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Find video protocols related to scientific articles indexed in Pubmed.
Diabetes and breast cancer in Taiwanese women: a detection bias?
Eur. J. Clin. Invest.
PUBLISHED: 08-25-2014
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To evaluate whether diabetes is a risk factor for breast cancer considering confounders and potential detection examinations.
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A Review on the Relationship between SGLT2 Inhibitors and Cancer.
Int J Endocrinol
PUBLISHED: 08-05-2014
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Risk of increasing breast and bladder cancer remains a safety issue of SGLT2 (sodium glucose cotransporter type 2) inhibitors, a novel class of antidiabetic agent. We reviewed related papers published before January 29, 2014, through Pubmed search. Dapagliflozin and canagliflozin are the first two approved SGLT2 inhibitors for diabetes therapy. Although preclinical animal toxicology did not suggest a cancer risk of dapagliflozin and overall tumor did not increase, excess numbers of female breast cancer and male bladder cancer were noted in preclinical trials (without statistical significance). This concern of cancer risk hindered its approval by the US FDA in January, 2012. New clinical data suggested that the imbalance of bladder and breast cancer might be due to early diagnosis rather than a real increase of cancer incidence. No increased risk of overall bladder or breast cancer was noted for canagliflozin. Therefore, the imbalance observed with dapagliflozin treatment should not be considered as a class effect of SGLT2 inhibitors and the relationship with cancer for each specific SGLT2 inhibitor should be examined individually. Relationship between SGLT2 inhibition and cancer formation is still inconclusive and studies with larger sample size, longer exposure duration, and different ethnicities are warranted.
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Treatment with human insulin does not increase thyroid cancer risk in patients with type 2 diabetes.
Eur. J. Clin. Invest.
PUBLISHED: 06-11-2014
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Whether human insulin therapy may increase thyroid cancer risk in patients with type 2 diabetes mellitus (T2DM) has not been investigated.
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Electrospun microcrimped fibers with nonlinear mechanical properties enhance ligament fibroblast phenotype.
Biofabrication
PUBLISHED: 05-28-2014
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Fiber structure and order greatly impact the mechanical behavior of fibrous materials. In biological tissues, the nonlinear mechanics of fibrous scaffolds contribute to the functionality of the material. The nonlinear mechanical properties of the wavy structure (crimp) in collagen allow tissue flexibility while preventing over-extension. A number of approaches have tried to recreate this complex mechanical functionality. We generated microcrimped fibers by briefly heating electrospun parallel fibers over the glass transition temperature or by ethanol treatment. The crimp structure is similar to those of collagen fibers found in native aorta, intestines, or ligaments. Using poly-L-lactic acid fibers, we demonstrated that the bulk materials exhibit changed stress-strain behaviors with a significant increase in the toe region in correlation to the degree of crimp, similar to those observed in collagenous tissues. In addition to mimicking the stress-strain behavior of biological tissues, the microcrimped fibers are instructive in cell morphology and promote ligament phenotypic gene expression. This effect can be further enhanced by dynamic tensile loading, a physiological perturbation in vivo. This rapid and economical approach for microcrimped fiber production provides an accessible platform to study structure-function relationships and a novel functional scaffold for tissue engineering and cell mechanobiology studies.
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Pioglitazone does not affect the risk of kidney cancer in patients with type 2 diabetes.
Metab. Clin. Exp.
PUBLISHED: 04-29-2014
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To investigate whether pioglitazone treatment of patients with type 2 diabetes mellitus was associated with an increased risk of kidney cancer.
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Metformin may reduce breast cancer risk in Taiwanese women with type 2 diabetes.
Breast Cancer Res. Treat.
PUBLISHED: 04-24-2014
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Whether metformin therapy affects breast cancer risk in Asian patients with type 2 diabetes mellitus (T2DM) has not been investigated. The reimbursement databases of Taiwanese female patients with a new diagnosis of T2DM between 1998 and 2002 (n = 476,282) were retrieved from the National Health Insurance for follow-up of breast cancer until the end of 2009. Metformin was treated as a time-dependent variable; and of these patients, 285,087 were never-users and 191,195 were ever-users. A time-dependent approach was used to calculate breast cancer incidence and estimate hazard ratios by Cox regression for ever-users, never-users, and subgroups of metformin exposure (tertiles of cumulative duration and cumulative dose). During follow-up, 2,412 (1.26 %) metformin ever-users and 9,322 (2.10 %) never-users developed breast cancer, representing an incidence of 201.08 and 535.88 per 100,000 person-years, respectively. The overall multivariable-adjusted hazard ratio (95 % confidence intervals) for ever- versus never-users was 0.630 (0.597-0.665). The multivariable-adjusted hazard ratios for the first, second, and third tertiles of cumulative duration of metformin therapy were 1.122 (1.043-1.207), 0.754 (0.692-0.820), and 0.280 (0.253-0.310), respectively, (P-trend <0.0001); and 1.099 (1.021-1.182), 0.664 (0.611-0.723), and 0.311 (0.281-0.344), respectively, (P-trend <0.0001), for cumulative dose of metformin. Metformin use is associated with a decreased risk of breast cancer.
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Metformin significantly reduces incident prostate cancer risk in Taiwanese men with type 2 diabetes mellitus.
Eur. J. Cancer
PUBLISHED: 03-24-2014
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Whether metformin therapy affects incident prostate cancer risk in Asian patients with type 2 diabetes mellitus (T2DM) has not been investigated.
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A review on thiazolidinediones and bladder cancer in human studies.
J Environ Sci Health C Environ Carcinog Ecotoxicol Rev
PUBLISHED: 03-07-2014
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There is a concern of an increased risk of bladder cancer associated with the use of thiazolidinediones, a class of oral glucose-lowering drugs commonly used in patients with type 2 diabetes with a mechanism of improving insulin resistance. Human studies on related issues are reviewed, followed by a discussion on potential concerns on the causal inference in current studies. Pioglitazone and rosiglitazone are discussed separately, and findings from different geographical regions are presented. Randomized controlled trials designed for primarily answering such a cancer link are lacking, and evidence from clinical trials with available data for evaluating the association may not be informative. Observational studies have been reported with the use of population-based administrative databases, single-hospital records, drug adverse event reporting system, and case series collection. Meta-analysis has also been performed by six different groups of investigators. These studies showed a signal of higher risk of bladder cancer associated with pioglitazone, especially at a higher cumulative dose or after prolonged exposure; however, a weaker signal or null association is observed with rosiglitazone. In addition, there are some concerns on the causal inference, which may be related to the use of secondary databases, biases in sampling, differential detection, and confounding by indications. Lack of full control of smoking and potential biases related to study designs and statistical approaches such as prevalent user bias and immortal time bias may be major limitations in some studies. Overlapping populations and opposing conclusions in studies using the same databases may be of concern and weaken the reported conclusions of the studies. Because randomized controlled trials are expensive and unethical in providing an answer to this cancer issue, observational studies are expected to be the main source in providing an answer in the future. Furthermore, international comparison studies using well-designed and uniform methodology to clarify the risk in specific sexes, ethnicities, and other subgroups and to evaluate the interaction with other environmental risk factors or medications will be helpful to identify patients at risk.
