29 results on '"Melvin L. K. Chua"'
Search Results
2. Radiomics in precision oncology: hype or ludum mutante
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Shi Hui Tay, Xin Zhang, and Melvin L. K. Chua
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Radiomics ,Imaging ,Precision oncology ,Explainable AI ,Nasopharyngeal cancer ,Medicine - Published
- 2023
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Catalog
3. Clinical efficacy and biomarker analysis of dual PD-1/CTLA-4 blockade in recurrent/metastatic EBV-associated nasopharyngeal carcinoma
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Darren Wan-Teck Lim, Hsiang-Fong Kao, Lisda Suteja, Constance H. Li, Hong Sheng Quah, Daniel Shao-Weng Tan, Sze-Huey Tan, Eng-Huat Tan, Wan-Ling Tan, Justina Nadia Lee, Felicia Yu-Ting Wee, Amit Jain, Boon-Cher Goh, Melvin L. K. Chua, Bin-Chi Liao, Quan Sing Ng, Ruey-Long Hong, Mei-Kim Ang, Joe Poh-Sheng Yeong, and N. Gopalakrishna Iyer more...
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Science - Abstract
Abstract Single-agent checkpoint inhibitor (CPI) activity in Epstein-Barr Virus (EBV) related nasopharyngeal carcinoma (NPC) is limited. Dual CPI shows increased activity in solid cancers. In this single-arm phase II trial (NCT03097939), 40 patients with recurrent/metastatic EBV-positive NPC who failed prior chemotherapy receive nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks. Primary outcome of best overall response rate (BOR) and secondary outcomes (progression-free survival [PFS], clinical benefit rate, adverse events, duration of response, time to progression, overall survival [OS]) are reported. The BOR is 38% with median PFS and OS of 5.3 and 19.5 months, respectively. This regimen is well-tolerated and treatment-related adverse events requiring discontinuation are low. Biomarker analysis shows no correlation of outcomes to PD-L1 expression or tumor mutation burden. While the BOR does not meet pre-planned estimates, patients with low plasma EBV-DNA titre ( more...
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- 2023
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4. Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy
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Matt Lechner, Volker H. Schartinger, Christopher D. Steele, Wen Long Nei, Marc Lucas Ooft, Liesa-Marie Schreiber, Christodoulos P. Pipinikas, Grace Tin-Yun Chung, Yuk Yu Chan, Feng Wu, Ka-Fai To, Chi Man Tsang, Wayne Pearce, Daniele Morelli, Martin Philpott, Liam Masterson, Reshma Nibhani, Graham Wells, Christopher G. Bell, Julia Koller, Susanne Delecluse, Yim Ling Yip, Jacklyn Liu, Cillian T. Forde, Martin D. Forster, Amrita Jay, József Dudás, Annika Krapp, Simon Wan, Christian Uprimny, Susanne Sprung, Johannes Haybaeck, Tim R. Fenton, Kerry Chester, Christina Thirlwell, Gary Royle, Teresa Marafioti, Rajeev Gupta, Sagung Rai Indrasari, Camelia Herdini, Mohd Afiq Mohd Slim, I. Indrawati, Liam Sutton, Renske Fles, Bing Tan, Joe Yeong, Amit Jain, Shuting Han, Haitao Wang, Kelvin S. H. Loke, Wan He, Ruilian Xu, Hongtao Jin, Zhiqiang Cheng, David Howard, Peter H. Hwang, Quynh-Thu Le, Joshua K. Tay, Robert B. West, Sai Wah Tsao, Tim Meyer, Herbert Riechelmann, Udo Oppermann, Henri-Jacques Delecluse, Stefan M. Willems, Melvin L. K. Chua, Pierre Busson, Kwok Wai Lo, Guido Wollmann, Nischalan Pillay, Bart Vanhaesebroeck, and Valerie J. Lund more...
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Science - Abstract
Nasopharyngeal carcinoma (NPC) lacks effective diagnostic and therapeutic strategies, in particular at advanced stages. Here, the authors show that expression of the somatostatin receptor 2 is induced by Epstein-Barr virus in NPC and has a key role in the diagnosis, imaging, targeted therapies and prognosis of NPC. more...
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- 2021
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5. Electronic tumor board presentations as the basis for the development of a head and neck cancer database
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Mahalakshmi Rangabashyam, Hide E. Wee, Weining Wang, Stefan Mueller, Khairul A. B. A. Karim, Thakshayeni Skanthakumar, Bhuvaneshwari Hariraman, Kiattisa Sommat, Yoke‐Lim Soong, Melvin L. K. Chua, Gerald Tay, Ngian ‐Chye Tan, Hiang Khoon‐ Tan, and N. Gopalakrishna Iyer more...
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audit ,electronic medical records (EMRs) ,multidisciplinary team (MDT) ,research databases ,synoptic ,Otorhinolaryngology ,RF1-547 ,Surgery ,RD1-811 - Abstract
Abstract Background Multidisciplinary team meetings or tumor boards (TBs) form a pivotal component of oncology practice. The crux of a TB revolves around making treatment decisions based on succinct head and neck cancer (HNC) patient data presentations, which can be challenging and complex. Apart from meticulous TB presentations, discussions and treatment plan documentation is equally important. The aim of this study was to structure an electronic synoptic TB data presentation to address all these areas. The overarching benefits of systematic TB data collection include facilitating audits and research. Methods We utilized a secure web‐based tool that was used for common scientific research purposes but customized to store HNC patient data. The data points were tabulated across eight TB pages: (a) TB scheduling, (b) patient biodata, (c) diagnosis details, (d) index presentation, (e) images, (f) management and histopathology, (g) TB presentation, and (h) TB discussion and decisions. Each data point leads to additional fields by branching logic to permit further relevant data entry. This was integrated within the patient electronic medical records allowing for a direct internal trajectory to recall TB data. Results From October 2015 to October 2018, we recorded over 2000 presentations for 1279 individual patients. This is a quality improvement initiative, and hence, the results are more of a broad analysis of our TB presentation process. The most common cancers were squamous cell (523, 41%), thyroid (207, 16%), and nasopharyngeal (139, 11%) carcinomas. Importantly, this system has formed the basis for a number of clinical and translational research projects and audit outcomes. Conclusion Despite TBs being vital to oncologic practice, little attempt has been made to report TB data management. In this study, we present an efficient system that permits the integration of dual functions: TB data presentation and oncologic data collection for research, recall, and audit purposes. more...
