99 results on '"Anne Wing-Mui Lee"'
Search Results
2. Inhibition of lysyl oxidase‐like 2 overcomes adhesion‐dependent drug resistance in the collagen‐enriched liver cancer microenvironment
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Lanqi Gong, Yu Zhang, Yuma Yang, Qian Yan, Jifeng Ren, Jie Luo, Yuen Chak Tiu, Xiaona Fang, Beilei Liu, Raymond Hiu Wai Lam, Ka‐On Lam, Anne Wing‐Mui Lee, and Xin‐Yuan Guan
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract The tumor microenvironment (TME) is considered to be one of the vital mediators of tumor progression. Extracellular matrix (ECM), infiltrating immune cells, and stromal cells collectively constitute the complex ecosystem with varied biochemical and biophysical properties. The development of liver cancer is strongly tied with fibrosis and cirrhosis that alters the microenvironmental landscape, especially ECM composition. Enhanced deposition and cross‐linking of type I collagen are frequently detected in patients with liver cancer and have been shown to facilitate tumor growth and metastasis by epithelial‐to‐mesenchymal transition. However, information on the effect of collagen enrichment on drug resistance is lacking. Thus, the present study has comprehensively illustrated phenotypical and mechanistic changes in an in vitro mimicry of collagen‐enriched TME and revealed that collagen enrichment could induce 5‐fluorouracil (5FU) and sorafenib resistance in liver cancer cells through hypoxia‐induced up‐regulation of lysyl oxidase‐like 2 (LOXL2). LOXL2, an enzyme that facilitates collagen cross‐linking, enhances cell adhesion‐mediated drug resistance by activating the integrin alpha 5 (ITGA5)/focal adhesion kinase (FAK)/phosphoinositide 3‐kinase (PI3K)/rho‐associated kinase 1 (ROCK1) signaling axis. Conclusion: We demonstrated that inhibition of LOXL2 in a collagen‐enriched microenvironment synergistically promotes the efficacy of sorafenib and 5FU through deterioration of focal adhesion signaling. These findings have clinical implications for developing LOXL2‐targeted strategies in patients with chemoresistant liver cancer and especially for those patients with advanced fibrosis and cirrhosis.
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- 2022
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3. Tuberculosis reactivation at ileum following immune checkpoint inhibition with pembrolizumab for metastatic nasopharyngeal carcinoma: a case report
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Kin-Sang Lau, Ben Man-Fei Cheung, Ka-On Lam, Sum-Yin Chan, Ka-Ming Lam, Chun-Fai Yeung, Ivan Fan-Ngai Hung, Dora Lai-Wan Kwong, Chi-Chung Tong, To-Wai Leung, Mai-Yee Luk, Anne Wing-Mui Lee, Kwok-Keung Yuen, and Victor Ho-Fun Lee
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Nasopharyngeal carcinoma ,Immune checkpoint inhibitors ,Tuberculosis reactivation ,IGRA ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Tuberculosis (TB) reactivation has been increasingly identified following immune checkpoint inhibitor (ICI) therapy for cancer patients. However there has been no report on TB reactivation in the gastrointestinal tract. In the report, we describe a patient who developed TB ileitis after pembrolizumab for her metastatic nasopharyngeal carcinoma (NPC). Rechallenge with pembrolizumab after its temporary interruption together with anti-TB therapy produced continuous tumor response but without further TB reactivation. Case presentation A 29-year-old lady with metastatic NPC involving the cervical nodes, lungs and bones started pembrolizumab after failure to multiple lines of chemotherapy. She complained of sudden onset of abdominal pain, vomiting and bloody diarrhea with mucus 21 months after pembrolizumab. Colonoscopy revealed terminal ileitis with multiple caseating granulomas with Langerhan cells. Serum interferon gamma release assay was strongly positive. She was treated with anti-TB medication and was later rechallenged with pembrolizumab for her progressive lung metastases without further TB relapse while her lung metastases were brought under control again. Conclusion To date, this is the first gastrointestinal TB reactivation after ICI therapy for cancer. Guidelines to screen for TB before initiation of ICIs in endemic areas should be established.
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- 2021
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4. Epigenomic landscape study reveals molecular subtypes and EBV-associated regulatory epigenome reprogramming in nasopharyngeal carcinomaResearch in context
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Larry Ka-Yue Chow, Dittman Lai-Shun Chung, Lihua Tao, Kui Fat Chan, Stewart Yuk Tung, Roger Kai Cheong Ngan, Wai Tong Ng, Anne Wing-Mui Lee, Chun Chung Yau, Dora Lai-Wan Kwong, Victor Ho-Fun Lee, Ka-On Lam, Jiayan Liu, Honglin Chen, Wei Dai, and Maria Li Lung
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Epstein-Barr virus ,Nasopharyngeal carcinoma ,Host-virus interaction ,Whole-genome bisulfite sequencing ,Chromatin accessibility ,Tumor microenvironment ,Medicine ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Epstein-Barr virus (EBV) latent infection is associated with genome-wide epigenomic changes in several malignancies, but its role in epigenetic dysregulation remains unclear in nasopharyngeal carcinoma (NPC). Methods: To investigate EBV-associated epigenetic dysregulation, we performed a multi-omics study by integrating whole-genome bisulfite sequencing (WGBS), assay for transposase-accessible chromatin using sequencing (ATAC-Seq), whole-exome sequencing (WES), and single-cell RNA sequencing (scRNA-Seq) data. Findings: In addition to the known global DNA hypermethylated subtype, we discovered a novel subtype with global hypomethylation in EBV + NPC. The consistent EBV-specific differentially methylated regions (EBV-DMRs) in the human genome were identified from both subtypes and associated with loss of CTCF binding (P
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- 2022
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5. Comprehensive single-cell sequencing reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of nasopharyngeal carcinoma
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Lanqi Gong, Dora Lai-Wan Kwong, Wei Dai, Pingan Wu, Shanshan Li, Qian Yan, Yu Zhang, Baifeng Zhang, Xiaona Fang, Li Liu, Min Luo, Beilei Liu, Larry Ka-Yue Chow, Qingyun Chen, Jinlin Huang, Victor Ho-Fun Lee, Ka-On Lam, Anthony Wing-Ip Lo, Zhiwei Chen, Yan Wang, Anne Wing-Mui Lee, and Xin-Yuan Guan
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Science - Abstract
The tumor microenvironment can influence patient survival response to therapy. Here, the authors used single-cell sequencing to investigate the microenvironment of nasopharyngeal cancer and identify tumor-specific signatures in five stromal clusters of cells that may influence patient survival.
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- 2021
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6. Dietary fiber intake from fresh and preserved food and risk of nasopharyngeal carcinoma: observational evidence from a Chinese population
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Zhi-Ming MAI, Roger Kai-Cheong NGAN, Dora Lai-Wan KWONG, Wai-Tong NG, Kam-Tong Yuen, Dennis Kai-Ming Ip, Yap-Hang CHAN, Anne Wing-Mui LEE, Sai-Yin HO, Maria Li LUNG, and Tai-Hing LAM
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Dietary fiber ,Fresh vegetable and fruit ,Soybean product ,Preserved food, Epstein-Barr virus ,Nasopharyngeal carcinoma ,Nutrition. Foods and food supply ,TX341-641 ,Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Abstract Background The role of dietary fiber intake on risk of nasopharyngeal carcinoma (NPC) remains unclear. We examined the associations of dietary fiber intake on the risk of NPC adjusting for a comprehensive list of potential confounders. Methods Using data from a multicenter case-control study, we included 815 histologically confirmed NPC incident cases and 1502 controls in Hong Kong, China recruited in 2014–2017. Odds ratios (ORs) of NPC (cases vs controls) for dietary fiber intake from different sources at different life periods (age 13–18, age 19–30, and 10 years before recruitment) were evaluated using unconditional logistic regression, adjusting for sex, age, socioeconomic status, smoking and drinking status, occupational hazards, family history of cancer, salted fish, and total energy intake in Model 1, Epstein-Barr virus viral capsid antigen serological status in Model 2, and duration of sun exposure and circulating 25-hydroxyvitamin D in Model 3. Results Higher intake of total dietary fiber 10 years before recruitment was significantly associated with decreased NPC risk, with demonstrable dose-response relationship (P-values for trend = 0.001, 0.020 and 0.024 in Models 1–3, respectively). The adjusted ORs (95% CI) in the highest versus the lowest quartile were 0.51 (0.38–0.69) in Model 1, 0.48 (0.33–0.69) in Model 2, and 0.48 (0.33–0.70) in Model 3. However, the association was less clear after adjustment of other potential confounders (e.g. EBV) in the two younger periods (age of 13–18 and 19–30 years). Risks of NPC were significantly lower for dietary fiber intake from fresh vegetables and fruits and soybean products over all three periods, with dose-response relationships observed in all Models (P-values for trend for age 13–18, age 19–30 and 10 years before recruitment were, respectively, 0.002, 0.009 and 0.001 for Model1; 0.020, 0.031 and 0.003 for Model 2; and 0.022, 0.037 and 0.004 for Model 3). No clear association of NPC risk with dietary fiber intake from preserved vegetables, fruits and condiments was observed. Conclusion Our study has shown the protective role of dietary fiber from fresh food items in NPC risk, but no association for total dietary fiber intake was observed, probably because total intake also included intake of preserved food. Further studies with detailed dietary information and in prospective settings are needed to confirm this finding, and to explore the possible underlying biological mechanisms.
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- 2021
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7. Nasopharyngeal carcinoma MHC region deep sequencing identifies HLA and novel non-HLA TRIM31 and TRIM39 loci
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Lvwen Ning, Josephine Mun-Yee Ko, Valen Zhuoyou Yu, Hoi Yan Ng, Candy King-Chi Chan, Lihua Tao, Shiu-Yeung Lam, Merrin Man-Long Leong, Roger Kai-Cheong Ngan, Dora Lai-Wan Kwong, Anne Wing-Mui Lee, Wai-Tong Ng, Ashley Cheng, Stewart Tung, Victor Ho-Fun Lee, Ka-On Lam, Chung-Kong Kwan, Wing-Sum Li, Stephen Yau, Jin-Xin Bei, and Maria Li Lung
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Biology (General) ,QH301-705.5 - Abstract
Here the authors report a major histocompatibility complex (MHC) association analysis for nasopharyngeal carcinoma in Chinese individuals from Hong Kong, finding 8 independent associated loci associated with lower risk for developing nasopharyngeal carcinoma. Two non-human leukocyte antigen (HLA) genes are E3 ubiquitin ligases, TRIM31 and TRIM39, having a role in the innate immune response and implicating the importance of host Epstein-Barr virus interactions in this cancer.
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- 2020
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8. The Stromal and Immune Landscape of Nasopharyngeal Carcinoma and Its Implications for Precision Medicine Targeting the Tumor Microenvironment
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Lanqi Gong, Dora Lai-Wan Kwong, Wei Dai, Pingan Wu, Yan Wang, Anne Wing-Mui Lee, and Xin-Yuan Guan
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nasophanrygeal carcinoma ,tumor microenvionment ,precision medicine ,single-cell sequencing ,immune regulation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The evolution of the tumor microenvironment (TME) is a cancer-dependent and dynamic process. The TME is often a complex ecosystem with immunosuppressive and tumor-promoting functions. Conventional chemotherapy and radiotherapy, primarily focus on inducing tumor apoptosis and hijacking tumor growth, whereas the tumor-protective microenvironment cannot be altered or destructed. Thus, tumor cells can quickly escape from extraneous attack and develop therapeutic resistance, eventually leading to treatment failure. As an Epstein Barr virus (EBV)-associated malignancy, nasopharyngeal carcinoma (NPC) is frequently infiltrated with varied stromal cells, making its microenvironment a highly heterogeneous and suppressive harbor protecting tumor cells from drug penetration, immune attack, and facilitating tumor development. In the last decade, targeted therapy and immunotherapy have emerged as promising options to treat advanced, metastatic, recurrent, and resistant NPC, but lack of understanding of the TME had hindered the therapeutic development and optimization. Single-cell sequencing of NPC-infiltrating cells has recently deciphered stromal composition and functional dynamics in the TME and non-malignant counterpart. In this review, we aim to depict the stromal landscape of NPC in detail based on recent advances, and propose various microenvironment-based approaches for precision therapy.
