no statistically detectable difference between the Assurance GDS Escherichia coli O157:H7 assay and the reference culture methods for the detection of E. coli O157:H7, other than the low level of inoculation for leaf lettuce for which the GDS gave noticeably higher recovery [difference in Probability of Detection between candidate methods (dPODc = +0.45)]. There were also suggestions of moderate differences (dPODc = +0.15 to +0.20) for ground beef and the high level of leaf lettuce, but the study size was too small to detect differences of this size. Results showed that the Assurance GDS Shiga Toxin Genes (0157) method is equivalent to the reference culture methods for the detection of Shiga toxigenic E. coli O157:H7.
Related JoVE Video
Comparative validation study to demonstrate the equivalence of a minor modification to AOAC official method 2005.04 assurance GdS E. coli 0157:H7 method to the reference culture method: 375 gram sample size.
J AOAC Int
PUBLISHED: 09-05-2013
Show Abstract
Hide Abstract
The Assurance GDS Escherichia coli (E. col) O157:H7, AOAC Official Method 2005.04, has been modified to include a larger sample size of 375 g. A methods comparison study was conducted to demonstrate the equivalence of this modification to the reference culture method. Ninety samples and controls, representing three foods, were analyzed. Results show no statistically detectable difference between the Assurance GDS E. coli O157:H7 assay and the reference culture methods for the detection of E. coli O157:H7, other than the low level of inoculation for leaf lettuce, for which the GDS gave noticeably higher recovery [difference in probability of detection between candidate methods (dPODc = +0.45)]. There were also suggestions of moderate differences (dPODc = +0.15 to +0.20) for ground beef and the high level of leaf lettuce, but the study size was too small to detect differences of this size. Results showed that the Assurance GDS E. coli O157:H7 method is equivalent to reference culture methods for the detection of E. coli O157:H7.
Related JoVE Video
Two longterm studies of seasonal variation in depressive symptoms among community participants.
J Affect Disord
PUBLISHED: 06-21-2013
Show Abstract
Hide Abstract
There is evidence that seasonal variation in depressive symptoms is common in the population. However, research is limited by a reliance on longterm retrospective methods.
Related JoVE Video
Epigenetic contribution to individual variation in response to lipopolysaccharide in bovine dermal fibroblasts.
Vet. Immunol. Immunopathol.
PUBLISHED: 05-13-2013
Show Abstract
Hide Abstract
The innate immune signaling pathway plays a crucial role in the recognition and early response to pathogens associated with disease. Genetic analysis has been unable to completely account for individual variability in the strength of the innate immune response. The aim of this study was to determine the role of the epigenetic markers (DNA methylation or histone acetylation) in controlling bovine gene expression in relation to the response to lipopolysaccharide (LPS). To determine the impact epigenetics may have in controlling innate immunity, dermal fibroblasts from fifteen dairy heifers having previously displayed a differential response to LPS were exposed to 5-aza-2-deoxycytidine (AZA) and trichostatin A (TSA); de-methylating and hyper-acetylating agents, respectively. The AZA-TSA exposure resulted in a loss of variability between individuals response to LPS as measured by fibroblast IL-8 protein production. Transcriptomic analysis by microarray was used to elucidate the role of epigenetics in innate immune signaling at 2, 4, and 8h post-LPS exposure. A subset of genes displayed altered expression due to AZA-TSA alone, suggesting an epigenetic regulatory element modifying expression under normal conditions. Treatment with AZA-TSA also led to increased expression of IL-8 (7.0-fold), IL-6 (2.5-fold), TNF-? (1.6-fold), and serum amyloid A 3 (SAA3) (11.3-fold) among other genes compared to control cultures for at least one of the measured times following LPS exposure. These data support the conclusion that epigenetic regulation significantly alters LPS-induced responses and constitutive cytokine gene expression.
Related JoVE Video
Survival in stage II/III colorectal cancer is independently predicted by chromosomal and microsatellite instability, but not by specific driver mutations.
Am. J. Gastroenterol.
PUBLISHED: 05-11-2013
Show Abstract
Hide Abstract
Microsatellite instability (MSI) is an established marker of good prognosis in colorectal cancer (CRC). Chromosomal instability (CIN) is strongly negatively associated with MSI and has been shown to be a marker of poor prognosis in a small number of studies. However, a substantial group of "double-negative" (MSI-/CIN-) CRCs exists. The prognosis of these patients is unclear. Furthermore, MSI and CIN are each associated with specific molecular changes, such as mutations in KRAS and BRAF, that have been associated with prognosis. It is not known which of MSI, CIN, and the specific gene mutations are primary predictors of survival.
Related JoVE Video
Use of multivariate analysis to suggest a new molecular classification of colorectal cancer.
J. Pathol.
PUBLISHED: 03-21-2013
Show Abstract
Hide Abstract
Molecular classification of colorectal cancer (CRC) is currently based on microsatellite instability (MSI), KRAS or BRAF mutation and, occasionally, chromosomal instability (CIN). Whilst useful, these categories may not fully represent the underlying molecular subgroups. We screened 906 stage II/III CRCs from the VICTOR clinical trial for somatic mutations. Multivariate analyses (logistic regression, clustering, Bayesian networks) identified the primary molecular associations. Positive associations occurred between: CIN and TP53 mutation; MSI and BRAF mutation; and KRAS and PIK3CA mutations. Negative associations occurred between: MSI and CIN; MSI and NRAS mutation; and KRAS mutation, and each of NRAS, TP53 and BRAF mutations. Some complex relationships were elucidated: KRAS and TP53 mutations had both a direct negative association and a weaker, confounding, positive association via TP53-CIN-MSI-BRAF-KRAS. Our results suggested a new molecular classification of CRCs: (1) MSI(+) and/or BRAF-mutant; (2) CIN(+) and/or TP53(-) mutant, with wild-type KRAS and PIK3CA; (3) KRAS- and/or PIK3CA-mutant, CIN(+) , TP53-wild-type; (4) KRAS(-) and/or PIK3CA-mutant, CIN(-) , TP53-wild-type; (5) NRAS-mutant; (6) no mutations; (7) others. As expected, group 1 cancers were mostly proximal and poorly differentiated, usually occurring in women. Unexpectedly, two different types of CIN(+) CRC were found: group 2 cancers were usually distal and occurred in men, whereas group 3 showed neither of these associations but were of higher stage. CIN(+) cancers have conventionally been associated with all three of these variables, because they have been tested en masse. Our classification also showed potentially improved prognostic capabilities, with group 3, and possibly group 1, independently predicting disease-free survival.
Related JoVE Video
The predictive and prognostic value of sex in early-stage colon cancer: a pooled analysis of 33,345 patients from the ACCENT database.
Clin Colorectal Cancer
PUBLISHED: 03-08-2013
Show Abstract
Hide Abstract
To compare long-term outcomes between men and women in a large cohort of clinical trial participants with early-stage colon cancer, specifically by examining whether the prognostic effect of sex varies based on age, stage of disease, and type of adjuvant therapy received.
Related JoVE Video
Depressive symptom trajectories among girls in the juvenile justice system: 24-month outcomes of an RCT of Multidimensional Treatment Foster Care.
