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Pan-CDK inhibition augments cisplatin lethality in nasopharyngeal carcinoma cell lines and xenograft models

Signal Transduction and Targeted Therapy 2018年第1期3卷 237-245页

作者： Nicholas LSyn Pei Li Lim Li Ren Kong Lingzhi Wang Andrea Li-Ann Wong Chwee Ming Lim Thomas Kwok Seng Loh Gerhard Siemeister boon cher goh Wen-Son Hsieh Cancer Science Institute of Singapore National University of SingaporeSingaporeSingapore Department of Haematology-Oncology National University Cancer InstituteSingaporeSingapore Department of Pharmacology Yong Loo Lin School of MedicineNational University Health SystemSingaporeSingapore Department of Otolaryngology-Head and Neck Surgery National University Health SystemSingaporeSingapore Drug Discovery TRG OncologyBayer Pharma AGBerlinGermany

In addition to their canonical roles in regulating cell cycle transition and transcription,cyclin-dependent kinases(CDKs)have been shown to coordinate DNA damage response pathways,suggesting a rational pairing of CDK inhibitors with genotoxic chemotherapeutic agents in the treatment of human ***,we report that roniciclib(BAY1000394),a potent pan-CDK inhibitor,displays promising anti-neoplastic activity as a single agent and potentiates cisplatin lethality in preclinical nasopharyngeal carcinoma(NPC)*** of the NPC cell lines HONE-1,CNE-2,C666-1,and HK-1 was effectively curbed by roniciclib treatment,with IC_(50)values between 11 and 38 nmol/*** anticancer effects were mediated by pleiotropic mechanisms consistent with successful blockade of cell cycle CDKs 1,2,3,and 4 and transcriptional CDKs 7 and 9,ultimately resulting in arrest at G1/S and G2/M,downregulation of the transcriptional apparatus,and repression of anti-apoptotic *** enhanced tumor cell apoptosis was achieved following combined treatment with 10 nmol/L roniciclib and 2.0μmol/L cisplatin;this combination therapy achieved a response over 250%greater than either drug *** roniciclib chemosensitized NPC cells to cisplatin,it did not sensitize untransformed(NP69)*** administration of 0.5 mg/kg roniciclib to BALB/c xenograft mice was well tolerated and effectively restrained tumor growth comparable to treatment with 6 mg/kg cisplatin,whereas combining these two agents produced far greater tumor suppression than either of the *** summary,these data demonstrate that roniciclib has strong anti-NPC activity and synergizes with cisplatin chemotherapy at clinically relevant doses,thus justifying further evaluation of this combinatorial approach in clinical settings.

关键词： cisplatin nasopharyngeal doses

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新型阿霉素抗耐药性隐形脂质体的体外细胞毒和体内毒性研究

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药学学报 2005年第5期40卷 475-480页

作者：王坚成刘晓岩吕万良 How-Sung Lee boon-cher goh 张强北京大学药学院药剂系北京100083 北京大学药学院细胞与分子药理系北京100083 新加坡国立大学医学院药理系新加坡117597 新加坡国立大学医院肿瘤研究所新加坡117597

目的　多药耐药(multidrugresistance,MDR)是目前临床肿瘤治疗的主要障碍。本文研制了新型阿霉素抗耐药性隐形脂质体(DARSLs),并对其体外细胞毒和体内毒性进行评价。方法　采用硫酸铵梯度法将阿霉素(DOX)和维拉帕米(VER)药物同时包载到... 详细信息

目的　多药耐药(multidrugresistance,MDR)是目前临床肿瘤治疗的主要障碍。本文研制了新型阿霉素抗耐药性隐形脂质体(DARSLs),并对其体外细胞毒和体内毒性进行评价。方法　采用硫酸铵梯度法将阿霉素(DOX)和维拉帕米(VER)药物同时包载到隐形脂质体内,制备成DARSLs;采用耐药性鼠前列腺肿瘤细胞株MLLB2和人子宫肉瘤细胞株MES SA/DX5进行体外细胞毒性评价;采用SD大鼠对阿霉素抗耐药性隐形脂质体进行体内毒性评价。结果　在药脂比(DOX/VER/Lipid,w/w/w)为1∶0 11∶10时,阿霉素包封率大于90%,维拉帕米包封率约为70%。平均粒径为(118 .1±22. 3)nm。体外细胞毒性实验证实该脂质体能够在体外有效地逆转肿瘤细胞耐药性,并导致耐药肿瘤细胞生长抑制。体内系统毒性及心脏毒性实验结果显示,该脂质体能够明显改善游离阿霉素单独使用或与维拉帕米联合使用时产生的全身毒性,尤其是心脏毒性。结论　DARSLs具有相对较低的毒性,且能有效抑制耐药肿瘤的生长。