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- 2020
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6. Bevacizumab Combined with Corticosteroids Does Not Improve the Clinical Outcome of Nasopharyngeal Carcinoma Patients With Radiation-Induced Brain Necrosis
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Honghong Li, Xiaoming Rong, Weihan Hu, Yuhua Yang, Ming Lei, Wenjie Wen, Zongwei Yue, Xiaolong Huang, Melvin L. K. Chua, Yi Li, Jinhua Cai, Lei He, Dong Pan, Jinping Cheng, Yaxuan Pi, Ruiqi Xue, Yongteng Xu, and Yamei Tang more...
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radiation-induced brain necrosis ,bevacizumab combined with corticosteroid ,real-world data ,nasopharyngeal carcinoma ,bevacizumab monotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
ObjectiveOur aim was to compare the clinical outcomes of patients treated with bevacizumab combined with corticosteroids and those with bevacizumab monotherapy from a radiation-induced brain necrosis (RN) registry cohort (NCT03908502).MethodsWe utilized clinical data from a prospective RN registry cohort (NCT03908502) from July 2017 to June 2020. Patients were considered eligible if they had symptomatic RN after radiotherapy for nasopharyngeal carcinoma (NPC) and received bevacizumab (5 mg/kg, two to four cycles) with a minimum follow-up time of 3 months. The primary outcome was a 2-month response rate determined by MRI and clinical symptoms. Secondary outcomes included quality of life [evaluated by the abbreviated World Health Organization Quality of Life (WHOQOL-BREF) questionnaire] and cognitive function (evaluated by the Montreal Cognitive Assessment scale) at 2 months, RN recurrence during follow-up, and adverse events.ResultsA total of 123 patients (34 in the combined therapy group and 89 in the monotherapy group) were enrolled in our study with a median follow-up time of 0.97 year [interquartile range (IQR) = 0.35–2.60 years]. The clinical efficacy of RN did not differ significantly between patients in these two groups [odds ratio (OR) = 1.642, 95%CI = 0.584–4.614, p = 0.347]. Furthermore, bevacizumab combined with corticosteroids did not reduce recurrence compared with bevacizumab monotherapy [hazard ratio (HR) = 1.329, 95%CI = 0.849–2.079, p = 0.213]. The most common adverse events of bevacizumab were hypertension (17.89%), followed by nosebleed (8.13%) and fatigue (8.13%). There was no difference in grade 2 or more severe adverse events between the two groups (p = 0.811).InterpretationOur results showed that the treatment strategy of combining bevacizumab with corticosteroids did not lead to better clinical outcomes for RN patients with a background of radiotherapy for nasopharyngeal carcinoma. more...
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- 2021
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7. Upconversion superballs for programmable photoactivation of therapeutics
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Zhen Zhang, Muthu Kumara Gnanasammandhan Jayakumar, Xiang Zheng, Swati Shikha, Yi Zhang, Akshaya Bansal, Dennis J. J. Poon, Pek Lim Chu, Eugenia L. L. Yeo, Melvin L. K. Chua, Soo Khee Chee, and Yong Zhang more...
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Science - Abstract
The synthesis of nanoparticles capable of orthogonal photo-activity is complex. Here, the authors report on an assembly process of two distinct nanoparticles into composite nanoparticles as a simple method and report on the application in photodynamic therapy and siRNA delivery in tumour therapy. more...
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- 2019
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8. Liquid biopsy tracking during sequential chemo-radiotherapy identifies distinct prognostic phenotypes in nasopharyngeal carcinoma
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Jiawei Lv, Yupei Chen, Guanqun Zhou, Zhenyu Qi, Kuan Rui Lloyd Tan, Haitao Wang, Li Lin, Foping Chen, Lulu Zhang, Xiaodan Huang, Ruiqi Liu, Sisi Xu, Yue Chen, Jun Ma, Melvin L. K. Chua, and Ying Sun
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Science - Abstract
Liquid biopsies are emerging as a useful method for diagnosis and prognosis in cancer. Here, the authors show the prognostic value of monitoring the level of circulating Epstein-barr virus DNA throughout induction chemotherapy and chemo-radiotherapy and its potential utility for risk-adapted individualised therapy in nasopharyngeal carcinomapatients. more...
