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Effects of palbociclib on oral squamous cell carcinoma and the role of PIK3CA in conferring resistance

Cancer Biology & Medicine 2019年第2期16卷 264-275页

作者： Nur Syafinaz Zainal Bernard Kok Bang Lee Zheng Wei Wong Iuan Sheau chin Pei San yee Chai Phei Gan Kein Seong Mun Zainal Ariff Abdul Rahman J. Silvio Gutkind Vyomesh Patel Sok ching Cheong Head and Neck Team Cancer Research Malaysia Selangor 47500 Malaysia Department of Oral & Maxillofacial Clinical Sciences Faculty of Dentistry University of Malaya Kuala Lumpur 50603 Malaysia Department of Pathology Faculty of Medicine University of Malaya Kuala Lumpur 50603 Malaysia Oral Cancer Research and Co-ordinating Centre (OCRCC) Faculty of Dentistry University of Malaya Kuala Lumpur 50603 Malaysia Department of Pharmacology University of California San Diego 92093-5004 CA USA

Objective: Lack of effective therapies remains a problem in the treatment of oral squamous cell carcinoma(OSCC), especially in patients with advanced tumors. OSCC development is driven by multiple aberrancies within the cell cycle pathway, including amplification of cyclin D1 and loss of p16. Hence, cell cycle inhibitors of the CDK4/6-cyclin D axis are appealing targets for OSCC treatment. Here, we determined the potency of palbociclib and identified genetic features that are associated with the response of palbociclib in ***: The effect of palbociclib was evaluated in a panel of well-characterized OSCC cell lines by cell proliferation assays and further confirmed by in vivo evaluation in xenograft models. PIK3CA-mutant isogenic cell lines were used to investigate the effect of PIK3CA mutation towards palbociclib ***: We demonstrated that 80% of OSCC cell lines are sensitive to palbociclib at sub-micromolar ***, palbociclib was effective in controlling tumor growth in mice. We identified that palbociclib-resistant cells harbored mutations in PIK3CA. Using isogenic cell lines, we showed that PIK3CA mutant cells are less responsive to palbociclib as compared to wild-type cells with concurrent upregulation of CDK2 and cyclin E1 protein levels. We further demonstrated that the combination of a PI3 K/mTOR inhibitor(PF-04691502) and palbociclib completely controlled tumor growth in ***: This study demonstrated the potency of palbociclib in OSCC models and provides a rationale for the inclusion of PIK3CA testing in the clinical evaluation of CDK4/6 inhibitors and suggests combination approaches for further clinical studies.

关键词： OSCC palbociclib CDK4/6 inhibitors PIK3CA

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华裔马来西亚作家杨谦来小说中的华人主体建构

华裔马来西亚作家杨谦来小说中的华人主体建构

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作者：王慧仪（ong Huoi yee）北京大学

学位级别：硕士

本文研究的主题是华裔马来西亚作家杨谦来小说中的华人主体建构,以其在1986至2011年期间出版的马来文小说中为主。力图展示以居住国语言创作的杨谦来,如何通过其小说中的华人主体建构对马来文化、文学为主导的国家体系作出回应,以及这... 详细信息

本文研究的主题是华裔马来西亚作家杨谦来小说中的华人主体建构,以其在1986至2011年期间出版的马来文小说中为主。力图展示以居住国语言创作的杨谦来,如何通过其小说中的华人主体建构对马来文化、文学为主导的国家体系作出回应,以及这种回应背后所蕴含的意义。本文将从马来西亚华人写作的背景展开论述,包括马来西亚华人以华文和马来文写作的情形,以便能够在较大的背景下识别杨谦来的马来文写作在马来西亚整个大的文学版图中的坐标与定位,并试图厘清这个定位与其写作尤其是“华人”建构的关系与意义。接下来,本文将对于杨谦来的小说创作做一个概括性的整理,梳理杨谦来小说主要关心的对象与主题。然后本文将从杨谦来作品整体所表现的主题与关注对象,集中至他对华人主体的构建,以从中窥见华人在其小说中的位置或定位,这也是本文探讨的重点。同时,本文将把杨谦来笔下的“华人”与现实或历史中的华人相互参照,以便在更大的谱系中关照杨谦来所构建的“华人”及其政治、文化意涵。本文最后探讨杨谦来小说中的华人主体何以如此建构,并对其“华人”建构进行追根溯源,探讨其“华人”建构背后的意义以及杨谦来在小说中所呈现的身份认同问题。杨谦来的马来文创作对于以中文作为主流语言的马来西亚华人来说,几乎可算是华人文学中的边缘文学,然而因创作的语言为国语而进入了主流或马来“视”界,成为了有机会被听见和看见的华人作家。笔者以为认识杨谦来的华人主体建构是极其重要的,除了籍此了解华人以怎样的面貌体现在他族尤其是主流世界(马来世界)面前,也能籍此理解该作家何以选择以此面貌呈现华人,这些都应该为华人世界所了解,尤其是马来西亚华人世界,这是他们不能否认掉的一部分。杨谦来的华人建构提供了马来西亚华人另一种可能和思考,同时也展现了有别于该国华文作家对华人族群在该国如何自处的思考与抉择。