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- 2021
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9. Dose-Response Reduction in Risk of Nasopharyngeal Carcinoma From Smoking Cessation: A Multicenter Case-Control Study in Hong Kong, China
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Lijun Wang, Zhi-Ming Mai, Roger Kai-Cheong Ngan, Wai-Tong Ng, Jia-Huang Lin, Dora Lai-Wan Kwong, Shing-Chun Chiang, Kam-Tong Yuen, Alice Wan-Ying Ng, Dennis Kai-Ming Ip, Yap-Hang Chan, Anne Wing-Mui Lee, Maria Li Lung, Sai Yin Ho, and Tai-Hing Lam
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nasopharyngeal carcinoma ,cigarette smoking ,smoking cessation ,case-control study ,dose-response relation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundCigarette smoking is associated with nasopharyngeal cancer (NPC) risk. Whether quitting reduces the risk is unclear. We investigated the associations of NPC with duration of and age at quitting in an endemic region.MethodsWe investigated the associations between NPC and quitting in a multicenter case-control study in Hong Kong with 676 newly diagnosed NPC cases and 1,285 hospital controls between 2014 and 2017, using a computer-assisted self-administered questionnaire. Multivariable unconditional logistic regression yielded adjusted odds ratios (AORs) of NPC by quitting status, duration and age of quitting, combinations of duration and age of quitting, and quitting to smoking duration ratio, compared with current smoking.ResultsQuitting (AOR: 0.72; 95% CI: 0.53–0.98) and never smoking (0.73, 0.56–0.95) were associated with lower NPC risk. NPC risk decreased with (i) longer quitting duration (p < 0.01), reaching significance after 11–20 (0.62, 0.39–0.99) and 21+ years (0.54, 0.31–0.92) of quitting; (ii) younger quitting age (p = 0.01), reaching significance for quitting at
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- 2021
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10. Incidence and Demographics of Nasopharyngeal Carcinoma in Cheung Chau Island of Hong Kong—A Distinct Geographical Area With Minimal Residential Mobility and Restricted Public Healthcare Referral Network
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Sik-Kwan Chan BSc, Sze-Chun Chau BSc, Sum-Yin Chan FRCR, Chi-Chung Tong FRCR, Ka-On Lam FRCR, Dora Lai-Wan Kwong MD, To-Wai Leung MD, Mai-Yee Luk FRCR, Anne Wing-Mui Lee MD, Horace Cheuk-Wai Choi PhD, and Victor Ho-Fun Lee MD
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Nasopharyngeal carcinoma (NPC) is endemic in Hong Kong with a skewed geographical and ethnic distribution. We performed an epidemiological study of NPC in Cheung Chau Island, a fishing village with very minimal residential mobility, and compared its demographics and survival with the rest of Hong Kong. Methods NPC data in Cheung Chau and non–Cheung Chau residents between 2006 and 2017 treated in our tertiary center were collected. The incidence, stage distribution, and mortality of Cheung Chau NPC residents were compared with those of their counterparts in the whole Hong Kong obtained from the Hong Kong Cancer Registry. Propensity score matching (PSM) was performed between Cheung Chau and non–Cheung Chau cases in a 1:4 ratio. Overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS) were compared between these two cohorts by product limit estimation and log-rank tests. Results Sixty-one patients residing in Cheung Chau were identified between 2006 and 2017. There was a significantly higher NPC incidence ( P < .001) but an insignificant difference in the mortality rate in Cheung Chau compared to the whole Hong Kong data. After PSM with 237 non–Cheung Chau patients, the Cheung Chau cohort revealed a stronger NPC family history ( P < .001). However, there were no significant differences in OS ( P = .170), PFS ( P = .053), and CSS ( P = .160) between these two cohorts. Conclusion Our results revealed that Cheung Chau had a higher NPC incidence but similar survival outcomes compared to the whole of Hong Kong. Further prospective studies are warranted to verify this finding and to explore the possible underlying mechanisms.
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- 2021
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11. Treatment Outcomes of Computer Tomography-Guided Brachytherapy in Cervical Cancer in Hong Kong: A Retrospective Review
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Wing-Lok Chan, Matthew Ho-Fai Cheng, Jacky Tsun-Kit Wu, Cheuk-Wai Choi, Rosa Piu-Ying Tse, Patty Piu-Ying Ho, Emina Edith Cheung, Andy Cheung, Ka-Yu Test, Karen Kar-Loen Chan, Hexane Yuen-Sheung Ngan, Steven Wai-Kwan Siu, Roger Kai-Cheong Ngan, and Anne Wing-Mui Lee
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cervical cancer ,image-guided brachytherapy ,long-term outcome ,adenocarcinoma ,local control ,computer tomography ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
(1) Background: To report the long-term clinical outcomes of computer-tomography (CT)-guided brachytherapy (BT) for locally advanced cervical cancer. (2) Methods: A total of 135 patients with FIGO stage IB-IVA cervical cancer treated with definitive radiotherapy +/− chemotherapy with an IGABT boost at Queen Mary Hospital, Hong Kong, between November 2013 and December 2019 were included. Treatment included pelvic radiotherapy 40 Gy/20 Fr/4 weeks +/− chemotherapy then CT-guided BT (7 Gy × 4 Fr) and a sequential parametrial boost. The primary outcome was local control. Secondary outcomes were pelvic control, distant metastasis-free survival, overall survival (OS) and late toxicities. (3) Results: The median follow-up was 53.6 months (3.0–99.6 months). The five-year local control, pelvic control, distant metastasis-free survival and OS rates were 90.7%, 84.3%, 80.0% and 87.2%, respectively. The incidence of G3/4 long-term toxicities was 6.7%, including proctitis (2.2%), radiation cystitis (1.5%), bowel perforation (0.7%), ureteric stricture (0.7%) and vaginal stenosis and fistula (0.7%). Patients with adenocarcinomas had worse local control (HR 5.82, 95% CI 1.84–18.34, p = 0.003), pelvic control (HR 4.41, 95% CI 1.83–10.60, p = 0.001), distant metastasis-free survival (HR 2.83, 95% CI 1.17–6.84, p = 0.021) and OS (HR 4.38, 95% CI: 1.52–12.67, p = 0.003) rates. Distant metastasis-free survival was associated with HR-CTV volume ≥ 30 cm3 (HR 3.44, 95% CI 1.18–9.42, p = 0.025) and the presence of pelvic lymph node (HR 3.44, 95% CI 1.18–9.42, p = 0.025). OS was better in patients with concurrent chemotherapy (HR 4.33, 95% CI: 1.40–13.33, p = 0.011). (4) Conclusions: CT-guided BT for cervical cancer achieved excellent long-term local control and OS. Adenocarcinoma was associated with worse clinical outcomes. (4) Conclusion: CT-guided BT for cervical cancer achieved excellent long-term local control and OS. Adenocarcinoma was associated with worse clinical outcomes.
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- 2022
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12. The Most Efficacious Induction Chemotherapy Regimen for Locoregionally Advanced Nasopharyngeal Carcinoma: A Network Meta-Analysis
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Horace Cheuk-Wai Choi, Sik-Kwan Chan, Ka-On Lam, Sum-Yin Chan, Sze-Chun Chau, Dora Lai-Wan Kwong, To-Wai Leung, Mai-Yee Luk, Anne Wing-Mui Lee, and Victor Ho-Fun Lee
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nasopharyngeal carcinoma ,induction chemotherapy ,survival outcome ,network meta-analysis ,efficacy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundInduction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) for non-metastatic locoregionally advanced nasopharyngeal carcinoma (NPC) has gained considerable attention. However, the most efficacious IC regimens remain investigational. We aimed to compare the survival benefits of all available IC regimens followed by CCRT in this network meta-analysis.MethodsAll randomized-controlled trials of CCRT with or without IC in non-metastatic locoregionally advanced NPC were included, with an overall nine trials of 2,705 patients counted in the analysis. CCRT alone was the reference category. Eight IC regimens followed by CCRT were analyzed: docetaxel + cisplatin (DC), gemcitabine + carboplatin + paclitaxel (GCP), gemcitabine + cisplatin (GP), mitomycin + epirubicin + cisplatin + fluorouracil + leucovorin (MEPFL), cisplatin + epirubicin + paclitaxel (PET), cisplatin + fluorouracil (PF), cisplatin + capecitabine (PX) and cisplatin + fluorouracil (PF), cisplatin + capecitabine (PX). Fixed-effects frequentist network meta-analysis models was applied and P-score was used to rank the treatments.ResultsDC, GP, and PX were the top three IC regimens with the highest probability of benefit on overall survival (OS). Their corresponding hazard ratios (HRs) (95% CIs) compared with CCRT alone were of 0.24 (0.08–0.73), 0.43 (0.24–0.77), and 0.54 (0.27–1.09) and the respective P-scores were 94%, 82%, and 68%. The first three IC regimens showing significantly improved progression-free survival (PFS) were PX, followed by GP and DC with respective HRs of 0.46 (0.24–0.88), 0.51 (0.34–0.77), and 0.49 (0.20–1.20), and P-scores of 82%, 78%, and 74%. Among the studies in the intensity-modulated radiation therapy (IMRT) era, GP and PX were the best performed IC regimens, whilst DC performed the best among non-IMRT studies. Doublet and gemcitabine-based IC regimens had better survival benefits compared to triplet and taxane-based IC regimens, respectively.ConclusionsGiven its consistent superiority in both OS and PFS, DC, GP, and PX ranked among the three most efficacious IC regimens in both the overall and subgroup analysis of IMRT or non-IMRT studies. Exploratory analyses suggested that doublet and gemcitabine-based IC regimens showed better survival performance.