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- 2019
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9. Lactate dehydrogenase kinetics predict chemotherapy response in recurrent metastatic nasopharyngeal carcinoma
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Luo Huang, Adelene Y. L. Sim, Yongzhong Wu, Zhongguo Liang, Kaiguo Li, Youqin Du, Enya H. W. Ong, Hong Qi Tan, Joseph T. S. Wee, Yue Xie, Xiaolei Shu, Ying Wang, Melvin L. K. Chua, and Xiaodong Zhu
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Lactate dehydrogenase (LDH) is a known prognostic biomarker for the endemic variant of nasopharyngeal carcinoma (NPC). Here, we investigate whether serial changes in LDH level between chemotherapy (CT) cycles are associated with tumour response to CT. Methods: Patients with biopsy-proven, recurrent or treatment-naïve metastatic NPC (mNPC) were recruited. All patients had received at least two cycles of platinum-based doublet or triplet CT, with serial assessment of LDH prior to every cycle of chemotherapy (CT1–6). Patients harbouring conditions that affect LDH levels (IU/L) were excluded. Tumour response was assessed after every two cycles of CT by RECIST v1.1. Results: A total of 158 patients were analysed, including 77 with recurrent and 81 with treatment-naïve mNPC. High pre-CT LDH was associated with an inferior overall survival [hazard ratio 1.93 for ⩾240 versus more...
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- 2020
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10. Germline Polymorphisms and Length of Survival of Nasopharyngeal Carcinoma: An Exome‐Wide Association Study in Multiple Cohorts
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Yun‐Miao Guo, Jie‐Rong Chen, Yan‐Chun Feng, Melvin L. K. Chua, Yanni Zeng, Edwin Pun Hui, Allen K. C. Chan, Lin‐Quan Tang, Lin Wang, Qian Cui, Hui‐Qiong Han, Chun‐Ling Luo, Guo‐Wang Lin, Yan Liang, Yang Liu, Zhong‐Lian He, Yu‐Xiang Liu, Pan‐Pan Wei, Chu‐Jun Liu, Wan Peng, Bo‐Wei Han, Xiao‐Yu Zuo, Enya H. W. Ong, Eugenia L. L. Yeo, Kar Perng Low, Gek San Tan, Tony K. H. Lim, Jacqueline S. G. Hwang, Bo Li, Qi‐Sheng Feng, Xiaojun Xia, Yun‐Fei Xia, Josephine Ko, Wei Dai, Maria L. Lung, Anthony T. C. Chan, Dennis Y. M. Lo, Mu‐Sheng Zeng, Hai‐Qiang Mai, Jianjun Liu, Yi‐Xin Zeng, and Jin‐Xin Bei more...
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biomarkers ,cancer prognosis ,germline polymorphisms ,nasopharyngeal carcinoma ,RPA1 ,single nucleotide polymorphisms ,Science - Abstract
Abstract Germline polymorphisms are linked with differential survival outcomes in cancers but are not well studied in nasopharyngeal carcinoma (NPC). Here, a two‐phase association study is conducted to discover germline polymorphisms that are associated with the prognosis of NPC. The discovery phase includes two consecutive hospital cohorts of patients with NPC from Southern China. Exome‐wide genotypes at 246 173 single nucleotide polymorphisms (SNPs) are determined, followed by survival analysis for each SNP under Cox proportional hazard regression model. Candidate SNP is replicated in another two independent cohorts from Southern China and Singapore. Meta‐analysis of all samples (n = 5553) confirms that the presence of rs1131636‐T, located in the 3′‐UTR of RPA1, confers an inferior overall survival (HR = 1.33, 95% CI = 1.20–1.47, P = 6.31 × 10−8). Bioinformatics and biological assays show that rs1131636 has regulatory effects on upstream RPA1. Functional studies further demonstrate that RPA1 promotes the growth, invasion, migration, and radioresistance of NPC cells. Additionally, miR‐1253 is identified as a suppressor for RPA1 expression, likely through regulation of its binding affinity to rs1131636 locus. Collectively, these findings provide a promising biomarker aiding in stratifying patients with poor survival, as well as a potential drug target for NPC. more...
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- 2020
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11. Optimal sequencing of chemotherapy with chemoradiotherapy based on TNM stage classification and EBV DNA in locoregionally advanced nasopharyngeal carcinoma
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Li-Ting Liu, Melvin L. K. Chua, Yungan Tao, Lin-Quan Tang, and Hai-Qiang Mai
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2019
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12. Mitochondrial mutations drive prostate cancer aggression
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Julia F. Hopkins, Veronica Y. Sabelnykova, Joachim Weischenfeldt, Ronald Simon, Jennifer A. Aguiar, Rached Alkallas, Lawrence E. Heisler, Junyan Zhang, John D. Watson, Melvin L. K. Chua, Michael Fraser, Francesco Favero, Chris Lawerenz, Christoph Plass, Guido Sauter, John D. McPherson, Theodorus van der Kwast, Jan Korbel, Thorsten Schlomm, Robert G. Bristow, and Paul C. Boutros more...
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Science - Abstract
In prostate cancer, the role of mutations in the maternally-inherited mitochondrial genome are not well known. Here, the authors demonstrate frequent, age-dependent mitochondrial mutation in prostate cancer. Strong links between mitochondrial and nuclear mutational profiles are associated with clinical aggressivity. more...
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- 2017
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13. Patient‐reported functional outcomes and oncological control after primary focal cryotherapy for clinically significant prostate cancer: A Phase II mandatory biopsy‐monitored study
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Yu G. Tan, Yan M. Law, Nye T. Ngo, Li Y. Khor, Puay H. Tan, Enya H. W. Ong, John S. P. Yuen, Henry S. S. Ho, Jeffrey K. L. Tuan, Ravindran Kanesvaran, Rajan T. Gupta, Steven Rozen, Melvin L. K. Chua, Thomas J. Polascik, and Kae Jack Tay more...