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Diabetes and gastric cancer: the potential links.
World J. Gastroenterol.
PUBLISHED: 03-04-2014
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This article reviews the epidemiological evidence linking diabetes and gastric cancer and discusses some of the potential mechanisms, confounders and biases in the evaluation of such an association. Findings from four meta-analyses published from 2011 to 2013 suggest a positive link, which may be more remarkable in females and in the Asian populations. Putative mechanisms may involve shared risk factors, hyperglycemia, Helicobacter pylori (H. pylori) infection, high salt intake, medications and comorbidities. Diabetes may increase the risk of gastric cancer through shared risk factors including obesity, insulin resistance, hyperinsulinemia and smoking. Hyperglycemia, even before the clinical diagnosis of diabetes, may predict gastric cancer in some epidemiological studies, which is supported by in vitro, and in vivo studies. Patients with diabetes may also have a higher risk of gastric cancer through the higher infection rate, lower eradication rate and higher reinfection rate of H. pylori. High salt intake can act synergistically with H. pylori infection in the induction of gastric cancer. Whether a higher risk of gastric cancer in patients with diabetes may be ascribed to a higher intake of salt due to the loss of taste sensation awaits further investigation. The use of medications such as insulin, metformin, sulfonylureas, aspirin, statins and antibiotics may also influence the risk of gastric cancer, but most of them have not been extensively studied. Comorbidities may affect the development of gastric cancer through the use of medications and changes in lifestyle, dietary intake, and the metabolism of drugs. Finally, a potential detection bias related to gastrointestinal symptoms more commonly seen in patients with diabetes and with multiple comorbidities should be pointed out. Taking into account the inconsistent findings and the potential confounders and detection bias in previous epidemiological studies, it is expected that there are still more to be explored for the clarification of the association between diabetes and gastric cancer.
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Metformin may reduce bladder cancer risk in Taiwanese patients with type 2 diabetes.
Acta Diabetol
PUBLISHED: 01-25-2014
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Whether metformin therapy affects bladder cancer risk in patients with type 2 diabetes mellitus (T2DM) has not been extensively investigated. The reimbursement databases of all Taiwanese patients with a new diagnosis of T2DM between 1998 and 2002 (n = 940,708) were retrieved from the National Health Insurance for follow-up of bladder cancer up to the end of 2009. Metformin was treated as a time-dependent variable, and of these patients, 532,519 were never-users and 408,189 were ever-users of metformin. A time-dependent approach was applied in the calculation of bladder cancer incidence and in the estimation of hazard ratios by Cox regression for ever-users, never-users, and subgroups of metformin exposure (using tertile cutoffs of cumulative duration of therapy and cumulative dose). During the study period, 1,847 (0.45%) metformin ever-users and 6,213 (1.17%) metformin never-users developed bladder cancer, representing an incidence of 72.03 and 189.22 per 100,000 person-years, respectively. The age-sex-adjusted and multivariable-adjusted hazard ratios (95% confidence intervals) for ever- versus never-users were 0.382 (0.360-0.405) and 0.600 (0.564-0.638), respectively. The multivariable-adjusted hazard ratios for the first, second, and third tertiles of cumulative duration of metformin therapy were 1.034 (0.954-1.120), 0.696 (0.632-0.766), and 0.258 (0.229-0.291), respectively (P trend <0.0001). Similarly, the multivariable-adjusted hazard ratios for the first, second, and third tertiles of cumulative dose of metformin were 0.997 (0.920-1.080), 0.615 (0.559-0.677), and 0.285 (0.253-0.321), respectively (P trend <0.0001). This study suggests that metformin use is associated with a decreased risk of bladder cancer in patients with T2DM.
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Painful ophthalmoplegia with normal cranial imaging.
BMC Neurol
PUBLISHED: 01-07-2014
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Painful ophthalmoplegia with normal cranial imaging is rare and confined to limited etiologies. In this study, we aimed to elucidate these causes by evaluating clinical presentations and treatment responses.
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Metformin reduces thyroid cancer risk in taiwanese patients with type 2 diabetes.
PLoS ONE
PUBLISHED: 01-01-2014
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Whether metformin may affect thyroid cancer risk has not been studied. This study investigated the association between metformin use and thyroid cancer risk in Taiwanese patients with type 2 diabetes mellitus.
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Diabetes but not insulin increases the risk of lung cancer: a Taiwanese population-based study.
PLoS ONE
PUBLISHED: 01-01-2014
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The trend of lung cancer incidence in Taiwan is unknown, and the association between type 2 diabetes/insulin use and lung cancer is rarely studied.
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Distinct structural features of the peroxide response regulator from group a streptococcus drive DNA binding.
PLoS ONE
PUBLISHED: 01-01-2014
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Group A streptococcus (GAS, Streptococcus pyogenes) is a strict human pathogen that causes severe, invasive diseases. GAS does not produce catalase, but has an ability to resist killing by reactive oxygen species (ROS) through novel mechanisms. The peroxide response regulator (PerR), a member of ferric uptake regulator (Fur) family, plays a key role for GAS to cope with oxidative stress by regulating the expression of multiple genes. Our previous studies have found that expression of an iron-binding protein, Dpr, is under the direct control of PerR. To elucidate the molecular interactions of PerR with its cognate promoter, we have carried out structural studies on PerR and PerR-DNA complex. By combining crystallography and small-angle X-ray scattering (SAXS), we confirmed that the determined PerR crystal structure reflects its conformation in solution. Through mutagenesis and biochemical analysis, we have identified DNA-binding residues suggesting that PerR binds to the dpr promoter at the per box through a winged-helix motif. Furthermore, we have performed SAXS analysis and resolved the molecular architecture of PerR-DNA complex, in which two 30 bp DNA fragments wrap around two PerR homodimers by interacting with the adjacent positively-charged winged-helix motifs. Overall, we provide structural insights into molecular recognition of DNA by PerR and define the hollow structural arrangement of PerR-30bpDNA complex, which displays a unique topology distinct from currently proposed DNA-binding models for Fur family regulators.