Prev Sci
PUBLISHED: 02-19-2013
Show Abstract
Hide Abstract
Youth depression is a significant and growing international public health problem. Youth who engage in high levels of delinquency are at particularly high risk for developing problems with depression. The present study examined the impact of a behavioral intervention designed to reduce delinquency (Multidimensional Treatment Foster Care; MTFC) compared to a group care intervention (GC; i.e., services as usual) on trajectories of depressive symptoms among adolescent girls in the juvenile justice system. MTFC has documented effects on preventing girls recidivism, but its effects on preventing the normative rise in girls depressive symptoms across adolescence have not been examined. This indicated prevention sample included 166 girls (13-17 years at T1) who had at least one criminal referral in the past 12 months and who were mandated to out-of-home care; girls were randomized to MTFC or GC. Intent-to-treat analyses examined the main effects of MTFC on depression symptoms and clinical cut-offs, and whether benefits were greatest for girls most at risk. Depressive symptom trajectories were specified in hierarchical linear growth models over a 2 year period using five waves of data at 6 month intervals. Depression clinical cut-off scores were specified as nonlinear probability growth models. Results showed significantly greater rates of deceleration for girls in MTFC versus GC for depressive symptoms and for clinical cut-off scores. The MTFC intervention also showed greater benefits for girls with higher levels of initial depressive symptoms. Possible mechanisms of effect are discussed, given MTFCs effectiveness on targeted and nontargeted outcomes.
Related JoVE Video
Influences of biological and adoptive mothers depression and antisocial behavior on adoptees early behavior trajectories.
J Abnorm Child Psychol
PUBLISHED: 02-15-2013
Show Abstract
Hide Abstract
Research clearly demonstrates that parents pass risk for depression and antisocial behavior on to their children. However, most research confounds genetic and environmental mechanisms by studying genetically related individuals. Furthermore, most studies focus on either depression or antisocial behavior in parents or children, despite evidence of co-occurrence and shared etiology, and few consider the early origins of these problems in childhood. We estimated the influence of biological and adoptive mothers depression and antisocial behavior on growth in child externalizing and internalizing behaviors across early childhood using data from a prospective adoption study. Participants were 346 matched triads of physically healthy children (196 boys; 150 girls), biological mothers (BM), and adoptive mothers (AM). Latent growth curve models were estimated using AM reports of child internalizing and externalizing behaviors at ages 18, 27, and 54 months. Predictors of intercept (18 months) but not slope were identified. BM lifetime histories of major depressive disorder predicted child externalizing behaviors and BM antisocial behavior predicted child internalizing behavior. AM depressive symptoms and antisocial behavior were associated with both child outcomes. AM paths, but not BM paths were partially replicated using adopted fathers reports of child outcomes. BM obstetric complications, prenatal depressive symptoms, and postnatal adoptive family contact with BM did not account for BM paths. This adoption study distinguished risks conferred by biological mothers depression and antisocial behavior to childrens behaviors from those associated with adoptive mothers related symptoms. Future studies should examine gene-environment interplay to explain the emergence of serious problem trajectories in later childhood.
Related JoVE Video
Refinement of the associations between risk of colorectal cancer and polymorphisms on chromosomes 1q41 and 12q13.13.
Hum. Mol. Genet.
PUBLISHED: 11-10-2011
Show Abstract
Hide Abstract
In genome-wide association studies (GWASs) of colorectal cancer, we have identified two genomic regions in which pairs of tagging-single nucleotide polymorphisms (tagSNPs) are associated with disease; these comprise chromosomes 1q41 (rs6691170, rs6687758) and 12q13.13 (rs7163702, rs11169552). We investigated these regions further, aiming to determine whether they contain more than one independent association signal and/or to identify the SNPs most strongly associated with disease. Genotyping of additional sample sets at the original tagSNPs showed that, for both regions, the two tagSNPs were unlikely to identify a single haplotype on which the functional variation lay. Conversely, one of the pair of SNPs did not fully capture the association signal in each region. We therefore undertook more detailed analyses, using imputation, logistic regression, genealogical analysis using the GENECLUSTER program and haplotype analysis. In the 1q41 region, the SNP rs11118883 emerged as a strong candidate based on all these analyses, sufficient to account for the signals at both rs6691170 and rs6687758. rs11118883 lies within a region with strong evidence of transcriptional regulatory activity and has been associated with expression of PDGFRB mRNA. For 12q13.13, a complex situation was found: SNP rs7972465 showed stronger association than either rs11169552 or rs7136702, and GENECLUSTER found no good evidence for a two-SNP model. However, logistic regression and haplotype analyses supported a two-SNP model, in which a signal at the SNP rs706793 was added to that at rs11169552. Post-GWAS fine-mapping studies are challenging, but the use of multiple tools can assist in identifying candidate functional variants in at least some cases.
Related JoVE Video
Related JoVE Video
Challenges of cancer control in developing countries: current status and future perspective.
Future Oncol
PUBLISHED: 10-14-2011
Show Abstract
Hide Abstract
Cancer is a global problem accounting for almost 13% of all deaths worldwide. This equates to over 7 million people a year, more than is caused by HIV/AIDS, TB and malaria combined. Now is the time to strengthen the health systems of developing countries to deal with cancer, to avoid a future crisis similar to the HIV/AIDS pandemic. In this article we discuss the current state of cancer in the developing world, how we need to advocate for a change in cancer control policy with the governments of developing nations/transnational governmental bodies (e.g., the UN and WHO etc) and how we think cancer care could be improved in developing countries. We feel the only way to overcome the growing burden of cancer in the developing world is working in partnership with, nongovernmental organizations, international nongovernmental organizations, transnational governmental bodies and governmental bodies.
Related JoVE Video
Changes in At-Risk American Mens Crime and Substance Use Trajectories Following Fatherhood.
J Marriage Fam
PUBLISHED: 10-11-2011
Show Abstract
Hide Abstract
Fatherhood can be a turning point in development and in mens crime and substance use trajectories. At-risk boys (N = 206) were assessed annually from ages 12 to 31 years. Crime, arrest, and tobacco, alcohol, and marijuana use trajectories were examined. Marriage was associated with lower levels of crime and less frequent substance use. Following the birth of a first biological child, mens crime trajectories showed slope decreases, and tobacco and alcohol use trajectories showed level decreases. The older men were when they became fathers, the greater the level decreases were in crime and alcohol use and the less the slope decreases were in tobacco and marijuana use. Patterns are consistent with theories of social control and social timetables.
Related JoVE Video
Delivering affordable cancer care in high-income countries.
Lancet Oncol.
