Ocean Park Hong Kong: The Risen Dead Miracle of Hong Kong

Terence Chun-Ho CHEUNG,Cheryl Tze-Ying AW,Jessica Chun-Ying CHAN,Jeni Yin-Ming CHEUNG Academy of Asian Business (AAB) 2015 Academy of Asian Business Review Vol.1 No.2

The purpose of this study is to identify the strategies that Ocean Park used to face different kinds of threats and challenges, and discover the success factors that transformed the park from a local theme park with little global vision and recognition into one of the most popular amusement parks in the world. The major challenges include the Financial Crisis in 1997, the closure of Water Park in 1999, the outbreak of SARS in 2003 and, most critically, the emergence of Hong Kong Disneyland in 2005. Based on our analysis on relevant data, we found that the key success factors of Ocean Park are speedy repositioning and flexible in coping with major challenges by adopting relevant strategic actions such as (1) redefining the market position, (2) adding innovative attraction, education, and charity programs, (3) creating effective social cause marketing with UNICEF, and (4) committing to major redevelopment programs. We believe that Ocean Park will have great development and performance if it maintains these factors. Hopefully, this study will be useful in understanding and exploring the success of a theme park or a business in Hong Kong.

SREBP2 Activation Drives Drug Resistance through Promotion of Cholesterol Biosynthesis-Driven Sonic Hedgehog Signaling (SHH) Pathway in Hepatocellular Carcinoma

( Etienne Ho Kit Mok ),( Carmen Oi Ning Leung ),( Martina Mang Leng Lei ),( Terence Kin Wah Lee ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Acquired drug resistance is a hurdle for effective treatment for hepatocellular carcinoma (HCC) patients. We have established sorafenib-resistant HCC patient-derived xenografts and found that cholesterol biosynthesis was most significantly upregulated in sorafenib-resistant PDTX cells with enhanced cholesterol deposition. This observation is similarly observed in lenvatinib- resistant HCC xenografts. This, together with an observation that SREBP2-mediated cholesterol biosynthesis was activated in enriched liver CSC populations, prompt us to investigate the role of SREBP2-mediated cholesterol biosynthesis in regulation of drug resistance of HCC via augmentation of liver CSCs. Methods: We evaluated the clinic-pathological relevance of SREBP2 and its correlation with sorafenib resistance in HCC samples by immunohistochemistry. CRISPR activation and knockdown approaches were performed to characterize the functional roles of SREBP2 in regulating liver CSCs. Pathways mediating the phenotypic alterations was identified through RNA sequencing analysis. The combinatorial effect of Simvastatin and sorafenib was tested using patient-derived tumour xenograft (PDTX) model. Results: We found that SREBP2-mediated cholesterol biosynthesis was found to critically involve in regulation of liver CSCs, including self-renewal, cell invasiveness and tumorigenicity, and bears clinical significance. Strikingly, this process is a crucial determinant for drug resistance in HCC cells, and correlated with sorafenib resistance in sorafenib-treated HCC patients. Exogenous cholesterol also exerted the similar effect on cancer stemness, drug resistance, and expansion of HCC organoids. Sorafenib/lenvatinib induced nuclear translocation of SREBP2 from endoplasmic reticulum, resulting in activation of cholesterol biosynthesis-driven sonic hedgehog signaling (SHH) pathway. Simvastatin, a FDA-approved cholesterol lowering drug, sensitized the effects to sorafenib/lenvatinib via hampering liver CSC populations. Using PDTX model, we found that simvastatin at the clinically equivalent dose (40 mg) not only suppressed HCC tumor growth but also sensitized the effect to sorafenib. Conclusions: We reveal a previously unrecognized link between SREBP2-mediated cholesterol biosynthesis and cancer stemness that modulates acquired drug resistance of cancer cells.

Cardiac evaluation for end-stage kidney disease patients on the transplant waitlist: a single-center cohort study

Swati Vijayan,Quan Yao Ho,Choong Hou Koh,Ian Tatt Liew,Sobhana Thangaraju,Ningyan Wong,Yann Shan Keh,Zi Hui Sharel Ong,Jia Qin Tan,Khung Keong Yeo,Terrance Siang Jin Chua,Terence Kee 대한이식학회 2022 Korean Journal of Transplantation Vol.36 No.3

