The prognostic role of ACSL4 in postoperative adjuvant TACE-treated HCC: implications for therapeutic response and mechanistic insights.

Background: The response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE) treatment and its underlying mechanisms remain elusive. This study investigates the role of enzymes involved in fatty acid activation, specifically Acyl-CoA synthetase long chain 4 (ACSL4), in HCC patients treated with postoperative adjuvant TACE (PA-TACE) and in nutrient-deprived HCC cells.

Methods: We examined the expression of ACSL4 and its family members in HCC clinical samples and cell lines.

The role of artificial intelligence in knowledge management for medical students and doctors.

The skill of knowledge management empowers practitioners to efficiently integrate and apply knowledge in the clinical context. Current medical knowledge is vast which is beyond the human capacity to retain. Hence, modern-day learning is not just knowledge acquisition, but the organization of knowledge in a retrievable manner.

Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy.

Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death.

A professionalism program in medical education and training - From broad values to specific applications: YLL School of Medicine, Singapore.

The process for introducing and developing a program for teaching medical professionalism at the National University of Singapore, School of Medicine is outlined. Professionalism was recognised as embracing 'honesty and integrity,' 'responsibility and participation,' 'respect and sensitivity,' and 'compassion and empathy.' Those broad values are expressed as specific attitudes and behaviours that are taught and assessed throughout the course.

Cytoskeletal Proteins in Cancer and Intracellular Stress: A Therapeutic Perspective.

Cytoskeletal proteins, which consist of different sub-families of proteins including microtubules, actin and intermediate filaments, are essential for survival and cellular processes in both normal as well as cancer cells. However, in cancer cells, these mechanisms can be altered to promote tumour development and progression, whereby the functions of cytoskeletal proteins are co-opted to facilitate increased migrative and invasive capabilities, proliferation, as well as resistance to cellular and environmental stresses. Herein, we discuss the cytoskeletal responses to important intracellular stresses (such as mitochondrial, endoplasmic reticulum and oxidative stresses), and delineate the consequences of these responses, including effects on oncogenic signalling.

Histone deacetylases up-regulate C/EBPα expression through reduction of miR-124-3p and miR-25 in hepatocellular carcinoma.

Background: CCAAT enhancer binding protein α (C/EBPα), as an important transcription factor involved in cell proliferation, differentiation and metabolism, was up-regulated in primary hepatocellular carcinoma (HCC) and predicted poorer prognosis. In this study, we explored how histone deacetylases (HDACs) up-regulated C/EBPα in HCC.

Methods: The protein expressions of HDAC1, HDAC2 were associated with C/EBPα by immunohistochemistry staining in a HCC tissue microarray.

The pro-survival function of DLEC1 and its protection of cancer cells against 5-FU-induced apoptosis through up-regulation of BCL-XL.

The tumor suppressor DLEC1 has been shown to promote cell proliferation when AP-2α2 is down-regulated in HCT116 stable clones, suggesting its pro-survival nature. However, the pro-survival function of DLEC1 has not been confirmed in other cells and its underlying mechanisms remain elusive. Therefore, we knocked down DLEC1 in a panel of cell lines and found that DLEC1 depletion caused various extents of cell death through intrinsic pathway.

Improving a newly adapted teaching and learning approach: Collaborative Learning Cases using an action research.

Purpose: Although medical curricula are now better structured for integration of biomedical sciences and clinical training, most teaching and learning activities still follow the older teacher-centric discipline-specific formats. A newer pedagogical approach, known as Collaborative Learning Cases (CLCs), was adopted in the medical school to facilitate integration and collaborative learning. Before incorporating CLCs into the curriculum of year 1 students, two pilot runs using the action research method was carried out to improve the design of CLCs.

Fatty acid activation in carcinogenesis and cancer development: Essential roles of long-chain acyl-CoA synthetases.

The significance of fatty acid metabolism in cancer initiation and development is increasingly accepted by scientists and the public due to the high prevalence of overweight and obese individuals. Fatty acids have different turnovers in the body: Either breakdown into acetyl-CoA to aid ATP generation through catabolic metabolism or incorporation into triacylglycerol and phospholipid through anabolic metabolism. However, these two distinct pathways require a common initial step known as fatty acid activation.

AKT activation was not essential for hepatocellular carcinoma cell survival under glucose deprivation.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, with a dismal 5-year survival rate less than 15%. The present study aimed to investigate whether AKT inhibition and glucose deprivation could synergistically kill HCC cells and the molecular mechanisms involved. HCC cells were starved in glucose deprivation, and then the resultant cell death was determined by flow cytometry and mitochondrial oxygen consumption rates using a Seahorse XF-24 Extracellular Flux Analyzer.

Gelsolin-Cu/ZnSOD interaction alters intracellular reactive oxygen species levels to promote cancer cell invasion.

The actin-binding protein, gelsolin, is a well known regulator of cancer cell invasion. However, the mechanisms by which gelsolin promotes invasion are not well established. As reactive oxygen species (ROS) have been shown to promote cancer cell invasion, we investigated on the hypothesis that gelsolin-induced changes in ROS levels may mediate the invasive capacity of colon cancer cells.

Complex and novel determinants of empathy change in medical students.