PUBLISHED: 10-01-2011
Show Abstract
Hide Abstract
The burden of cancer is growing, and the disease is becoming a major economic expenditure for all developed countries. In 2008, the worldwide cost of cancer due to premature death and disability (not including direct medical costs) was estimated to be US$895 billion. This is not simply due to an increase in absolute numbers, but also the rate of increase of expenditure on cancer. What are the drivers and solutions to the so-called cancer-cost curve in developed countries? How are we going to afford to deliver high quality and equitable care? Here, expert opinion from health-care professionals, policy makers, and cancer survivors has been gathered to address the barriers and solutions to delivering affordable cancer care. Although many of the drivers and themes are specific to a particular field-eg, the huge development costs for cancer medicines-there is strong concordance running through each contribution. Several drivers of cost, such as over-use, rapid expansion, and shortening life cycles of cancer technologies (such as medicines and imaging modalities), and the lack of suitable clinical research and integrated health economic studies, have converged with more defensive medical practice, a less informed regulatory system, a lack of evidence-based sociopolitical debate, and a declining degree of fairness for all patients with cancer. Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. A radical shift in cancer policy is also required. Political toleration of unfairness in access to affordable cancer treatment is unacceptable. The cancer profession and industry should take responsibility and not accept a substandard evidence base and an ethos of very small benefit at whatever cost; rather, we need delivery of fair prices and real value from new technologies.
Related JoVE Video
Acute hypoglycemia decreases myocardial blood flow reserve in patients with type 1 diabetes mellitus and in healthy humans.
Circulation
PUBLISHED: 09-12-2011
Show Abstract
Hide Abstract
Hypoglycemia is associated with increased cardiovascular mortality, but the reason for this association is poorly understood. We tested the hypothesis that the myocardial blood flow reserve (MBFR) is decreased during hypoglycemia using myocardial contrast echocardiography in patients with type 1 diabetes mellitus (DM) and in healthy control subjects.
Related JoVE Video
Insulin pump therapy with automated insulin suspension in response to hypoglycemia: reduction in nocturnal hypoglycemia in those at greatest risk.
Diabetes Care
PUBLISHED: 08-27-2011
Show Abstract
Hide Abstract
To evaluate a sensor-augmented insulin pump with a low glucose suspend (LGS) feature that automatically suspends basal insulin delivery for up to 2 h in response to sensor-detected hypoglycemia.
Related JoVE Video
Predictive biomarkers: a paradigm shift towards personalized cancer medicine.
Nat Rev Clin Oncol
PUBLISHED: 08-23-2011
Show Abstract
Hide Abstract
Advances in our understanding of the intricate molecular mechanisms for transformation of a normal cell to a cancer cell, and the aberrant control of complementary pathways, have presented a much more complex set of challenges for the diagnostic and therapeutic disciplines than originally appreciated. The oncology field has entered an era of personalized medicine where treatment selection for each cancer patient is becoming individualized or customized. This advance reflects the molecular and genetic composition of the tumors and progress in biomarker technology, which allow us to align the most appropriate treatment according to the patients disease. There is a worldwide acceptance that advances in our ability to identify predictive biomarkers and provide them as companion diagnostics for stratifying and subgrouping patients represents the next leap forward in improving the quality of clinical care in oncology. As such, we are progressing from a population-based empirical one drug fits all treatment model, to a focused personalized approach where rational companion diagnostic tests support the drugs clinical utility by identifying the most responsive patient subgroup.
Related JoVE Video
The timing of smoking onset, prolonged abstinence and relapse in men: a prospective study from ages 18 to 32 years.
Addiction
PUBLISHED: 07-27-2011
Show Abstract
Hide Abstract
To describe the rate and timing of smoking onset, prolonged abstinence (?1 year) and relapses from ages 18 to 32 years in initially smoking and non-smoking men.
Related JoVE Video
Documenting the natural history of patients with resected stage II adenocarcinoma of the colon after random assignment to adjuvant treatment with edrecolomab or observation: results from CALGB 9581.
J. Clin. Oncol.
PUBLISHED: 07-11-2011
Show Abstract
Hide Abstract
We conducted a randomized trial comparing adjuvant treatment with edrecolomab versus observation in patients with resected, low-risk, stage II colon cancer. This study also prospectively studied patient- and tumor-specific markers of treatment outcome.
Related JoVE Video
Deus ex machina: the use of technology in type 1 diabetes.
Prim Care Diabetes
PUBLISHED: 07-02-2011
Show Abstract
Hide Abstract
Deus ex machina: in ancient Greek theatre, towards the end of a performance, a crane-like device was often used to lower an actor playing a god onto the stage in order to solve an apparently intractable problem in a plot-line. Nowadays, perceived wisdom believes that difficult clinical scenarios in diabetes can be alleviated by the introduction of technologies such as insulin pump therapy and glucose sensing. This "God from the Machine" approach to problem solving has been enthusiastically embraced by a small number of enthusiasts within the diabetes care community but access to these technologies is still very limited in the UK. The question is can the use of technology reduce or even eliminate the biological and psychological variables that prevent people living with diabetes achieving the standard of blood glucose control desired and if so should availability be more widespread?
Related JoVE Video
The emergence of omics for the management of colorectal cancer.
Curr Opin Oncol
PUBLISHED: 05-18-2011
Show Abstract
Hide Abstract
The past couple of years have seen a flurry of publications detailing potential prognostic and predictive biomarkers for colorectal cancer. However, most studies have been underpowered and demonstrate elements of a statistical fishing exercise, that is the carrying out of a huge number of analyses to find a hint of importance for a particular marker.
Related JoVE Video
Fine-mapping of colorectal cancer susceptibility loci at 8q23.3, 16q22.1 and 19q13.11: refinement of association signals and use of in silico analysis to suggest functional variation and unexpected candidate target genes.
Hum. Mol. Genet.
PUBLISHED: 04-29-2011
Show Abstract
Hide Abstract
We have previously identified several colorectal cancer (CRC)-associated polymorphisms using genome-wide association (GWA) analysis. We sought to fine-map the location of the functional variants for three of these regions at 8q23.3 (EIF3H), 16q22.1 (CDH1/CDH3) and 19q13.11 (RHPN2). We genotyped two case-control sets at high density in the selected regions and used existing data from four other case-control sets, comprising a total of 9328 CRC cases and 10 480 controls. To improve marker density, we imputed genotypes from the 1000 Genomes Project and Hapmap3 data sets. All three regions contained smaller areas in which a cluster of single nucleotide polymorphisms (SNPs) showed clearly stronger association signals than surrounding SNPs, allowing us to assign those areas as the most likely location of the disease-associated functional variant. Further fine-mapping within those areas was generally unhelpful in identifying the functional variation based on strengths of association. However, functional annotation suggested a relatively small number of functional SNPs, including some with potential regulatory function at 8q23.3 and 16q22.1 and a non-synonymous SNP in RPHN2. Interestingly, the expression quantitative trait locus browser showed a number of highly associated SNP alleles correlated with mRNA expression levels not of EIF3H and CDH1 or CDH3, but of UTP23 and ZFP90, respectively. In contrast, none of the top SNPs within these regions was associated with transcript levels at EIF3H, CDH1 or CDH3. Our post-GWA study highlights benefits of fine-mapping of common disease variants in combination with publicly available data sets. In addition, caution should be exercised when assigning functionality to candidate genes in regions discovered through GWA analysis.
Related JoVE Video
Randomized, placebo-controlled, phase III study of first-line oxaliplatin-based chemotherapy plus PTK787/ZK 222584, an oral vascular endothelial growth factor receptor inhibitor, in patients with metastatic colorectal adenocarcinoma.