Background: Cardiac evaluation before deceased donor kidney transplant (DDKT) remains a matter of debate. Data on Asian countries and countries with prolonged waiting times are lacking. This study aimed to assess the outcomes of patients referred for DDKT after a cardiac evaluation at an Asian tertiary transplant center. Methods: This single-center retrospective review analyzed patients who were referred for waitlist placement and underwent cardiac stress testing between January 2009 and December 2015. Patients with cardiac symptoms were excluded. The primary outcome was three-point major adverse cardiovascular events (MACE), a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. Results: Of 468 patients referred for DDKT, 198 who underwent cardiac stress testing (myocardial perfusion studies in 159 patients and stress echocardiography in 39 patients) were analyzed. MACE occurred in 20.7% of the patients over a median follow-up of 4.6 years. Cardiac stress tests were positive for ischemia in 19.7% of the patients. Coronary angiography was performed in 63 patients, including 29 patients with diabetic kidney disease and negative cardiac stress tests. Significant coronary artery disease (CAD) was detected in 27 patients (42.8%), of whom 18 underwent revascularization. MACE was associated with significant CAD on coronary angiography in the multivariable analysis. Cardiac stress test results were not associated with MACE. Amongst diabetic patients who had negative cardiac stress tests, 37.9% had significant CAD on coronary angiography. Conclusions: The cardiovascular disease burden is significant amongst DDKT waitlist candidates. Pretransplant cardiac screening may identify patients with significant CAD at higher risk of MACE.

UBE2T: A Molecular Regulator for Cancer Stemness in Hepatocellular Carcinoma

( Nicole Pui-yu Ho ),( Terence Kin Wah Lee ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Increasing evidence showed that cancer stem cells (CSCs) play a critical role in regulating the tumor relapse and therapeutic resistance of hepatocellular carcinoma (HCC). Given high molecular similarities between liver CSCs and normal liver stem cells, we have enriched the normal stem cell populations by establishing a mouse partial hepactectomy model order to identify critical molecules involved in regulation of liver CSCs. By comparing the expression profiles between the early regenerating liver and intact one, UBE2T was found to be highly upregulated. This, together with the data showing upregulation of UBE2T in enriched liver CSC populations, suggest the role of UBE2T on regulating liver CSCs. Methods: We evaluated the clinic-pathological relevance of UBE2T by qPCR, western blot and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize the functional roles of UBE2T in regulating liver CSCs. The protein binding partner of UBE2T was identified by mass spectrometry analysis. Results: By qPCR analysis, UBE2T mRNA overexpression is found in over 90% of HCC samples and is associated with aggressive tumor behavior and poorer patients’ survival. Overexpression of UBE2T protein level in HCC clinical samples was further confirmed by western blot and IHC analyses. Using lentiviral based knockdown approach, suppression of UBE2T inhibited liver CSC properties, including self-renewal, tumorigenicity, drug resistance and expression of liver CSC markers. Using orthotopic liver xenograft model, UBE2T suppression led to decrease in tumor burden as well as lung metastasis in vivo. Mechanistically, we found UBE2T interacts with E3 ligase Mule and regulates its expression via ubiquitation. Since we further found that UBE2T mediates liver CSC function through Mule-mediated β-catenin activation. Conclusions: We have uncovered a novel UBE2T mediated signaling cascade in regulation of liver CSCs. Developing a specific inhibitor targeting this pathway may be a novel approach for HCC treatment.

Interleukin-1 Receptor Kinase 1 Augments Cancer Stemness and Drug Resistance via AP-1/AKR1B10 Signaling Cascade in Hepatocellular Carcinoma

( Nicole Pui Yu Ho ),( Bowie Lik Ling Cheng ),( Irene Oi Lin Ng ),( Terence Kin Wah Lee ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Frequent relapse and drug resistance may be attributed to the existence of tumor-initiating cells (T-ICs) in hepatocellular carcinoma (HCC). We investigated the functional role and clinical significance of Interleukin-receptor associated kinase 1 (IRAK1) in regulation of liver tumor-initiating cells (T-ICs) and sorafenib resistance, aiming to develop a novel therapeutic strategy against HCC. Methods: We evaluated the clinic-pathological relevance of IRAK1 in HCC clinical samples by qPCR and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize functional roles of IRAK1 in regulation of liver T-ICs and sorafenib resistance. Molecular pathways mediating the phenotypic alterations was identified through RNA sequencing analysis and functional rescue experiments. The combinatorial effect of IRAK1/4 inhibitor and sorafenib was tested in vivo. Results: From transcriptome sequencing, we identified IRAK1 in TLR/IRAK pathway to be significantly upregulated in HCC. IRAK1 overexpression in HCC was further confirmed at mRNA and protein levels, and correlated with larger tumor size. Interestingly, IRAK4, an upstream regulator of IRAK1, was also found to be consistently upregulated. Through lentiviral based knockdown and overexpression approaches, we demonstrated that IRAK1 regulates traits of liver T-ICs. Similar phenotypic effects were observed when HCC cells were treated with IRAK1/4 inhibitor. Through RNA sequencing analysis by comparing expression profiles between sh-IRAK1 and control cells, we identified Aldo-Keto Reductase Family 1, Member 10 (AKR1B10) as a downstream target of IRAK1. AKR1B10 was found to be overexpressed in HCC, and correlated with IRAK1 expression. Functional analysis demonstrated that knockdown of AKR1B10 offset the IRAK1 induced T-IC functions through regulating AP-1 complex. Using HCC xenograft model, we found that IRAK1/4 inhibitor in combination with sorafenib demonstrated a maximal tumor suppressive effect. Conclusions: IRAK1/AP-1/AKR1B10 signaling cascade regulates liver T-ICs and sorafenib sensitivity. Targeting IRAK1 alone or in combination with sorafenib might be a novel strategy against HCC.