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Human insulin does not increase bladder cancer risk.
PLoS ONE
PUBLISHED: 01-01-2014
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Whether human insulin can induce bladder cancer is rarely studied.
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Does medication adherence lead to lower healthcare expenses for patients with diabetes?
Am J Manag Care
PUBLISHED: 12-06-2013
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To examine the relationship between medication adherence and healthcare outcomes and expenses and to investigate whether the duration of type 2 diabetes mellitus (T2DM) has a role in the aforementioned relationship.
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Rosiglitazone may reduce thyroid cancer risk in patients with type 2 diabetes.
Ann. Med.
PUBLISHED: 11-12-2013
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Whether rosiglitazone use in patients with type 2 diabetes may affect thyroid cancer risk has not been investigated.
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Diabetes, insulin use, and gastric cancer: a population-based analysis of the Taiwanese.
J. Clin. Gastroenterol.
PUBLISHED: 10-29-2013
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The association between diabetes and gastric cancer is rarely studied, and the risk associated with insulin use is not known.
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Postprandial blood glucose is associated with generalized pruritus in patients with type 2 diabetes.
Eur J Dermatol
PUBLISHED: 09-05-2013
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Although pruritus is a common complaint in patients with diabetes, little is known about its relation with glycemic control. Objectives: We investigated whether generalized pruritus is associated with glycemic control in patients with type 2 diabetes. A total of 385 patients with type 2 diabetes who attended the diabetes care system underwent cutaneous examination by a dermatologist at a teaching hospital in Taiwan. A detailed interview questionnaire including visual analogue scale was used to assess various characteristics and the intensity of pruritus. Multivariate logistic regression was used to assess the association between postprandial blood glucose, preprandial blood glucose, and glycosylated hemoglobin with generalized pruritus. Generalized pruritus was noted in 27.5% of the patients. As a result of pruritus, 24.5% of the patients had difficulties in falling asleep, 15.1% had disturbance of sleep, and 9.5% needed soporifics. Patients who had a higher postprandial glucose level had a higher probability of having generalized pruritus [OR?=?1.41 (95% C.I.: 1.05-1.90), P?=?0.02] in type 2 diabetic patients. This study showed positive associations between postprandial blood glucose and generalized pruritus and suggested that a better control of postprandial glucose might be beneficial to relieve generalized pruritus in diabetic patients.
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The role of triglyceride in cardiovascular disease in asian patients with type 2 diabetes - a systematic review.
Rev Diabet Stud
PUBLISHED: 08-10-2013
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In Asian populations, diabetes mellitus is increasing and has become an important health problem in recent decades. Cardiovascular disease (CVD) is one of the most important complications and the most common cause of death in diabetic patients. Among the risk factors of CVD, elevated low-density lipoprotein cholesterol has been a major concern. Studies suggested that serum triglyceride may also play a role in predicting CVD in patients with type 2 diabetes mellitus, but the association is still debated. In this review, we summarized published studies focusing on the relationship between serum triglyceride and CVD disease in Asian diabetic patients. Ten studies conducted in six different Asian countries (three from Hong Kong, two from Taiwan, tow from Japan, one from Indonesia, one from South India, and one from South Korea) were summarized and discussed. CVD was subdivided into coronary heart disease, stroke, and peripheral arterial disease. Of the ten studies analyzed, one focused on CVD, five on coronary heart disease, three on stroke, three on peripheral arterial disease, and one on mortality from CVD. Studies from Hong Kong, Taiwan, and Japan suggested that triglyceride is a significant and independent risk factor for coronary heart disease, but not a significant risk factor for stroke (studies conducted in Japan and South Korea) or peripheral arterial disease (studies conducted in Taiwan, Indonesia, and South India). Although serum triglyceride may be a significant risk factor for coronary heart disease in Asian diabetic patients, clinical trials evaluating whether lowering triglycerides using fibrates can reduce the risk of coronary heart disease in these patients need to be initiated.
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Dyslipidemia, kidney disease, and cardiovascular disease in diabetic patients.
Rev Diabet Stud
PUBLISHED: 08-10-2013
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This article reviews the relationship between dyslipidemia, chronic kidney disease, and cardiovascular diseases in patients with diabetes. Diabetes mellitus is associated with complications in the cardiovascular and renal system, and is increasing in prevalence worldwide. Modification of the multifactorial risk factors, in particular dyslipidemia, has been suggested to reduce the rates of diabetes-related complications. Dyslipidemia in diabetes is a condition that includes hypertriglyceridemia, low high-density lipoprotein levels, and increased small and dense low-density lipoprotein particles. This condition is associated with higher cardiovascular risk and mortality in diabetic patients. Current treatment guidelines focus on lowering the low-density lipoprotein cholesterol level; multiple trials have confirmed the cardiovascular benefits of treatment with statins. Chronic kidney disease also contributes to dyslipidemia, and dyslipidemia in turn is related to the occurrence and progression of diabetic nephropathy. Different patterns of dyslipidemia are associated with different stages of diabetic nephropathy. Some trials have shown that treatment with statins not only decreased the risk of cardiovascular events, but also delayed the progression of diabetic nephropathy. However, studies using statins as the sole treatment of hyperlipidemia in patients on dialysis have not shown benefits with respect to cardiovascular risk. Diabetic patients with nephropathy have a higher risk of cardiovascular events than those without nephropathy. The degree of albuminuria and the reduction in estimated glomerular filtration rate are also correlated with the risk of cardiovascular events. Treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to reduce albuminuria in diabetic patients has been shown to decrease the risk of cardiovascular morbidity and mortality.
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Pioglitazone and oral cancer risk in patients with type 2 diabetes.
Oral Oncol.
PUBLISHED: 07-31-2013
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Pioglitazone has shown an inhibitory effect on the growth of cell lines derived from human salivary gland and human oral squamous cell carcinoma. However, whether this effect can be applied to patients with type 2 diabetes mellitus who use pioglitazone for glycemic control remains unanswered.
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New-onset diabetes with a history of dyslipidemia predicts pancreatic cancer.