J. Clin. Oncol.
PUBLISHED: 04-04-2011
Show Abstract
Hide Abstract
PTK787/ZK 222584 (PTK/ZK; vatalanib), an orally active, multitargeted angiogenesis inhibitor, has shown tolerability and promising activity in early-phase studies, which led to a phase III trial in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4).
Related JoVE Video
Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer.
J. Clin. Oncol.
PUBLISHED: 03-07-2011
Show Abstract
Hide Abstract
It is uncertain whether modest benefits from adjuvant chemotherapy in stage II colorectal cancer justify the toxicity, cost, and inconvenience. We investigated the usefulness of defective mismatch repair (dMMR), BRAF, and KRAS mutations in predicting tumor recurrence and sensitivity to chemotherapy.
Related JoVE Video
Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer.
PLoS Genet.
PUBLISHED: 03-05-2011
Show Abstract
Hide Abstract
Genome-wide association studies (GWAS) have identified 14 tagging single nucleotide polymorphisms (tagSNPs) that are associated with the risk of colorectal cancer (CRC), and several of these tagSNPs are near bone morphogenetic protein (BMP) pathway loci. The penalty of multiple testing implicit in GWAS increases the attraction of complementary approaches for disease gene discovery, including candidate gene- or pathway-based analyses. The strongest candidate loci for additional predisposition SNPs are arguably those already known both to have functional relevance and to be involved in disease risk. To investigate this proposition, we searched for novel CRC susceptibility variants close to the BMP pathway genes GREM1 (15q13.3), BMP4 (14q22.2), and BMP2 (20p12.3) using sample sets totalling 24,910 CRC cases and 26,275 controls. We identified new, independent CRC predisposition SNPs close to BMP4 (rs1957636, P = 3.93×10(-10)) and BMP2 (rs4813802, P = 4.65×10(-11)). Near GREM1, we found using fine-mapping that the previously-identified association between tagSNP rs4779584 and CRC actually resulted from two independent signals represented by rs16969681 (P = 5.33×10(-8)) and rs11632715 (P = 2.30×10(-10)). As low-penetrance predisposition variants become harder to identify-owing to small effect sizes and/or low risk allele frequencies-approaches based on informed candidate gene selection may become increasingly attractive. Our data emphasise that genetic fine-mapping studies can deconvolute associations that have arisen owing to independent correlation of a tagSNP with more than one functional SNP, thus explaining some of the apparently missing heritability of common diseases.
Related JoVE Video
Actionable self-monitoring of blood glucose: redefining the role for patients using multiple daily injection therapy.
J Diabetes Sci Technol
PUBLISHED: 02-14-2011
Show Abstract
Hide Abstract
Self-monitoring of blood glucose (SMBG) values is an accepted requirement for patients with diabetes using multiple daily injections of insulin. Nevertheless, for many patients, the full value of SMBG has yet to be realized due to a number of factors that contribute to patients not taking appropriate action based on the achieved result. The reasons for this are complex but are related to the burden imposed by performing the tests, the need for complex numerical calculations, and the demand for undertaking this activity multiple times each day. In the near future, SMBG devices are likely to include technological innovations that are aimed at overcoming these barriers, offering "actionable" SMBG for patients using insulin. These innovations should include technologies that will allow customization and individualization based upon specific therapy regimens.
Related JoVE Video
Consensus report: the current role of self-monitoring of blood glucose in non-insulin-treated type 2 diabetes.
J Diabetes Sci Technol
PUBLISHED: 02-14-2011
Show Abstract
Hide Abstract
The Coalition for Clinical Research--Self-Monitoring of Blood Glucose Scientific Board convened a meeting in San Francisco, CA, July 20-21, 2011, to discuss the current practice of self-monitoring of blood glucose (SMBG) in non-insulin-treated (NIT) type 2 diabetes mellitus (T2DM). Twelve physician panel members from academia, practice, and government attended this meeting. These experts came from the United States, Brazil, Canada, France, Germany, Italy, and the United Kingdom. In addition, three consultants from Australia, Germany, and the United States contributed to the groups final report. This coalition was organized by Diabetes Technology Society. Self-monitoring of blood glucose was studied from eight perspectives related to patients with NIT T2DM: (1) epidemiological studies; (2) randomized controlled trials (RCT)s and meta-analyses; (3) targets, timing, and frequency of SMBG use; (4) incidence and role of SMBG in preventing hypoglycemia with single-drug regimens and combination regimens consisting of antihyperglycemic agents other than secretagogues and insulin; (5) comparison of SMBG with continuous glucose monitoring; (6) technological capabilities and limitations of SMBG; (7) barriers to appropriate use of SMBG; and (8) methods and end points for appropriate future clinical trials. The panel emphasized recent studies, which reflect the current approach for applying this intervention. Among the participants there was consensus that: SMBG is an established practice for patients with NIT T2DM, and to be most effective, it should be performed in a structured format where information obtained from this measurement is used to guide treatment; New, high-quality efficacy data from RCTs have demonstrated efficacy of SMBG in NIT T2DM in trials reported since 2008; Both patients and health care professionals require education on how to respond to the data for SMBG to be effective; and Additional well-defined studies are needed to assess the benefits and costs of SMBG with end points not limited to hemoglobin A1c.
Related JoVE Video
KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer.
Clin. Cancer Res.
PUBLISHED: 01-14-2011
Show Abstract
Hide Abstract
Oncogene mutations contribute to colorectal cancer development. We searched for differences in oncogene mutation profiles between colorectal cancer metastases from different sites and evaluated these as markers for site of relapse.
Related JoVE Video
Biomarkers in clinical medicine.
IARC Sci. Publ.
PUBLISHED: 01-01-2011
Show Abstract
Hide Abstract
Biomarkers have been used in clinical medicine for decades. With the rise of genomics and other advances in molecular biology, biomarker studies have entered a whole new era and hold promise for early diagnosis and effective treatment of many diseases. A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacologic responses to a therapeutic intervention (1). They can be classified into five categories based on their application in different disease stages: 1) antecedent biomarkers to identify the risk of developing an illness, 2) screening biomarkers to screen for subclinical disease, 3) diagnostic biomarkers to recognize overt disease, 4) staging biomarkers to categorise disease severity, and 5) prognostic biomarkers to predict future disease course, including recurrence, response to therapy, and monitoring efficacy of therapy (1). Biomarkers can indicate a variety of health or disease characteristics, including the level or type of exposure to an environmental factor, genetic susceptibility, genetic responses to environmental exposures, markers of subclinical or clinical disease, or indicators of response to therapy. This chapter will focus on how these biomarkers have been used in preventive medicine, diagnostics, therapeutics and prognostics, as well as public health and their current status in clinical practice.
Related JoVE Video
Reversible blindness: severe pneumococcal induced uveitis following septicaemia.
BMJ Case Rep
PUBLISHED: 01-01-2011
Show Abstract
Hide Abstract
This study illustrates the case of a middle-aged woman who presented with sepsis and purpura fulminans, found to be due to Streptococcus pneumoniae infection. She later developed blindness from a dramatic ocular inflammatory response provoked by pneumococcal antigens.