关键词：马来西亚华人马来小说认同

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The Importance of RTL DFT Check In ASIC Design

The Importance of RTL DFT Check In ASIC Design

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7th Workshop on RTL and High Level Testing

作者： Ng,Wei Tee ong,chin Hu Ang,Boon Hui Marvell Semiconductor Marvell Semiconductor Marvell Semiconductor

＜正＞This paper discusses the RTL DFT check in ASIC design flow for achieving faster turn-around time. We discuss the key RTL DFT design rules and flow followed by its general benefits. The correlation between RTL an... 详细信息

关键词： DFT ATPG Scan Design RTL DFT

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Matrisomal genes in squamous cell carcinoma of head and neck influence tumor cell motility and response to cetuximab treatment

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Cancer Communications 2022年第4期42卷 355-359页

作者： Kah yee Goh Kah Weng Lau Terence You De Cheng Su chin Tham Chwee Teck Lim Narayanan Gopalakrishna Iyer Su Bin Lim Darren Wan-Teck Lim Division of Medical Oncology National Cancer Centre SingaporeSingapore 169610 Department of Pathology National University HospitalSingapore 119074 A*STAR ProteosInstitute of Molecular and Cell BiologySingapore 138673 Department of Biomedical Engineering Mechanobiology InstituteNational University of SingaporeT-LabSingapore 117411 Institute for Health Innovation and Technology(iHealthtech) National University of SingaporeMD6Singapore 117599 Department of Head and Neck Surgery National Cancer Centre Singapore11 Hospital CrescentSingapore 169610 Office of Academic and Clinical Development Duke-NUS Medical SchoolSingapore 169857 Department of Biochemistry and Molecular Biology Ajou University School of MedicineYeongtong-GuSuwon 16499South Korea

Dear Editor,Head and neck squamous cell carcinoma(HNSCC)is the sixth most common cancer globally[1,2].Despite the improvement in treatment modalities,up to 50%of HNSCC patients still develop recurrent/metastatic(R/M)disease[3],and platinum-based chemotherapy with cetuximab and/or pembrolizumab has become the standard of care[4].However,R/M HNSCC is challenging to treat,the prognosis is poor,and there is an unmet need for new therapeutic targets.

关键词： chemotherapy cetuximab treatment

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Overview of finite elements simulation of temperature profile to estimate properties of materials 3D-printed by laser powder-bed fusion

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chinese Physics B 2020年第4期29卷 98-109页

作者： Habimana Jean Willy Xinwei Li Yong Hao Tan Zhe Chen Mehmet Cagirici Ramadan Borayek Tun Seng Herng Chun yee Aaron ong Chaojiang Li Jun Ding Department of Materials Science and Engineering Faculty of EngineeringNational University of Singapore9 Engineering Drive 1Singapore 117576Singapore

Laser powder bed fusion(LPBF),like many other additive manufacturing techniques,offers flexibility in design expected to become a disruption to the manufacturing *** current cost of LPBF process does not favor a try-anderror way of research,which makes modelling and simulation a field of superior importance in that area of *** this work,various methods used to overcome challenges in modeling at different levels of approximation of LPBF process are *** efforts made towards a reliable and computationally effective model to simulate LPBF process using finite element(FE)codes are presented.A combination of ray-tracing technique,the solution of the radiation transfer equation and absorption measurements has been used to establish an analytical equation,which gives a more accurate approximation of laser energy deposition in powder-substrate *** this new analytical energy deposition model is used in in FE simulation,with other physics carefully set,it enables us to get reliable cooling curves and melt track morphology that agree well with experimental *** use of more computationally effective approximation,without explicit topological changes,allows to simulate wider geometries and longer scanning time leading to many applications in real engineering *** applications are herein presented including:prediction of printing quality through the simulated overlapping of consecutive melt tracks,simulation of LPBF of a mixture of materials and estimation of martensite inclusion in printed steel.