UBE2T: A Molecular Regulator for Cancer Stemness in Hepatocellular Carcinoma

( Nicole Pui-yu Ho ),( Terence Kin Wah Lee ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Increasing evidence showed that cancer stem cells (CSCs) play a critical role in regulating the tumor relapse and therapeutic resistance of hepatocellular carcinoma (HCC). Given high molecular similarities between liver CSCs and normal liver stem cells, we have enriched the normal stem cell populations by establishing a mouse partial hepactectomy model order to identify critical molecules involved in regulation of liver CSCs. By comparing the expression profiles between the early regenerating liver and intact one, UBE2T was found to be highly upregulated. This, together with the data showing upregulation of UBE2T in enriched liver CSC populations, suggest the role of UBE2T on regulating liver CSCs. Methods: We evaluated the clinic-pathological relevance of UBE2T by qPCR, western blot and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize the functional roles of UBE2T in regulating liver CSCs. The protein binding partner of UBE2T was identified by mass spectrometry analysis. Results: By qPCR analysis, UBE2T mRNA overexpression is found in over 90% of HCC samples and is associated with aggressive tumor behavior and poorer patients’ survival. Overexpression of UBE2T protein level in HCC clinical samples was further confirmed by western blot and IHC analyses. Using lentiviral based knockdown approach, suppression of UBE2T inhibited liver CSC properties, including self-renewal, tumorigenicity, drug resistance and expression of liver CSC markers. Using orthotopic liver xenograft model, UBE2T suppression led to decrease in tumor burden as well as lung metastasis in vivo. Mechanistically, we found UBE2T interacts with E3 ligase Mule and regulates its expression via ubiquitation. Since we further found that UBE2T mediates liver CSC function through Mule-mediated β-catenin activation. Conclusions: We have uncovered a novel UBE2T mediated signaling cascade in regulation of liver CSCs. Developing a specific inhibitor targeting this pathway may be a novel approach for HCC treatment.

Sputum Inflammometry to Manage Chronic Obstructive Pulmonary Disease Exacerbations: Beyond Guidelines

( Carmen Venegas ),( Nan Zhao ),( Terence Ho ),( Parameswaran Nair ) 대한결핵 및 호흡기학회 2020 Tuberculosis and Respiratory Diseases Vol.83 No.3

Quantitative sputum cytometry facilitates in assessing the nature of bronchitis associated with exacerbations of chronic obstructive pulmonary disease (COPD). This is not assessed in most clinical trials that evaluate the effectiveness of strategies to prevent or to treat exacerbations. While up to a quarter of exacerbations may be associated with raised eosinophil numbers, the vast majority of exacerbations are associated with neutrophilic bronchitis that may indicate airway infections. While eosinophilia may be a predictor of response to corticosteroids (oral and inhaled), the limited efficacy of anti-interleukin 5 therapies would suggest that eosinophils may not directly contribute to those exacerbations. However, they may contribute to airspace enlargement in patients with COPD through various mechanisms involving the interleukin 13 and matrix metalloprotease pathways. The absence of eosinophils may facilitate in limiting the unnecessary use of corticosteroids. The presence of neutrophiia could prompt an investigation for the specific pathogens in the airway. Additionally, sputum measurements may also provide insight into the mechanisms of susceptibility to airway infections. Iron within sputum macrophages, identified by hemosiderin staining (and by more direct quantification) may impair macrophage functions while the low levels of immunoglobulins in sputum may also contribute to airway infections. The assessment of sputum at the time of exacerbations thus would facilitate in customizing treatment and treat current exacerbations and reduce future risk of exacerbations.