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- 2021
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13. An Exploratory Study of Refining TNM-8 M1 Categories and Prognostic Subgroups Using Plasma EBV DNA for Previously Untreated De Novo Metastatic Nasopharyngeal Carcinoma
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Sik-Kwan Chan, Brian O’Sullivan, Shao Hui Huang, Tin-Ching Chau, Ka-On Lam, Sum-Yin Chan, Chi-Chung Tong, Varut Vardhanabhuti, Dora Lai-Wan Kwong, Chor-Yi Ng, To-Wai Leung, Mai-Yee Luk, Anne Wing-Mui Lee, Horace Cheuk-Wai Choi, and Victor Ho-Fun Lee
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nasopharyngeal carcinoma ,metastatic ,M1 categories ,plasma EBV DNA ,recursive partitioning analysis ,TNM ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
(1) Background: NPC patients with de novo distant metastasis appears to be a heterogeneous group who demonstrate a wide range of survival, as suggested by growing evidence. Nevertheless, the current 8th edition of TNM staging (TNM-8) grouping all these patients into the M1 category is not able to identify their survival differences. We sought to identify any anatomic and non-anatomic subgroups in this study. (2) Methods: Sixty-nine patients with treatment-naive de novo M1 NPC (training cohort) were prospectively recruited from 2007 to 2018. We performed univariable and multivariable analyses (UVA and MVA) to explore anatomic distant metastasis factors, which were significantly prognostic of overall survival (OS). Recursive partitioning analysis (RPA) with the incorporation of significant factors from MVA was then performed to derive a new set of RPA stage groups with OS segregation (Set 1 Anatomic-RPA stage groups); another run of MVA was performed with the addition of pre-treatment plasma EBV DNA. A second-round RPA with significant prognostic factors of OS identified in this round of MVA was performed again to derive another set of stage groups (Set 2 Prognostic-RPA stage groups). Both sets were then validated externally with an independent validation cohort of 67 patients with distant relapses of their initially non-metastatic NPC (rM1) after radical treatment. The performance of models in survival segregation was evaluated by the Akaike information criterion (AIC) and concordance index (C-index) under 1000 bootstrapping samples for the validation cohort; (3) Results: The 3-year OS and median follow-up in the training cohort were 36.0% and 17.8 months, respectively. Co-existence of liver-bone metastases was the only significant prognostic factor of OS in the first round UVA and MVA. Set 1 RPA based on anatomic factors that subdivide the M1 category into two groups: M1a (absence of co-existing liver-bone metastases; median OS 28.1 months) and M1b (co-existing liver-bone metastases; median OS 19.2 months, p = 0.023). When pre-treatment plasma EBV DNA was also added, it became the only significant prognostic factor in UVA (p = 0.001) and MVA (p = 0.015), while co-existing liver-bone metastases was only significant in UVA. Set 2 RPA with the incorporation of pre-treatment plasma EBV DNA yielded good segregation (M1a: EBV DNA ≤ 2500 copies/mL and M1b: EBV DNA > 2500 copies/mL; median OS 44.2 and 19.7 months, respectively, p < 0.001). Set 2 Prognostic-RPA groups (AIC: 228.1 [95% CI: 194.8–251.8] is superior to Set 1 Anatomic-RPA groups (AIC: 278.5 [254.6–301.2]) in the OS prediction (p < 0.001). Set 2 RPA groups (C-index 0.59 [95% CI: 0.54–0.67]) also performed better prediction agreement in the validation cohort (vs. Set 1: C-index 0.47 [95% CI: 0.41–0.53]) (p < 0.001); (4) Conclusions: Our Anatomic-RPA stage groups yielded good segregation for de novo M1 NPC, and prognostication was further improved by incorporating plasma EBV DNA. These new RPA stage groups for M1 NPC can be applied to countries/regions regardless of whether reliable and sensitive plasma EBV DNA assays are available or not.
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- 2022
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14. Prognostic Biomarkers for Survival in Nasopharyngeal Carcinoma: A Systematic Review of the Literature
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Kazi Anisha Islam, Larry Ka-Yue Chow, Ngar Woon Kam, Ying Wang, Chi Leung Chiang, Horace Cheuk-Wai Choi, Yun-Fei Xia, Anne Wing-Mui Lee, Wai Tong Ng, and Wei Dai
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nasopharyngeal carcinoma ,prognosis ,biomarkers ,survival ,systematic review ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
This systematic review aims to identify prognostic molecular biomarkers which demonstrate strong evidence and a low risk of bias in predicting the survival of nasopharyngeal carcinoma (NPC) patients. The literature was searched for on PubMed to identify original clinical studies and meta-analyses which reported associations between molecular biomarkers and survival, including ≥150 patients with a survival analysis, and the results were validated in at least one independent cohort, while meta-analyses must include ≥1000 patients with a survival analysis. Seventeen studies fulfilled these criteria—two studies on single nucleotide polymorphisms (SNPs), three studies on methylation biomarkers, two studies on microRNA biomarkers, one study on mutational signature, six studies on gene expression panels, and three meta-analyses on gene expressions. The comparison between the hazard ratios of high-risk and low-risk patients along with a multivariate analysis are used to indicate that these biomarkers have significant independent prognostic values for survival. The biomarkers also indicate a response to certain treatments and whether they could be used as therapeutic targets. This review highlights that patients’ genetics, epigenetics, and signatures of cancer and immune cells in the tumor microenvironment (TME) play a vital role in determining their survival.
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- 2022
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15. Prognostication of Half-Life Clearance of Plasma EBV DNA in Previously Untreated Non-metastatic Nasopharyngeal Carcinoma Treated With Radical Intensity-Modulated Radiation Therapy
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Sik-Kwan Chan, Sum-Yin Chan, Horace Cheuk-Wai Choi, Chi-Chung Tong, Ka-On Lam, Dora Lai-Wan Kwong, Varut Vardhanabhuti, To-Wai Leung, Mai-Yee Luk, Anne Wing-Mui Lee, and Victor Ho-Fun Lee
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nasopharyngeal carcinoma ,intensity-modulated radiation therapy ,plasma Epstein–Barr virus deoxyribonucleic acid ,half-life clearance ,prognostication ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: The prognostic role of plasma Epstein–Barr virus (EBV) DNA clearance when intensity-modulated radiotherapy (IMRT) and the 8th edition of American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM Staging Classification are fully implemented remains undeciphered. We investigated if its half-life clearance during radical treatment for non-metastatic nasopharyngeal carcinoma (NPC) was an early prognosticator.Patients and methods: Patients with previously untreated non-metastatic NPC were prospectively treated with radical IMRT and concurrent chemotherapy +/– induction/adjuvant chemotherapy from 2014 to 2018. Their plasma EBV DNA was measured immediately before treatment followed by weekly schedules until 0 copy/ml in two consecutive measurements. Cox regression models were employed to identify prognostic factors.Results: Forty-five patients were prospectively recruited and analyzed. After a median follow-up of 30.3 months, 2 (4.5%), 1 (2.3%), and 6 (13.6%) patients experienced local, regional, and distant relapses, respectively. The median half-life clearance of plasma EBV DNA was 7.92 days. Those with half-life clearance of >15 days had a worse 3-years progression-free survival (PFS) (79.5 vs. 25.0%, p = 0.005), distant metastasis-free survival (DMFS) (85.0 vs. 31.3%, p = 0.009), and overall survival (OS) (91.3 vs. 75.0%, p = 0.024) when compared to those with a shorter half-life. Multivariable analyses demonstrated that only half-life (>15 days) was prognostic of DMFS [HR (95% CI): 4.91 (1.31; 18.39), p = 0.01] and OS [HR (95% CI): 5.24 (1.06; 26.05)] while half-life (>15 days) [HR (95% CI): 5.14 (1.28; 22.73), p = 0.02] and sum of pretreatment gross tumor volumes of the primary nasopharyngeal tumor and the radiologically positive neck nodes (GTV_P+N) [HR (95% CI): 1.01 (1.00; 1.03), p = 0.02] were prognostic of PFS.Conclusion: The half-life clearance of plasma EBV DNA was prognostic in non-metastatic NPC staged and treated in the contemporary era. Earlier biomarker surveillance during treatment should be considered.Clinical Trial Registration: This study has been registered with ClinicalTrials.gov (Identifier: NCT03830996).
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- 2020
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16. Test-retest reliability of a computer-assisted self-administered questionnaire on early life exposure in a nasopharyngeal carcinoma case-control study
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Zhi-Ming Mai, Jia-Huang Lin, Shing-Chun Chiang, Roger Kai-Cheong Ngan, Dora Lai-Wan Kwong, Wai-Tong Ng, Alice Wan-Ying Ng, Kam-Tong Yuen, Kai-Ming Ip, Yap-Hang Chan, Anne Wing-Mui Lee, Sai-Yin Ho, Maria Li Lung, and Tai-Hing Lam
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Medicine ,Science - Abstract
Abstract We evaluated the reliability of early life nasopharyngeal carcinoma (NPC) aetiology factors in the questionnaire of an NPC case-control study in Hong Kong during 2014–2017. 140 subjects aged 18+ completed the same computer-assisted questionnaire twice, separated by at least 2 weeks. The questionnaire included most known NPC aetiology factors and the present analysis focused on early life exposure. Test-retest reliability of all the 285 questionnaire items was assessed in all subjects and in 5 subgroups defined by cases/controls, sex, time between 1st and 2nd questionnaire (2–29/≥30 weeks), education (secondary or less/postsecondary), and age (25–44/45–59/60+ years) at the first questionnaire. The reliability of items on dietary habits, body figure, skin tone and sun exposure in early life periods (age 6–12 and 13–18) was moderate-to-almost perfect, and most other items had fair-to-substantial reliability in all life periods (age 6–12, 13–18 and 19–30, and 10 years ago). Differences in reliability by strata of the 5 subgroups were only observed in a few items. This study is the first to report the reliability of an NPC questionnaire, and make the questionnaire available online. Overall, our questionnaire had acceptable reliability, suggesting that previous NPC study results on the same risk factors would have similar reliability.
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- 2018
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17. Milk Consumption Across Life Periods in Relation to Lower Risk of Nasopharyngeal Carcinoma: A Multicentre Case-Control Study
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Zhi-Ming Mai, Jia-Huang Lin, Roger Kai-Cheong Ngan, Dora Lai-Wan Kwong, Wai-Tong Ng, Alice Wan-Ying Ng, Kam-Tong Yuen, Dennis Kai Ming Ip, Yap-Hang Chan, Anne Wing-Mui Lee, Sai-Yin Ho, Maria Li Lung, and Tai-Hing Lam
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milk ,nasopharyngeal carcinoma ,case-control study ,life-course ,multiple imputation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: The much higher incidence of nasopharyngeal carcinoma (NPC) in men suggests sex hormones as a risk factor, and dairy products contain measurable amounts of steroid hormones. Milk consumption has greatly increased in endemic regions of NPC. We investigated the association between NPC and milk consumption across life periods in Hong Kong.Methods: A multicentre case-control study included 815 histologically confirmed NPC incident cases and 1,502 controls who were frequency-matched on age and sex at five major hospitals in Hong Kong in 2014–2017. Odds ratios (ORs) of NPC (cases vs. controls) for milk consumption at different life periods were estimated by unconditional logistic regression, adjusting for sex, age, socioeconomic status score, smoking and alcohol drinking status, exposure to occupational hazards, family history of cancer, IgA against Epstein-Barr virus viral capsid antigen, and total energy intake.Results: Compared with abstainers, lower risks of NPC were consistently observed in regular users (consuming ≥5 glasses of milk [fresh and powdered combined] per month) across four life periods of age 6–12 (adjusted OR 0.74, 95% CI 0.54–0.86), 13–18 (0.68, 0.55–0.84), 19–30 (0.68, 0.55–0.84), and 10 years before recruitment (0.72, 0.59–0.87). Long-term average milk consumption of ≤2.5, >2.5, and ≤12.5, >12.5 glasses per month yielded adjusted OR (95% CI) of 1.00 (0.80–1.26), 0.98 (0.81–1.18), 0.95 (0.76–1.18), and 0.55 (0.43–0.70), respectively (all P-values for trend < 0.05).Conclusion: Consumption of milk across life periods was associated with lower risks of NPC. If confirmed to be causal, this has important implications for dairy product consumption and prevention of NPC.
