Hormonal control of the metabolic machinery of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most fatal malignancies worldwide. It is an aggressive cancer with low cure rate, frequent metastasis, and highly resistant to conventional chemotherapies. Better knowledge regarding the molecular and metabolic alterations in HCC will be instrumental to the development of novel therapeutic interventions against HCC. In the August 2015 issue of Hepatology, Nie et al. reports an important molecular pathway that contributes to the Warburg Effect in HCC. They have beautifully demonstrated that the loss of a component of a hormonal system, the mineralocorticoid receptor (MR), reprogrammed the metabolic machinery of HCC cells to aerobic glycolysis through the miR-338-3p-PKL/R axis. The implication could be that in addition to drugs that directly target the metabolic enzymes in cancer cells, more translational efforts could be focused on the development of drugs that involve the activation of the MR-aldosterone system or other hormonal systems to target the Warburg effect.published_or_final_versio

Helicobacter pylori associated gastric intestinal metaplasia: Treatment and surveillance

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Patient-specific instrument can achieve same accuracy with less resection time than navigation assistance in periacetabular pelvic tumor surgery: A cadaveric study

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EZH2-Mediated H3K27me3 Is Involved in Epigenetic Repression of Deleted in Liver Cancer 1 in Human Cancers

Enhancer of zeste homolog 2 (EZH2), the histone methyltransferase of the Polycomb Repressive complex 2 catalyzing histone H3 lysine 27 tri-methylation (H3K27me3), is frequently up-regulated in human cancers. In this study, we identified the tumor suppressor Deleted in liver cancer 1 (DLC1) as a target of repression by EZH2-mediated H3K27me3. DLC1 is a GTPase-activating protein for Rho family proteins. Inactivation of DLC1 results in hyper-activated Rho/ROCK signaling and is implicated in actin cytoskeleton reorganization to promote cancer metastasis. By chromatin immunoprecipitation assay, we demonstrated that H3K27me3 was significantly enriched at the DLC1 promoter region of a DLC1-nonexpressing HCC cell line, MHCC97L. Depletion of EZH2 in MHCC97L by shRNA reduced H3K27me3 level at DLC1 promoter and induced DLC1 gene re-expression. Conversely, transient overexpression of GFP-EZH2 in DLC1-expressing Huh7 cells reduced DLC1 mRNA level with a concomitant enrichment of EZH2 on DLC1 promoter. An inverse relation between EZH2 and DLC1 expression was observed in the liver, lung, breast, prostate, and ovarian cancer tissues. Treating cancer cells with the EZH2 small molecular inhibitor, 3-Deazaneplanocin A (DZNep), restored DLC1 expression in different cancer cell lines, indicating that EZH2-mediated H3K27me3 epigenetic regulation of DLC1 was a common mechanism in human cancers. Importantly, we found that DZNep treatment inhibited HCC cell migration through disrupting actin cytoskeleton network, suggesting the therapeutic potential of DZNep in targeting cancer metastasis. Taken together, our study has shed mechanistic insight into EZH2-H3K27me3 epigenetic repression of DLC1 and advocated the significant pro-metastatic role of EZH2 via repressing tumor and metastasis suppressors.published_or_final_versio

Age-period-cohort projections of ischaemic heart disease mortality by socio-economic position in a rapidly transitioning Chinese population

Background:With economic development and population aging, ischaemic heart disease (IHD) is becoming a leading cause of mortality with widening inequalities in China. To forewarn the trends in China we projected IHD trends in the most economically developed part of China, i.e., Hong Kong.Methods:Based on sex-specific IHD mortality rates from 1976 to 2005, we projected mortality rates by neighborhood-level socio-economic position (i.e., low- or high-income groups) to 2020 in Hong Kong using Poisson age-period-cohort models with autoregressive priors.Results:In the low-income group, age-standardized IHD mortality rates among women declined from 33.3 deaths in 1976-1980 to 19.7 per 100,000 in 2016-2020 (from 55.5 deaths to 34.2 per 100,000 among men). The rates in the high-income group were initially higher in both sexes, particularly among men, but this had reversed by the end of the study periods. The rates declined faster for the high-income group than for the low-income group in both sexes. The rates were projected to decline faster in the high-income group, such that by the end of the projection period the high-income group would have lower IHD mortality rates, particularly for women. Birth cohort effects varied with sex, with a marked upturn in IHD mortality around 1945, i.e., for the first generation of men to grow up in a more economically developed environment. There was no such upturn in women. Birth cohort effects were the main drivers of change in IHD mortality rates.Conclusion:IHD mortality rates are declining in Hong Kong and are projected to continue to do so, even taking into account greater vulnerability for the first generation of men born into a more developed environment. At the same time social disparities in IHD have reversed and are widening, partly as a result of a cohort effect, with corresponding implications for prevention. © 2013 Wong et al.published_or_final_versio

