Waking up dormant tumors

As appreciation grows for the contribution of the tumor microenvironment to the progression of cancer, new evidence accumulates to support that the participation of stromal cells can extend beyond the local environment. Recently, Elkabets and colleagues demonstrated a systemic interaction between cancer cells and distant bone marrow cells to support the growth of otherwise indolent tumor cells at a secondary site, raising thought-provoking questions regarding the involvement of stromal cells in maintaining metastatic dormancy.National Institutes of Health (U.S.) (NIH grant CA125550)National Institutes of Health (U.S.) (NIH grant CA155370)National Institutes of Health (U.S.) (NIH grant CA151925)National Institutes of Health (U.S.) (NIH grant DK081576)United States. Dept. of Defense (Breast Cancer Research Program Predoctoral Traineeship Award

Using glycosylated haemoglobin to define the metabolic syndrome in adults in the United States

Introduction: Recently, the American Diabetes Association has proposed the use of glycosylated haemoglobin (GHb) in the definition of diabetes and the category of increased diabetes risk. We therefore investigated whether GHb can be used instead of fasting plasma glucose in identifying individuals with the metabolic syndrome, which is associated with increased risk of cardiovascular diseases. Methods: Participants of the US National Health and Nutrition Examination Survey (NHANES) 1999-2006 who had fasting blood glucose were included (n=3551 in 1999-2002 and n=3412 in 2003-2006). The metabolic syndrome was defined using International Diabetes Federation criteria in 2009. Raised blood glucose was defined either as fasting glucose ≥100 mg/dL (5.6 mmol/L), or as GHb ≥5.7%. Results: In 2003-2006, there was 91.3% agreement between GHb and fasting glucose when either is used to define the metabolic syndrome, although the use of GHb slightly lowered the syndrome’s prevalence (34.8% vs 38.8%, P=0.012). The agreement was good (≥87%) irrespective of age, sex, race/ethnicity and body mass index. Only 2.3% of the sample population had the metabolic syndrome defined using GHb but not using fasting glucose. The syndrome, defined using GHb alone, was associated with cardiovascular diseases (ischaemic heart disease, heart failure or stroke) [OR=1.95, P=0.002]. Similar results were found in 1999-2002. Conclusions: Using GHb instead of fasting glucose to define the metabolic syndrome is feasible. The syndrome defined in this way also identifies individuals with increased cardiovascular risk.published_or_final_versio

Relationship of genetic variants in gene encoding adrenomedullin with hypertension and dysglycaemia in Hong Kong Chinese

published_or_final_versionThe 15th Annual Research Conference of the Department of Medicine, The University of Hong Kong, Hong Kong, 16 January 2010. In Hong Kong Medical Journal, 2010, v. 16, suppl. 1, p. 50, abstract no. 8

Gamma-glutamyl transferase level predicts the development of hypertension in Hong Kong Chinese

Introduction: Liver enzymes are elevated in cardiometabolic diseases, particularly when there is non-alcoholic fatty liver disease. We therefore investigated if hypertension is associated with elevated levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase and γ-glutamyl transferase (GGT). Methods: We included 235 hypertensive and 708 normotensive subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) in 2000-2004 who had fewer than one alcoholic drink a week. In the follow-up study in 2005-2008 (CRISPS-3), 126 out of the 708 subjects had developed hypertension. Results: In CRISPS-2, plasma ALT (OR=1.31 per SD of log-transformed level, P=0.005) and GGT (OR=1.52 per SD of log-transformed level, P<0.001) were significantly associated with prevalent hypertension after adjusting for age, sex and body mass index (BMI). Among subjects not on anti-hypertensive medication, plasma ALP and GGT were significantly associated with both systolic blood pressure (beta=0.141, P<0.001 for ALP and beta=0.096, P=0.004 for GGT) and diastolic blood pressure (beta=0.131, P<0.001 for ALP and beta=0.102, P=0.004 for GGT). In forward stepwise logistic regression analysis of subjects normotensive at CRISPS-2, the highest tertile of plasma GGT level was an independent predictor of the development of hypertension in CRISPS-3 (OR=2.40, P=0.010), together with age, BMI, systolic blood pressure and plasma CRP at baseline, and change in BMI. The other liver enzymes were not significantly predictors of new-onset hypertension. Conclusions: Among the four liver enzymes, elevated GGT level is the strongest risk factor for hypertension in Hong Kong Chinese. Acknowledgement: This study was funded by Hong Kong Research Grant Council grants (HKU7229/01M and HKU7626/07M) and the Sun Chieh Yeh Heart Foundation.published_or_final_versio

Role of genetic variants in gene encoding lipocalin-2 in the development of elevated blood pressure