关键词：阿霉素维拉帕米隐形脂质体多药耐药性毒性

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非小细胞肺癌联合治疗的现状与展望

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中国癌症杂志 2005年第3期15卷 201-205页

作者： John Wong boon cher goh Jiade Lu 罗晓阳 The Cancer Institute National Healthcare GroupSingapore 上海交通大学附属第六人民医院胸心外科

对T1、T2期没有淋巴结受侵的NSCLC患者只要能耐受手术、肺叶切除术应作为首选。对Ⅰ、Ⅱ、ⅢA期符合手术指征的患者单纯手术是不够的,必须进行辅助化疗并从中受益,但辅助放疗因显著的副作用,使Ⅰ、Ⅱ期患者反而有害。对ⅢA期NSCLC患者... 详细信息

对T1、T2期没有淋巴结受侵的NSCLC患者只要能耐受手术、肺叶切除术应作为首选。对Ⅰ、Ⅱ、ⅢA期符合手术指征的患者单纯手术是不够的,必须进行辅助化疗并从中受益,但辅助放疗因显著的副作用,使Ⅰ、Ⅱ期患者反而有害。对ⅢA期NSCLC患者术后使用放化疗,亦无益于改善局控率和延长生存期。关于可切除的Ⅰ、Ⅱ、ⅢA期NSCLC的新辅助化疗尚有争议。一项RTOG和SWOG的Ⅲ期随机对照临床试验(ⅢA期NSCLC患者先联合放化疗,后行手术和化疗)以评估ⅢANSCLC患者的预后已启动。本文综述了一系列重要文献及临床试验。讨论了各期NSCLC联合治疗的现状及展望未来的发展方向。

关键词：肺肿瘤癌,非小细胞肺/综合治疗预后生活质量

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Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers

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中国药理学与毒理学杂志 2015年第S1期29卷 80-80页

作者： Feng Li Muthu K. Shanmugam Kodappully Sivaraman Siveen Fan Wang Tina H. Ong Ser Yue Loo Mahadeva M.M. Swamy Somnath Mandal Alan Prem Kumar boon cher goh Tapas Kundu Kwang Seok Ahn Ling Zhi Wang Kam Man Hui Gautam Sethi Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Singapore 117957 Cancer Science Institute of Singapore Centre for Translational Medicine Singapore 117957 Division of Cellular and Molecular Research Humphrey Oei Institute of Cancer Research National Cancer Centre Singapore 169610 Genome Institute of Singapore Agency for Science Technology and Research (A*STAR) Singapore Jawaharlal Nehru Centre for Advanced Scientific Research Molecular Biology and Genetics Unit Transcription and Disease Laboratory Bangalore 560064 India School of Biomedical Sciences Faculty of Health Sciences Curtin University Western Australia 6009 Australia Department of Biological Sciences University of North Texas Denton Texas 76203 Department of Haematology-Oncology National University Health System Singapore 117957 College of Korean Medicine Kyung Hee University Seoul 130-701 Republic of Korea