关键词： selective laser melting powder bed fusion finite element modeling laser absorption

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Vertical Distributions of Ozone and Nitrogen Dioxide Observed in a Polluted Marine Boundary Layer around Kaohsiung City

Vertical Distributions of Ozone and Nitrogen Dioxide Observe...

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第七届亚洲气溶胶会议

作者： ching-Ho Lin chin-Hsing Lai yee-Lin Wu Department of Environmental Engineering and Science Fooyin University Department of Environmental Engineering National Cheng-Kung University

In a coastal region, ozone pollution is usually dominated by a sea-breeze circulation. However, vertical structures of ozone and its precursors within the circulation are seldom observed. Some preliminary results obtained during a 10-day field study are presented in this work. The field study was conducted in October 2009 at a small island, Little Liuqui, 15 km from the nearest coastline of southern Taiwan and 25 km to the Kaohsiung City. A tethered sounding system was installed at the shoreline of the small island to measure vertical features of meteorological parameters, ozone and nitrogen dioxide over polluted marine area. Elevated plumes at 400-800 m over the sea were detected, noticed by low ozone concentrations and high nitrogen dioxide at night. Elevated ozone layers with concentrations more than 100 ppb were observed at day above marine boundary layers with a typical depth at 250-500 m. The results suggested the observed elevated ozone layers were possibly formed by the emission of large point sources around the Kaohsiung City and the ozone within the layers may be brought into the marine boundary layers by the subsidence and the turbulent diffusion.

关键词： Vertical distribution ozone nitrogen dioxide marine boundary layer point source

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64-row multi-dector computed tomography coronary image from a center with early experience: first illustration of learning curve

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Journal of Geriatric Cardiology 2006年第1期3卷 29-34页

作者： Sze Piaw chin Tiong Kiam ong Chee Khoon LIEW M.Tobias Seyfarth Fong Yean Yip ALAN Houng Bang LIEW Kui Hian SIM Dept of Cardiology Sarawak General Hospital Siemens Cardiac Solutions Erlangen Germany

Background and objectives The recent joint ACCF/AHA clinical competence statement on cardiac imaging with multi-detector computed tomography recommended a minimum of 6 months training and 300 contrast examinations, of which the candidate must be directly involved in at least 100 studies. Whether this is adequate to become proficient in interpretation of coronary computed tomogsignificant coronary stenosis in a center with 1 year's experience using a 64-row scanner. Methods A total of 778 patients underwent contrast-enhanced CTA between January and December 2005. Out of these patients, 301 patients also underwent contrast-enhanced conventional coronary angiography (CCA). These patients were divided into 4 groups according to the time the examination was underwent. Group Q1: first quarter of the year (n=20), Group Q2: second quarter (n=128), Group Q3: third quarter (n=134), and Group Results The sensitivity, specificity, positive, and negative predictive values were Q1 - 64%, 89%, 49% and 94%, respectively; Q2 -79%, 96%, 74% and 97%, respectively; Q3 - 78%, 96%, 74%, 97%, respectively, and Q4 - 100% for all. Conclusions In a center with formal training and high caseload, our accuracy in CTA analysis reached a plateau after 6 months experience. Test-bolus protocols produce better image quality and can improve accuracy. New centers embarking on CTA will need to overcome an initial 6-month learning curve depending upon the caseload during which time they should consider correlation with CCA.

关键词： computed tomography training angiography coronary artery disease

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Endogenous endophthalmitis secondary to melioidosis in paediatric patients: Case series and review article

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Journal of Acute Disease 2018年第6期7卷 234-240页

作者： Wendy ong chin Feng Wee Min Teh Wan-Hazabbah Wan Hitam Haslina Mohammad Ali Department of Ophthalmology School of Medical SciencesHealth CampusUniversiti Sains MalaysiaKubang Kerian16150KelantanMalaysia Hospital Universiti Sains Malaysia Kubang KerianKelantanMalaysia Hospital Sultanah Bahiyah Alor SetarKedahMalaysia