Related JoVE Video
Multicenter user evaluation of ACCU-CHEK® Combo, an integrated system for continuous subcutaneous insulin infusion.
J Diabetes Sci Technol
PUBLISHED: 12-07-2010
Show Abstract
Hide Abstract
The aim of this study was to evaluate a newly developed system for insulin delivery incorporating a multifunctional blood glucose meter and a remotely controlled insulin pump (ACCU-CHEK® Combo system) in established pump users with type 1 diabetes. The technology was assessed both from device performance and subject usability perspectives.
Related JoVE Video
Theory of mind and emotion understanding predict moral development in early childhood.
Br J Dev Psychol
PUBLISHED: 12-03-2010
Show Abstract
Hide Abstract
The current study utilized longitudinal data to investigate how theory of mind (ToM) and emotion understanding (EU) concurrently and prospectively predicted young childrens moral reasoning and decision making. One hundred twenty-eight children were assessed on measures of ToM and EU at 3.5 and 5.5 years of age. At 5.5 years, children were also assessed on the quality of moral reasoning and decision making they used to negotiate prosocial moral dilemmas, in which the needs of a story protagonist conflict with the needs of another story character. More sophisticated EU predicted greater use of physical- and material-needs reasoning, and a more advanced ToM predicted greater use of psychological-needs reasoning. Most intriguing, ToM and EU jointly predicted greater use of higher-level acceptance-authority reasoning, which is likely a product of childrens increasing appreciation for the knowledge held by trusted adults and childrens desire to behave in accordance with social expectations.
Related JoVE Video
Cyclin D1 rare variants in UK multiple adenoma and early-onset colorectal cancer patients.
J. Hum. Genet.
PUBLISHED: 11-25-2010
Show Abstract
Hide Abstract
We examined the influence that rare variants and low-frequency polymorphisms in the cancer candidate gene CCND1 have on the development of multiple intestinal adenomas and the early onset of colorectal cancer. Individuals with <100 multiple polyps and patients with colorectal cancer diagnosed before 50 years of age were recruited in UK, and screened for sequence changes in the coding and regulatory regions of CCND1. A set of about 800 UK control individuals was genotyped for the variants discovered in the cases. Variants in the promoter, intron-exon boundaries and untranslated regions of the CCND1 gene had higher frequencies in cases than in controls. Five of these variants were typed in a set of French multiple adenoma and early-onset patients, who also showed higher allele frequencies than UK controls. When pooled together, variants with frequencies lower than 1% conferred an increased risk of disease that was significant in the multiple adenoma group (odds ratio (OR) 2.2; 95% confidence interval, 1.1-4.4; P = 0.03). Most variants had a putative functional effect when assessed in silico. We conclude that rare variants of CCND1 are risk factors for colorectal cancer, with considerably larger effects than common polymorphisms, and as such should be systematically evaluated in susceptibility studies.
Related JoVE Video
Related JoVE Video
Assessment of cheating behavior in young school-age children: distinguishing normative behaviors from risk markers of externalizing psychopathology.
J Clin Child Adolesc Psychol
PUBLISHED: 11-09-2010
Show Abstract
Hide Abstract
The central goal of this longitudinal study was to develop a laboratory-based index of childrens covert cheating behavior that distinguished normative rule violations from those that signal risk for antisocial behavior. Participants (N = 215 children) were drawn from a community population and oversampled for externalizing behavior problems (EXT). Cheating behavior was measured using two resistance-to-temptation tasks and coded for extent of cheating, latency to cheat, and inappropriate positive affect. Mothers rated internalized conduct and three forms of self-regulation: inhibitory control, impulsivity, and affective distress. Mothers and teachers reported EXT concurrently (T1) and 4 years later, when children averaged 10 years of age (T2). Children categorized as severe cheaters manifested lower inhibitory control, greater impulsivity, and lower levels of internalized conduct at T1. Children in this group also manifested higher levels of EXT in home and school settings at T1 and more EXT in the school setting at T2, even after accounting for T1 ratings.
Related JoVE Video
Roles of tetrahydrobiopterin in promoting tumor angiogenesis.
Am. J. Pathol.
PUBLISHED: 09-16-2010
Show Abstract
Hide Abstract
Nitric oxide (NO), which is derived from endothelial NO synthase (eNOS), provides crucial signals for angiogenesis in the tumor microenvironment. Tetrahydrobiopterin (BH4) is an absolute requirement for eNOS activity. In this study, we investigated whether this activation is both maintained by a wild-type Ras/phosphatidylinositol 3-kinase (PI3K)/Akt-positive feedback loop in endothelial cells and affects tumor angiogenesis. We found that supplementation of BH4 (via the pterin salvage pathway with Sep) increased Akt/eNOS phosphorylation in both human eNOS-transfected COS-7 cells and endothelial cells concomitant with increases in NO production, cell proliferation, migration, and tube formation. This augmentation was abrogated by a PI3K inhibitor. Sepiapterin (Sep) also increased GTP-bound wild-type Ras and PI3K/Akt/eNOS activation, which was prevented by the eNOS inhibitor, N?-Nitro-L-arginine methyl ester (L-NAME). Furthermore, expression of GTP cyclohydrolase I (the rate-limiting enzyme in de novo BH4 synthesis) under doxycycline control potentiated in vivo tumorigenesis, tumor cell proliferation, as well as angiogenesis. Conversely, both switching off GTP cyclohydrolase I expression as well as inhibiting its enzymatic activity significantly decreased eNOS expression and tumor vascularization. This study demonstrates an important role for BH4 synthesis in angiogenesis by the activation of eNOS for NO production, which is maintained by a PI3K/Akt-positive feedback loop through effects on wild-type Ras in endothelial cells. Our findings suggest that BH4 synthesis may be a rational target for antiangiogenesis therapy for tumors.
Related JoVE Video
Phase III randomized trial assessing rofecoxib in the adjuvant setting of colorectal cancer: final results of the VICTOR trial.
J. Clin. Oncol.
PUBLISHED: 09-13-2010
Show Abstract
Hide Abstract
Laboratory and case-control studies suggest a pivotal role for the cyclooxygenase-2 (COX-2) pathway in colorectal carcinogenesis. The purpose of this study was to test whether the COX-2 inhibitor rofecoxib could reduce recurrence and improve survival when administered in the adjuvant setting of colorectal cancer (CRC).
Related JoVE Video
Quinone oxidoreductase-2-mediated prodrug cancer therapy.
Sci Transl Med
PUBLISHED: 07-16-2010
Show Abstract
Hide Abstract
DNA-damaging agents are widely used in cancer treatment despite their lack of tumor specificity. Human NQO2 (quinone oxidoreductase-2) is an atypical oxidoreductase because no endogenous electron donor has been identified to date. The enzyme converts CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide], in the presence of the synthetic nicotinamide cofactor analog EP0152R, to a cytotoxic bifunctional alkylating agent. NQO2 activity in hepatocellular tumor tissue is higher than that in other cancer types by a factor of 6 and higher than that in bone marrow by a factor of 20. Structural data from x-ray crystallography and nuclear magnetic resonance spectroscopy allowed us to construct a model of CB1954 and EP0152R binding to NQO2, which suggested an optimal infusion schedule for a phase I trial combining the two agents. Thirty-two patients were treated, and diarrhea and serum transaminase concentrations defined a maximum tolerated dose for the drug combination. There was a clear pharmacokinetic interaction, with EP0152R inducing a marked increase in clearance of CB1954, in keeping with model predictions. We detected DNA interstrand cross-links caused by nitroreduced CB1954 in tumor biopsies from treated patients, demonstrating that the activated prodrug exerts its cytotoxic properties through DNA base alkylation.