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Oncology ,Urology - Published
- 2023
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14. Recommendations for Epstein-Barr virus–based screening for nasopharyngeal cancer in high- and intermediate-risk regions
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W K Jacky Lam, Ann D King, Jacob A Miller, Zhiwei Liu, Kelly J Yu, Melvin L K Chua, Brigette B Y Ma, Ming Yuan Chen, Benjamin A Pinsky, Pei-Jen Lou, John K S Woo, Wan-Lun Hsu, Julia Simon, Denise L Doolan, Tim Waterboer, Edwin P Hui, Hui Li, Raymond K Tsang, Kenneth C W Wong, Julian P Goh, Alexander C Vlantis, Qi Yong Ai, Lun M Wong, Victor Abdullah, Jin Ching Lin, Chien-Jen Chen, Ruth M Pfeiffer, Quynh-Thu Le, Anne W M Lee, Mingfang Ji, Sumei Cao, Jun Ma, Anthony T C Chan, K C Allen Chan, and Allan Hildesheim more...
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Cancer Research ,Oncology - Abstract
A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)–based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program. more...
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- 2023
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15. A phase 2 study of thalidomide for the treatment of radiation-induced blood-brain barrier injury
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Jinping Cheng, Jingru Jiang, Baixuan He, Wei-Jye Lin, Yi Li, Jingjing Duan, Honghong Li, Xiaolong Huang, Jinhua Cai, Jiatian Xie, Zhan Zhang, Yuhua Yang, Yongteng Xu, Xia Hu, Minyi Wu, Xiaohuang Zhuo, Qiang Liu, Zhongshan Shi, Pei Yu, Xiaoming Rong, Xiaojing Ye, Phei Er Saw, Long-Jun Wu, Charles B. Simone, Melvin L. K. Chua, Hai-Qiang Mai, and Yamei Tang more...
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General Medicine - Abstract
Radiation-induced brain injury (RIBI) is a debilitating sequela after radiotherapy to treat head and neck cancer, and 20 to 30% of patients with RIBI fail to respond to or have contraindications to the first-line treatments of bevacizumab and corticosteroids. Here, we reported a Simon’s minmax two-stage, single-arm, phase 2 clinical trial (NCT03208413) to assess the efficacy of thalidomide in patients with RIBI who were unresponsive to or had contraindications to bevacizumab and corticosteroid therapies. The trial met its primary endpoint, with 27 of 58 patients enrolled showing ≥25% reduction in the volume of cerebral edema on fluid-attenuated inversion recovery–magnetic resonance imaging (FLAIR-MRI) after treatment (overall response rate, 46.6%; 95% CI, 33.3 to 60.1%). Twenty-five (43.1%) patients demonstrated a clinical improvement based on the Late Effects Normal Tissues–Subjective, Objective, Management, Analytic (LENT/SOMA) scale, and 36 (62.1%) experienced cognitive improvement based on the Montreal Cognitive Assessment (MoCA) scores. In a mouse model of RIBI, thalidomide restored the blood-brain barrier and cerebral perfusion, which were attributed to the functional rescue of pericytes secondary to elevation of platelet-derived growth factor receptor β (PDGFRβ) expression by thalidomide. Our data thus demonstrate the therapeutic potential of thalidomide for the treatment of radiation-induced cerebral vasculature impairment. more...
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- 2023
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16. Nonpharmaceutical interventions reduce the incidence and mortality of COVID-19: A study based on the survey from the International COVID-19 Research Network (ICRN)
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Seung Hyun Park, Sung Hwi Hong, Kwanghyun Kim, Seung Won Lee, Dong Keon Yon, Sun Jae Jung, Ziad Abdeen, Ramy Abou Ghayda, Mohamed Lemine Cheikh Brahim Ahmed, Abdulwahed Al Serouri, Waleed Al‐Herz, Humaid O. Al‐Shamsi, Sheeza Ali, Kosar Ali, Oidov Baatarkhuu, Henning Bay Nielsen, Enrico Bernini‐Carri, Anastasiia Bondarenko, Ayun Cassell, Akway Cham, Melvin L. K. Chua, Sufia Dadabhai, Tchin Darre, Hayk Davtyan, Elena Dragioti, Barbora East, Robert Jeffrey Edwards, Martina Ferioli, Tsvetoslav Georgiev, Lilian A. Ghandour, Harapan Harapan, Po‐Ren Hsueh, Saad I. Mallah, Aamer Ikram, Shigeru Inoue, Louis Jacob, Slobodan M. Janković, Umesh Jayarajah, Milos Jesenak, Pramath Kakodkar, Nathan Kapata, Yohannes Kebede, Yousef Khader, Meron Kifle, David Koh, Višnja Kokić Maleš, Katarzyna Kotfis, Ai Koyanagi, James‐Paul Kretchy, Sulaiman Lakoh, Jinhee Lee, Jun Young Lee, Maria da Luz Lima Mendonça, Lowell Ling, Jorge Llibre‐Guerra, Masaki Machida, Richard Makurumidze, Ziad A. Memish, Ivan Mendoza, Sergey Moiseev, Thomas Nadasdy, Chen Nahshon, Silvio A. Ñamendys‐Silva, Blaise Nguendo Yongsi, Amalea Dulcene Nicolasora, Zhamilya Nugmanova, Hans Oh, Atte Oksanen, Oluwatomi Owopetu, Zeynep Ozge Ozguler, Konstantinos Parperis, Gonzalo Emanuel Perez, Krit Pongpirul, Marius Rademaker, Nemanja Radojevic, Anna Roca, Alfonso J. Rodriguez‐Morales, Enver Roshi, Khwaja Mir Islam Saeed, Ranjit Sah, Boris Sakakushev, Dina E. Sallam, Brijesh Sathian, Patrick Schober, P. Shaik Syed Ali, Zoran Simonović, Tanu Singhal, Natia Skhvitaridze, Marco Solmi, Kannan Subbaram, Kalthoum Tizaoui, John Thato Tlhakanelo, Julio Torales, Junior Smith Torres‐Roman, Dimitrios Tsartsalis, Jadamba Tsolmon, Duarte Nuno Vieira, Sandro G. Viveiros Rosa, Guy Wanghi, Uwe Wollina, Ren‐He Xu, Lin Yang, Kashif Zia, Muharem Zildzic, Jae Il Shin, Lee Smith, Anesthesiology, ACS - Microcirculation, APH - Methodology, APH - Quality of Care, Family Medicine and Chronic Care, Gerontology, and Faculty of Medicine and Pharmacy more...