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- 2019
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18. Role of miR-96/EVI1/miR-449a Axis in the Nasopharyngeal Carcinoma Cell Migration and Tumor Sphere Formation
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Lai-Sheung Chan, Hong-Lok Lung, Roger Kai-Cheong Ngan, Anne Wing-Mui Lee, Sai Wah Tsao, Kwok-Wai Lo, Michael Kahn, Maria Li Lung, Rotraud Wieser, and Nai-Ki Mak
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nasopharyngeal carcinoma ,EVI1 ,miR-96 ,miR-449a ,ICG-001 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The Wnt signaling pathway is one of the major signaling pathways used by cancer stem cells (CSC). Ecotropic Viral Integration Site 1 (EVI1) has recently been shown to regulate oncogenic development of tumor cells by interacting with multiple signaling pathways, including the Wnt signaling. In the present study, we found that the Wnt modulator ICG-001 could inhibit the expression of EVI1 in nasopharyngeal carcinoma (NPC) cells. Results from loss-of-function and gain-of-function studies revealed that EVI1 expression positively regulated both NPC cell migration and growth of CSC-enriched tumor spheres. Subsequent studies indicated ICG-001 inhibited EVI1 expression via upregulated expression of miR-96. Results from EVI1 3′UTR luciferase reporter assay confirmed that EVI1 is a direct target of miR-96. Further mechanistic studies revealed that ICG-001, overexpression of miR-96, or knockdown of EVI1 expression could restore the expression of miR-449a. The suppressive effect of miR-449a on the cell migration and tumor sphere formation was confirmed in NPC cells. Taken together, the miR-96/EVI1/miR-449a axis is a novel pathway involved in ICG-001-mediated inhibition of NPC cell migration and growth of the tumor spheres.
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- 2020
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19. Thermal-sensitive lipid nanoparticles potentiate anti-PD therapy through enhancing drug penetration and T lymphocytes infiltration in metastatic tumor
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Yong-Peng Li, Jian-Dong Huang, Fu-Qiang Hu, Anne Wing-Mui Lee, Ya-Nan Tan, Shan-Shan Li, Xin Yuan Guan, and Min Luo
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Cancer Research ,Indoles ,Pyridines ,Programmed Cell Death 1 Receptor ,CD8-Positive T-Lymphocytes ,B7-H1 Antigen ,Metastasis ,Lymphocytes, Tumor-Infiltrating ,Immune system ,Antigen ,Cell Line, Tumor ,Neoplasms ,Acetamides ,Immune Tolerance ,Tumor Microenvironment ,medicine ,Humans ,Cytotoxic T cell ,Photosensitizer ,Low-Level Light Therapy ,Lipid bilayer ,Cell Proliferation ,Tumor microenvironment ,Chemistry ,medicine.disease ,Oncology ,Liposomes ,Cancer research ,Nanoparticles ,Immunotherapy ,Infiltration (medical) ,T-Lymphocytes, Cytotoxic - Abstract
The response rate of anti-PD therapy in most cancer patients remains low. Therapeutic drug and tumor-infiltrating lymphocytes (TILs) are usually obstructed by the stromal region within tumor microenvironment (TME) rather than distributed around tumor cells, thus unable to induce the immune response of cytotoxic T cells. Here, we constructed the cationic thermosensitive lipid nanoparticles IR780/DPPC/BMS by introducing cationic NIR photosensitizer IR-780 iodide (IR780) modified lipid components, thermosensitive lipid DPPC and PD-1/PD-L1 inhibitor BMS202 (BMS). Upon laser irradiation, IR780/DPPC/BMS penetrated into deep tumor, and reduced cancer-associated fibroblasts (CAFs) around tumor cells to remodel the spatial distribution of TILs in TME. Interestingly, the cationic IR780/DPPC/BMS could capture released tumor-associated antigens (TAAs), thereby enhancing the antigen-presenting ability of DCs to activate cytotoxic T lymphocytes. Moreover, IR780/DPPC/BMS initiated gel-liquid crystal phase transition under laser irradiation, accelerating the disintegration of lipid bilayer structure and leading to the responsive release of BMS, which would reverse the tumor immunosuppression state by blocking PD-1/PD-L1 pathway for a long term. This combination treatment can synergistically exert the antitumor immune response and inhibit the tumor growth and metastasis.
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- 2021
20. Tuberculosis reactivation at ileum following immune checkpoint inhibition with pembrolizumab for metastatic nasopharyngeal carcinoma: a case report
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Ben Man-Fei Cheung, To-Wai Leung, Dora L.W. Kwong, Sum-Yin Chan, Chun-Fai Yeung, Victor Ho-Fun Lee, Ka-Ming Lam, Kin-Sang Lau, Kwok-Keung Yuen, Ivan Hung, Mai-Yee Luk, Ka-On Lam, Anne Wing-Mui Lee, and Chi-Chung Tong
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Adult ,medicine.medical_specialty ,Tuberculosis ,medicine.medical_treatment ,Interferon gamma release assay ,Case Report ,Pembrolizumab ,Infectious and parasitic diseases ,RC109-216 ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Immune checkpoint inhibitors ,Ileum ,Internal medicine ,medicine ,Nasopharyngeal carcinoma ,Humans ,Ileitis ,Tuberculosis reactivation ,Chemotherapy ,IGRA ,business.industry ,Cancer ,Nasopharyngeal Neoplasms ,medicine.disease ,Immune checkpoint ,Infectious Diseases ,Female ,Neoplasm Recurrence, Local ,business - Abstract
Background Tuberculosis (TB) reactivation has been increasingly identified following immune checkpoint inhibitor (ICI) therapy for cancer patients. However there has been no report on TB reactivation in the gastrointestinal tract. In the report, we describe a patient who developed TB ileitis after pembrolizumab for her metastatic nasopharyngeal carcinoma (NPC). Rechallenge with pembrolizumab after its temporary interruption together with anti-TB therapy produced continuous tumor response but without further TB reactivation. Case presentation A 29-year-old lady with metastatic NPC involving the cervical nodes, lungs and bones started pembrolizumab after failure to multiple lines of chemotherapy. She complained of sudden onset of abdominal pain, vomiting and bloody diarrhea with mucus 21 months after pembrolizumab. Colonoscopy revealed terminal ileitis with multiple caseating granulomas with Langerhan cells. Serum interferon gamma release assay was strongly positive. She was treated with anti-TB medication and was later rechallenged with pembrolizumab for her progressive lung metastases without further TB relapse while her lung metastases were brought under control again. Conclusion To date, this is the first gastrointestinal TB reactivation after ICI therapy for cancer. Guidelines to screen for TB before initiation of ICIs in endemic areas should be established.
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- 2021
21. Prognostic Factors for Overall Survival in Nasopharyngeal Cancer and Implication for TNM Staging by UICC: A Systematic Review of the Literature
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Tianzhu Lu, Eric Sze Chun Chau, Anne Wing Mui Lee, Jianji Pan, Wenqi Chen, Qiaojuan Guo, Peter Ho Yin Luk, Youping Xiao, Shao Hui Huang, Shaojun Lin, Brian O'Sullivan, Chi-Leung Chiang, Wai Tong Ng, Zhiyuan Xu, Jishi Li, Tiffany Sze Wai Ma, and Horace Cheuk Wai Choi
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Oncology ,Cancer Research ,medicine.medical_specialty ,anatomical criteria ,systematic review ,Internal medicine ,medicine ,Overall survival ,Lymph node ,RC254-282 ,Nasopharyngeal cancer ,TMN classification ,business.industry ,nasopharyngeal carcinoma ,Parotid lymph node ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,prognostic factors ,Evidence-based medicine ,medicine.disease ,Primary tumor ,AJCC/UICC staging system ,medicine.anatomical_structure ,Nasopharyngeal carcinoma ,TNM Staging ,business - Abstract
This study aims to identify prognostic factors in nasopharyngeal carcinoma (NPC) to improve the current 8th edition TNM classification. A systematic review of the literature reported between 2013 and 2019 in PubMed, Embase, and Scopus was conducted. Studies were included if (1) original clinical studies, (2) ≥50 NPC patients, and (3) analyses on the association between prognostic factors and overall survival. The data elements of eligible studies were abstracted and analyzed. A level of evidence was synthesized for each suggested change to the TNM staging and prognostic factors. Of 5,595 studies screened, 108 studies (44 studies on anatomical criteria and 64 on non-anatomical factors) were selected. Proposed changes/factors with strong evidence included the upstaging paranasal sinus to T4, defining parotid lymph node as N3, upstaging N-category based on presence of lymph node necrosis, as well as the incorporation of non-TNM factors including EBV-DNA level, primary gross tumor volume (GTV), nodal GTV, neutrophil-lymphocyte ratio, lactate dehydrogenase, C-reactive protein/albumin ratio, platelet count, SUVmax of the primary tumor, and total lesion glycolysis. This systematic review provides a useful summary of suggestions and prognostic factors that potentially improve the current staging system. Further validation studies are warranted to confirm their significance.
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- 2021
22. The Stromal and Immune Landscape of Nasopharyngeal Carcinoma and Its Implications for Precision Medicine Targeting the Tumor Microenvironment
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P.M. Wu, Wei Dai, Lanqi Gong, Xin Yuan Guan, Yan Wang, Dora L.W. Kwong, and Anne Wing-Mui Lee
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Cancer Research ,Tumor microenvironment ,Stromal cell ,business.industry ,medicine.medical_treatment ,precision medicine ,immune regulation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,nasophanrygeal carcinoma ,Immunotherapy ,Review ,single-cell sequencing ,Precision medicine ,medicine.disease ,Targeted therapy ,tumor microenvionment ,Immune system ,Single cell sequencing ,Nasopharyngeal carcinoma ,Oncology ,Cancer research ,Medicine ,business ,RC254-282 - Abstract
The evolution of the tumor microenvironment (TME) is a cancer-dependent and dynamic process. The TME is often a complex ecosystem with immunosuppressive and tumor-promoting functions. Conventional chemotherapy and radiotherapy, primarily focus on inducing tumor apoptosis and hijacking tumor growth, whereas the tumor-protective microenvironment cannot be altered or destructed. Thus, tumor cells can quickly escape from extraneous attack and develop therapeutic resistance, eventually leading to treatment failure. As an Epstein Barr virus (EBV)-associated malignancy, nasopharyngeal carcinoma (NPC) is frequently infiltrated with varied stromal cells, making its microenvironment a highly heterogeneous and suppressive harbor protecting tumor cells from drug penetration, immune attack, and facilitating tumor development. In the last decade, targeted therapy and immunotherapy have emerged as promising options to treat advanced, metastatic, recurrent, and resistant NPC, but lack of understanding of the TME had hindered the therapeutic development and optimization. Single-cell sequencing of NPC-infiltrating cells has recently deciphered stromal composition and functional dynamics in the TME and non-malignant counterpart. In this review, we aim to depict the stromal landscape of NPC in detail based on recent advances, and propose various microenvironment-based approaches for precision therapy.
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- 2021
23. A Cross-sectional Study on the Unmet Supportive Care Needs of Cancer Patients Under the COVID-19 Pandemic
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Denise Shuk Ting Cheung, Naomi Takemura, Helen Yun-Fong Lui, Wen-Pei Chang, Chi-Leung Chiang, Wing-Ho Mui, Alina Yee Man Ng, Pui Hing Chau, Anne Wing Mui Lee, and Chia-Chin Lin
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- 2022
24. Negative plasma Epstein-Barr virus DNA nasopharyngeal carcinoma in an endemic region and its influence on liquid biopsy screening programmes
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Sum-Yin Chan, To-Wai Leung, Chi-Chung Tong, Ka-On Lam, John M. Nicholls, Sik-Kwan Chan, Victor Ho-Fun Lee, Mai-Yee Luk, Ka-Chun Tsang, Dora L.W. Kwong, Cheuk-Wai Choi, Anne Wing-Mui Lee, Tsz-Him So, and Pek-Lan Khong
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Male ,Cancer Research ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Endemic Diseases ,Gastroenterology ,Tumour biomarkers ,0302 clinical medicine ,hemic and lymphatic diseases ,Young adult ,Stage (cooking) ,Head and neck cancer ,Early Detection of Cancer ,Radical treatment ,Aged, 80 and over ,0303 health sciences ,Nasopharyngeal Carcinoma ,Middle Aged ,Prognosis ,Tumor Burden ,Survival Rate ,Oncology ,030220 oncology & carcinogenesis ,Hong Kong ,RNA, Viral ,Female ,Adult ,medicine.medical_specialty ,Adolescent ,Virus ,Article ,Cancer screening ,03 medical and health sciences ,Young Adult ,Internal medicine ,medicine ,Humans ,Liquid biopsy ,Survival rate ,030304 developmental biology ,Aged ,Neoplasm Staging ,business.industry ,Epstein-Barr virus DNA ,Liquid Biopsy ,Nasopharyngeal Neoplasms ,medicine.disease ,Nasopharyngeal carcinoma ,DNA, Viral ,business - Abstract
Background Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) in endemic regions may have undetectable plasma EBV DNA. Methods We prospectively recruited 518 patients with non-metastatic NPC and measured their pre-treatment plasma EBV DNA. The stage distribution and prognosis between pre-treatment plasma EBV DNA-negative (0–20 copies/ml) and EBV DNA-positive (>20 copies/ml) patients following radical treatment were compared. Results Seventy-eight patients (15.1%) were plasma EBV DNA-negative, and 62 in this subset (12.0%) had 0 copy/ml. Only 23/78 (29.5%) plasma EBV DNA-negative patients with advanced NPC (stage III-IVA) had strong EBV encoded RNA (EBER) positivity (score 3) in their tumours compared to 342/440 (77.7%) EBV DNA-positive patients of the same stages (p p p Conclusions Patients with low-volume NPC may not be identified by plasma/serum tumour markers and caution should be taken in its utility as a screening tool for NPC even in endemic regions. Clinical trial registration Clinicaltrials.gov Identifier: NCT02476669.