Pancreas
PUBLISHED: 05-31-2013
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This study aimed to investigate whether the reported relationship between diabetes and pancreatic cancer (PC) could result from detection bias and whether dyslipidemia and/or new-onset diabetes (diagnosed within 1 year) could predict PC.
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Human Insulin Does Not Increase Prostate Cancer Risk in Taiwanese.
Clin Genitourin Cancer
PUBLISHED: 05-29-2013
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Whether human insulin can increase the risk of prostate cancer is rarely studied.
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Pioglitazone does not affect the risk of ovarian cancer: analysis of a nationwide reimbursement database in Taiwan.
Gynecol. Oncol.
PUBLISHED: 04-30-2013
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The association between pioglitazone and ovarian cancer has not been studied.
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Continuity of care, medication adherence, and health care outcomes among patients with newly diagnosed type 2 diabetes: a longitudinal analysis.
Med Care
PUBLISHED: 04-09-2013
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The effects of continuity of care (COC) on health care outcomes are well established. However, the mechanism of this association is not fully understood.
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Aryl hydrocarbon receptor controls murine mast cell homeostasis.
Blood
PUBLISHED: 03-05-2013
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We propose that the aryl hydrocarbon receptor (AhR), a unique chemical sensor, is critical in controlling mast cell differentiation, growth, and function in vitro and in vivo. In antigen-stimulated mast cells, exposure to AhR ligands resulted in a calcium- and reactive oxygen species (ROS)-dependent increase of reversible oxidation in and reduced activity of SHP-2 phosphatase, leading to enhanced mast cell signaling, degranulation, and mediator and cytokine release, as well as the in vivo anaphylactic response. Surprisingly, significant mast cell deficiency was noted in AhR-null mice due to defective calcium signaling and mitochondrial function, concomitant with reduced expression of c-kit and cytosolic STAT proteins, as well as enhanced intracellular ROS and apoptosis. Consequently, AhR-null mast cells responded poorly to stimulation, demonstrating a critical role of AhR signaling in maintaining mast cell homeostasis.
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Insulin use and smoking jointly increase the risk of bladder cancer mortality in patients with type 2 diabetes.
Clin Genitourin Cancer
PUBLISHED: 02-26-2013
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Whether insulin use predicts bladder cancer mortality has not been investigated. Furthermore, it is not known whether insulin use and smoking jointly influence the risk.
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Rosiglitazone is not associated with an increased risk of bladder cancer.
Cancer Epidemiol
PUBLISHED: 02-06-2013
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Whether rosiglitazone may increase bladder cancer risk has not been extensively investigated.
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Choroidal thickness and biometric markers for the screening of lacquer cracks in patients with high myopia.
PLoS ONE
PUBLISHED: 01-22-2013
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Validation of choroidal thickness and other biometrics measured by spectral domain optical coherence tomography (SD-OCT) in predicting lacquer cracks formation in highly myopic eyes.
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Higher risk of mortality from lung cancer in Taiwanese people with diabetes.
Diabetes Res. Clin. Pract.
PUBLISHED: 01-17-2013
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The association between diabetes and lung cancer is rarely studied in the Asian populations. This study investigated lung cancer mortality trends, mortality rate ratios between people with diabetes and the general population, and associated risk factors in people with diabetes in Taiwan.
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Diabetes is not an independent risk factor for hepatocellular carcinoma.
Diabetes Metab. Res. Rev.
PUBLISHED: 01-16-2013
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It is controversial whether diabetes is a risk factor for hepatocellular carcinoma (HCC) in countries with high prevalence of viral hepatitis such as Taiwan.
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Diabetes, insulin use, smoking, and pancreatic cancer mortality in Taiwan.
Acta Diabetol
PUBLISHED: 01-10-2013
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The aim of the study was to evaluate the link between diabetes and pancreatic cancer (PC) mortality and the joint effect of smoking and insulin use on PC mortality. A total of 39,988 men and 46,909 women with type 2 diabetes, aged ?25 years and recruited in 1995-1998, were followed to 2006 for PC mortality. Age-sex-specific mortality rate ratios for diabetic patients versus the general population were calculated. Cox regression was used to evaluate hazard ratios for PC mortality for covariates including age, sex, diabetes duration, body mass index, smoking, insulin use, and area of residence. The interaction and joint effect of smoking and insulin use were also evaluated. A total of 89 men and 63 women died of PC. The mortality rate ratios (95 % CI) showed a significantly higher risk in diabetic patients with a magnitude most remarkable at the youngest age: 1.51 (1.15, 1.98), 2.02 (1.35, 3.03), and 8.36 (5.39, 12.98) for ?65, 55-64, and 25-54 years old, respectively, for men; and 1.16 (0.84, 1.59), 2.12 (1.39, 3.23) and 3.33 (1.14, 9.68), respectively, for women. In multivariable Cox regression analysis, only age was significantly predictive for PC mortality. Although smoking and insulin use might be associated with a 50 % higher risk when analyzed as individual risk factors, they did not reach statistical significance. The interaction term of smoking and insulin use was also not statistically significant in additional modeling. However, smoking and insulin use jointly increased the risk with an adjusted hazard ratio (95 % CI) of 3.04 (1.37, 6.73) when compared to patients who did not smoke and did not use insulin. Diabetic patients have a significantly higher risk of PC mortality. In patients with type 2 diabetes, smoking and insulin use may jointly increase the risk by threefold.
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Diabetes and thyroid cancer mortality: a 12-year prospective follow-up of Taiwanese.
Eur. J. Clin. Invest.
PUBLISHED: 01-09-2013
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The association between diabetes and thyroid cancer is rarely studied. This study evaluated thyroid cancer mortality trend in Taiwanese population, mortality rate ratios between diabetic patients and general population, and risk factors in diabetic patients.
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Benign prostatic hyperplasia is a significant risk factor for bladder cancer in diabetic patients: a population-based cohort study using the National Health Insurance in Taiwan.
BMC Cancer
PUBLISHED: 01-02-2013
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Diabetic patients have a higher risk of bladder cancer and benign prostatic hyperplasia (BPH). Theoretically, BPH patients may have an increased risk of bladder cancer because residual urine in the bladder surely increases the contact time between urinary excreted carcinogens and the urothelium. However, whether BPH increases bladder cancer risk in patients with type 2 diabetes has not been studied.
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Pioglitazone and bladder cancer: a population-based study of Taiwanese.