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Infectious Diseases ,Virology - Abstract
The recently emerged novel coronavirus, "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)", caused a highly contagious disease called coronavirus disease 2019 (COVID-19). It has severely damaged the world's most developed countries and has turned into a major threat for low- and middle-income countries. Since its emergence in late 2019, medical interventions have been substantial, and most countries relied on public health measures collectively known as nonpharmaceutical interventions.To centralize the accumulative knowledge on non-pharmaceutical interventions (NPIs) against COVID-19 for each country under one worldwide consortium.International COVID-19 Research Network collaborators developed a cross-sectional online-survey to assess the implications of NPIs and sanitary supply on incidence and mortality of COVID-19. Survey was conducted between January 1 and February 1, 2021, and participants from 92 countries/territories completed it. The association between NPIs, sanitation supplies and incidence and mortality were examined by multivariate regression, with log-transformed value of population as an offset value.Majority of countries/territories applied several preventive strategies including social distancing (100.0%), quarantine (100.0%), isolation (98.9%), and school closure (97.8%). Individual-level preventive measures such as personal hygiene (100.0%) and wearing facial mask (94.6% at hospital; 93.5% at mass transportation; 91.3% in mass gathering facilities) were also frequently applied. Quarantine at a designated place was negatively associated with incidence and mortality compared to home quarantine. Isolation at a designated place was also associated with reduced mortality compared to home isolation. Recommendations to use sanitizer for personal hygiene reduced incidence compared to recommendation to use soap did. Deprivation of mask was associated with increased incidence. Higher incidence and mortality were found in countries/territories with higher economic level. Mask deprivation was pervasive regardless of economic level.NPIs against COVID-19 such as using sanitizer, quarantine, and isolation can decrease incidence and mortality of COVID-19. This article is protected by copyright. All rights reserved. more...
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- 2023
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17. Hyperfractionation for reirradiation of recurrent nasopharyngeal carcinoma
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Melvin L K Chua, Victor H F Lee, and Anne W M Lee
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General Medicine - Published
- 2023
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18. Management of the neck in nasopharyngeal carcinoma—time for a radical change?
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Melvin L. K. Chua, Joanne Y. H. Lua, Wai-Tong Ng, and Anne W. M. Lee
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Oncology ,General Medicine - Published
- 2023
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19. Efficacy, toxicity, and quality‐of‐life outcomes of ultrahypofractionated radiotherapy in patients with localized prostate cancer: A single‐arm phase 2 trial from Asia
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Janice S. H. Tan, Jonathan Y. H. Teh, Laura L. Y. Tan, Sheena X. F. Tan, You Quan Li, Terence W. K. Tan, Michael L. C. Wang, Ravindran Kanesvaran, Enya H. W. Ong, Kae Jack Tay, Lui Shiong Lee, Jeffrey K. L. Tuan, Daniel Y. H. Tan, and Melvin L. K. Chua more...
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Male ,Oncology ,Gastrointestinal Diseases ,Quality of Life ,Humans ,Prostatic Neoplasms ,Radiation Dose Hypofractionation ,Dose Fractionation, Radiation ,Radiotherapy, Intensity-Modulated ,General Medicine ,Middle Aged ,Aged - Abstract
Ultra-hypofractionated radiotherapy (UHF-RT) is widely utilized in men with localized prostate cancer (PCa). There are limited data in Asian cohorts. We report the outcomes of a single-arm, phase II trial of UHF-RT from an Asian center.We recruited men with histologically confirmed, nonmetastatic localized PCa. UHF-RT regimens were 36.25 Gy (Cohort A) and 37.5 Gy (Cohort B) delivered in five fractions every other day over 1.5-2.5 weeks. Primary endpoint was physician-scored late genitourinary (GU) and gastrointestinal (GI) adverse events (AEs). Quality-of-life (QoL) was assessed by Expanded Prostate Cancer Index Composite (EPIC) at baseline, 1- and 2-year post-UHF-RT.Between March 2014 and August 2019, 105 men were recruited; four were subsequently excluded from analysis. Median age was 68.0 (Interquartile range (IQR): 63.8-73.0) years. 26 (24.8%) and 68 (64.8%) men had NCCN-defined low-and intermediate-risk PCa, respectively. No late ≥G3 GU or GI toxicities were reported in both cohorts. Peak incidence of acute ≥G2 GU AEs at 14 days post-UHF-RT was 23.6% (17/72) and 24.0% (6/25) in Cohorts A and B, respectively; ≥G2 GI AEs were observed in 9.7% (7/72) and 36.0% (9/25), respectively. Late ≥G2 GU and GI AEs occurred in 4.7% and 3.1% of Cohort A patients, and 5.0% in Cohort B at 12 months, with no AEs at 24 months. EPIC scores changed minimally across all domains. At a median follow-up of 44.9 months, we recorded one (1.3%) biochemical relapse by the Phoenix criteria (Cohort A).UHF-RT is well tolerated in Asian men and can be a recommended fractionation schema for localized PCa. more...