Introduction: Lipocalin-2 is recently recognised as a biomarker of obesity and inflammation, which are both risk factors for hypertension. We therefore investigated the association of common single nucleotide polymorphisms (SNPs) in the gene encoding lipocalin-2 (LCN2) with elevated blood pressure in Hong Kong Chinese. Methods: Five tagging SNPs were genotyped in 1936 subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) with a median follow-up period of 6.4 years. Elevated blood pressure was defined as ≥130/85 mm Hg or taking anti-hypertensive medication. Results: There were only two haplotypes with frequency of >5%, namely AGATC (45.5%) and GGTCC (41.2%). Haplotype GGTCC was associated with elevated blood pressure at follow-up (OR=1.17 compared to haplotype AGATC, P=0.031 after adjusting for age and sex). Among 1381 subjects without elevated blood pressure at baseline, 321 subjects developed elevated blood pressure at follow-up. Haplotype GGTCC was associated with the development of elevated blood pressure at follow-up (OR=1.30 compared to haplotype AGATC, P=0.011 after adjusting for age, sex, systolic blood pressure, and follow-up duration; OR=1.44, P=0.0015 after further adjusting for other covariates). Among subjects not taking anti-hypertensive medication, carriers of the haplotype GGTCC had higher systolic blood pressure than non-carriers (119.7±16.4 mm Hg vs 117.9±17.3 mm Hg, P=0.043). Conclusion: Our findings suggest, for the first time, that genetic variants in LCN2 may affect blood pressure. Further studies on the role of lipocalin-2 in blood pressure regulation are warranted. Acknowledgement: This study was funded by Hong Kong Research Grant Council grants (HKU7229/01M and HKU7626/07M) and the Sun Chieh Yeh Heart Foundation.published_or_final_versio

Gamma-glutamyl transferase level predicts the development of hypertension in Hong Kong Chinese

Background: Plasma activities of alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase, and γ-glutamyl transferase (GGT) are often increased in cardiometabolic diseases. We investigated if hypertension is associated with increased activities of these plasma markers. Methods: We included 235 hypertensive and 708 normotensive subjects (mean age 47.3 ± 9.6 and 58.0 ± 10.2. years respectively) from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) in 2000-2004 who had drank < 1/week. In the follow-up study in 2005-2008 (CRISPS-3), 126 out of the 708 subjects had developed hypertension. Results: Raised plasma ALT (OR = 1.22 per SD of log-transformed level, P=0.045) and GGT (OR = 1.38 per SD of log-transformed level, P=0.001) levels were associated with hypertension at baseline in CRISPS-2 after adjusting for covariates. Among subjects not on anti-hypertensive medications, plasma ALP, ALT and GGT were related to blood pressure (P< 0.01). In subjects normotensive at CRISPS-2, plasma GGT, but not ALP, ALT and AST, was an independent predictor of new-onset hypertension at CRISPS-3 (OR = 1.38 per SD of log-transformed level, P=0.020 and OR = 2.68 for 3rd tertile vs. 1st tertile, P=0.004) after adjusting for covariates. Conclusions: Among the 4 plasma markers, increased GGT activity is the strongest predictor for existing and new-onset hypertension in Hong Kong Chinese. © 2011 Elsevier B.V.postprin

Relationship of plasma interleukin-6 and its genetic variants with hypertension in Hong Kong Chinese

published_or_final_versionThe 15th Annual Research Conference of the Department of Medicine, The University of Hong Kong, Hong Kong, 16 January 2010. In Hong Kong Medical Journal, 2010, v. 16, suppl. 1, p. 50, abstract no. 8

Association of a genetic variant in adrenomedullin gene with its plasma level

published_or_final_versionThe 16th Annual Research Conference of the Department of Medicine, The University of Hong Kong, Hong Kong, 22 January 2011. In Hong Kong Medical Journal, 2011, v. 17, suppl. 1, p. 19, abstract no. 1

Association of a genetic polymorphism in the gene encoding fibrinogen beta chain with hypertension in Hong Kong Chinese

published_or_final_versionThe 15th Annual Research Conference of the Department of Medicine, The University of Hong Kong, Hong Kong, 16 January 2010. In Hong Kong Medical Journal, 2010, v. 16, suppl. 1, p. 51, abstract no. 8

Mendelian randomisation analysis suggests that plasma interleukin-6 is raised in hypertension but does not cause its development

Introduction: Interleukin-6 (IL-6) plays a central role in inflammation and insulin resistance as well as atherogenesis. We investigated the associations of plasma IL-6 and its genetic variants with hypertension in both cross-sectional and prospective study designs. Methods: Plasma IL-6 was measured in 648 normotensive and 294 hypertensive subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) in 2000-2004 and three tagging SNPs in the IL-6 gene (IL6) were genotyped. Among subjects normotensive in CRISPS-2, 515 subjects were followed up in CRISPS-3 in 2005- 2008 and 100 of them had developed hypertension. Results: Plasma IL-6 correlated with systolic blood pressure (r=0.128, P<0.001), pulse pressure (r=0.144, P<0.001), and mean arterial pressure (r=0.086, P=0.008). Hypertensive subjects have significantly higher plasma IL-6 level after adjusting for age and sex (geometric mean [95% CI]=0.60 [0.54-0.65] vs 0.47 [0.44-0.50] pg/mL, P=0.021). In stepwise logistic regression, plasma IL-6 was associated with hypertension in women (P=0.004), but not in men. The SNP rs1800796 was associated with plasma IL-6 (beta= –0.098, P=0.002) in stepwise linear regression. However, this SNP was not associated with hypertension or blood pressure. Among subjects normotensive in CRISPS-2, plasma IL-6 was not associated with the development of hypertension in CRISPS-3. Conclusion: Elevated plasma IL-6 is associated with hypertension, especially in women. Plasma IL-6 is influenced by the SNP rs1800796. However, this SNP is not associated with hypertension, suggesting that hypertension is caused by other factors that elevate plasma IL-6. Acknowledgement: This study was funded by Hong Kong Research Grant Council grants (HKU7229/01M and HKU7626/07M) and the Sun Chieh Yeh Heart Foundation.published_or_final_versio