OBJECTIVE Platinum compounds such as cisplatin and carboplatin are frequently used as the first-line chemotherapy for the treatment of the head and neck squamous cell carcinoma(HNSCC).In the present study,we investigated whether garcinol,apolyisoprenylated benzophenone can chemosensitize HNSCC to *** The effect of garcinol and cisplatin on HNSCC was assessed by MTT,Western blotting,real time PCR,FACS,immunohistochemistry,DNA binding assay and xenograft mouse *** We found that garcinol inhibited the viability of a panel of diverse HNSCC cell lines,enhanced the apoptotic effect of cisplatin,suppressed constitutive as well as cisplatin-induced NF-κB activation,and downregulated the expression of various oncogenic gene products(cyclin D1,Bcl-2,survivin and VEGF).In vivo study showed that administration of garcinol alone(0.5 mg·kg-1,ip five times/week)significantly suppressed the growth of the tumor,and this effect was further increased by *** the markers of proliferation index(Ki-67)and microvessel density(CD31)were downregulated in tumor tissues by the combination of cisplatin and *** pharmacokinetic results of garcinol indicated that good systemic exposure was achievable after ip administration of garcinol at 0.5and 2mg·kg-1 with mean peak concentration(cmax)of 1825.4 and 6635.7nmol·L-1 in the mouse serum,*** Overall,our results suggest that garcinol can indeed potentiate the effects of cisplatin by negative regulation of various inflammatory and proliferative biomarkers.

关键词： HNSCC chemoresistance NF-κB proliferation garcinol

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Accelerated initiation of oblique detonation induced by disturbance in detonative zone

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Chinese Journal of Aeronautics 2023年第11期36卷 153-164页

作者： Yichen ZHANG Gaoxiang XIANG Jia YU Ke JIN Kek boon goh Institute of Extreme Mechanics Northwestern Polytechnical UniversityXi’an 710129China Research and Development Institute Northwestern Polytechnical University in ShenzhenShenzhen 518057China Innovation Center NPU Chongqing Northwestern Polytechnical UniversityChongqing 401135China School of Aerospace Science and Technology Xidian UniversityXi’an 710126China Department of Mechanical Engineering School of EngineeringMonash University MalaysiaSelangor 47500Malaysia

In the real flow for high altitude,the initiation mechanism of the oblique detonation involves the coupling of complex wave structures and combustion waves,which may result in the phenomenon of *** approach of stable initiation is one of the key factors that restricting the oblique detonation engine from theory to *** wave structure,initiation characteristics and characteristic parameters of the flow field are analyzed,the two-dimensional Euler equation considering the detailed chemical reactions of multi-component are ***,the approaches of blunt bump and transverse jet are combined used to shorten the detonation distance of the oblique *** show that these methods can promote the accelerated initiation of the oblique detonation effectively,and the detonation distance can be shortened more than 90%.There are two wave structures induced by the blunt bump:weak coupled and strong coupled,adding the transverse jet promotes the transition between these two wave ***,the shape of the bump and the characteristic parameters of the transverse jet are *** streamline-shape bump can eliminate the recirculation zone formed after the circle bump and the ellipse *** transverse jet will produce an oblique detonation wave at the front of the jet position,which changes the wave structure and initiation mode of the oblique detonation *** is expected to reveal the accelerated initiation mechanism of oblique detonation under the induction zone disturbance and complex flow environment,deepen the understanding of the detonation law of oblique detonation wave under real flow conditions,and provide a scientific basic for the development of the combustor of the oblique detonation engine.

关键词： Acetylene Oblique detonation Initiation acceleration Blunt bump Transverse jet Numerical simulation

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Modeling and Simulation for Transient Thermal Analyses Using a Voltage-in-Current Latency Insertion Method

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Journal of Electronic Science and Technology 2022年第4期20卷 383-395页

作者： Wei Chun Chin boon Chun New Nur Syazreen Ahmad Patrick goh School of Electrical and Electronic Engineering Universiti Sains MalaysiaPenang 14300

This article presents a modeling and simulation method for transient thermal analyses of integrated circuits(ICs)using the original and voltage-in-current(VinC)latency insertion method(LIM).LIM-based algorithms are a set of fast transient simulation methods that solve electrical circuits in a leapfrog updating manner without relying on large matrix operations used in conventional Simulation Program with Integrated Circuit Emphasis(SPICE)-based methods which can significantly slow down the solution *** conversion from the thermal to electrical model is performed first by using the analogy between heat and electrical *** electrical inductance has no thermal equivalence,a modified VinC LIM formulation is presented which removes the requirement of the insertion of fictitious *** examples are presented,which show that the modified VinC LIM formulation outperforms the basic LIM formulation,in terms of both stability and accuracy in the transient thermal simulation of ICs.