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- 2019
25. Cutaneous Angiosarcoma Secondary to Lymphoedema or Radiation Therapy — A Systematic Review
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A. Kwong and Anne Wing-Mui Lee
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Adult ,medicine.medical_specialty ,Palliative care ,Adolescent ,medicine.medical_treatment ,Hemangiosarcoma ,MEDLINE ,030218 nuclear medicine & medical imaging ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Angiosarcoma ,Lymphedema ,Aged ,Aged, 80 and over ,Adjuvant radiotherapy ,business.industry ,Middle Aged ,medicine.disease ,Radiation therapy ,Oncology ,Amputation ,030220 oncology & carcinogenesis ,Female ,Radiotherapy, Adjuvant ,business ,Mastectomy - Abstract
Aims Secondary angiosarcoma is known to be associated with lymphoedema or radiation after cancer treatment. This systematic review aims to evaluate the clinical features and outcomes of secondary angiosarcoma commonly arising after breast cancer treatment. Materials and methods A systematic review was carried out according to the PRISMA protocol. Medline, EMBASE, CINAHL and Cochrane databases were searched for English articles to April 2018 with predefined strategy. Retrieved studies were independently screened and rated for relevance. Data were extracted by two researchers. Results There were 72 secondary angiosarcomas of the limbs. Most patients (n = 68, 94.4%) had a history of lymphoedema. The median latent period was 15 years (range 3–40 years). Thirty-eight (52.8%) patients received wide excision or amputation as a treatment for the angiosarcoma, two (2.8%) patients received isolated limb perfusion and one (1.4%) patient received systemic chemotherapy. The remaining patients received palliative care/undocumented treatment. The pooled median duration to mortality was 10.5 months (range 1–144 months). Of note, obesity was documented in seven (9.7%) patients. There were 83 breast angiosarcomas; all with known breast cancer history. Thirty-one (37.3%) patients received mastectomy as breast cancer treatment. Fifty-four (65.1%) patients had a history of adjuvant radiotherapy for the primary breast cancer. The median latent period was 6 years (range 2–50 years); the median size was 40 mm (range 8–200 mm). Forty-one (49.4%) patients received wide excision, 19 (22.9%) patients received completion mastectomy and 23 (27.7%) patients have undocumented treatment for angiosarcoma. The pooled median duration to mortality was 31 months (range 6–168 months). Conclusion Angiosarcoma in lympedematous upper limbs or after breast cancer irradiation remains uncommon. However, its long latency and high mortality warrant long-term vigilant surveillance.
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- 2019
26. Low vitamin D exposure and risk of nasopharyngeal carcinoma: Observational and genetic evidence from a multicenter case-control study
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Roger Kai Cheong Ngan, Dennis Kai-Ming Ip, Wai Tong Ng, Kam-Tong Yuen, Tai Hing Lam, Jia-Huang Lin, Yap-Hang Chan, Cheuk-Kwong Lee, Sai Yin Ho, J. N. S. Leung, Zhi-Ming Mai, Dora L.W. Kwong, Maria Li Lung, and Anne Wing-Mui Lee
- Subjects
Oncology ,Male ,medicine.medical_specialty ,Critical Care and Intensive Care Medicine ,Logistic regression ,Risk Assessment ,vitamin D deficiency ,Body Mass Index ,Risk Factors ,Internal medicine ,Epidemiology ,medicine ,Vitamin D and neurology ,Odds Ratio ,Humans ,Genetic Predisposition to Disease ,Vitamin D ,Early Detection of Cancer ,Nutrition and Dietetics ,Nasopharyngeal Carcinoma ,business.industry ,Confounding ,Case-control study ,Nasopharyngeal Neoplasms ,Middle Aged ,medicine.disease ,Vitamin D Deficiency ,Logistic Models ,Nasopharyngeal carcinoma ,Social Class ,Case-Control Studies ,Etiology ,Hong Kong ,Female ,business - Abstract
Summary Background & aims Little is known about the risk of nasopharyngeal carcinoma (NPC) in relation to vitamin D exposure. The aim of this study was to examine the associations of NPC risk with serum level of 25-hydroxyvitamin D (25OHD) and genetic predicted 25OHD, and potential effect modification by several putative risk factors of NPC. Methods Our multicenter case–control study in Hong Kong recruited 815 NPC cases and 1502 frequency-matched (by sex and age) hospital controls from five major regional hospitals, and recruited 299 healthy subjects from blood donation centers (2014–2017). Circulating level of 25-hydroxyvitamin D (25OHD) and genetic predicted 25OHD (rs12785878, rs11234027, rs12794714, rs4588 and rs6013897) were measured by validated enzyme immunoassay and the iPLEX assay on the MassARRAY System, respectively. Data were also collected on demographics, lifestyle factors, ultraviolet radiation exposure, and potential confounders using a computer-assisted, self-administered questionnaire with satisfactory test-retest reliability. Unconditional logistic regression models were used to estimate ORs and 95% CIs. Results Despite no significant association of NPC risk with circulating 25OHD and genetic predicted 25OHD, there was evidence for an inverse association in participants with normal body mass index (between 18.5 and 27.5) across categories of 25OHD (Ptrend = 0.003), and a positive association in those with low socioeconomic status across categories based on the genetic score (Ptrend = 0.005). In addition, risk of NPC diagnosed at an early stage was higher for genetically lower 25OHD level (adjusted OR = 3.09, 95% CI = 1.04–9.21, Ptrend = 0.022). Conclusions Findings of this first comprehensive study to investigate the positive association of NPC risk with vitamin D deficiency need to be confirmed and be best interpreted with results of further similar studies. Our findings may inform possible etiological mechanisms of the associations with several putative risk/protective factors of NPC.
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- 2021
27. Comprehensive single-cell sequencing reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of nasopharyngeal carcinoma
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Ka-On Lam, Anthony Wing Ip Lo, Baifeng Zhang, Victor Ho-Fun Lee, Xiaona Fang, Wei Dai, Qing-Yun Chen, Xin Yuan Guan, Jinlin Huang, Lanqi Gong, Beilei Liu, Shan-Shan Li, Qian Yan, Yu Zhang, Anne Wing-Mui Lee, Larry Ka-Yue Chow, Zhiwei Chen, P.M. Wu, Min Luo, Yan Wang, Li Liu, and Dora L.W. Kwong
- Subjects
0301 basic medicine ,Cancer microenvironment ,Stromal cell ,Science ,T-Lymphocytes ,Population ,General Physics and Astronomy ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Tumor Microenvironment ,Humans ,Myeloid Cells ,education ,Head and neck cancer ,education.field_of_study ,Tumor microenvironment ,B-Lymphocytes ,Multidisciplinary ,Nasopharyngeal Carcinoma ,Sequence Analysis, RNA ,Cancer ,Nasopharyngeal Neoplasms ,General Chemistry ,Fibroblasts ,medicine.disease ,Prognosis ,Phenotype ,Progression-Free Survival ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Single cell sequencing ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Cancer research ,Stromal Cells - Abstract
The tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC) harbors a heterogeneous and dynamic stromal population. A comprehensive understanding of this tumor-specific ecosystem is necessary to enhance cancer diagnosis, therapeutics, and prognosis. However, recent advances based on bulk RNA sequencing remain insufficient to construct an in-depth landscape of infiltrating stromal cells in NPC. Here we apply single-cell RNA sequencing to 66,627 cells from 14 patients, integrated with clonotype identification on T and B cells. We identify and characterize five major stromal clusters and 36 distinct subpopulations based on genetic profiling. By comparing with the infiltrating cells in the non-malignant microenvironment, we report highly representative features in the TME, including phenotypic abundance, genetic alternations, immune dynamics, clonal expansion, developmental trajectory, and molecular interactions that profoundly influence patient prognosis and therapeutic outcome. The key findings are further independently validated in two single-cell RNA sequencing cohorts and two bulk RNA-sequencing cohorts. In the present study, we reveal the correlation between NPC-specific characteristics and progression-free survival. Together, these data facilitate the understanding of the stromal landscape and immune dynamics in NPC patients and provides deeper insights into the development of prognostic biomarkers and therapeutic targets in the TME., The tumor microenvironment can influence patient survival response to therapy. Here, the authors used single-cell sequencing to investigate the microenvironment of nasopharyngeal cancer and identify tumor-specific signatures in five stromal clusters of cells that may influence patient survival.
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- 2021
28. Dietary fiber intake from fresh and preserved food and risk of nasopharyngeal carcinoma: observational evidence from a Chinese population
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Wai Tong Ng, Yap-Hang Chan, Roger Kai Cheong Ngan, Maria Li Lung, Tai Hing Lam, Zhi-Ming Mai, Sai Yin Ho, Dennis Kai-Ming Ip, Kam-Tong Yuen, Dora L.W. Kwong, and Anne Wing-Mui Lee
- Subjects
Dietary Fiber ,0301 basic medicine ,China ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Adolescent ,Soybean product ,Short Report ,Medicine (miscellaneous) ,Physiology ,lcsh:TX341-641 ,Clinical nutrition ,Logistic regression ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Food, Preserved ,medicine ,Humans ,Prospective Studies ,Family history ,lcsh:RC620-627 ,Preserved food, Epstein-Barr virus ,Nasopharyngeal Carcinoma ,Nutrition and Dietetics ,business.industry ,Confounding ,Nasopharyngeal Neoplasms ,Odds ratio ,medicine.disease ,lcsh:Nutritional diseases. Deficiency diseases ,030104 developmental biology ,Seafood ,Quartile ,Nasopharyngeal carcinoma ,Case-Control Studies ,030220 oncology & carcinogenesis ,business ,lcsh:Nutrition. Foods and food supply ,Fresh vegetable and fruit ,Salted fish - Abstract
Background The role of dietary fiber intake on risk of nasopharyngeal carcinoma (NPC) remains unclear. We examined the associations of dietary fiber intake on the risk of NPC adjusting for a comprehensive list of potential confounders. Methods Using data from a multicenter case-control study, we included 815 histologically confirmed NPC incident cases and 1502 controls in Hong Kong, China recruited in 2014–2017. Odds ratios (ORs) of NPC (cases vs controls) for dietary fiber intake from different sources at different life periods (age 13–18, age 19–30, and 10 years before recruitment) were evaluated using unconditional logistic regression, adjusting for sex, age, socioeconomic status, smoking and drinking status, occupational hazards, family history of cancer, salted fish, and total energy intake in Model 1, Epstein-Barr virus viral capsid antigen serological status in Model 2, and duration of sun exposure and circulating 25-hydroxyvitamin D in Model 3. Results Higher intake of total dietary fiber 10 years before recruitment was significantly associated with decreased NPC risk, with demonstrable dose-response relationship (P-values for trend = 0.001, 0.020 and 0.024 in Models 1–3, respectively). The adjusted ORs (95% CI) in the highest versus the lowest quartile were 0.51 (0.38–0.69) in Model 1, 0.48 (0.33–0.69) in Model 2, and 0.48 (0.33–0.70) in Model 3. However, the association was less clear after adjustment of other potential confounders (e.g. EBV) in the two younger periods (age of 13–18 and 19–30 years). Risks of NPC were significantly lower for dietary fiber intake from fresh vegetables and fruits and soybean products over all three periods, with dose-response relationships observed in all Models (P-values for trend for age 13–18, age 19–30 and 10 years before recruitment were, respectively, 0.002, 0.009 and 0.001 for Model1; 0.020, 0.031 and 0.003 for Model 2; and 0.022, 0.037 and 0.004 for Model 3). No clear association of NPC risk with dietary fiber intake from preserved vegetables, fruits and condiments was observed. Conclusion Our study has shown the protective role of dietary fiber from fresh food items in NPC risk, but no association for total dietary fiber intake was observed, probably because total intake also included intake of preserved food. Further studies with detailed dietary information and in prospective settings are needed to confirm this finding, and to explore the possible underlying biological mechanisms.