Generalised cost-effectiveness analysis for breast cancer prevention and care in Hong Kong Chinese

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Trends in mortality from septicaemia and pneumonia with economic development: An age-period-cohort analysis

Background: Hong Kong population has experienced drastic changes in its economic development in the 1940s. Taking advantage of Hong Kong's unique demographic and socioeconomic history, characterized by massive, punctuated migration waves from Southern China, and recent, rapid transition from a pre-industrialized society to the first ethnic Chinese community reaching "first world" status over the last 60 years (i.e., in two or three generations), we examined the longitudinal trends in infection related mortality including septicemia compared to trends in non-bacterial pneumonia to generate hypotheses for further testing in other recently transitioned economies and to provide generalized aetiological insights on how economic transition affects infection-related mortality. Methods: We used deaths from septicemia and pneumonia not specified as bacterial, and population figures in Hong Kong from 1976-2005. We fitted age-period-cohort models to decompose septicemia and non-bacterial pneumonia mortality rates into age, period and cohort effects. Results: Septicaemia-related deaths increased exponentially with age, with a downturn by period. The birth cohort curves had downward inflections in both sexes in the 1940s, with a steeper deceleration for women. Non-bacterial pneumonia-related deaths also increased exponentially with age, but the birth cohort patterns showed no downturns for those born in the 1940s. Conclusion: The observed changes appeared to suggest that better early life conditions may enable better development of adaptive immunity, thus enhancing immunity against bacterial infections, with greater benefits for women than men. Given the interaction between the immune system and the gonadotropic axis, these observations are compatible with the hypothesis that upregulation of the gonadotropic axis underlies some of the changes in disease patterns with economic development. © 2012 Wong et al.published_or_final_versio

Functional characterization of liver-enriched transcription factor CREB-H (poster 1989)

Tissue-Specific Gene Expression (1985-2002) Sessionpublished_or_final_versio

PTEN underexpression was associated with more aggressive tumor behaviour in hepatocellular carcinoma and PTEN suppressed cell invasion by downregulating NF-κB signaling pathway

Top Scored Posters: P-006postprintThe 3rd Annual Conference of the International Liver Cancer Association (ILCA 2009), Milan, Italy, 4-6 September 2009. In Abstract Book of ILCA 2009, 2009, p. 20, abstract no. P-00

Towards informed decisions on breast cancer screening: Development and pilot testing of a decision aid for Chinese women

OBJECTIVE: To pilot-test a novel, self-use breast cancer (BC) screening decision aid (DA) targeting Hong Kong (HK) Chinese women at average risk of BC. METHODS: Women were recruited through a population-based telephone survey using random digit dialling between October 2013 and January 2014. Eligible participants completed our baseline survey and then received the DA by post. Participants (n=90) completed follow-up telephone interviews one month later. RESULTS: Most participants thought that all/most DA content was presented clearly (86.7%), and was useful in helping women make screening-related decisions (88.9%). It also achieved its expected impact of improving informed decision-making and increasing shared-participation preference without increasing participants' anxiety levels. Participants showed a modest non-statistical increase in their screening knowledge scores. Older women rated the perceived severity of a BC diagnosis as significantly lower, and more educated women reported significantly lower perceived anxiety about the disease. CONCLUSION: Our DA appears acceptable and feasible for self-use by HK Chinese women who need to make an informed decision about BC screening without increasing overall anxiety levels. PRACTICE IMPLICATIONS: This study supports the potential of self-use DAs for cancer screening-related decision support in a Chinese population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.postprin