Endogenous endophthalmitis is a devastating infection of the eye which can lead to permanent blindness. We report two rare cases of paediatric endogenous endophthalmitis secondary to melioidosis with contrasting visual outcomes. Both patients presented with acute painful visual loss with poor vision on presentation after exposure to open water sources (swimming at two separate locations with waterfalls). Both were diagnosed to have melioidosis endogenous endophthalmitis based on the ocular features clinically and via positive melioidosis serology. They otherwise did not exhibit any symptoms and signs suggestive of systemic melioidosis infection. Even though the two children demonstrated severe ocular involvement, ocular culture from vitreous and aqueous sampling taken from one of the patients did not yield any positive results. No ocular sampling was taken from the other patient. After standard antimicrobial treatment, the first patient responded well with good visual recovery without requiring any surgical intervention for the endophthalmitis. In contrast, our second patient ended up with poor visual outcome despite undergoing multiple intravitreal antibiotic injections and early pars plana vitrectomy. This is because he developed extensive retinal detachment due to the aggressive ocular infection. The diagnosis of endogenous endophthalmitis due to ocular melioidosis remains challenging and requires a high index of suspicion in areas endemic for the causative organism. Early empirical antibiotic treatment should be initiated in suspicious cases, even though the treatment outcomes may vary greatly.

关键词： Ocular melioidosis Endogenous endophthalmitis Vitrectomy Intravitreal antibiotics

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The Efficacy of Plant-Based Ionizers in Removing Aerosol for COVID-19 Mitigation

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Research 2021年第1期2021卷 70-80页

作者： Ady Suwardi chin Chun Ooi Dan Daniel Chee Kiang Ivan Tan Hongying Li Ou Yang Zhong Liang Yuanting Karen Tang Jing yee Chee Anton Sadovoy Shu-Ye Jiang Srinivasan Ramachandran Enyi Ye Chang Wei Kang Wun Chet Davy Cheong Keng Hui Lim Xian Jun Loh Institute of Materials Research and Engineering 2 Fusionopolis WayAgency for ScienceTechnology and ResearchSingapore 138634 Institute of High Performance Computing 1 Fusionopolis WayAgency for ScienceTechnology and ResearchSingapore 138632 Temasek Life Sciences Laboratory 1 Research LinkNational University of SingaporeSingapore 117604

Small-sized droplets/aerosol transmission is one of the factors responsible for the spread of COVID-19,in addition to large droplets and surface contamination(fomites).While large droplets and surface contamination can be relatively easier to deal with(i.e.,using mask and proper hygiene measures),aerosol presents a different challenge due to their ability to remain airborne for a long *** calls for mitigation solutions that can rapidly eliminate the airborne ***-COVID-19,air ionizers have been touted as effective tools to eliminate small *** this work,we sought to evaluate the efficacy of a novel plant-based ionizer in eliminating *** was found that factors such as the ion concentration,humidity,and ventilation can drastically affect the efficacy of aerosol *** aerosol removal rate was quantified in terms of ACH(air changes per hour)and CADR-(clean air delivery rate-)equivalent unit,with ACH as high as 12 and CADR as high as 141 ft^(3)/minute being achieved by a plant-based ionizer in a small isolated *** work provides an important and timely guidance on the effective deployment of ionizers in minimizing the risk of COVID-19 spread via airborne aerosol,especially in a poorly-ventilated environment.

关键词： aerosol eliminate sized

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Ischaemic Monomelic Neuropathy in a Diabetic Patient after Brachio-Basilic Arteriovenous Fistula Creation

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Case Reports in Clinical Medicine 2016年第6期5卷 199-202页

作者： Nicholas B. Shannon Siew Ping Chng Chieh Suai Tan chin-Ann Johnny ong Duke-NUS Graduate Medical School Singapore City Singapore Singapore General Hospital Singapore City Singapore

Introduction: The number of people with diabetes is increasing in every country. Recent estimates put the prevalence at 8.3% of adults, with a predicted rise to 10.1 in 2035 [1]. Although less than 1% of patients with diabetes require definitive haemodialysis, this still represents a significant number who may require arteriovenous fistula creation. Presentation: We report a case of IMN occurring in a patient with end stage diabetic nephropathy following brachio-basilic arteriovenous fistula creation for chronic maintenance haemodialysis. Discussion: Ischaemicmonomelic neuropathy (IMN) has developed as a distinct clinical entity involving dysfunction of multiple peripheral nerves following vascular access. Symptom onset is usually immediate, and neurological symptoms are dominant, generally in the absence of significant clinical ischaemia. Acute neurological symptoms may be disabling and irreversible, but prompt ligation of arteriovenous fistula can prevent permanent disability. Conclusion: Ischaemicmonomelic neuropathy (IMN) is a rare but serious complication of vascular access for arteriovenous fistula for haemodialysis and should be considered in the differential diagnosis of hand dysfunction following such surgery. While the condition is not preventable or predictable, prompt recognition and treatment can lead to prevention of permanent disability.

关键词： Diabetes Vascular Neuropathy

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