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Apoptotic and cytostatic actions of maslinic acid in colorectal cancer cells through possible IKK-β inhibition

Asian Pacific Journal of Tropical Biomedicine 2021年第3期11卷 122-131页

作者： Kai Xin Ooi Menaga Subramaniam Lai Yen Fong hoe han goh Soo Beng Alan Khoo Yang Mooi Lim Centre for Cancer Research Faculty of Medicine and Health SciencesUniversiti Tunku Abdul RahmanLOT PT 21144.Jalan Sungai LongBandar Sungai LongCheras 43000 KajangSelangorMalaysia Department of Pre-Clinical Sciences Faculty of Medicine and Health SciencesUniversiti Tunku Abdul RahmanLOT PT 21144.Jalan Sungai LongBandar Sungai LongCheras 43000 KajangSelangorMalaysia Institute of Systems Biology Universiti Kebangsaan Malaysia43600 BangiSelangor Darul EhsanMalaysia Molecular Pathology Unit Cancer Research CentreInstitute for Medical ResearchKuala LumpurMalaysia

Objective:To explore the anti-cancer activity of maslinic acid against colorectal cancer(CRC)cell lines and its possible ***:The inhibitory effect of maslinic acid was screened against five CRC cell lines(HT-29,HCT 116,SW480,SW48,and LS 174 T)via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide *** and cell cycle analyses were carried out using annexinⅤ-FITC/propidium iodide staining and propidium iodide staining,respectively and subjected to fluorescence-activated cell sorting *** expression studies of inhibitor ofκB kinase-β(IKK-β),checkpoint kinase 1(Chk1)and cyclin D1 were conducted using the JESS ***:Maslinic acid exhibited growth inhibitory effect in a doseand time-dependent manner in HT-29 and HCT 116 cell lines.A more prominent apoptosis induced by maslinic acid was observed in HCT 116 cell ***,in HT-29 cell line,maslinic acid induced cell cycle arrest by inhibiting the G1-S transition,which was accompanied by the downregulation of cyclin *** expression of unphosphorylated IKK-βprotein was increased in both(HT-29 and HCT 116)cell lines after maslinic acid ***:Maslinic acid inhibits the growth of HT-29 and HCT 116 cells in a different manner,induces cell cycle arrest in HT-29 cells and causes apoptosis in HCT 116 cells partially via NF-κB pathway inhibition.

关键词： Maslinic acid Colorectal cancer Apoptosis Cell cycle arrest NF-κB pathway IKK-β

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Nitric oxide synthase and heme oxygenase expressions in human liver cirrhosis

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World Journal of Gastroenterology 2006年第4期12卷 588-594页

作者： Beatrice J goh Bee Tee Tan Wei Min Hon Kang hoe Lee Hoon Eng Khoo Department of Biochemistry Yong Loo Lin School of Medicine National University ofSingapore Department of Medicine Yong Loo Lin School of Medicine National University of Singapore Research Biolabs Pte Ltd

AIM： Portal hypertension is a common complication of liver cirrhosis. Intrahepatic pressure can be elevated in several ways. Abnormal architecture affecting the vasculature, an increase in vasoconstrictors and increased circulation from the splanchnic viscera into the portal system may all contribute. It follows that endogenous vasodilators may be able to alleviate the hypertension. We therefore aimed to investigate the levels of endogenous vasodilators, nitric oxide （NO） and carbon monoxide （CO） through the expression of nitric oxide synthase （NOS） and heme oxygenase （HO）. METHOD： Cirrhotic （n = 20） and non-cirrhotic （n = 20） livers were obtained from patients who had undergone surgery. The mRNA and protein expressions of the various isoforms of NOS and HO were examined using competitive PCR, Western Blot and immunohistochemistry. RESULTS： There was no significant change in either inducible NOS （iNOS） or neuronal NOS （nNOS） expressions while endothelial NOS （eNOS） was up- regulated in cirrhotic livers. Concomitantly, caveolin-1, an established down-regulator of eNOS, was upregulated. Inducible HO-1 and constitutive HO-2 were found to show increased expression in cirrhotic livers albeit in different Iocalizations. CONCLUSION： The differences of NOS expression might be due to their differing roles in maintaining liver homeostasis and/or involvement in the pathology of cirrhosis. Sheer stress within the hypertensive liver may induce increased expression of eNOS. In turn, caveolin-1 is also increased. Whether this serves as a defense mechanism against further cirrhosis or is a consequence of cirrhosis, is yet unknown. The elevated expression of HO-1 and HO-2 suggest that CO may compensate in its role as a vasodilator albeit weakly. It is possible that CO and NO have parallel or coordinated functions within the liver and may work antagonistically in the pathophysiology of portal hypertension.