Related JoVE Video
Gene profiling in early stage disease.
Cancer J
PUBLISHED: 06-08-2010
Show Abstract
Hide Abstract
Although we have made steady progress in the adjuvant chemotherapy of colorectal cancer, it is clear that any population benefits accrued stem from overtreatment of the majority of patients. For example, we have to treat 100 stage II patients to cure 3 or 4, while accepting that up to 40% of those treated will suffer significant toxicity and all will face the distinct social (and often financial) inconvenience of outpatient chemotherapy for 6 months. This has prompted much effort in the field of molecular diagnostics to develop "tools," which may allow selection of patients who will benefit most (or least) from chemotherapy. The majority of translational research to identify prognostic and/or predictive biomarkers has been somewhat confounded by studies of small sample size, insufficient statistical power, variable methodology, and incomplete clinical data sets, so other than conventional histopathological staging, there are no widely accepted molecular markers of prognosis and prediction. A novel reverse transcriptase polymerase chain reaction multigene assay, performed on RNA extracted from paraffin-embedded tumor tissue has been validated in a series of 1436 patients with stage II colon cancer and was found to be predict recurrence risk (HR/25 units = 1.58; 95% CI, 1.15-2.15; P = 0.004). This may become established as a prognostic tool of choice for stage II colon cancer.
Related JoVE Video
Pascals wager: combining continuous glucose monitoring and continuous subcutaneous insulin infusion.
Diabetes Technol. Ther.
PUBLISHED: 06-03-2010
Show Abstract
Hide Abstract
Pascals Wager is a suggestion posed by the French Philosopher, Blaise Pascal, that even though the existence of God cannot be determined through reason, a person should wager that God exists because he or she has everything to gain and nothing to lose. In the area of consideration here, the optimum experimental trial of the combined use of continuous subcutaneous insulin infusion and real-time continuous glucose monitoring in free-living individuals with type 1 diabetes providing rock-solid evidence of clinical benefit has not been performed. Nevertheless, there is considerable enthusiasm for combining the technologies among healthcare professionals, patients, and manufacturers based on the belief that this approach to diabetes care must be beneficial beyond the available evidence (i.e., reason).
Related JoVE Video
Regional hepatic chemotherapies in the treatment of colorectal cancer metastases to the liver.
Semin. Oncol.
PUBLISHED: 05-25-2010
Show Abstract
Hide Abstract
The liver is the most common site of metastatic spread of colorectal cancer (CRC). Liver may be the only site of spread in as many as 30% to 40% of patients with advanced disease and can be treated with regional therapies directed toward their liver tumors. Surgery is currently the only potentially curative treatment, with a 5-year survival rate as high as 30% to 40% in selected patients. However, fewer than 25% of cases are candidates for curative resection. A number of other locoregional therapies, such as radiofrequency or microwave ablation, cryotherapy, and chemotherapy, may be offered to patients with unresectable but isolated liver metastases. However, for most patients with metastatic spread beyond the liver, systemic chemotherapy rather than regional therapy is a more appropriate option. We review the status of various regional hepatic chemotherapies in the treatment of colorectal metastases to the liver in the light of the available, published prospective, randomized trials; this discipline has not yet been properly applied to the burgeoning use of locally ablative techniques. The regional strategies reviewed include portal venous infusion (PVI) of 5-fluorouracil (5-FU), intra-arterial chemotherapy (hepatic arterial infusion [HAI]), chemoembolization, and selective internal radiation therapy (SIRT).
Related JoVE Video
International network of cancer genome projects.
, Thomas J Hudson, Warwick Anderson, Axel Artez, Anna D Barker, Cindy Bell, Rosa R Bernabé, M K Bhan, Fabien Calvo, Iiro Eerola, Daniela S Gerhard, Alan Guttmacher, Mark Guyer, Fiona M Hemsley, Jennifer L Jennings, David Kerr, Peter Klatt, Patrik Kolar, Jun Kusada, David P Lane, Frank Laplace, Lu Youyong, Gerd Nettekoven, Brad Ozenberger, Jane Peterson, T S Rao, Jacques Remacle, Alan J Schafer, Tatsuhiro Shibata, Michael R Stratton, Joseph G Vockley, Koichi Watanabe, Huanming Yang, Matthew M F Yuen, Bartha M Knoppers, Martin Bobrow, Anne Cambon-Thomsen, Lynn G Dressler, Stephanie O M Dyke, Yann Joly, Kazuto Kato, Karen L Kennedy, Pilar Nicolás, Michael J Parker, Emmanuelle Rial-Sebbag, Carlos M Romeo-Casabona, Kenna M Shaw, Susan Wallace, Georgia L Wiesner, Nikolajs Zeps, Peter Lichter, Andrew V Biankin, Christian Chabannon, Lynda Chin, Bruno Clément, Enrique De Alava, Françoise Degos, Martin L Ferguson, Peter Geary, D Neil Hayes, Amber L Johns, Arek Kasprzyk, Hidewaki Nakagawa, Robert Penny, Miguel A Piris, Rajiv Sarin, Aldo Scarpa, Marc van de Vijver, P Andrew Futreal, Hiroyuki Aburatani, Mònica Bayés, David D L Botwell, Peter J Campbell, Xavier Estivill, Sean M Grimmond, Ivo Gut, Martin Hirst, Carlos Lopez-Otin, Partha Majumder, Marco Marra, John D McPherson, Zemin Ning, Xose S Puente, Yijun Ruan, Hendrik G Stunnenberg, Harold Swerdlow, Victor E Velculescu, Richard K Wilson, Hong H Xue, Liu Yang, Paul T Spellman, Gary D Bader, Paul C Boutros, Paul Flicek, Gad Getz, Roderic Guigo, Guangwu Guo, David Haussler, Simon Heath, Tim J Hubbard, Tao Jiang, Steven M Jones, Qibin Li, Nuria López-Bigas, Ruibang Luo, Lakshmi Muthuswamy, B F Francis Ouellette, John V Pearson, Víctor Quesada, Benjamin J Raphael, Chris Sander, Terence P Speed, Lincoln D Stein, Joshua M Stuart, Jon W Teague, Yasushi Totoki, Tatsuhiko Tsunoda, Alfonso Valencia, David A Wheeler, Honglong Wu, Shancen Zhao, Guangyu Zhou, Mark Lathrop, Gilles Thomas, Teruhiko Yoshida, Myles Axton, Chris Gunter, Linda J Miller, Junjun Zhang, Syed A Haider, Jianxin Wang, Christina K Yung, Anthony Cros, Anthony Cross, Yong Liang, Saravanamuttu Gnaneshan, Jonathan Guberman, Jack Hsu, Don R C Chalmers, Karl W Hasel, Terry S H Kaan, William W Lowrance, Tohru Masui, Laura Lyman Rodriguez, Catherine Vergely, David D L Bowtell, Nicole Cloonan, Anna deFazio, James R Eshleman, Dariush