Diabetes Care
PUBLISHED: 12-30-2011
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The association between pioglitazone and bladder cancer has not been investigated in Asians. We aimed to investigate this association.
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Cytoskeleton network and cellular migration modulated by nuclear-localized receptor tyrosine kinase ROR1.
Anticancer Res.
PUBLISHED: 12-27-2011
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Biological functions of receptor tyrosine kinase-like orphan receptor 1 (ROR1) remain to be elucidated due to the lack of identified genuine ligands. Previously, transiently expressed ROR1 was unexpectedly found to exhibit nuclear localization, the functions of which are unknown.
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Enhancement of focused ultrasound with microbubbles on the treatments of anticancer nanodrug in mouse tumors.
Nanomedicine
PUBLISHED: 06-01-2011
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Ultrasound sonication with microbubbles (MBs) has the potential to enhance the delivery of nanoparticles into the sonicated tumors. In this study, we investigated the feasibility of focused ultrasound (FUS) sonication with MBs to improve nanodrug delivery and tumor treatment. Tumor-bearing mice were first injected with MBs (SonoVue) intravenously, were then sonicated at the tumors with FUS sonication, and were finally injected with the PEGylated liposomal doxorubicin (DOX). The accumulation of DOX in tumors with time, the tumor growth responses for initial treated tumor size and DOX dosage, and the response for an additional sonication after DOX injection were studied. The results demonstrate that FUS sonication with MBs can significantly enhance DOX accumulation in the sonicated tumor at 24 hours after treatment. A significant hindrance to tumor growth is achieved for a small tumor with a low dose, whereas large tumors require a higher dose.
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Angiotensin-converting enzyme genotype and peripheral arterial disease in diabetic patients.
Exp Diabetes Res
PUBLISHED: 05-31-2011
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We investigated the effect of traditional risk factors (hypertension, dyslipidemia and smoking) on the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and peripheral arterial disease (PAD) in 945 (454 men and 491 women) Taiwanese type 2 diabetic patients with a mean age of 63.5 (SD: 11.4) years. Among them, 81 (31 men and 50 women) had PAD (ankle-brachial index <0.9). The adjusted odds ratios (95% confidence intervals) were 2.48 (1.18-5.21), 1.69 (1.00-2.85) and 1.64 (1.12-2.39), respectively, for recessive (DD versus II + ID), dominant (DD + ID versus II) and additive (II = 0, ID = 1 and DD = 2) models. While analyzing the interaction between DD and the individual risk factor of hypertension, smoking and dyslipidemia, patients with the risk factor and with DD had the highest risk compared to referent patients without the risk factor and with II/ID. The respective adjusted odds ratios were 5.41 (2.05-14.31), 7.38 (1.87-29.06) and 4.64 (1.70-12.64). We did not find a significant interaction between DD and any of the risk factors under multiplicative or additive scale. In conclusion, traditional risk factors (hypertension, smoking and dyslipidemia) play an important role in the association between ACE genotypes and PAD. Patients with DD genotype and traditional risk factors are at the highest risk.
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Uric acid level as a risk marker for metabolic syndrome: a Chinese cohort study.
Atherosclerosis
PUBLISHED: 04-22-2011
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Despite some epidemiologic research demonstrating a positive relationship between serum uric acid (SUA) levels and the prevalence of metabolic syndrome (MetS), prospective data on SUA as a predictor of MetS incidence are limited.
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Factors that influence acceptance of web-based e-learning systems for the in-service education of junior high school teachers in Taiwan.
Eval Program Plann
PUBLISHED: 02-01-2011
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Web-based e-learning is not restricted by time or place and can provide teachers with a learning environment that is flexible and convenient, enabling them to efficiently learn, quickly develop their professional expertise, and advance professionally. Many research reports on web-based e-learning have neglected the role of the teachers perspective in the acceptance of using web-based e-learning systems for in-service education. We distributed questionnaires to 402 junior high school teachers in central Taiwan. This study used the Technology Acceptance Model (TAM) as our theoretical foundation and employed the Structure Equation Model (SEM) to examine factors that influenced intentions to use in-service training conducted through web-based e-learning. The results showed that motivation to use and Internet self-efficacy were significantly positively associated with behavioral intentions regarding the use of web-based e-learning for in-service training through the factors of perceived usefulness and perceived ease of use. The factor of computer anxiety had a significantly negative effect on behavioral intentions toward web-based e-learning in-service training through the factor of perceived ease of use. Perceived usefulness and motivation to use were the primary reasons for the acceptance by junior high school teachers of web-based e-learning systems for in-service training.
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Prostate cancer mortality in Taiwanese men: increasing age-standardized trend in general population and increased risk in diabetic men.
Ann. Med.
PUBLISHED: 02-01-2011
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To evaluate the trend of prostate cancer mortality in Taiwanese general population and the association between diabetes and prostate cancer mortality.
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Diabetes and risk of prostate cancer: a study using the National Health Insurance.
Diabetes Care
PUBLISHED: 01-27-2011
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The link between diabetes and prostate cancer is rarely studied in Asians.
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Diabetes conveys a higher risk of gastric cancer mortality despite an age-standardised decreasing trend in the general population in Taiwan.
Gut
PUBLISHED: 12-30-2010
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The association between diabetes and gastric cancer has been rarely studied.
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Clinical features of heart failure hospitalization in younger and elderly patients in Taiwan.
Eur. J. Clin. Invest.
PUBLISHED: 12-15-2010
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? This study compared the comorbidities, drugs, expenses and in-hospital mortality between younger and elderly patients hospitalized with heart failure.
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Betel nut chewing and subclinical ischemic heart disease in diabetic patients.
Cardiol Res Pract
PUBLISHED: 08-17-2010
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Background. This study investigated the association between betel nut chewing and subclinical ischemic heart disease (IHD) in Taiwanese type 2 diabetic patients. Methods. A total of 394 male patients aging ?45 years and without previous heart disease were studied. Among them 349 had no habit of chewing betel nut and 45 possessed the habit for ?5 years. Subclinical IHD was diagnosed by a Minnesota-coded resting electrocardiogram and was present in 71 cases. Statistical analyses were performed considering confounding effects of age, diabetic duration, smoking, body mass index, blood pressure, dyslipidemia, and metabolic control status. Results. Betel nut chewers were younger and had higher prevalence of smoking (86.7% versus 60.5%), higher body mass index, poorer glycemic control, and higher prevalence of subclinical IHD (28.9% versus 16.6%). Patients with subclinical IHD were older and had higher prevalence of betel nut chewing (18.0% versus 9.9%). The multivariate-adjusted odds ratio for subclinical IHD for chewers versus nonchewers was 4.640 (1.958-10.999). The adjusted odds ratios in younger or older patients divided by the median age of 63 years were similar: 4.724 (1.346-16.581) and 4.666 (1.278-17.028), respectively. Conclusions. Betel nut chewing is significantly associated with increased risk of subclinical IHD.
