Sox9 confers stemness properties in hepatocellular carcinoma through Frizzled-7 mediated Wnt/β-catenin signaling

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RhoE/ROCK signaling modulates chemoresistance in HCC through IL6/JAK2/STAT3 pathways

Conference Theme: New Horizons in Cancer Research Conference: Harnessing Breakthroughs - Targeting CuresPoster Session B: Tumor Biology: no. B40Liver cancer (hepatocellular carcinoma, HCC) is a major malignancy worldwide and the second commonest fatal cancer in Southeast Asia and China including Hong Kong, due to the high prevalence of hepatitis B viral infection. HCC is highly chemoresistant, limiting treatment options to patients. There is an urgent need to delineate the underlying molecular mechanism of HCC chemoresistance so as to identify novel therapeutic targets for this aggressive cancer. Deregulation of Rho GTPase pathway is demonstrated to play important roles in HCC tumorigenesis. RhoE/Rnd3 belongs to the Rnd subfamily of the Rho GTPase which lacks the intrinsic GTPase activity. In our previous study, we have shown that RhoE is frequently downregulated in human HCCs and acts as a metastasis suppressor, whereas ROCK2 is upregulated in human HCCs. In this study, we aimed to investigate whether RhoE is also involved in the regulation of chemoresistance in HCC. Using short-hairpin RNA and ...published_or_final_versio

Regulatory role of miR-142-3p on the functional hepatic cancer stem cell marker CD133

Tumor relapse after therapy typifies hepatocellular carcinoma (HCC) and is believed to be attributable to residual cancer stem cells (CSCs) that survive treatment. We have previously identified a CSC population derived from HCC that is characterized by CD133. Despite our growing knowledge of the importance of this subset of cells in driving HCC, the regulatory mechanism of CD133 is not known. Epigenetic changes are believed to be essential in the control of cancer and stem cells. Here, we report the epigenetic regulation of CD133 by miR-142-3p. The interaction between CD133 and miR-142-3p was identified by in silico prediction and substantiated by luciferase reporter analysis. Expression of CD133 was found to be inversely correlated with miR-142-3p in HCC clinical samples as well as in cell lines. Importantly, lower miR-142-3p expression in HCC was significantly associated with worst survival. Functional studies with miR-142-3p stably transduced in HCC cells demonstrated a diminished ability to self-renew, initiate tumor growth, invade, migrate, induce angiogenesis and resist chemotherapy. Rescue experiments whereby CD133 and miR-142-3p is simultaneously overexpressed compensated the deregulated ability of the cells to confer these features. Thus, miR-142-3p directly targets CD133 to regulate its ability to confer cancer and stem cell-like features in HCC.published_or_final_versio

Using spatial analysis to demonstrate the heterogeneity of the cardiovascular drug-prescribing pattern in Taiwan

<p>Abstract</p> <p>Background</p> <p>Geographic Information Systems (GIS) combined with spatial analytical methods could be helpful in examining patterns of drug use. Little attention has been paid to geographic variation of cardiovascular prescription use in Taiwan. The main objective was to use local spatial association statistics to test whether or not the cardiovascular medication-prescribing pattern is homogenous across 352 townships in Taiwan.</p> <p>Methods</p> <p>The statistical methods used were the global measures of Moran's <it>I </it>and Local Indicators of Spatial Association (LISA). While Moran's <it>I </it>provides information on the overall spatial distribution of the data, LISA provides information on types of spatial association at the local level. LISA statistics can also be used to identify influential locations in spatial association analysis. The major classes of prescription cardiovascular drugs were taken from Taiwan's National Health Insurance Research Database (NHIRD), which has a coverage rate of over 97%. The dosage of each prescription was converted into defined daily doses to measure the consumption of each class of drugs. Data were analyzed with ArcGIS and GeoDa at the township level.</p> <p>Results</p> <p>The LISA statistics showed an unusual use of cardiovascular medications in the southern townships with high local variation. Patterns of drug use also showed more low-low spatial clusters (cold spots) than high-high spatial clusters (hot spots), and those low-low associations were clustered in the rural areas.</p> <p>Conclusions</p> <p>The cardiovascular drug prescribing patterns were heterogeneous across Taiwan. In particular, a clear pattern of north-south disparity exists. Such spatial clustering helps prioritize the target areas that require better education concerning drug use.</p

Building a Community of Learners on: A Social Constructivist Approach

In any of the education reforms advocated all over the world, no matter how sound the curriculum policies seem to be, teachers still find individual differences a major hindrance to the success of the reforms. While many educators consider diversity among students a classroom problem, some try to reduce the problem by streaming or offering different enrichment and remedial programs tailor-made for the individual student. The present study adopted an alternative approach and examined how individual differences could be taken as an important resource in developing a productive community of learners with a social constructivist basis. The positive findings of student performance in portfolio assessment reported in this study support the argument that learning should be aligned with assessment. To cater for individual differences, portfolio assessment should be adopted as it serves the following characteristics that are crucial for developing life-long learners and attaining 'success for all'. First, portfolio assessment requires students to collect and reflect on work samples, providing both an instructional component to the curriculum and offering an opportunity for authentic assessments. When carefully assembled, portfolios become an intersection of instruction and assessment which traditional assessment cannot achieve. Secondly, it yields an improved portrait of the students as ... [more]learners, using a process that encourages students to become metacognitive in regards to their learning. Thirdly, students are allowed to collect learning evidence from various sources, through multiple methods and over multiple points of time. Student diversity in intelligences is therefore being acknowledged. They do not need to compete or compare themselves with others, and therefore can learn in a safe environment.link_to_subscribed_fulltex

Cancer-associated fibroblasts in hepatocellular carcinoma and cholangiocarcinoma

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Building a community of learners on individual differences: A social constructivist approach

Many educators consider individual differences among pupils as a classroom problem and some try to reduce the problem by streaming. This paper presents an alternative approach, based on social constructivism, in which individual differences are taken as an important resource in enhancing learning in the classroom. The paper is based on a naturalistic study with two primary schools implementing many learning strategies with a social constructivist root. These include collaborative learning, peer scaffolding and portfolio assessment. The strategies were gradually introduced in the two schools through encouragement and support of the research team. The lessons using the new strategies were videotaped and the pupils' works were collected for analysis. To supplement, standardized tests developed independently were used to triangulate the qualitative study. Results show that the introduction of social constructivism has a significant impact on classroom practices, on interactions of pupils and on their level of active participation on learning. Qualitative analysis of pupils' work also shows promising results. The observed improvement in learning has further been confirmed by statistical analysis of standardized test results. The findings strongly argue the possibility to handling individual differences without resorting to streaming strategies

Developing a learning community in catering for individual differences

Research Report for Project on Catering for Individual Difference