Etemadmoghadam, Brooke B Gardiner, Brooke A Gardiner, James G Kench, Robert L Sutherland, Margaret A Tempero, Nicola J Waddell, Peter J Wilson, Steve Gallinger, Ming-Sound Tsao, Patricia A Shaw, Gloria M Petersen, Debabrata Mukhopadhyay, Ronald A DePinho, Sarah Thayer, Kamran Shazand, Timothy Beck, Michelle Sam, Lee Timms, Vanessa Ballin, Youyong Lu, Jiafu Ji, Xiuqing Zhang, Feng Chen, Xueda Hu, Qi Yang, Geng Tian, Lianhai Zhang, Xiaofang Xing, Xianghong Li, Zhenggang Zhu, Yingyan Yu, Jun Yu, Jörg Tost, Paul Brennan, Ivana Holcatova, David Zaridze, Alvis Brazma, Lars Egevard, Egor Prokhortchouk, Rosamonde Elizabeth Banks, Mathias Uhlén, Juris Viksna, Fredrik Ponten, Konstantin Skryabin, Ewan Birney, Ake Borg, Anne-Lise Børresen-Dale, Carlos Caldas, John A Foekens, Sancha Martin, Jorge S Reis-Filho, Andrea L Richardson, Christos Sotiriou, Giles Thoms, Laura van't Veer, Daniel Birnbaum, Hélène Blanché, Pascal Boucher, Sandrine Boyault, Jocelyne D Masson-Jacquemier, Iris Pauporté, Xavier Pivot, Anne Vincent-Salomon, Eric Tabone, Charles Theillet, Isabelle Treilleux, Paulette Bioulac-Sage, Thomas Decaens, Dominique Franco, Marta Gut, Didier Samuel, Jessica Zucman-Rossi, Roland Eils, Benedikt Brors, Jan O Korbel, Andrey Korshunov, Pablo Landgraf, Hans Lehrach, Stefan Pfister, Bernhard Radlwimmer, Guido Reifenberger, Michael D Taylor, Christof von Kalle, Partha P Majumder, Paolo Pederzoli, Rita A Lawlor, Massimo Delledonne, Alberto Bardelli, Thomas Gress, David Klimstra, Giuseppe Zamboni, Yusuke Nakamura, Satoru Miyano, Akihiro Fujimoto, Elias Campo, Silvia de Sanjosé, Emili Montserrat, Marcos Gonzalez-Díaz, Pedro Jares, Heinz Himmelbauer, Heinz Himmelbaue, Sílvia Beà, Samuel Aparicio, Douglas F Easton, Francis S Collins, Carolyn C Compton, Eric S Lander, Wylie Burke, Anthony R Green, Stanley R Hamilton, Olli P Kallioniemi, Timothy J Ley, Edison T Liu, Brandon J Wainwright.
Nature
PUBLISHED: 04-16-2010
Show Abstract
Hide Abstract
The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
Related JoVE Video
Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33.
Nat. Genet.
PUBLISHED: 04-09-2010
Show Abstract
Hide Abstract
Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (cases) and 4,628 controls followed by multiple validation analyses including a total of 18,095 cases and 20,197 controls. We identified associations at four new CRC risk loci: 1q41 (rs6691170, odds ratio (OR) = 1.06, P = 9.55 × 10?¹? and rs6687758, OR = 1.09, P = 2.27 × 10??, 3q26.2 (rs10936599, OR = 0.93, P = 3.39 × 10??), 12q13.13 (rs11169552, OR = 0.92, P = 1.89 × 10?¹? and rs7136702, OR = 1.06, P = 4.02 × 10??) and 20q13.33 (rs4925386, OR = 0.93, P = 1.89 × 10?¹?). In addition to identifying new CRC risk loci, this analysis provides evidence that additional CRC-associated variants of similar effect size remain to be discovered.
Related JoVE Video
Comprehensive assessment of variation at the transforming growth factor beta type 1 receptor locus and colorectal cancer predisposition.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-05-2010
Show Abstract
Hide Abstract
The role of transforming growth factor beta receptor type 1 (TGFBR1) polymorphisms, particularly a coding CGC insertion (rs11466445, TGFBR1*6A/9A) in exon 1, has been extensively investigated in regard to colorectal cancer (CRC) risk. These investigations have generated conflicting results. More recently, allele-specific expression (ASE) of TGFBR1 mRNA has been suggested as predisposing to CRC, with a relative risk of nearly 10-fold and a population attributable risk of approximately 10%. Owing to the potential importance of TGFBR1 variants in CRC, we performed a comprehensive examination of tagging SNPs at and around the gene in 3,101 CRC cases and 3,334 controls of northern European ancestry. To test whether rare or subpolymorphic TGFBR1 variants were associated with CRC risk, we sequenced the genes exons in a subset of patients. We also evaluated TGFBR1 ASE in a panel of CRC cases and controls. Overall, we found no association between TGFBR1 polymorphisms and CRC risk. The rare variant screen did not identify any changes of potentially pathogenic effects. No evidence of greater ASE in cases than controls was detected, and no haplotype around TGFBR1 could account for the ASE reported in other studies. We conclude that neither genetic variation nor ASE at TGFBR1 is likely to be a major CRC risk factor.
Related JoVE Video
Evaluation of the Assurance GDS for Salmonella method in foods and environmental surfaces: multilaboratory collaborative study.
J AOAC Int
PUBLISHED: 03-26-2010
Show Abstract
Hide Abstract
A multilaboratory collaborative study was conducted to compare the detection of Salmonella by the Assurance GDS for Salmonella method and the Reference culture methods. Six foods, representing a variety of low microbial and high microbial load foods were analyzed. Seventeen laboratories in the United States and Canada participated in this study. No statistical differences (P < 0.05) were observed between the Assurance GDS for Salmonella and the Reference culture methods for any inoculation level of any food type or naturally contaminated food, except for pasta, for which the Assurance GDS method had a higher number of confirmed test portions for Salmonella compared to the Reference method.
Related JoVE Video
Infant pathways to externalizing behavior: evidence of Genotype x Environment interaction.
Child Dev
PUBLISHED: 03-25-2010
Show Abstract
Hide Abstract
To further the understanding of the effects of early experiences, 9-month-old infants were observed during a frustration task. The analytical sample was composed of 348 linked triads of participants (adoptive parents, adopted child, and birth parent[s]) from a prospective adoption study. It was hypothesized that genetic risk for externalizing problems and affect dysregulation in the adoptive parents would independently and interactively predict a known precursor to externalizing problems: heightened infant attention to frustrating events. Results supported the moderation hypotheses involving adoptive mother affect dysregulation: Infants at genetic risk showed heightened attention to frustrating events only when the adoptive mother had higher levels of anxious and depressive symptoms. The Genotype x Environment interaction pattern held when substance use during pregnancy was considered.
Related JoVE Video
Driving with diabetes in the future: in-vehicle medical monitoring.
