Jason W. H. Wong

Bio: Jason W. H. Wong is an academic researcher from Li Ka Shing Faculty of Medicine, University of Hong Kong. The author has contributed to research in topics: Cancer & Gene. The author has an hindex of 46, co-authored 175 publications receiving 7382 citations. Previous affiliations of Jason W. H. Wong include University of New South Wales & University College Dublin.

Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma.

Abstract: We have shown that the proteasome inhibitor bortezomib (formerly known as PS-341) triggers significant antitumor activity in multiple myeloma (MM) in both preclinical models and patients with relapsed refractory disease. Recent studies have shown that unfolded and misfolded ubiquitinated proteins are degraded not only by proteasomes, but also by aggresomes, dependent on histone deacetylase 6 (HDAC6) activity. We therefore hypothesized that inhibition of both mechanisms of protein catabolism could induce accumulation of ubiquitinated proteins followed by significant cell stress and cytotoxicity in MM cells. To prove this hypothesis, we used bortezomib and tubacin to inhibit the proteasome and HDAC6, respectively. Tubacin specifically triggers acetylation of α-tubulin as a result of HDAC6 inhibition in a dose- and time-dependent fashion. It induces cytotoxicity in MM cells at 72 h with an IC50 of 5–20 μM, which is mediated by caspase-dependent apoptosis; no toxicity is observed in normal peripheral blood mononuclear cells. Tubacin inhibits the interaction of HDAC6 with dynein and induces marked accumulation of ubiquitinated proteins. It synergistically augments bortezomib-induced cytotoxicity by c-Jun NH2-terminal kinase/caspase activation. Importantly, this combination also induces significant cytotoxicity in plasma cells isolated from MM patient bone marrow. Finally, adherence of MM cells to bone marrow stromal cells confers growth and resistance to conventional treatments; in contrast, the combination of tubacin and bortezomib triggers toxicity even in adherent MM cells. Our studies therefore demonstrate that tubacin combined with bortezomib mediates significant anti-MM activity, providing the framework for clinical evaluation of combined therapy to improve patient outcome in MM.

Evaluation of preoperative hepatic function in patients with hepatocellular carcinoma undergoing hepatectomy

Abstract: Background Postoperative hepatic failure is the leading cause of hospital mortality following hepatectomy for hepatocellular carcinoma (HCC). This prospective study was performed to identify the best test for assessment of the adequacy of hepatic functional reserve in patients with HCC before hepatectomy. Methods Between April 1989 and June 1993, 127 patients with HCC underwent hepatectomy. Each patient was evaluated before operation with the indocyanine green (ICG) clearance test, the aminopyrine breath test and the amino acid clearance test. Results Fourteen patients (11 per cent) died after hepatectomy. ICG retention at 15 min showed significant differences between patients who survived or died. By discriminant analysis, the safety limit of ICG retention at 15 min for major hepatectomy was 14 per cent and the relative risk of hospital mortality was 3. Conclusion The ICG clearance test, expressed as the percentage of ICG retained at 15 min, is the best discriminating preoperative test for evaluating hepatic functional reserve in patients with HCC before hepatectomy.

Preoperative endoscopic drainage for malignant obstructive jaundice.

Abstract: The role of preoperative endoscopic drainage for patients with malignant obstructive jaundice was evaluated in a randomized controlled trial. A total of 87 patients were assigned to either early elective surgery (44 patients) or endoscopic biliary drainage followed by exploration (43). Thirty-seven patients underwent successful stent insertion and 25 had effective biliary drainage. Complications related to endoscopy occurred in 12 patients. After endoscopic drainage significant reductions of hyperbilirubinaemia, indocyanine green retention and serum albumin concentration were observed. Patients with hilar lesions had a significantly higher incidence of cholangitis and failed endoscopic drainage after stent placement. The overall morbidity rate (18 patients versus 16) and mortality rate (six patients in each group) were similar in the two treatment arms irrespective of the level of biliary obstruction. Despite the improvement of liver function, routine application of endoscopic drainage had no demonstrable benefit. Endoscopic drainage is indicated only when early surgery is not feasible, especially for patients with distal obstruction.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

edgeR: a Bioconductor package for differential expression analysis of digital gene expression data.

Abstract: Summary: It is expected that emerging digital gene expression (DGE) technologies will overtake microarray technologies in the near future for many functional genomics applications. One of the fundamental data analysis tasks, especially for gene expression studies, involves determining whether there is evidence that counts for a transcript or exon are significantly different across experimental conditions. edgeR is a Bioconductor software package for examining differential expression of replicated count data. An overdispersed Poisson model is used to account for both biological and technical variability. Empirical Bayes methods are used to moderate the degree of overdispersion across transcripts, improving the reliability of inference. The methodology can be used even with the most minimal levels of replication, provided at least one phenotype or experimental condition is replicated. The software may have other applications beyond sequencing data, such as proteome peptide count data. Availability: The package is freely available under the LGPL licence from the Bioconductor web site (http://bioconductor.org).

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Integrative analysis of 111 reference human epigenomes

Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.