关键词： Liver cirrhosis Nitric oxide synthase Heine oxygenase Gene expression Competitive PCR

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Critical evaluation of contemporary management in a new Pelvic Exenteration Unit: The first 25 consecutive cases

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World Journal of Gastrointestinal Oncology 2017年第5期9卷 218-227页

作者： Min hoe Chew Yu-Ting Yeh Ee-Lin Toh Stephen Aditya Sumarli Ghee Kheng Chew Lui Shiong Lee Mann Hong Tan Tiffany Priyanthi Hennedige Shin Yi Ng Say Kiat Lee Tze Tec Chong Hairil Rizal Abdullah Terence Lin Hon goh Mohamed Zulfikar Rasheed Kok Chai Tan Choong Leong Tang Department of Colorectal Surgery Singapore General Hospital Department of Obstetrics and Gynaecology Singapore General Hospital Department of Urology Singapore General Hospital Department of Orthopaedic Surgery Singapore General Hospital Division of Oncological Imaging National Cancer Centre Singapore Department of Anaesthesiology Singapore General Hospital Vascular Surgery Singapore General Hospital Department of Plastic Reconstructive and Aesthetic SurgerySingapore General Hospital

To critically appraise short-term outcomes in patients treated in a new Pelvic Exenteration (PE) Unit. METHODSThis retrospective observational study was conducted by analysing prospectively collected data for the first 25 patients (16 males, 9 females) who underwent PE for advanced pelvic tumours in our PE Unit between January 2012 and October 2016. Data evaluated included age, co-morbidities, American Society of Anesthesiologists (ASA) score, Eastern Cooperative Oncology Group (ECOG) status, preoperative adjuvant treatment, intra-operative blood loss, procedural duration, perioperative adverse event, lengths of intensive care unit (ICU) stay and hospital stay, and oncological outcome. Quantitative data were summarized as percentage or median and range, and statistically assessed by the χ2 test or Fisher’s exact test, as applicable. RESULTSAll 25 patients received comprehensive preoperative assessment via our dedicated multidisciplinary team approach. Long-course neoadjuvant chemoradiotherapy was provided, if indicated. The median age of the patients was 61.9-year-old. The median ASA and ECOG scores were 2 and 0, respectively. The indications for PE were locally invasive rectal adenocarcinoma (n = 13), advanced colonic adenocarcinoma (n = 5), recurrent cervical carcinoma (n = 3) and malignant sacral chordoma (n = 3). The procedures comprised 10 total PEs, 4 anterior PEs, 7 posterior PEs and 4 isolated lateral PEs. The median follow-up period was 17.6 mo. The median operative time was 11.5 h. The median volume of blood loss was 3306 mL, and the median volume of red cell transfusion was 1475 mL. The median lengths of ICU stay and of hospital stay were 1 d and 21 d, respectively. There was no case of mortality related to surgery. There were a total of 20 surgical morbidities, which occurred in 12 patients. The majority of the complications were grade 2 Clavien-Dindo. Only 2 patients experienced grade 3 Clavien-Dindo complications, and both required procedura

关键词： Colorectal cancer Advanced pelvic tumour Sacrectomy Oncological outcome Pelvic exenteration Chordoma

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铜引线键合中影响焊球硬度因素的研究(英文)

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电子工业专用设备 2009年第11期38卷 10-18页

作者： Hong Meng Ho Yee Chen Tan Heng Mui goh Wee Chong Tan Boon hoe Toh Jonathan Tan Zhao Wei Zhong Kulicke ＆ Sofia Pte. Ltd Kulicke ＆ Sofia （S.E.A.） Pte. Ltd Nanyang Technological University Serangoon North Ave 5 #03-16 Singapore 554910

