266 research outputs found
Abstract 4772: Stearoyl-CoA Desaturase (SCD1) regulates liver tumor initiating cells through modulating ER stress
Abstract
Sorafenib is the FDA approved drug for patients with advanced hepatocellular carcinoma (HCC), but the survival benefit is only modest, partly due to drug resistance. Increasing evidence shows that tumor-initiating cells (T-ICs) are intrinsically resistant to conventional treatments, and targeting signaling pathways in T-ICs provides potential therapeutic targets for HCC. In our established enriched T-IC population, we identified the activation of a lipogenesis pathway in which expression of stearoyl-CoA desaturase-1 (SCD1), an enzyme involved in the conversion of saturated into monounsaturated fatty acids, was most significant. SCD1 overexpression is frequently found in HCC samples and is significantly associated with poorer patient survival. Using overexpression and knockdown approaches, SCD1 was found to regulate the traits of T-ICs, including tumorigenicity, self-renewal, differentiation, drug resistance and the expression of liver T-IC markers. Interestingly, SCD1 was markedly upregulated in our established sorafenib-resistant cell lines as well as patient-derived xenografts (PDTXs), and its overexpression predicts the clinical response of HCC patients to sorafenib treatment. Consistently, pharmacological inhibition of SCD1 suppressed T-IC phenotypes and enhanced sensitivity to sorafenib treatment. Using a patient-derived xenograft model, we found that a novel SCD1 inhibitor (SSI-4) in combination with sorafenib demonstrated a maximal tumor suppressive effect. Induction of endoplasmic reticulum (ER) stress-mediated T-IC differentiation can account for the enhanced sensitivity towards sorafenib treatment upon SCD1 suppression. In conclusion, SCD1-induced ER stress may specifically increase the sensitivity of liver T-ICs to the effects of sorafenib treatment. Targeting SCD1 in combination with sorafenib therapy may be a novel therapeutic regimen against HCC.
Citation Format: Kin Fai Ma, Eunice Yuen Ting Lau, Irene Oi Lin Ng, Kin Wah Lee. Stearoyl-CoA Desaturase (SCD1) regulates liver tumor initiating cells through modulating ER stress [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4772. doi:10.1158/1538-7445.AM2017-4772</jats:p
Sustainable health and long-term care solutions for an aging population Advances in medical diagnosis, treatment, and care (AMDTC) book series./ [edited by] Ben Fong, Artie Ng, Peter Yuen.
"Premier Reference Source"--Cover image.Includes bibliographical references and index."This book explores the issues pertinent to health cost and ways of financing health care, development of innovative service models to meet the increased demands, designing infrastructure of collection and utilization of data for performance and quality improvement, and setting the framework for training and research in long-term care"--Provided by publisher.1. The economics of long term care : key concepts and major financing and delivery models / Peter Yuen -- 2. Moving Towards Universal Health Coverage : Challenges for the Present and Future in China / Chin Yuen Luke -- 3. Long-Term Care Spending Relevant to U.S. Medicaid Expansion : Medicaid Long-Term Care Spending / Mary Schmeida, Ramona Sue McNeal -- 4. The Continuum of Care : A Case Study of a Senior Service Centre for Geriatric Care in Toronto, Canada / Kwong Yuen Liu, Bonnie H.Y. Wong, Maria Chu, William Y.W. Leung -- 5. United Kingdom Health Promotion Initiatives for Healthy Aging / Susan Dawkes, Simon T. Cheung -- 6. Public private partnership in health and long-term care : the Hong Kong experience / Wing Tung Ho, Ben Yuk Fai Fong -- 7. Development of Accreditation Approach of Elderly Care Service Providers : Experience from East and West / Artie W. Ng, Tiffany C.H. Leung, Jacky C.K. Ho -- 8. Integrated Care as a Strategic Solution for Active Aging in the Community : Tools and Models / Eman Leung, Cheuk Wing Chau, Alison Lee, Youhua (Frank) Chen, Diana T.F. Lee -- 9. Knowledge Management for Health Care and Long-Term Care in the Technology-Organization-Environment Context / Man Fung Lo, Peggy Mei Lan Ng -- 10. Using pervasive computing for sustainable healthcare in an aging population / Adam Ka Lok Wong, Man Fung Lo -- 11. Corporate social responsibility of long-term care service enterprises : a Hong Kong perspective / Vincent T. Law, Candace W. Ng -- 12. Contributions of Volunteers in Long-Term Care in Hong Kong / Ting-leung Lau, Kin-yee Chan -- 13. SSLD and senior service : a comprehensive model for practice / Ka Tat Tsang, Chui Fan Linus Ip -- 14. Aging in place / Ben Yuk Fai Fong, Vincent T. Law -- 15. Preferred place of care and death among the terminally-ill : Asian perspectives and implications for Hong Kong / Raymond Kam-wing Woo, Annie Oi Ling Kwok, Doris Man Wah Tse -- 16. Community-Based Rehabilitation in Hong Kong : Opportunities and Challenges / Kar-wai Tong, Kenneth N.K. Fong -- 17. Chinese Herbal Medicine in the Management of Atherosclerosis-Related Chronic Conditions in an Aging Population / Enoch Chan, Sai Wang Seto, Tsoi Ming Au Yeung, Gabriel Hoi Huen Chan -- 18. Eating Habits of Young Persons for Healthy Aging : An Exploratory Study Involving University Students in Hong Kong / Simon T. Cheung, Susan Dawkes.1 online resource (xxii, 441 pages)
Phosphorylation of nucleophosmin at threonine 234/237 is associated with HCC metastasis