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Betel nut chewing and incidence of newly diagnosed type 2 diabetes mellitus in Taiwan.
BMC Res Notes
PUBLISHED: 08-09-2010
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Betel nut chewing is associated with type 2 diabetes mellitus (T2DM) in a recent prevalence study in Taiwan. The present study further investigated its link with the incidence of newly diagnosed T2DM during the years 1992-1996.
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Nuclear localization of orphan receptor protein kinase (Ror1) is mediated through the juxtamembrane domain.
BMC Cell Biol.
PUBLISHED: 06-30-2010
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Several receptor tyrosine kinases (RTKs) such as EGFR, FGFR, TRK, and VEGFR are capable of localizing in the cell nucleus in addition to their usual plasma membrane localization. Recent reports also demonstrate that nuclear-localized RTKs have important cellular functions such as transcriptional activation. On the basis of preliminary bioinformatic analysis, additional RTKs, including receptor tyrosine kinase-like orphan receptor 1 (Ror1) were predicted to have the potential for nuclear subcellular localization. Ror1 is a receptor protein tyrosine kinase that modulates neurite growth in the central nervous system. Because the nuclear localization capability of the Ror1 cytoplasmic domain has not been reported, we examined the cellular expression distribution of this region.
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Gender differences in trends in diabetes prevalence from 1993 to 2008 in Taiwan.
Diabetes Res. Clin. Pract.
PUBLISHED: 06-15-2010
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We examined time trends in the prevalence of diabetes using nationally representative samples, with a focus on gender differences. Data were from the Nutrition and Health Survey in Taiwan (NAHSIT), 1993-1996 (n = 2700), and NAHSIT 2004-2008 (n = 2258). Participants aged 19 years or older with adequate fasting glucose data were included. When needed, rates were standardized to the year 2000 WHO 5-year interval population for comparisons. The prevalence increased significantly in men, whose standardized rate increased from 4.6% to 9.3%. In women, the age standardized prevalence decreased slightly from 7.9% to 6.4%. High triglycerides (? 150 mg/dL) was associated with diabetes with odds ratios (OR) of 2.14, and 2.69 (all with p<0.05) in the two surveys. High waist circumference (men ? 90 cm; women ? 80 cm) was also associated with diabetes with ORs of 2.52, and 1.93 (all with p < 0.05). We recommend the development of innovative health promotion programs targeting not only the general population, but also high risk groups such as men, to further reduce diabetes.
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A population study on the association between leisure time physical activity and self-rated health among diabetics in Taiwan.
BMC Public Health
PUBLISHED: 05-26-2010
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There is strong evidence for the beneficial effects of physical activity in diabetes. There has been little research demonstrating a dose-response relationship between physical activity and self-rated health in diabetics. The aim of this study was to explore the dose-response association between leisure time physical activity and self-rated health among diabetics in Taiwan.
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Thyroid segmentation and volume estimation in ultrasound images.
IEEE Trans Biomed Eng
PUBLISHED: 02-17-2010
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Physicians usually diagnose the pathology of the thyroid gland by its volume. However, even if the thyroid glands are found and the shapes are hand-marked from ultrasound (US) images, most physicians still depend on computed tomography (CT) images, which are expensive to obtain, for precise measurements of the volume of the thyroid gland. This approach relies heavily on the experience of the physicians and is very time consuming. Patients are exposed to high radiation when obtaining CT images. In contrast, US imaging does not require ionizing radiation and is relatively inexpensive. US imaging is thus one of the most commonly used auxiliary tools in clinical diagnosis. The present study proposes a complete solution to estimate the volume of the thyroid gland directly from US images. The radial basis function neural network is used to classify blocks of the thyroid gland. The integral region is acquired by applying a specific-region-growing method to potential points of interest. The parameters for evaluating the thyroid volume are estimated using a particle swarm optimization algorithm. Experimental results of the thyroid region segmentation and volume estimation in US images show that the proposed approach is very promising.
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Metabolic syndrome components worsen lower urinary tract symptoms in women with type 2 diabetes.
J. Clin. Endocrinol. Metab.
PUBLISHED: 01-26-2010
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Context: Diabetic women are more susceptible to develop lower urinary tract symptoms (LUTS), especially overactive bladder (OAB). However, data regarding the effect of components of metabolic syndrome (MS) on this association are conflicting. Objective: The objective of the study was to examine the potential role of MS in the development of LUTS in diabetic women. Design: The study was a prevalence study conducted between 2005 and 2007. Setting: The study was conducted in a university hospital. Participants: A total of 518 women with type 2 diabetes aged 50-75 yr were included. They were subgrouped as MS (47.5%) and non-MS (52.5%) groups according to whether they fulfilled the criteria of MS. Main Outcome Measure: We used American Urological Association Symptom Index (AUA-SI) to evaluate LUTS and Indevus Urgency Severity Scale to evaluate OAB, respectively. Results: Women in the MS group had significantly higher storage and total AUA-SI scores as well as a higher prevalence of LUTS and OAB. Most intriguingly, the number of MS components was strongly associated with the LUTS severity because the AUA-SI scores increased in parallel to the number of components were present. Similar results were found between MS and OAB. Multivariate analysis revealed that peripheral neuropathy, but not MS, significantly predicted LUTS in diabetic women after age adjustment. However, MS remained significantly predictive for LUTS and OAB after additional adjustment for neuropathy. Conclusions: Our results suggest that MS may especially influence LUTS and OAB in diabetic women, probably by compounding the effect of peripheral neuropathy.
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Joint effects of hypertension, smoking, dyslipidemia and obesity and angiotensin-converting enzyme DD genotype on albuminuria in Taiwanese patients with type 2 diabetes mellitus.
Clin. Biochem.
PUBLISHED: 01-13-2010
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We investigated the individual and joint effects of hypertension, smoking, dyslipidemia, and obesity and angiotensin-converting enzyme (ACE) DD genotype on albuminuria in Taiwanese type 2 diabetic patients.