铜丝球焊由于其经济优势和优越的电气性能近来得到了普及,然而,在引线键合工艺中用铜丝取代金丝面临着一些技术上的挑战。多年来,IC芯片焊盘结构已经逐步适应了金丝球焊。铜在本质上比金硬度高,因此以铜线取代金线便引出了有关硬度的问... 详细信息

铜丝球焊由于其经济优势和优越的电气性能近来得到了普及,然而,在引线键合工艺中用铜丝取代金丝面临着一些技术上的挑战。多年来,IC芯片焊盘结构已经逐步适应了金丝球焊。铜在本质上比金硬度高,因此以铜线取代金线便引出了有关硬度的问题。研究了用25.4μm铜丝球焊中与键合机参数有关的铜焊球硬度特性。采用电子打火系统不同的电流和打火时间设置,用5%氢气和95%氮气组成的惰性保护气体形成了一个典型的25.4μm大小的铜焊球,研究了维氏硬度的焊球。用实验设计建立了第一和第二键合参数,进行了无空气焊球基本数据调整。通过改变电子打火系统参数,对硬度特性进行了进一步的测试。典型的键合球的大小和厚度的第一键合响应证实铜键合球的生产实力与电子打火系统的电流和打火时间有关。

关键词：铜丝键合电子打火系统无空气焊球维氏硬度实验设计

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Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma:the PLANET study

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National Science Review 2022年第3期9卷 96-109页

作者： Weiwei Zhai hannah Lai Neslihan Arife Kaya Jianbin Chen Hechuan Yang Bingxin Lu Jia Qi Lim Siming Ma Sin Chi Chew Khi Pin Chua Jacob Josiah Santiago Alvarez Pauline Jieqi Chen Mei Mei Chang Lingyan Wu Brian K.P.goh Alexander Yaw-Fui Chung Chung Yip Chan Peng Chung Cheow Ser Yee Lee Juinn Huar Kam Alfred Wei-Chieh Kow Iyer Shridhar Ganpathi Rawisak Chanwat Jidapa Thammasiri Boon Koon Yoong Diana Bee-Lan Ong Vanessa H.de Villa Rouchelle D.Dela Cruz Tracy Jiezhen Loh Wei Keat Wan Zeng Zeng Anders Jacobsen Skanderup Yin Huei Pang Krishnakumar Madhavan Tony Kiat-Hon Lim Glenn Bonney Wei Qiang Leow Valerie Chew Yock Young Dan Wai Leong Tam han Chong Toh Roger Sik-Yin Foo Pierce Kah-hoe Chow Genome Institute of Singapore Agency for Science Technology and Research Key Laboratory of Zoological Systematics and Evolution Institute of Zoology Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences School of Biological Sciences Nanyang Technological University Division of Biosciences Faculty of Life Sciences Division of Surgery and Surgical Oncology National Cancer Centre Department of Hepato-Pancreato-Biliary and Transplant Surgery Singapore General Hospital Division of Hepatobiliary and Pancreatic Surgery Department of Surgery University Surgical Cluster National University Health System Hepato-Pancreato-Biliary Surgery Unit Department of Surgery National Cancer Institute Division of Pathology National Cancer Institute Department of Surgery Faculty of Medicine University of Malaya Department of Surgery and Center for Liver Disease Management and Transplantation The Medical City 13. Department of Laboratories The Medical City Department of Pathology Singapore General Hospital Institute for Infocomm Research ASTAR Department of Pathology National University Health System Translational Immunology Institute (TII) Sing Health Duke-NUS Academic Medical Centre Division of Gastroenterology and Hepatology University Medicine Cluster National University Hospital Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore Cancer Science Institute of Singapore National University of Singapore Division of Medical Oncology National Cancer Center Singapore Cardiovascular Research Institute National University of Singapore National University Healthcare System Singhealth-Duke-NUS Academic Surgery Program Duke-NUS Graduate Medical School Institute of Molecular and Cell Biology Agency for Science Technology and Research

Intra-tumor heterogeneity(ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic(transcriptomic and immune)heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma(HCC)with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients(331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage Ⅱ patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.

关键词： hepatocellular carcinoma intra-tumor heterogeneity phenotypic evolution tumor evolution

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