Hepatocellular carcinoma (HCC) is frequently complicated by the occurrence of intrahepatic and extrahepatic metastases, leading to poor prognosis. To improve the prognosis for HCC patients, there is an urgent need to understand the molecular mechanisms of metastasis in HCC. Since protein Serine/Threonine phosphorylation emerges to be an important posttranslational modification critical in signaling process associated with cell proliferation, survival and metastasis, we employed a pair of primary tumor-derived and corresponding lung-metastatic counterparts (PLC/PRF/5-PT and PLC/PRF/5-LM) and aimed to identify these changes using CelluSpot<sup><small>TM</small></sup> Serine/Threonine kinase peptide array. Upon analysis, we found phosphorylated level of nucleophosmin (NPM) at Threonine 234/237 (p-NPM-Thr<sup>234/237</sup>) had remarkably high level in metastatic HCC cells (PLC-LM) than the corresponding primary HCC cell line (PLC-PT). Similar observation was observed in another match primary and their metastatic counterparts (MHCC-97L and MHCC-97H). By immunohistochemical staining, p-NPM-Thr<sup>234/237</sup> was consistently found to be preferentially expressed in metastatic HCCs when compared with primary HCC in 28 HCC cases (<em>p</em> < 0.0001). By overexpressing Flag-tagged NPM and its phosphorylation site mutant (Thr234/237A) into low p-NPM-Thr<sup>234/237</sup> expressing cells (Hep3B and Huh7) using a lentiviral based approach, we demonstrated that p-NPM-Thr<sup>234/237</sup> is critical in invasion and migration of HCC cells, and this effect was mediated by cyclin-dependent kinase 1 (CDK1). Wild-type NPM was found to physically interact with a metastatic gene, ROCK2, and defective in Thr234/237 phosphorylation decreased its binding affinity, resulting in decrease in ROCK2 mediated signaling pathway. Identification of CDK1/p-NPM/ROCK2 signaling pathway provides a novel target for molecular therapy against HCC metastasis
Psychometric properties of the Chinese version of the Intimacy, Passion, and Commitment Scale
Psychometric Properties of the Chinese Version of the Multidimensional Smartphone Use Scale
The Multidimensional Smartphone Use Scale (MSUS) developed by Geçer et al. (2024) measure four dimensions of smartphone-related problems: nomophobia, ringxiety, texiety, and phubbing. To date, the MSUS is not available in Chinese. This study aims to develop a Chinese version of the MSUS and examine its factor structure, internal consistency reliability, and concurrent validity with smartphone addiction using a sample of Chinese university students in Hong Kong
Perceived General Similarity and Relationship Satisfaction: The Role of Attributional Confidence
Perceived General Similarity and Relationship Satisfaction: The Role of Attributional Confidence
Stress Communication, Communication Satisfaction, and Relationship Satisfaction: An Actor-Partner Interdependence Mediation Model
Past research has revealed positive effects of stress communication by oneself and by the partner on relationship satisfaction. However, the mechanisms through which stress communication by oneself and by the partner influence relationship satisfaction have not been well studied. The purpose of the present study was to examine the effect of stress communication on relationship satisfaction and the mediating role of communication satisfaction in this association. A total of 227 unmarried heterosexual couples were recruited. An actor-partner interdependence mediation model was used to examine the hypothesized relationships. The results showed that the actor effects of stress communication on relationship satisfaction were mediated by the actor effects of communication satisfaction. Moreover, the indirect effect of male stress communication on female relationship satisfaction through female communication satisfaction was found to be significant. These findings provide insights into the mechanism through which stress communication influences relationship satisfaction. Theoretical and practical implications are discussed
Stress Communication, Communication Satisfaction, and Relationship Satisfaction: An Actor-Partner Interdependence Mediation Model
Past research has revealed positive effects of stress communication by oneself and by the partner on relationship satisfaction. However, the mechanisms through which stress communication by oneself and by the partner influence relationship satisfaction have not been well studied. The purpose of the present study was to examine the effect of stress communication on relationship satisfaction and the mediating role of communication satisfaction in this association. A total of 227 unmarried heterosexual couples were recruited. An actor-partner interdependence mediation model was used to examine the hypothesized relationships. The results showed that the actor effects of stress communication on relationship satisfaction were mediated by the actor effects of communication satisfaction. Moreover, the indirect effect of male stress communication on female relationship satisfaction through female communication satisfaction was found to be significant. These findings provide insights into the mechanism through which stress communication influences relationship satisfaction. Theoretical and practical implications are discussed
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