Bariatric Surgery in Kidney Transplant Candidates and Recipients: Experience at an Asian Center

Sarah Ying Tse Tan,Phong Ching Lee,Sonali Ganguly,Peng Chin Kek,Terence Kee,Quan Yao Ho,Sobhana Thangaraju 대한비만학회 2022 Journal of obesity & metabolic syndrome Vol.31 No.4

Background: Kidney transplant (KT) candidates and recipients with obesity experience more frequent complications such as infection, poorer allograft outcomes, diabetes, and mortality, limiting their eligibility for transplantation. Bariatric surgery (BS) is not commonly performed among KT patients given concerns about immunosuppression absorption, wound healing, infections, and graft outcomes. Its role has not been described before in an Asian KT patient setting. Methods: A retrospective review of patients who underwent BS at the largest KT center in Singapore from 2008 to 2020 was conducted. Metabolic outcomes, immunosuppression doses, graft outcomes, and mortality were studied. Results: Seven patients underwent BS and KT (4 underwent BS before KT, 3 underwent BS after KT; 4 underwent sleeve gastrectomy, 3 underwent gastric bypass). Mean total weight losses of 23.8% at 1 year and 18.6% at 5 years post-BS were achieved. Among the five patients with diabetes, glycemic control improved after BS. There were no deaths in the first 90 days or graft loss in the first year after KT and BS. Patients who underwent BS after KT had no significant changes in immunosuppression dose. Conclusion: BS can be safely performed in KT recipients and candidates and results in sustainable weight losses and improvements in metabolic comorbidities. Although no major complications were observed in our study, close monitoring of this complex group of patients is imperative.

Evolution in hardness and texture of a ZK60A magnesium alloy processed by high-pressure torsion

Lee, Han-Joo,Lee, Sang Kyung,Jung, Ki Ho,Lee, Geun An,Ahn, Byungmin,Kawasaki, Megumi,Langdon, Terence G. Elsevier 2015 Materials science & engineering. properties, micro Vol.630 No.-

<P><B>Abstract</B></P> <P>A ZK60A magnesium alloy was processed by high-pressure torsion (HPT) at room temperature at compressive pressures up to a maximum of 6.0GPa for up to 5 revolutions and this produced significant grain refinement and the development of a bi-modal microstructure. The evolution of hardness was evaluated using measurements of the Vickers microhardness and the change in texture was examined by X-ray diffraction (XRD) analysis. The hardness results demonstrated an evolution with increasing equivalent strain and a strain hardening behavior which may be quantified using a hardenability exponent of ~0.07 when processing under a pressure of 6.0GPa. An XRD analysis over the total disk surface showed that the texture changed from a typical extrusion prior to HPT towards a saturated very weak basal fiber texture which developed in the early stages of HPT and remained constant with additional torsional straining up to 5 turns. By contrast, an XRD analysis of the local microstructure taken at the edges of the processed disks demonstrated significant changes towards a strong basal fiber texture via different texture stages with increasing HPT revolutions. This study demonstrates the importance of carefully documenting the measurement areas selected for texture analysis in the ZK60A alloy after HPT because of the occurrence of significant microstructural variations within the samples.</P>

Safely navigating kidney transplantation during the COVID-19 pandemic: the Singapore General Hospital’s experience

Carolyn Shan-Yeu Tien,Ian Tatt Liew,Quan Yao Ho,Sobhana Thangaraju,Maslinna Binte Abdul Rahman,Constance Lee,Nicole Chelsi Xin Hui Leah,Xia He,Li Ting Siew,Terence Yi Shern Kee 대한이식학회 2023 Korean Journal of Transplantation Vol.37 No.2

Background: The coronavirus disease 2019 (COVID-19) pandemic curtailed transplant activities worldwide, driven by concerns about increased COVID-19-related mortality among kidney transplant recipients (KTRs), infections originating from donors, and decreased availability of surgical and intensive care resources as healthcare resources are reallocated for pandemic response. We examined the outcomes of KTRs at our center before and during the COVID-19 pandemic. Methods: We conducted a retrospective single-center cohort study examining the characteristics and outcomes of patients undergoing kidney transplantation during two periods: January 1, 2017 to December 31, 2019 (pre-COVID-19 era) and January 1, 2020 to June 30, 2022 (COVID-19 era). We reviewed perioperative and COVID-19 infection-related outcomes in both groups. Results: A total of 114 transplants were performed during the pre-COVID-19 era, while 74 transplants were conducted during the COVID-19 era. No differences in baseline demographics were observed. Additionally, there were no significant differences in perioperative outcomes, except for a longer cold ischemia time during the COVID-19 era. However, this did not result in an increased incidence of delayed graft function. Among the KTRs infected with COVID-19 during the pandemic era, no severe complications such as pneumonia, acute kidney injury, or death were reported. Conclusions: With the global transition to an endemic phase of COVID-19, it is imperative to revitalize organ transplant activities. Effective containment workflow, good vaccination uptake, and prompt COVID-19 treatment are essential to ensure that transplants can proceed safely.