关键词： Latency insertion method(LIM) numerical simulation thermal analysis transient simulation

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Considerations for bariatric surgery in patients with cirrhosis

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World Journal of Gastroenterology 2018年第28期24卷 3112-3119页

作者： George boon-Bee goh Philip R Schauer Arthur J McCullough Department of Gastroenterology and Hepatology Singapore General HospitalSingapore 169608Singapore Duke-NUS Graduate Medical School Singapore 169608Singapore Bariatric and Metabolic Institute Cleveland ClinicClevelandOH 44195United States Department of Gastroenterology Cleveland ClinicClevelandOH 44195United States Department of Pathobiology Cleveland ClinicClevelandOH 44195United States

With the ever increasing global obesity pandemic, clinical burden from obesity related complications are anticipated in parallel. Bariatric surgery, a treatment approved for weight loss in morbidly obese patients, has reported to be associated with good outcomes, such as reversal of type two diabetes mellitus and reducing all-cause mortality on a long term basis. However, complications from bariatric surgery have similarly been reported. In particular, with the onslaught of non-alcoholic fatty liver disease(NAFLD) epidemic, in associated with obesity and metabolic syndrome, there is increasing prevalence of NAFLD related liver cirrhosis, which potentially connotes more risk of specific complications for surgery. Bariatric surgeons may encounter, either expectedly or unexpectedly, patients with non-alcoholic steatohepatitis(NASH) and NASH related cirrhosis more frequently. As such, the issues and considerations surrounding their medical care/surgery warrant careful deliberation to ensure the best outcomes. These considerations include severity of cirrhosis, liver synthetic function, portal hypertension and the impact of surgical factors. This review explores these considerations comprehensively and emphasizes the best approach to managing cirrhotic patients in the context of bariatric surgery.

关键词： Cirrhosis Portal hypertension Non-alcoholic fatty liver disease Bariatric surgery Complications

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Barcelona Clinic Liver Cancer outperforms Hong Kong Liver Cancer staging of hepatocellular carcinoma in multiethnic Asians: Real-world perspective

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World Journal of Gastroenterology 2017年第22期23卷 4054-4063页

作者： James Weiquan Li boon-Bee George goh Pik-Eu Chang Chee-Kiat Tan Department of Gastroenterology and Hepatology Duke-NUS Medical School

To compare the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC) classification systems when applied to HCC patients from the largest tertiary-level centre in *** thousand two hundred and seventy hepatocellular carcinoma (HCC) patients prospectively enrolled in a tertiary-level centre registry in Singapore since 1988 were studied. Patients were grouped into their respective BCLC and HKLC stages. Data such as demography, aetiology of HCC and type of treatment were collected. Survival data was based on census with the National Registry of Births and Deaths on 31st October 2015. Statistical analyses were done using SPSS version 21 (Chicago, IL, United States). Survival analyses were done by the Kaplan-Meier method. Differences in survival rates were compared using the log-rank *** median age at presentation was 63 years (range 13-94); male 82.4%; Chinese 89.4%, Malay 7.1%, Indian, 2.8%. Hepatitis B was the predominant aetiology (75.0%; Hepatitis C 7.2%, Hepatitis B and C co-infection 3.8%, non-viral 14.0%). Both BCLC and HKLC staging systems showed good separation with overall log rank test confirming significant survival differences between stages in our cohort (P < 0.001). 206 out of the 240 patients (85.8%) assigned for curative treatment by the BCLC treatment algorithm received curative therapy for HCC [Stage 0 93.2% (68/73); Stage A 82.6% (138/167)]. In contrast, only 341/558 (61.1%) patients received curative treatment despite being assigned for curative treatment by the HKLC treatment algorithm [Stage I 72.7% (264/363); Stage II 40.2% (66/164); Stage Va 35.5% (11/31)]. Patients who were assigned to curative treatment by HKLC but did not receive curative treatment had significantly poorer ECOG (P < 0.001), higher Child-Pugh status (P < 0.001) and were older (median age 66 vs 61, P < 0.001) than those who received curative therapy. Median overall survival in patients assigned to curative treatment groups