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- 2021
29. Principle of Cancer Radiotherapy
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Anne Wing-Mui Lee and Victor Ho-Fun Lee
- Subjects
Liver injury ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Cancer ,medicine.disease ,Ionizing radiation ,Radiation therapy ,Hepatocellular carcinoma ,Cancer Radiotherapy ,Cancer cell ,medicine ,External beam radiotherapy ,Radiology ,business - Abstract
Radiotherapy is one of the most common types of nonsurgical anticancer treatment modality, employed in more than 50% of cases. Almost half of cancer patients are cured of their cancer by radiotherapy as part of their anticancer treatment. Radiotherapy kills cancer by the use of ionizing radiation which causes permanent and irreversible double-strand DNA breaks in cancer cells leading to cell death. Unfortunately, it can also kill normal cells leading to acute and chronic treatment-related complications. Traditionally, radiotherapy was seldom employed in the treatment of hepatocellular carcinoma (HCC) because of the risk of severe and sometimes irreversible radiation-induced liver injury (RILD), since a large volume of normal liver which took into account the physiological movement of the liver and the tumors inside during breathing might be irradiated. However, with the advent of new radiation technologies and motion management devices, radiation therapy can now be safely delivered to liver tumors. Further radiation dose escalation in the form of hypofractionated stereotactic body radiation therapy (SBRT) is also now feasible, which delivers a high dose of radiation to the tumors while sparing the adjacent normal organs from unnecessary irradiation, leading to a much better tumor response and favorable safety profile. Furthermore, endovascular radioembolization with radioisotope also produced encouraging results in the treatment of unresectable HCC. In this chapter, we will describe how radiotherapy works in cancer cells and elucidate different types of radiation therapy for HCC.
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- 2021
30. Relationship of subjective and objective sleep measures with physical performance in advanced-stage lung cancer patients
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Naomi Takemura, Chia Chin Lin, Anne Wing Mui Lee, Tsz Yeung Kam, Tai Chung Lam, Denise Shuk Ting Cheung, Jeannie Yin Kwan Chik, Daniel Y. T. Fong, and James Chung-Man Ho
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Adult ,Male ,medicine.medical_specialty ,Lung Neoplasms ,Science ,Polysomnography ,Population ,Walk Test ,Timed Up and Go test ,Article ,Pittsburgh Sleep Quality Index ,Surveys and Questionnaires ,medicine ,Humans ,Lung cancer ,education ,Exercise ,Aged ,Neoplasm Staging ,Aged, 80 and over ,education.field_of_study ,Multidisciplinary ,business.industry ,Actigraphy ,Middle Aged ,Physical Functional Performance ,medicine.disease ,Regression ,Oncology ,Risk factors ,Physical performance ,Multivariate Analysis ,Physical therapy ,Medicine ,Regression Analysis ,Female ,Sleep (system call) ,business ,Sleep - Abstract
Advanced lung cancer patients suffer from deteriorated physical function, which negatively impacts physical and psychological health. As little is known about sleep and physical function in this population, this study aimed to examine the association between subjective and objective sleep parameters and physical function among them. 164 advanced lung cancer patients were included. Objective sleep was measured by actigraphy (measured on non-dominant wrist for 72 h), and subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Performance-based physical function was measured by Timed Up and Go Test (TUGT), 6-Minute Walk Test (6MWT), Sit-to-Stand Test, and One-leg Standing Test. Univariable and multivariable regression analyses were employed to examine the association between sleep and physical function. Total sleep time (TST) was significantly associated with the 6MWT (β = 0.259; 95% CI 0.120, 0.398; P Trial registration: ClinicalTrials.gov, NCT03482323. Registered 29 March 2018, https://clinicaltrials.gov/ct2/show/NCT03482323; ClinicalTrials.gov, NCT04119778. Registered 8 October 2019, https://clinicaltrials.gov/ct2/show/NCT04119778.
- Published
- 2020
31. Therapeutic evaluation of palbociclib and its compatibility with other chemotherapies for primary and recurrent nasopharyngeal carcinoma
- Author
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Pek-Lan Khong, Lin Jia, Anne Wing Mui Lee, Lydia W.T. Cheung, Vivian Wai Yan Lui, Zhichao Xue, Kwok Wai Lo, Victor Ho Fan Lee, Hui Yuan, Xin Li, Sai Wah Tsao, Chanping You, Wenying Piao, Chi Man Tsang, and Yongshu Li
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Cell cycle checkpoint ,Pyridines ,Antineoplastic Agents ,Palbociclib ,Transfection ,Piperazines ,Mice ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,medicine ,otorhinolaryngologic diseases ,Animals ,Humans ,Cytotoxic T cell ,Cisplatin ,Nasopharyngeal Carcinoma ,business.industry ,Research ,SAHA ,Genomics ,medicine.disease ,Patient-derived xenografts ,stomatognathic diseases ,030104 developmental biology ,Oncology ,Nasopharyngeal carcinoma ,Apoptosis ,Cell culture ,Drug resistance ,030220 oncology & carcinogenesis ,Cancer research ,business ,medicine.drug - Abstract
Background Recent genomic analyses revealed that druggable molecule targets were only detectable in approximately 6% of patients with nasopharyngeal carcinoma (NPC). However, a dependency on dysregulated CDK4/6–cyclinD1 pathway signaling is an essential event in the pathogenesis of NPC. In this study, we aimed to evaluate the therapeutic efficacy of a specific CDK4/6 inhibitor, palbociclib, and its compatibility with other chemotherapeutic drugs for the treatment of NPC by using newly established xenograft models and cell lines derived from primary, recurrent, and metastatic NPC. Methods We evaluated the efficacies of palbociclib monotherapy and concurrent treatment with palbociclib and cisplatin or suberanilohydroxamic acid (SAHA) in NPC cell lines and xenograft models. RNA sequencing was then used to profile the drug response–related pathways. Palbociclib-resistant NPC cell lines were established to determine the potential use of cisplatin as a second-line treatment after the development of palbociclib resistance. We further examined the efficacy of palbociclib treatment against cisplatin-resistant NPC cells. Results In NPC cells, palbociclib monotherapy was confirmed to induce cell cycle arrest in the G1 phase in vitro. Palbociclib monotherapy also had significant inhibitory effects in all six tested NPC tumor models in vivo, as indicated by substantial reductions in the total tumor volumes and in Ki-67 proliferation marker expression. In NPC cells, concurrent palbociclib treatment mitigated the cytotoxic effect of cisplatin in vitro. Notably, concurrent treatment with palbociclib and SAHA synergistically promoted NPC cell death both in vitro and in vivo. This combination also further inhibited tumor growth by inducing autophagy-associated cell death. NPC cell lines with induced palbociclib or cisplatin resistance remained sensitive to treatment with cisplatin or palbociclib, respectively. Conclusions Our study findings provide essential support for the use of palbociclib as an alternative therapy for NPC and increase awareness of the effective timing of palbociclib administration with other chemotherapeutic drugs. Our results provide a foundation for the design of first-in-human clinical trials of palbociclib regimens in patients with NPC.
- Published
- 2020
32. Comparison of efficacy and safety of three induction chemotherapy regimens with gemcitabine plus cisplatin (GP), cisplatin plus fluorouracil (PF) and cisplatin plus capecitabine (PX) for locoregionally advanced previously untreated nasopharyngeal carcinoma: A pooled analysis of two prospective studies
- Author
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Victor Ho-Fun Lee, Anne Wing-Mui Lee, Sum-Yin Chan, Mai-Yee Luk, Chi-Chung Tong, To-Wai Leung, Ka-On Lam, Horace Cheuk-Wai Choi, Sik-Kwan Chan, and Dora L.W. Kwong
- Subjects
Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Population ,Deoxycytidine ,Capecitabine ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Prospective Studies ,030223 otorhinolaryngology ,education ,Prospective cohort study ,Aged ,Cisplatin ,education.field_of_study ,Nasopharyngeal Carcinoma ,business.industry ,Induction chemotherapy ,Induction Chemotherapy ,Middle Aged ,medicine.disease ,Gemcitabine ,Progression-Free Survival ,Treatment Outcome ,Nasopharyngeal carcinoma ,Fluorouracil ,030220 oncology & carcinogenesis ,Female ,Oral Surgery ,business ,medicine.drug - Abstract
Purpose We compared, in this pooled analysis, the differences in efficacy and safety between three induction chemotherapy regimens including gemcitabine plus cisplatin (GP), cisplatin plus fluorouracil (PF) and cisplatin plus capecitabine (PX) in patients recruited into our two prospective studies for previously untreated locoregionally advanced nasopharyngeal carcinoma (NPC). Methods GP, PF or PX followed by radical concurrent chemoradiotherapy was given to patients with previously untreated locoregionally advanced (stage III to IVA) NPC prospectively recruited into our two prospective studies. The study endpoints included progression-free survival (PFS) and overall survival (OS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and major acute and late treatment-related toxicities (grade ≥ 3). Results From 2006 to 2016, 278 patients were enrolled (84, 94 and 100 patients in GP, PF and PX group respectively). After a median follow-up of 80 months, the 3-year PFS, OS, LRFS, DMFS and CSS of the whole population were 78.7%, 88.1%, 84.9%, 80.9% and 89.8%, respectively. There were no significant differences in prespecified survival endpoints among GP, PF and PX in both stage III and stage IVA patients. GP had lower incidences of severe (grade ≥ 3) anemia and diarrhea in stage III patients, as well as severe anemia, dehydration, renal impairment and vomiting in stage IVA patients. The incidences of grade ≥ 3 late toxicities were similar among these 3 induction regimens. Conclusion GP had similar efficacy and potentially fewer treatment-related complications compared with PF and PX as induction chemotherapy for previously untreated locoregionally advanced NPC.