Purpose: Physician empathy is a core attribute in medical professionals, giving better patient outcomes. Medical school is an opportune time for building empathetic foundations. This study explores empathy change and focuses on contributory factors.

Tumor Suppressor DLEC1 can Stimulate the Proliferation of Cancer Cells When AP-2ɑ2 is Down-Regulated in HCT116.

Background: The molecular mechanisms of tumor suppressor gene DLEC1 are largely unknown.

Objectives: In this study, we established DLEC1 over-expression stable clones to study the cellular function of DLEC1 in the colorectal cancer cell line, HCT116.

Materials And Methods: Stable clones with DLEC1 over-expression were first established by the transfection of DLEC1 expression construct pcDNA31DLEC1 in HCT116.

HDAC1 and HDAC2 independently predict mortality in hepatocellular carcinoma by a competing risk regression model in a Southeast Asian population.

Histone deacetylases (HDACs) are enzymes involved in transcriptional repression. We aimed to examine the significance of HDAC1 and HDAC2 gene expression in the prediction of recurrence and survival in 156 patients with hepatocellular carcinoma (HCC) among a South East Asian population who underwent curative surgical resection in Singapore. We found that HDAC1 and HDAC2 were upregulated in the majority of HCC tissues.

Effectiveness of early cardiology undergraduate learning using simulation on retention, application of learning and level of confidence during clinical clerkships.

Introduction: This study aimed to assess the effectiveness of the use of a cardiopulmonary patient simulator in the teaching of second-year medical students. Effectiveness was measured in terms of the extent of knowledge retention and students' ability to apply the skills learned in subsequent real-life patient contact.

Methods: In this study, ten third-year medical students who had previously undergone simulator training as part of their second-year curriculum underwent an objective structured clinical examination (OSCE) and a multiple-choice question (MCQ) test to assess their ability to apply the knowledge gained during the simulator training when dealing with real patients.

Medical education in Singapore.

Allopathic medical education in Singapore extends for more than a century from its simple beginnings. In recent times, changes have been rapid, both in undergraduate and postgraduate specialty medical training. Over the last decade, undergraduate medical education has increased from a single to three medical schools and the postgraduate training has expanded further by incorporating the Accreditation Council for Graduate Medical Education International framework.

Comparison of virtual patient simulation with mannequin-based simulation for improving clinical performances in assessing and managing clinical deterioration: randomized controlled trial.

Background: Virtual patient simulation has grown substantially in health care education. A virtual patient simulation was developed as a refresher training course to reinforce nursing clinical performance in assessing and managing deteriorating patients.

Objective: The objective of this study was to describe the development of the virtual patient simulation and evaluate its efficacy, by comparing with a conventional mannequin-based simulation, for improving the nursing students' performances in assessing and managing patients with clinical deterioration.

Encouraging an environment to nurture lifelong learning: an Asian experience.

Introduction: Within an Asian context, this study examines the effect of changing from traditional course grades to a distinction/pass/fail (D/P/F) grading system on medical student self-perceived stress levels and on student exam performance.

Methods: At the end of the 2010-2011 academic year, the Perceived Stress Scale-10 (PSS-10) was administered to the cohort of students finishing their first year of medical studies. For the academic year 2011-2012, the grading system was changed to D/P/F for the first year of medical school.

Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade.

Gelsolin is a cytoskeletal protein which participates in actin filament dynamics and promotes cell motility and plasticity. Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells.

Proteomic analysis of colorectal cancer metastasis: stathmin-1 revealed as a player in cancer cell migration and prognostic marker.

Metastasis accounts largely for the high mortality rate of colorectal cancer (CRC) patients. In this study, we performed comparative proteome analysis of primary CRC cell lines HCT-116 and its metastatic derivative E1 using 2-D DIGE. We identified 74 differentially expressed proteins, many of which function in transcription, translation, angiogenesis signal transduction, or cytoskeletal remodeling pathways, which are indispensable cellular processes involved in the metastatic cascade.

Recognition and suppression of transfected plasmids by protein ZNF511-PRAP1, a potential molecular barrier to transgene expression.

Nonviral vectors present considerable advantages over viral counterparts in gene transfer. However, the poor expression efficiency of the transfected genes poses a challenge for their use in gene therapy, primarily due to the inability of these vectors to overcome various barriers, including the biological barriers. Here, we report that ZNF511-PRAP1 may be involved in the recognition and inactivation of transfected plasmids.

FOXQ1 regulates epithelial-mesenchymal transition in human cancers.

Epithelial-mesenchymal transition (EMT) in cancer cells plays a pivotal role in determining metastatic prowess, but knowledge of EMT regulation remains incomplete. In this study, we defined a critical functional role for the Forkhead transcription factor FOXQ1 in regulating EMT in breast cancer cells. FOXQ1 expression was correlated with high-grade basal-like breast cancers and was associated with poor clinical outcomes.

B55β-associated PP2A complex controls PDK1-directed myc signaling and modulates rapamycin sensitivity in colorectal cancer.

The PP2A serine/threonine protein phosphatase serves as a critical cellular regulator of cell growth, proliferation, and survival. However, how this pathway is altered in human cancer to confer growth advantage is largely unknown. Here, we show that PPP2R2B, encoding the B55β regulatory subunit of the PP2A complex, is epigenetically inactivated by DNA hypermethylation in colorectal cancer.