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Association of C-reactive protein and hyperuricemia with diabetic nephropathy in Chinese type 2 diabetic patients.
Acta Diabetol
PUBLISHED: 07-30-2009
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To investigate the relationship of micro-albuminuria with C-reactive protein (CRP) and hyperuricemia in Chinese patients with type 2 diabetes. All patients with type 2 diabetes, 40 years old and over were recruited consecutively from diabetic clinics at a medical center. Serum lipid, creatinine, uric acid, CRP, HbA(1C) and urinary albumin concentration were measured. A total of 515 patients, aged 60.3 +/- 10.7 years were recruited and the number (rate) of micro- and macro-albuminuria were 109 (21.2%) and 55 (10.7%). The prevalence of micro-albuminuria for the quartiles of CRP levels demonstrated a meaningful trend of increases between groups from 17.4, 21.1, 30.3, and 31.2% (P trend = 0.002). Besides, the median CRP concentrations was significantly higher in the patients with micro- and macro-albuminuria than those with non-albuminuria. Stepwise logistic regression analysis revealed that CRP was significantly associated with abnormal albuminuria (OR = 1.36, 95% CI = 1.12-1.64, P = 0.002). After excluding those subjects with angiotensin-converting enzyme inhibitors/angiotension II receptor blockers or/and statin usage, the observed relationship between serum CRP levels and albuminuria was still persistent (OR = 1.61, 95% CI = 1.24-2.08, P < 0.001). In addition, hyperuricemia were significantly associated with abnormal albuminuria in the patients without diuretics, uricosuric agents or alcohol usage. Both serum CRP levels and hyperuricemia were significantly related to the presence of albuminuria in patients with diabetes. In addition, Chinese type 2 diabetic patients with serum CRP levels in the lower range as other ethnic groups can lead to the development of micro-albuminuria.
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Optimal anthropometric factor cutoffs for hyperglycemia, hypertension and dyslipidemia for the Taiwanese population.
Atherosclerosis
PUBLISHED: 05-30-2009
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Optimal cutoffs for obesity indices are rarely studied in Asians. We evaluated these cutoffs for diabetes, hypertension, dyslipidemia and any risk factor for the Taiwanese general population.
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Bioactivity-guided screening identifies pheophytin a as a potent anti-hepatitis C virus compound from Lonicera hypoglauca Miq.
Biochem. Biophys. Res. Commun.
PUBLISHED: 04-26-2009
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Chronic hepatitis C virus (HCV) infection is a worldwide public issue. In this study, we performed bioactivity-guided screening of the Lonicera hypoglauca Miq. crude extracts to find for naturally chemical entities with anti-HCV activity. Pheophytin a was identified from the ethanol-soluble fraction of L. hypoglauca that elicited dose-dependent inhibition of HCV viral proteins and RNA expression in both replicon cells and cell culture infectious system. Computational modeling revealed that pheophytin a can bind to the active site of HCV-NS3, suggesting that NS3 is a potent molecular target of pheophytin a. Biochemical analysis further revealed that pheophytin a inhibited NS3 serine protease activity with IC(50)=0.89 microM. Notably, pheophytin a and IFNalpha-2a elicited synergistic anti-HCV activity in replicon cells with no significant cytotoxicity. This study thereby demonstrates for the first time that pheophytin a is a potent HCV-NS3 protease inhibitor and offers insight for development of novel anti-HCV regimens.
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Differential dyslipidemia associated with albuminuria in type 2 diabetic patients in Taiwan.
Clin. Biochem.
PUBLISHED: 03-07-2009
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This study evaluated the lipid abnormalities associated with different stages of albuminuria in type 2 diabetic patients.
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Age-related risk of mortality from bladder cancer in diabetic patients: a 12-year follow-up of a national cohort in Taiwan.
Ann. Med.
PUBLISHED: 02-05-2009
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To compare bladder cancer mortality between diabetic patients and the general population.
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A review on environmental factors regulating arsenic methylation in humans.
Toxicol. Appl. Pharmacol.
PUBLISHED: 01-27-2009
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Subjects exposed to arsenic show significant inter-individual variation in urinary patterns of arsenic metabolites but insignificant day-to-day intra-individual variation. The inter-individual variation in arsenic methylation can be partly responsible for the variation in susceptibility to arsenic toxicity. Wide inter-ethnic variation and family correlation in urinary arsenic profile suggest a genetic effect on arsenic metabolism. In this paper the environmental factors affecting arsenic metabolism are reviewed. Methylation capacity might reduce with increasing dosage of arsenic exposure. Furthermore, women, especially at pregnancy, have better methylation capacity than their men counterparts, probably due to the effect of estrogen. Children might have better methylation capacity than adults and age shows inconsistent relevance in adults. Smoking and alcohol consumption might be associated with a poorer methylation capacity. Nutritional status is important in the methylation capacity and folate may facilitate the methylation and excretion of arsenic. Besides, general health conditions and medications might influence the arsenic methylation capacity; and technical problems can cause biased estimates. The consumption of seafood, seaweed, rice and other food with high arsenic contents and the extent of cooking and arsenic-containing water used in food preparation may also interfere with the presentation of the urinary arsenic profile. Future studies are necessary to clarify the effects of the various arsenic metabolites including the trivalent methylated forms on the development of arsenic-induced human diseases with the consideration of the effects of confounding factors and the interactions with other effect modifiers.
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A protozoan parasite extraction scheme for digital microscopic images.
Comput Med Imaging Graph
PUBLISHED: 01-05-2009
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Pathogenic protozoan parasites can cause human to get many diseases, such as, amoebiasis, typhoid fever and cholera, etc. Different protozoan parasites vary greatly in their structural and biochemical properties. Digital images are extensively applied to medical fields for doctors and pathologists to analyze pathological sections and further diagnose diseases. The aim of this paper is to develop protozoan parasite extraction techniques to segment protozoan parasites from microscopic images. The proposed scheme has precise segmentation ability even if the image is with poor quality or complex background. Experimental results show that the proposed scheme can gain 96.64% average correct rate, and about 0.04, 0.45 and 0.06 of the average error rates: misclassification error (ME), region non-uniformity (RN) and relative foreground area error (RFAE), respectively.
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Thyroid cancer risk is not increased in diabetic patients.
PLoS ONE
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This study evaluated thyroid cancer risk with regards to diabetes status and diabetes duration, and with the use of anti-diabetic drugs including sulfonylurea, metformin, insulin, acarbose, pioglitazone and rosiglitazone, by using a population-based reimbursement database in Taiwan.