- Published
- 2020
33. Solar Ultraviolet Radiation and Vitamin D Deficiency on Epstein-Barr Virus Reactivation: Observational and Genetic Evidence From a Nasopharyngeal Carcinoma-Endemic Population
- Author
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Roger Kai Cheong Ngan, Anne Wing-Mui Lee, Yap-Hang Chan, Zhi-Ming Mai, Kai-Ming Ip, Alice Wan-Ying Ng, Wai Tong Ng, Tai Hing Lam, Jia-Huang Lin, Sai Yin Ho, Dora L.W. Kwong, and Maria Li Lung
- Subjects
ultraviolet radiation ,genetic epidemiology ,Population ,vitamin D ,vitamin D deficiency ,Major Articles ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Vitamin D and neurology ,Epstein-Barr virus ,030212 general & internal medicine ,education ,education.field_of_study ,business.industry ,nasopharyngeal carcinoma ,Confounding ,Odds ratio ,medicine.disease ,Infectious Diseases ,AcademicSubjects/MED00290 ,Oncology ,Genetic epidemiology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Immunology ,business ,Serostatus - Abstract
Background We investigated the relationship of Epstein-Barr virus viral capsid antigen (EBV VCA-IgA) serostatus with ambient and personal ultraviolet radiation (UVR) and vitamin D exposure. Methods Using data from a multicenter case-control study, we included 1026 controls subjects in 2014–2017 in Hong Kong, China. Odds ratios (ORs) and 95% confidence intervals (CIs) of the association between UVR exposure and EBV VCA-IgA (seropositivity vs seronegativity) were calculated using unconditional logistic regression models adjusted for potential confounders. Results We observed a large increase in seropositivity of EBV VCA-IgA in association with duration of sunlight exposures at both 10 years before recruitment and age 19–30 years (adjusted OR = 3.59, 95% CI = 1.46–8.77; and adjusted OR = 2.44, 95% CI = 1.04–5.73 for ≥8 vs Conclusions Our results suggest that personal UVR exposure may be associated with higher risk of EBV reactivation, but we did not find clear evidence of vitamin D exposure (observational or genetic), a molecular mediator of UVR exposure. Further prospective studies in other populations are needed to confirm this finding and to explore the underlying biological mechanisms. Information on photosensitizing agents, and serological markers of EBV, and biomarkers related to systemic immunity and inflammation should be collected and are also highly relevant in future studies.
- Published
- 2020
34. Prognostication of Half-Life Clearance of Plasma EBV DNA in Previously Untreated Non-metastatic Nasopharyngeal Carcinoma Treated With Radical Intensity-Modulated Radiation Therapy
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Horace Cheuk Wai Choi, Dora L.W. Kwong, Varut Vardhanabhuti, Anne Wing-Mui Lee, Sum-Yin Chan, Ka-On Lam, Victor Ho-Fun Lee, Mai-Yee Luk, To-Wai Leung, Sik-Kwan Chan, and Chi-Chung Tong
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,lcsh:RC254-282 ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,half-life clearance ,Internal medicine ,Medicine ,Original Research ,Proportional hazards model ,business.industry ,nasopharyngeal carcinoma ,Half-life ,Cancer ,Intensity-modulated radiation therapy ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Radiation therapy ,Clinical trial ,030104 developmental biology ,Oncology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,intensity-modulated radiation therapy ,prognostication ,business ,plasma Epstein–Barr virus deoxyribonucleic acid - Abstract
Introduction: The prognostic role of plasma Epstein–Barr virus (EBV) DNA clearance when intensity-modulated radiotherapy (IMRT) and the 8th edition of American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM Staging Classification are fully implemented remains undeciphered. We investigated if its half-life clearance during radical treatment for non-metastatic nasopharyngeal carcinoma (NPC) was an early prognosticator.Patients and methods: Patients with previously untreated non-metastatic NPC were prospectively treated with radical IMRT and concurrent chemotherapy +/– induction/adjuvant chemotherapy from 2014 to 2018. Their plasma EBV DNA was measured immediately before treatment followed by weekly schedules until 0 copy/ml in two consecutive measurements. Cox regression models were employed to identify prognostic factors.Results: Forty-five patients were prospectively recruited and analyzed. After a median follow-up of 30.3 months, 2 (4.5%), 1 (2.3%), and 6 (13.6%) patients experienced local, regional, and distant relapses, respectively. The median half-life clearance of plasma EBV DNA was 7.92 days. Those with half-life clearance of >15 days had a worse 3-years progression-free survival (PFS) (79.5 vs. 25.0%, p = 0.005), distant metastasis-free survival (DMFS) (85.0 vs. 31.3%, p = 0.009), and overall survival (OS) (91.3 vs. 75.0%, p = 0.024) when compared to those with a shorter half-life. Multivariable analyses demonstrated that only half-life (>15 days) was prognostic of DMFS [HR (95% CI): 4.91 (1.31; 18.39), p = 0.01] and OS [HR (95% CI): 5.24 (1.06; 26.05)] while half-life (>15 days) [HR (95% CI): 5.14 (1.28; 22.73), p = 0.02] and sum of pretreatment gross tumor volumes of the primary nasopharyngeal tumor and the radiologically positive neck nodes (GTV_P+N) [HR (95% CI): 1.01 (1.00; 1.03), p = 0.02] were prognostic of PFS.Conclusion: The half-life clearance of plasma EBV DNA was prognostic in non-metastatic NPC staged and treated in the contemporary era. Earlier biomarker surveillance during treatment should be considered.Clinical Trial Registration: This study has been registered with ClinicalTrials.gov (Identifier: NCT03830996).
- Published
- 2020
35. Role of miR-96/EVI1/miR-449a Axis in the Nasopharyngeal Carcinoma Cell Migration and Tumor Sphere Formation
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Nai Ki Mak, Rotraud Wieser, Roger Kai Cheong Ngan, Sai Wah Tsao, Anne Wing Mui Lee, LS Chan, Hong Lok Lung, Michael Kahn, Kwok Wai Lo, and Maria Li Lung
- Subjects
0301 basic medicine ,Article ,Catalysis ,Inorganic Chemistry ,lcsh:Chemistry ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Cell Movement ,Cancer stem cell ,Cell Line, Tumor ,medicine ,Nasopharyngeal carcinoma ,Humans ,miR-96 ,Physical and Theoretical Chemistry ,3' Untranslated Regions ,Wnt Signaling Pathway ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,Cell Proliferation ,Gene knockdown ,ICG-001 ,Chemistry ,Organic Chemistry ,Wnt signaling pathway ,Cell migration ,General Medicine ,medicine.disease ,MDS1 and EVI1 Complex Locus Protein ,Computer Science Applications ,Gene Expression Regulation, Neoplastic ,EVI1 ,MicroRNAs ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,030220 oncology & carcinogenesis ,Neoplastic Stem Cells ,Cancer research ,miR-449a ,Signal transduction ,Tumor sphere - Abstract
The Wnt signaling pathway is one of the major signaling pathways used by cancer stem cells (CSC). Ecotropic Viral Integration Site 1 (EVI1) has recently been shown to regulate oncogenic development of tumor cells by interacting with multiple signaling pathways, including the Wnt signaling. In the present study, we found that the Wnt modulator ICG-001 could inhibit the expression of EVI1 in nasopharyngeal carcinoma (NPC) cells. Results from loss-of-function and gain-of-function studies revealed that EVI1 expression positively regulated both NPC cell migration and growth of CSC-enriched tumor spheres. Subsequent studies indicated ICG-001 inhibited EVI1 expression via upregulated expression of miR-96. Results from EVI1 3&prime, UTR luciferase reporter assay confirmed that EVI1 is a direct target of miR-96. Further mechanistic studies revealed that ICG-001, overexpression of miR-96, or knockdown of EVI1 expression could restore the expression of miR-449a. The suppressive effect of miR-449a on the cell migration and tumor sphere formation was confirmed in NPC cells. Taken together, the miR-96/EVI1/miR-449a axis is a novel pathway involved in ICG-001-mediated inhibition of NPC cell migration and growth of the tumor spheres.
- Published
- 2020
36. Nasopharyngeal carcinoma MHC region deep sequencing identifies HLA and novel non-HLA TRIM31 and TRIM39 loci
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Hoi Yan Ng, Stephen S.-T. Yau, Dora L.W. Kwong, Chung-Kong Kwan, Wai Tong Ng, Wing-Sum Li, Stewart Tung, Lvwen Ning, Merrin Man-Long Leong, Ashley Cheng, Ka-On Lam, Shiu-Yeung Lam, Roger Kai Cheong Ngan, Lihua Tao, Anne Wing-Mui Lee, Jin-Xin Bei, Valen Zhuoyou Yu, Maria Li Lung, Victor Ho-Fun Lee, Candy King-Chi Chan, and Josephine Mun Yee Ko
- Subjects
0301 basic medicine ,Male ,QH301-705.5 ,Ubiquitin-Protein Ligases ,Medicine (miscellaneous) ,Human leukocyte antigen ,Immunogenetics ,Major histocompatibility complex ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Deep sequencing ,Article ,Tripartite Motif Proteins ,03 medical and health sciences ,Genetic Heterogeneity ,0302 clinical medicine ,INDEL Mutation ,HLA Antigens ,medicine ,Cancer genomics ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Biology (General) ,Allele ,Head and neck cancer ,Alleles ,Genetic association ,Aged ,Genetics ,Nasopharyngeal Carcinoma ,biology ,Haplotype ,Histocompatibility Antigens Class I ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,Middle Aged ,medicine.disease ,030104 developmental biology ,Nasopharyngeal carcinoma ,Amino Acid Substitution ,Haplotypes ,030220 oncology & carcinogenesis ,Case-Control Studies ,biology.protein ,Female ,General Agricultural and Biological Sciences ,Genome-Wide Association Study - Abstract
Despite pronounced associations of major histocompatibility complex (MHC) regions with nasopharyngeal carcinoma (NPC), causal variants underlying NPC pathogenesis remain elusive. Our large-scale comprehensive MHC region deep sequencing study of 5689 Hong Kong Chinese identifies eight independent NPC-associated signals and provides mechanistic insight for disrupted transcription factor binding, altering target gene transcription. Two novel protective variants, rs2517664 (Trs2517664 = 4.6%, P = 6.38 × 10−21) and rs117495548 (Grs117495548 = 3.0%, P = 4.53 × 10−13), map near TRIM31 and TRIM39/TRIM39-RPP21; multiple independent protective signals map near HLA-B including a previously unreported variant, rs2523589 (P = 1.77 × 10−36). The rare HLA-B*07:05 allele (OR, Here the authors report a major histocompatibility complex (MHC) association analysis for nasopharyngeal carcinoma in Chinese individuals from Hong Kong, finding 8 independent associated loci associated with lower risk for developing nasopharyngeal carcinoma. Two non-human leukocyte antigen (HLA) genes are E3 ubiquitin ligases, TRIM31 and TRIM39, having a role in the innate immune response and implicating the importance of host Epstein-Barr virus interactions in this cancer.