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- 2021
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20. NEAR trial: A single-arm phase II trial of neoadjuvant apalutamide monotherapy and radical prostatectomy in intermediate- and high-risk prostate cancer
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Lui Shiong Lee, Adelene Y. L. Sim, Chee Wee Ong, Xinyan Yang, Cedric C. Y. Ng, Wei Liu, Vikneswari Rajasegaran, Abner M. S. Lim, Edwin Jonathan Aslim, Nye-Thane Ngo, Li-Yan Khor, Ravindran Kanesvaran, John Carson Jr Allen, Kae Jack Tay, John Shyi Peng Yuen, Tsung Wen Chong, Sun Sien Henry Ho, Bin Tean Teh, and Melvin L. K. Chua more...
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Male ,Prostatectomy ,Cancer Research ,Oncology ,Receptors, Androgen ,Urology ,Prostate ,Humans ,Prostatic Neoplasms ,Androgen Antagonists ,Prostate-Specific Antigen ,Neoplasm Recurrence, Local ,Neoadjuvant Therapy - Abstract
Objective Treatment efficacy of androgen deprivation therapy with radical prostatectomy for intermediate- to high-risk prostate cancer is less well-studied. The NEAR trial is a single-arm, phase II investigation of neoadjuvant apalutamide monotherapy and radical prostatectomy (RP) in the treatment of D’Amico intermediate- and high-risk prostate cancer (NCT03124433). Materials and methods Patients with histologically-proven, D’Amico intermediate- to high-risk prostate adenocarcinoma received apalutamide 240 mg once-daily for 12 weeks followed by RP + /−lymphadenectomy. Primary outcome was pathological complete response (pCR) rate. Secondary outcomes included rate of biochemical response (defined by PSA Results From 2017 to 2019, 30 patients were recruited, of which 20 and 10 were high and intermediate risk, respectively; 25 completed treatment as per-protocol. We did not observe any pCR on trial; median reduction of cancer burden was 41.7% (IQR: 33.3%–60.0%). 18 out of 25 patients were classified as having a biochemical response (4 did not achieve PSA of N = 16; 53.3%), fatigue (N = 10; 33.3%) and skin rash (N = 9; 30.0%) were the most common adverse events, and there was no major peri-operative complication. We observed an association between tumours of low androgen receptor activity and PAM50 basal status with biochemical non-responders, albeit these molecular phenotypes were not associated with pathological response. Conclusions A 12-week course of neoadjuvant apalutamide prior to RP did not meet the primary endpoint of pCR in this trial. Tumours with low androgen receptor activity or of the PAM50 basal subtype may have a reduced response to apalutamide. more...
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- 2021
21. Adjuvant Capecitabine Following Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma
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Jingjing Miao, Lin Wang, Sze Huey Tan, Jin-gao Li, Junlin Yi, Enya H.W. Ong, Laura L.Y. Tan, Ye Zhang, Xiaochang Gong, Qiuyan Chen, Yan-qun Xiang, Ming-yuan Chen, Ying Guo, Xing Lv, Wei-xiong Xia, Linquan Tang, Xiaowu Deng, Xiang Guo, Fei Han, Hai-qiang Mai, Melvin L. K. Chua, and Chong Zhao more...
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Cancer Research ,Oncology - Abstract
ImportanceInduction or adjuvant chemotherapy with concurrent chemoradiotherapy (CCRT) are first-line treatment options for treatment of locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Adjuvant platinum regimens are, however, poorly tolerated, highlighting the unmet need for an efficacious, tolerable adjuvant regimen.ObjectiveTo investigate the efficacy and safety of adjuvant capecitabine with CCRT for the treatment of patients with LA-NPC.Design, Setting, and ParticipantsThis open-label randomized clinical trial recruited patients from March 31, 2014, to July 27, 2018, at 3 institutions in China, with at least 3 years of follow-up. The data collection cutoff date was February 9, 2022. Eligibility included stage III-IVb nasopharyngeal carcinoma and at least 1 of the following: T3-4N2 or T1-4N3; plasma Epstein-Barr virus DNA titer higher than 20 000 copies/mL; primary gross tumor volume larger than 30.0 cm3; fluorodeoxyglucose F 18 positron emission tomography/computed tomography maximum standard uptake value of the primary gross tumor volume larger than 10.0; or multiple nodal metastases and any larger than 4.0 cm.InterventionsPatients were randomly assigned 1:1 to receive either capecitabine (1000 mg/m2 twice daily for 14 days every 3 weeks for 8 cycles) or observation following CCRT (100 mg/m2 cisplatin every 3 weeks for 2 to 3 cycles, depending on duration of radiotherapy).Main Outcomes and MeasuresFailure-free survival in the intention-to-treat cohort was assessed using Kaplan-Meier survival curves compared with the log-rank test. Unstratified Cox proportional hazards regression models were used to estimate hazard ratios, with corresponding 95% CIs based on the Wald test.ResultsThere were 180 patients enrolled (median [IQR] age, 47 [40-55] years; 143 [79.4%] men). Among 90 patients in the capecitabine group, 76 (84.4%) had at least 2 high-risk factors; among 90 patients in the control group, 80 (88.9%) had at least 2 high-risk factors. All patients completed CCRT, except 1 patient in the capecitabine group who received 1 cycle of cisplatin. Of the 90 patients in the capecitabine group, 85 (94.4%) received capecitabine, with 71 (78.9%) completing 8 cycles. With a median (IQR) follow-up of 58.0 (49.5-80.1) months, 18 events were recorded in the capecitabine group vs 31 events in the control group. Failure-free survival was improved with adjuvant capecitabine (3 years, 83.3% vs 72.2%; 5 years, 78.5% vs 65.9%; hazard ratio, 0.53 [95% CI, 0.30-0.94]; P = .03). The incidence of grade 3 treatment-related adverse events (TRAEs) was higher in the capecitabine group than in the control group (54 of 90 patients [60.0%] vs 46 of 90 patients [51.1%]). Treatment-related adverse events included xerostomia (17 [18.9%] vs 9 [10.0%] patients), mucositis (21 [23.3%] vs 15 [16.7%] patients), and anorexia (8 [8.9%] vs 4 [4.4%] patients). The incidence of grade 3 delayed treatment-related adverse events was comparable in both groups (9 of 83 [10.8%] vs 7 of 81 [8.6%] patients).Conclusions and RelevanceIn this randomized clinical trial, adjuvant capecitabine at the full dose following CCRT was well tolerated and improved failure-free survival among patients with LA-NPC and high-risk factors. Further investigations assessing optimal dose and duration are warranted.Trial RegistrationClinicalTrials.gov Identifier: NCT02143388 more...