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Peroxisome proliferator-activated receptor agonists and bladder cancer: lessons from animal studies.
J Environ Sci Health C Environ Carcinog Ecotoxicol Rev
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This article reviews available animal studies on the possible link between the use of peroxisome proliferator-activated receptor (PPAR) agonists and bladder cancer, with further discussion on the possible implications to humans. Carcinogenicity studies suggest that the PPAR? agonist pioglitazone and dual PPAR?/? agonists such as ragaglitazar, muraglitazar, and naveglitazar may increase the risk of bladder cancer in a dose-responsive pattern in rats. It is interesting that bladder cancer related to PPAR agonists shows remarkable species- and sex-specificity and has a predilection to occur in the ventral dome of bladder in rodents. While male rats treated with pioglitazone or muraglitazar have a higher propensity to develop bladder cancer than female rats, mice of both sexes do not develop bladder cancer even when exposed to very high doses. Direct genotoxicity or cytotoxicity of PPAR agonists is unlikely to be the mode of action because most of the parent compounds or their metabolites of the PPAR agonists are neither mutagenic nor genotoxic, and they are rarely excreted in the urine; but a receptor-mediated PPAR effect cannot be excluded. Some suggest a "urolithiasis hypothesis" referring to the formation of urinary solids and calculi, which subsequently causes bladder necrosis, regenerative proliferation, hypertrophy, and cancer. However, whether these animal findings could have human relevance is not yet fully understood. Some argue that the urolithiasis-induced bladder cancer might be rat-specific and would probably not be applicable to humans. An effect of increased urinary growth factors induced by PPAR agonists has also been proposed, but this requires more investigations. Before fully clarified, a balance between the risks and benefits of the use of pioglitazone, an approved oral antidiabetic agent that has recently been linked to an increased but not yet confirmed risk of bladder cancer in humans, should be justified for individual use.
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Obesity paradox: differential effects on cancer and noncancer mortality in patients with type 2 diabetes mellitus.
Atherosclerosis
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To investigate associations between body mass index (BMI) and cause-specific mortality in patients with type 2 diabetes mellitus (T2DM).
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Diabetes but not insulin is associated with higher colon cancer mortality.
World J. Gastroenterol.
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To evaluate whether diabetic patients had a higher risk of colon cancer mortality and its associated risk factors.
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Oral cancer in Taiwan: is diabetes a risk factor?
Clin Oral Investig
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The association between diabetes and oral cancer is rarely studied. We investigated the trends of oral cancer in the Taiwanese general population and the possible link with diabetes.
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Evaluation of the association between arsenic and diabetes: a National Toxicology Program workshop review.
Environ. Health Perspect.
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Diabetes affects an estimated 346 million persons globally, and total deaths from diabetes are projected to increase > 50% in the next decade. Understanding the role of environmental chemicals in the development or progression of diabetes is an emerging issue in environmental health. In 2011, the National Toxicology Program (NTP) organized a workshop to assess the literature for evidence of associations between certain chemicals, including inorganic arsenic, and diabetes and/or obesity to help develop a focused research agenda. This review is derived from discussions at that workshop.
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Quercetin 3-O-methyl ether protects FL83B cells from copper induced oxidative stress through the PI3K/Akt and MAPK/Erk pathway.
Toxicol. Appl. Pharmacol.
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Quercetin is a bioflavonoid that exhibits several biological functions in vitro and in vivo. Quercetin 3-O-methyl ether (Q3) is a natural product reported to have pharmaceutical activities, including antioxidative and anticancer activities. However, little is known about the mechanism by which it protects cells from oxidative stress. This study was designed to investigate the mechanisms by which Q3 protects against Cu(2+)-induced cytotoxicity. Exposure to Cu(2+) resulted in the death of mouse liver FL83B cells, characterized by apparent apoptotic features, including DNA fragmentation and increased nuclear condensation. Q3 markedly suppressed Cu(2+)-induced apoptosis and mitochondrial dysfunction, characterized by reduced mitochondrial membrane potential, caspase-3 activation, and PARP cleavage, in Cu(2+)-exposed cells. The involvement of PI3K, Akt, Erk, FOXO3A, and Mn-superoxide dismutase (MnSOD) was shown to be critical to the survival of Q3-treated FL83B cells. The liver of both larval and adult zebrafish showed severe damage after exposure to Cu(2+) at a concentration of 5?M. Hepatic damage induced by Cu(2+) was reduced by cotreatment with Q3. Survival of Cu(2+)-exposed larval zebrafish was significantly increased by cotreatment with 15?M Q3. Our results indicated that Cu(2+)-induced apoptosis in FL83B cells occurred via the generation of ROS, upregulation and phosphorylation of Erk, overexpression of 14-3-3, inactivation of Akt, and the downregulation of FOXO3A and MnSOD. Hence, these results also demonstrated that Q3 plays a protective role against oxidative damage in zebrafish liver and remarked the potential of Q3 to be used as an antioxidant for hepatocytes.
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Diabetes and thyroid cancer risk: literature review.
Exp Diabetes Res
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Diabetic patients have a higher risk of various types of cancer. However, whether diabetes may increase the risk of thyroid cancer has not been extensively studied. This paper reviews and summarizes the current literature studying the relationship between diabetes mellitus and thyroid cancer, and the possible mechanisms linking such an association. Epidemiologic studies showed significant or nonsignificant increases in thyroid cancer risk in diabetic women and nonsignificant increase or no change in thyroid cancer risk in diabetic men. A recent pooled analysis, including 5 prospective studies from the USA, showed that the summary hazard ratio (95% confidence interval) for women was 1.19 (0.84-1.69) and was 0.96 (0.65-1.42) for men. Therefore, the results are controversial and the association between diabetes and thyroid cancer is probably weak. Further studies are necessary to confirm their relationship. Proposed mechanisms for such a possible link between diabetes and thyroid cancer include elevated levels of thyroid-stimulating hormone, insulin, glucose and triglycerides, insulin resistance, obesity, vitamin D deficiency, and antidiabetic medications such as insulin or sulfonylureas.
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Diabetes, metformin use, and colon cancer: a population-based cohort study in Taiwan.
Eur. J. Endocrinol.
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A retrospective cohort study, using a population-based reimbursement database, was conducted for investigating the relationship between diabetes and colon cancer and assessing whether metformin had a protective effect.
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