关键词： Hepatocellular carcinoma Barcelona Clinic Liver Cancer Hong Kong Liver Cancer Staging systems Prognosis Survival

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Current Modalities of Fibrosis Assessment in Non-alcoholic Fatty Liver Disease

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Journal of Clinical and Translational Hepatology 2017年第3期5卷 261-271页

作者： Mark CC Cheah Arthur J McCullough George boon-Bee goh Department of Gastroenterology & Hepatology Singapore General Hospital Singapore Department of Gastroenterology Cleveland Clinic Ohio USA Department of Pathobiology Cleveland Clinic Ohio USA Department of Gastroenterology & Hepatology Singapore General Hospital Singapore Duke-NUS Medical School Singapore

Non-alcoholic fatty liver disease (NAFLD) is a burgeoning global health *** the subset of NAFLD patients with non-alcoholic steatohepatitis (NASH),the presence of significant fibrosis at index assessment is associated with poor prognosis and increased ***,there is a growing need to accurately assess and stage *** biopsy,the current gold standard,has limitations with sampling error and is invasive,with associated inherent *** has led to a host of non-invasive means of assessing fibrosis,which has garnered relevance in a disease that requires serial assessment of fibrosis longitudinally over *** review discusses,comprehensively,the various tools available to the clinician for the assessment of fibrosis,including the various scoring systems used in liver biopsy,the non-invasive means of serum biomarkers,such as the highly-validated NAFLD fibrosis score,and the imaging-based modalities,such as transient elastography and magnetic resonance elastography.

关键词： NAFLD Fibrosis assessment Modalities

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An Implementation of Multiscale Line Detection and Mathematical Morphology for Efficient and Precise Blood Vessel Segmentation in Fundus Images

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Computers, Materials & Continua 2024年第5期79卷 2565-2583页

作者： Syed Ayaz Ali Shah Aamir Shahzad Musaed Alhussein Chuan Meng goh Khursheed Aurangzeb Tong boon Tang Muhammad Awais Department of Electrical and Computer Engineering COMSATS University IslamabadAbbottabad CampusAbbottabad22060Pakistan Department of Computer Engineering College of Computer and Information SciencesKing Saud UniversityP.O.Box 51178Riyadh11543Saudi Arabia Faculty of Information and Communication Technology University Tunku Abdul RehmanKampar CampusKampar31900Malaysia Centre for Intelligent Signal and Imaging Research University Teknologi PETRONASBandar Seri IskandarPerak32610Malaysia School of Computing Sciences University of East AngliaNorwichNR47TJUK

Diagnosing various diseases such as glaucoma,age-related macular degeneration,cardiovascular conditions,and diabetic retinopathy involves segmenting retinal blood *** task is particularly challenging when dealing with color fundus images due to issues like non-uniformillumination,low contrast,and variations in vessel appearance,especially in the presence of different ***,the speed of the retinal vessel segmentation system is of utmost *** the surge of now available big data,the speed of the algorithm becomes increasingly important,carrying almost equivalent weightage to the accuracy of the *** address these challenges,we present a novel approach for retinal vessel segmentation,leveraging efficient and robust techniques based on multiscale line detection and mathematical *** algorithm’s performance is evaluated on two publicly available datasets,namely the Digital Retinal Images for Vessel Extraction dataset(DRIVE)and the Structure Analysis of Retina(STARE)*** experimental results demonstrate the effectiveness of our method,withmean accuracy values of 0.9467 forDRIVE and 0.9535 for STARE datasets,aswell as sensitivity values of 0.6952 forDRIVE and 0.6809 for STARE ***,our algorithmexhibits competitive performance with state-of-the-art ***,it operates at an average speed of 3.73 s per image for DRIVE and 3.75 s for STARE *** is worth noting that these results were achieved using Matlab scripts containing multiple *** suggests that the processing time can be further reduced by replacing loops with *** the proposed algorithm can be deployed in real time *** summary,our proposed system strikes a fine balance between swift computation and accuracy that is on par with the best available methods in the field.

关键词： Line detector vessel detection localization mathematical morphology image processing

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