J Diabetes Sci Technol
PUBLISHED: 03-24-2010
Show Abstract
Hide Abstract
The motor car is a ubiquitous feature of modern life, and most of us spend significant amounts of time in a car, behind the wheel. Driving a vehicle requires complex coordination of cognitive, motor, and sensory skills. All of these aspects can be affected adversely by diabetes per se, with hypoglycemia being the main concern for people with diabetes who drive. Here we introduce the concept of using the motor vehicle as a device to collect and deliver physiological and clinical information, which, in turn, may enable more people to drive more safely by reducing the chances of medical mishaps behind the wheel. This is particularly relevant for people living with diabetes who are at risk from a number of medical conditions that have the potential to have an impact on safe driving. The development of in-vehicle medical monitoring presents a new opportunity for novel collaborations between two industries, which have safety as a core value.
Related JoVE Video
HR23B is a biomarker for tumor sensitivity to HDAC inhibitor-based therapy.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 03-22-2010
Show Abstract
Hide Abstract
Histone deacetylase (HDAC) inhibitors are emergent cancer drugs. HR23B is a candidate cancer biomarker identified in a genome-wide loss-of-function screen which influences sensitivity to HDAC inhibitors. Because HDAC inhibitors have found clinical utility in cutaneous T-cell lymphoma (CTCL), we evaluated the role of HR23B in CTCL cells. Our results show that HR23B governs the sensitivity of CTCL cells to HDAC inhibitors. Furthermore, proteasome activity is deregulated in HDAC inhibitor-treated CTCL cells through a mechanism dependent upon HR23B, and HDAC inhibitors sensitize CTCL cells to the effects of proteasome inhibitors. The predictive power of HR23B for clinical response to HDAC inhibitors was investigated through an analysis of a unique collection of CTCL biopsies taken from a phase II clinical trial, where there was a frequent coincidence between HR23B expression and clinical response to HDAC inhibitor. Our study supports the personalized medicine approach for treating cancer and the increasing drive to translate laboratory-based findings into clinical utility.
Related JoVE Video
Metastasis-Associated Gene Expression Changes Predict Poor Outcomes in Patients with Dukes Stage B and C Colorectal Cancer.
Clin. Cancer Res.
PUBLISHED: 12-08-2009
Show Abstract
Hide Abstract
PURPOSE: Colorectal cancer prognosis is currently predicted from pathologic staging, providing limited discrimination for Dukes stage B and C disease. Additional markers for outcome are required to help guide therapy selection for individual patients. EXPERIMENTAL DESIGN: A multisite single-platform microarray study was done on 553 colorectal cancers. Gene expression changes were identified between stage A and D tumors (three training sets) and assessed as a prognosis signature in stage B and C tumors (independent test and external validation sets). RESULTS: One hundred twenty-eight genes showed reproducible expression changes between three sets of stage A and D cancers. Using consistent genes, stage B and C cancers clustered into two groups resembling early-stage and metastatic tumors. A Prediction Analysis of Microarray algorithm was developed to classify individual intermediate-stage cancers into stage A-like/good prognosis or stage D-like/poor prognosis types. For stage B patients, the treatment adjusted hazard ratio for 6-year recurrence in individuals with stage D-like cancers was 10.3 (95% confidence interval, 1.3-80.0; P = 0.011). For stage C patients, the adjusted hazard ratio was 2.9 (95% confidence interval, 1.1-7.6; P = 0.016). Similar results were obtained for an external set of stage B and C patients. The prognosis signature was enriched for downregulated immune response genes and upregulated cell signaling and extracellular matrix genes. Accordingly, sparse tumor infiltration with mononuclear chronic inflammatory cells was associated with poor outcome in independent patients. CONCLUSIONS: Metastasis-associated gene expression changes can be used to refine traditional outcome prediction, providing a rational approach for tailoring treatments to subsets of patients. (Clin Cancer Res 2009;15(24):7642-51).
Related JoVE Video
Comparative validation study to demonstrate the equivalence of a minor modification to AOAC Method 999.09 Visual Immunoprecipitate (VIP) for Salmonella method to the reference culture method.
J AOAC Int
PUBLISHED: 11-18-2009
Show Abstract
Hide Abstract
The Visual Immunoprecipitate (VIP) for the Detection of Salmonella in Foods, AOAC Official Method 999.09, has been modified to change the color of the test and control lines of the device. A methods comparison study was conducted to demonstrate the equivalence of this modification to the reference culture method. Three foods were analyzed. In total, there were valid results from 155 samples and controls. Results showed that the modified VIP Gold for Salmonella is equivalent to the reference culture methods for the detection of Salmonella.
Related JoVE Video
Comparative validation study to demonstrate the equivalence of a minor modification to AOAC Method 997.03 Visual Immunoprecipitate (VIP) for Listeria to the reference culture method.
J AOAC Int
PUBLISHED: 11-18-2009
Show Abstract
Hide Abstract
The Visual Immunoprecipitate (VIP) for the Detection of Listeria in Foods and Environmental Surfaces, AOAC Official Method 997.03, has been modified to change the color of the test and control lines of the device. A methods comparison study was conducted to demonstrate the equivalence of this modification to the reference culture method. Two food matrixes and one environmental surface were analyzed. In total, there were valid results from 100 samples and controls. Results showed that the modified VIP Gold for Listeria spp. is equivalent to the reference culture methods for the detection of Listeria.
Related JoVE Video
Comparative validation study to demonstrate the equivalence of a minor modification to AOAC Method 996.09 Visual Immunoprecipitate (VIP) for E. coli O157:H7 method to the reference culture method.
J AOAC Int
PUBLISHED: 11-18-2009
Show Abstract
Hide Abstract
The Visual Immunoprecipitate (VIP) for the Detection of Escherichia coli 0157:H7 in Foods, AOAC Official Method 996.09, has been modified to change the color of the test and control lines of the device. A methods comparison study was conducted to demonstrate the equivalence of this modification to the reference culture method. Three foods were analyzed. In total, there were valid results from 225 samples and controls. Results showed that the VIP Gold for E. coli O157:H7 is equivalent to the reference culture methods for the detection of E. coli O157:H7.
Related JoVE Video
Malignant peritoneal mesothelioma. Is there a new treatment?
Rare Tumors
PUBLISHED: 10-30-2009
Show Abstract
Hide Abstract
The authors report a novel, alternative approach to treat malignant peritoneal mesothelioma (MPeM) targeting, vascular endothelial growth factor (VEGF) using anti-VEGF (bevacizumab) chemotherapy combination.
Related JoVE Video
What is the role and impact of molecular markers on treatment decisions for colorectal cancer in the adjuvant setting?
Discov Med
PUBLISHED: 10-17-2009
Show Abstract
Hide Abstract
The new mantra for delivering optimal cancer treatment is "personalized care." This extends beyond the holistic to using germline and somatic tumoral mutations to link a specific therapy to some prognostic or predictive factor which defines a particularly responsive patient subgroup who might benefit most from treatment. Furthermore, inherited polymorphisms have the potential to greatly modulate the side effects of treatment, especially for chemotherapy which has a notoriously narrow therapeutic window.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.