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- 2022
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22. The hunt for the perfect biomarker in nasopharyngeal carcinoma—the RRAS 'race' beyond Epstein-Barr virus?
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Mark T. L. Tan, Joseph T. S. Wee, and Melvin L. K. Chua
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Cancer Research ,Oncology ,Radiology, Nuclear Medicine and imaging - Published
- 2019
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23. Germline Variants Associated with Nasopharyngeal Carcinoma Predisposition Identified through Whole-Exome Sequencing
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Ning-Yuan Lee, Melissa Hum, Pei-Yi Ong, Matthew Khine Myint, Enya H. W. Ong, Kar-Perng Low, Zheng Li, Boon-Cher Goh, Joshua K. Tay, Kwok-Seng Loh, Melvin L. K. Chua, Soo-Chin Lee, Chiea-Chuen Khor, and Ann S. G. Lee more...
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Cancer Research ,nasopharyngeal carcinoma ,exome sequencing ,germline variants ,genetic predisposition ,Oncology - Abstract
The current understanding of genetic susceptibility factors for nasopharyngeal carcinoma (NPC) is still incomplete. To identify novel germline variants associated with NPC predisposition, we analysed whole-exome sequencing data from 119 NPC patients from Singapore with a family history of NPC and/or with early-onset NPC, together with 1337 Singaporean participants without NPC. Variants were prioritised and filtered by selecting variants with minor allele frequencies of 20). Using single-variant testing, we identified 17 rare pathogenic variants in 17 genes that were associated with NPC. Consistent evidence of enrichment in NPC patients was observed for five of these variants (in JAK2, PRDM16, LRP1B, NIN, and NKX2-1) from an independent case-control comparison of 156 NPC patients and 9770 unaffected individuals. In a family with five siblings, a FANCE variant (p. P445S) was detected in two affected members, but not in three unaffected members. Gene-based burden testing recapitulated variants in NKX2-1 and FANCE as being associated with NPC risk. Using pathway analysis, endocytosis and immune-modulating pathways were found to be enriched for mutation burden. This study has identified NPC-predisposing variants and genes which could shed new insights into the genetic predisposition of NPC. more...
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- 2022
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24. Maintenance Capecitabine in Recurrent or Metastatic Nasopharyngeal Carcinoma—Magic Bullet or Pandora’s Box?
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Wai-Tong Ng, Melvin L. K. Chua, and Anne W. M. Lee
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Cancer Research ,Oncology - Published
- 2022
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25. Correction to: NEAR trial: A single-arm phase II trial of neoadjuvant apalutamide monotherapy and radical prostatectomy in intermediate- and high-risk prostate cancer
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Lui Shiong Lee, Adelene Y. L. Sim, Chee Wee Ong, Xinyan Yang, Cedric C. Y. Ng, Wei Liu, Vikneswari Rajasegaran, Abner M. S. Lim, Edwin Jonathan Aslim, Nye-Thane Ngo, Li-Yan Khor, Ravindran Kanesvaran, John Carson Jr Allen, Kae Jack Tay, John Shyi Peng Yuen, Tsung Wen Chong, Sun Sien Henry Ho, Bin Tean Teh, and Melvin L. K. Chua more...
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Cancer Research ,Oncology ,Urology - Published
- 2022
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26. Impact of cancer diagnoses on the outcomes of patients with COVID-19: a systematic review and meta-analysis
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Shuting Han, Qingyuan Zhuang, Jianbang Chiang, Sze Huey Tan, Gail Wan Ying Chua, Conghua Xie, Melvin L K Chua, Yu Yang Soon, and Valerie Shiwen Yang
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Databases, Factual ,SARS-CoV-2 ,Neoplasms ,Medicine ,COVID-19 ,Humans ,General Medicine - Abstract
BackgroundThe COVID-19 has caused significant mortality and morbidity across the globe. Patients with cancer are especially vulnerable given their immunocompromised state. We aimed to determine the proportion of COVID-19 patients with cancer, their severity and mortality outcomes through a systematic review and meta-analysis (MA).MethodsSystematic review was performed through online databases, PubMed, Medline and Google Scholar, with keywords listed in the Methods section (1 November 2019–31 December 2020). Studies with clinical outcomes of at least 10 COVID-19 patients and at least one with a diagnosis of cancer were included. The studies for MA were assessed with PRISMA guidelines and appraised with Newcastle-Ottawa Scale. The data were pooled using a random-effects model using STATA software. The main outcomes were planned before data collection, including proportion of patients with cancer among COVID-19 populations, relative risk (RR) of severe outcomes and death of patients with cancer compared with general COVID-19 patients.ResultsWe identified 57 case series (63 413 patients), with 230 patients with cancer with individual patient data (IPD). We found that the pooled proportion of cancer among COVID-19 patients was 0.04 (95% CI 0.03 to 0.05, I2=97.69%, pConclusionPatients with cancer were at a higher risk of severe and death outcomes from COVID-19 infection as compared with general COVID-19 populations. Limitations of this study include publication bias. A collaborative effort is required for a more complete database. more...
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- 2022
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27. Dysregulation of the MiR-449b target TGFBI alters the TGFβ pathway to induce cisplatin resistance in nasopharyngeal carcinoma
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Melvin L. K. Chua, Fei-Fei Liu, Wei Shi, Jacqueline H. Law, Pierre-Antoine Bissey, Kenneth W. Yip, Jeff Bruce, and Aline Renoult
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0301 basic medicine ,Cancer Research ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,medicine ,PTEN ,Molecular Biology ,Protein kinase B ,Cisplatin ,biology ,Chemistry ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,eye diseases ,3. Good health ,030104 developmental biology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Immunohistochemistry ,Transforming growth factor ,medicine.drug ,TGFBI - Abstract
Despite the improvement in locoregional control of nasopharyngeal carcinoma (NPC), distant metastasis (DM), and chemoresistance persist as major causes of mortality. This study identified a novel role for miR-449b, an overexpressed gene in a validated four-miRNA signature for NPC DM, leading to chemoresistance via the direct targeting of transforming growth factor beta-induced (TGFBI). In vitro shRNA-mediated downregulation of TGFBI induced phosphorylation of PTEN and AKT, increasing cisplatin resistance. Conversely, the overexpression of TGFBI sensitized the NPC cells to cisplatin. In NPC patients treated with concurrent chemoradiotherapy (CRT), the overall survival (OS) was significantly inversely correlated with miR-449b, and directly correlated with both TGFBI mRNA and protein expression, as assessed by RNA sequencing and immunohistochemistry (IHC). Mechanistically, co-immunoprecipitation demonstrated that TGFBI competes with pro-TGFβ1 for integrin receptor binding. Decreased TGFBI led to increased pro-TGFβ1 activation and TGFβ1 canonical/noncanonical pathway-induced cisplatin resistance. Thus, overexpression of miR-449b decreases TGFBI, thereby altering the balance between TGFBI and pro-TGFβ1, revealing a novel mechanism of chemoresistance in NPC. more...
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- 2018
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28. Duration-dependent margins for prostate radiotherapy-a practical motion mitigation strategy
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Eric Pei Ping, Pang, Kellie, Knight, Sung Yong, Park, Weixiang, Lian, Zubin, Master, Marilyn, Baird, Jason Wei Xiang, Chan, Michael Lian Chek, Wang, Terence Wee Kiat, Tan, Melvin L K, Chua, Eu Tiong, Chua, Wen Shen, Looi, Wen Long, Nei, and Jeffrey Kit Loong, Tuan more...
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Male ,Time Factors ,Prostate ,Prostatic Neoplasms ,Adenocarcinoma ,Radiotherapy Setup Errors ,Perineum ,Patient Positioning ,Motion ,Computer Systems ,Humans ,Radiotherapy, Intensity-Modulated ,Artifacts ,Ultrasonography - Abstract
The magnitude of intra-fractional prostate displacement (change from initial position over time) is associated with the duration of the patient lying on the radiotherapy treatment couch. This study reports a minute-by-minute association and calculates the impact of this displacement on duration-dependent margins using real-time intra-fractional position data monitored by four-dimensional transperineal ultrasound (4D TPUS).A total of 55 patients were recruited prospectively. Intra-fractional position of the prostate was monitored in real-time using a 4D TPUS Clarity® system. A total of 1745 monitoring sessions were analysed. Van Herk's margin recipe (2.5∑ + 1.64((σThe mean intra-fractional position was 0.76 mm Inferior (Inf), 0 mm Lateral (Lat) and 0.94 mm Posterior (Post) at the 15th minute. A minimum margin expansion of 2.42 mm (Superior/Inf), 1.02 mm (Left/Right) and 2.65 mm (Anterior/Post) was required for an 8‑minute treatment compared to 4.29 mm (Sup/Inf), 1.84 mm (Lt/Rt) and 4.63 mm (Ant/Post) for a 15-minute treatment. The required margin expansion increased linearly (RWe report our experience in deriving the minimum duration-dependant margin to generate the required planning target volume for prostate radiotherapy. The required margin increases linearly in all directions within the 15-min duration; thus, the margin will depend on the duration of the technique chosen (IMRT/VMAT/3DCRT/proton). more...
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- 2019
29. Nasopharyngeal carcinoma
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Melvin L K Chua, Joseph T S Wee, Edwin P Hui, and Anthony T C Chan
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Nasopharyngeal Carcinoma ,Carcinoma ,Humans ,Nasopharyngeal Neoplasms ,General Medicine - Abstract
Epidemiological trends during the past decade suggest that although incidence of nasopharyngeal carcinoma is gradually declining, even in endemic regions, mortality from the disease has fallen substantially. This finding is probably a result of a combination of lifestyle modification, population screening coupled with better imaging, advances in radiotherapy, and effective systemic agents. In particular, intensity-modulated radiotherapy has driven the improvement in tumour control and reduction in toxic effects in survivors. Clinical use of Epstein-Barr virus (EBV) as a surrogate biomarker in nasopharyngeal carcinoma continues to increase, with quantitative assessment of circulating EBV DNA used for population screening, prognostication, and disease surveillance. Randomised trials are investigating the role of EBV DNA in stratification of patients for treatment intensification and deintensification. Among the exciting developments in nasopharyngeal carcinoma, vascular endothelial growth factor inhibition and novel immunotherapies targeted at immune checkpoint and EBV-specific tumour antigens offer promising alternatives to patients with metastatic disease. more...
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- 2015
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