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- 2020
37. Leukocyte telomere length associates with nasopharyngeal carcinoma risk and survival in Hong Kong Chinese
- Author
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Sheyne Sta Ana Choi, Roger Kai Cheong Ngan, Stewart Tung, Josephine Mun Yee Ko, Maria Li Lung, Candy King-Chi Chan, Dora Lai-Wan Kwong, Wei Dai, Ashley Cheng, Victor Ho-Fun Lee, Wai Tong Ng, Ka-On Lam, Kay Hiu-Ki Tsang, Merrin Man-Long Leong, and Anne Wing-Mui Lee
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Proportional hazards model ,Hazard ratio ,Odds ratio ,medicine.disease ,Logistic regression ,Confidence interval ,stomatognathic diseases ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Quartile ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Internal medicine ,otorhinolaryngologic diseases ,medicine ,business ,Survival analysis - Abstract
Telomere shortening occurs as an early event in tumorigenesis. The TERT-CLPTM1L locus associates with nasopharyngeal carcinoma (NPC) risk. It remains unknown if leukocyte telomere length (LTL) associates with NPC risk and survival. The relative LTL (rLTL) was measured by quantitative-PCR in 2,996 individuals comprised of 1,284 NPC cases and 1712 matched controls. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistic regression. The hazard ratio (HR) and 95% CI were calculated by Cox regression for survival analysis with rLTL and other clinical parameters in 1,243 NPC with a minimum follow-up period of 25 months. NPC patients had significantly shorter telomere length than controls. Shorter rLTL significantly associated with increased NPC risk, when the individuals were dichotomized into long and short telomeres based on median-split rLTL in the control group (OR = 2.317; 95% CI = 1.989-2.700, p = 4.10 × 10-27 ). We observed a significant dose-response association (ptrend = 3.26 × 10-34 ) between rLTL and NPC risk with OR being 3.555 (95% CI = 2.853-4.429) for the individuals in the first quartile (shortest) compared with normal individuals in the fourth quartile (longest). A multivariate Cox regression analysis adjusted by age demonstrated an independent effect of rLTL on NPC survival for late-stage NPC patients, when the individuals were categorized into suboptimal rLTL versus the medium rLTL based on a threshold set from normal (HR = 1.471, 95% CI = 1.056-2.048, p = 0.022). Shorter blood telomeres may be markers for higher susceptibility for NPC risk. Suboptimal rLTL may be a poor prognostic factor for advanced NPC patients, as it associates independently with poor survival.
- Published
- 2018
38. New hope for advanced nasopharyngeal cancer—an Epstein-Barr virus-driven endemic malignancy?
- Author
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Sum-Yin Chan, Ka-On Lam, Dora Lai-Wan Kwong, Anne Wing-Mui Lee, Chi-Chung Tong, Victor Ho-Fun Lee, and To-Wai Leung
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,medicine.disease_cause ,Malignancy ,medicine.disease ,Epstein–Barr virus ,Highly sensitive ,Southeast asia ,Radiation therapy ,Internal medicine ,medicine ,Advanced disease ,Radiology, Nuclear Medicine and imaging ,business ,Nasopharyngeal cancer - Abstract
It is well-known that the nasopharyngeal cancer (NPC) is highly endemic with the high incidences in Southern China and Southeast Asia (1). The undifferentiated histological subtype is the most common in endemic regions, which is highly sensitive to radiation therapy and chemotherapy. Intensity-modulated radiation therapy as the most commonly employed technique in the contemporary era is the mainstay of treatment for previously untreated early-stage NPC while concurrent chemoradiation is indicated in locoregionally advanced disease (2-5). That said, about 30% of patients develop relapse either as locoregional recurrence or distant metastasis despite intensive aggressive treatment (6).
- Published
- 2018
39. Near‐Infrared Responsive Membrane Nanovesicles Amplify Homologous Targeting Delivery of Anti‐PD Immunotherapy against Metastatic Tumors
- Author
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Ya‐Nan Tan, Jian‐Dong Huang, Yong‐Peng Li, Shan‐Shan Li, Min Luo, Jie Luo, Anne Wing‐Mui Lee, Li Fu, Fu‐Qiang Hu, and Xin‐Yuan Guan
- Subjects
Biomaterials ,Mice ,Drug Delivery Systems ,Cell Line, Tumor ,Neoplasms ,Tumor Microenvironment ,Biomedical Engineering ,Animals ,Nanoparticles ,Pharmaceutical Science ,Immunotherapy - Abstract
The major obstacles of anti-PD therapy in metastatic tumors are limited drug delivery in primary tumors and metastatic foci, and the lack of tumor-infiltrating lymphocytes (TILs). Here, the authors constructed a novel cellular membrane nanovesicles platform (M/IR NPs) based on homologous targeting and near-infrared (NIR) responsive release strategy to potentiate PD-1/PD-L1 blockade therapy against metastatic tumors. In tumor-bearing mice, biomimetic M/IR NPs targeted both primary tumors and their lung metastases. Upon laser irradiation, M/IR NPs reduced cancer-associated fibroblasts (CAFs) in tumor microenvironment, thus increasing the penetration of TILs. When shed from homologous tumor cell membranes, positively charged nanoparticles (IR NPs) core can capture released tumor-associated antigens, thereby enhancing the antigen-presenting ability of DCs to activate cytotoxic T lymphocytes. When the photothermal conversion temperature under NIR-laser is higher than 42 °C, M/IR NPs initiated the rupture of cell membranes and the responsive release of PD-1/PD-L1 inhibitor BMS, which significantly attenuated tumor-associated immunosuppression and synergistically induced T cellular immunity to inhibit the tumor growth and metastasis. Overall, biomimetic M/IR NPs can improve the targeting and therapeutic efficacy of anti-PD therapy in primary tumors and metastases, opening up a new avenue for the diagnosis and treatment of metastatic tumors in the future.
- Published
- 2021
40. Crucifera sulforaphane (SFN) inhibits the growth of nasopharyngeal carcinoma through DNA methyltransferase 1 (DNMT1)/Wnt inhibitory factor 1 (WIF1) axis
- Author
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Roger Kai Cheong Ngan, Nai Ki Mak, George S.W. Tsao, Hong Lok Lung, Anne Wing Mui Lee, Wai Tong Ng, Timothy Tak Chun Yip, LS Chan, Kwok Wai Lo, Maria Li Lung, Jonathan W C Wong, and Luo Chen
- Subjects
DNA (Cytosine-5-)-Methyltransferase 1 ,Male ,Small interfering RNA ,Population ,Cell ,Pharmaceutical Science ,Mice, Nude ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,SOX2 ,Cancer stem cell ,Isothiocyanates ,Cell Line, Tumor ,Drug Discovery ,Antineoplastic Combined Chemotherapy Protocols ,otorhinolaryngologic diseases ,medicine ,Animals ,Humans ,education ,030304 developmental biology ,Adaptor Proteins, Signal Transducing ,Pharmacology ,0303 health sciences ,education.field_of_study ,Mice, Inbred BALB C ,Nasopharyngeal Carcinoma ,SOXB1 Transcription Factors ,Wnt signaling pathway ,Nasopharyngeal Neoplasms ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Xenograft Model Antitumor Assays ,stomatognathic diseases ,medicine.anatomical_structure ,Complementary and alternative medicine ,chemistry ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Sulfoxides ,Brassicaceae ,Cancer research ,Neoplastic Stem Cells ,Molecular Medicine ,Cisplatin ,Sulforaphane - Abstract
Background Sulforaphane (SFN), a natural compound present in cruciferous vegetable, has been shown to possess anti-cancer activities. Cancer stem cell (CSC) in bulk tumor is generally considered as treatment resistant cell and involved in cancer recurrence. The effects of SFN on nasopharyngeal carcinoma (NPC) CSCs have not yet been explored. Purpose The present study aims to examine the anti-tumor activities of SFN on NPC cells with CSC-like properties and the underlying mechanisms. Methods NPC cells growing in monolayer culture, CSCs-enriched NPC tumor spheres, and also the NPC nude mice xenograft were used to study the anti-tumor activities of SFN on NPC. The population of cells expressing CSC-associated markers was evaluated using flow cytometry and aldehyde dehydrogenase (ALDH) activity assay. The effect of DNA methyltransferase 1 (DNMT1) on the growth of NPC cells was analyzed by using small interfering RNA (siRNA)-mediated silencing method. Results SFN was found to inhibit the formation of CSC-enriched NPC tumor spheres and reduce the population of cells with CSC-associated properties (SRY (Sex determining Region Y)-box 2 (SOX2) and ALDH). In the functional study, SFN was found to restore the expression of Wnt inhibitory factor 1 (WIF1) and the effect was accompanied with the downregulation of DNMT1. The functional activities of WIF1 and DNMT1 were confirmed using exogenously added recombinant WIF1 and siRNA knockdown of DNMT1. Moreover, SFN was found to inhibit the in vivo growth of C666-1 cells and enhance the anti-tumor effects of cisplatin. Conclusion Taken together, we demonstrated that SFN could suppress the growth of NPC cells via the DNMT1/WIF1 axis.
- Published
- 2018
41. Feasibility of Aerobic Exercise and Tai-Chi Interventions in Advanced Lung Cancer Patients: A Randomized Controlled Trial
- Author
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Robert Smith, Wen Deng, Anne Wing Mui Lee, Chia Chin Lin, Denise Shuk Ting Cheung, James Chung-Man Ho, Naomi Takemura, Tai Chung Lam, and Yinxia Yan
- Subjects
medicine.medical_specialty ,tai-chi ,Lung Neoplasms ,Psychological intervention ,survival ,law.invention ,Randomized controlled trial ,Quality of life ,law ,medicine ,advanced cancer ,Humans ,Aerobic exercise ,Lung cancer ,Exercise ,RC254-282 ,business.industry ,Advanced stage ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Advanced cancer ,lung cancer ,aerobic exercise ,quality of life ,Complementary and alternative medicine ,Oncology ,Physical therapy ,Feasibility Studies ,Tai Ji ,business ,Research Article - Abstract
Background A majority of lung cancer patients are diagnosed at advanced stages. Although there is considerable evidence of the benefits of aerobic exercise and tai-chi for lung cancer patients, little is known about the comparative effectiveness of the 2 exercise modes in advanced lung cancer patients. Objectives To explore the feasibility and preliminary effects of aerobic exercise and tai-chi interventions on survival and well-being among advanced lung cancer patients. Methods In an assessor-blinded, exploratory randomized controlled trial, 30 advanced lung cancer patients were randomized to an aerobic exercise group, a tai-chi group (both attending 12-week, twice-weekly supervised sessions), or a self-management control group (receiving written exercise guidelines). The primary outcomes focused on feasibility including intervention completion, exercise adherence, and adverse events, while the secondary outcomes addressed preliminary effects and included 1-year survival, cancer symptoms (Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Score, Brief Fatigue Inventory), quality of life (EORTC QLQ-C30, QLQ-LC13), physical performance (6-minute walk test, up-and-go, sit-to-stand, 1-leg standing), activity levels (actigraph), and circadian rhythms (salivary cortisol). Results Intervention feasibility was established with a satisfactory completion rate at post-intervention for the aerobic exercise group (80%) and the tai-chi group (78%). The tai-chi group attained higher adherence than the exercise group in terms of attendance in supervised sessions (89% vs 75% of scheduled classes) and self-practice (225% vs 87% of the prescribed amount). Higher adherence to self-practice in the tai-chi group remained at the 6-month follow-up (81% vs 38% of the prescribed amount). No adverse event as a result of the intervention was reported. Effect-related outcomes did not show statistically significant changes in any group, except an improvement post-intervention in the up-and-go (−2.26, 95% CI: −4.04, −0.48) and sit-to-stand tests (4.52, 95% CI: 2.19, 6.85) in the aerobic exercise group. Conclusions The findings support the feasibility of aerobic exercise and tai-chi interventions in advanced lung cancer patients. A future study with a larger sample from multiple sites is recommended to confirm the comparative effects of the 2 exercise interventions relative to the self-management group and to enhance the generalizability of the findings.
- Published
- 2021
42. Development and validation of M1 substages for previously untreated metastatic nasopharyngeal carcinoma
- Author
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Dora L.W. Kwong, Sik-Kwan Chan, Anne Wing-Mui Lee, To-Wai Leung, S.K. Chan, Victor Ho-Fun Lee, Ka-On Lam, C. W. Choi, T.C. Chau, Sze-Chun Chau, Chi-Chung Tong, Wendy W L Chan, and Mai-Yee Luk
- Subjects
Oncology ,Radical treatment ,medicine.medical_specialty ,Metastatic lesions ,business.industry ,Cancer ,Bone metastasis ,Recursive partitioning ,Hematology ,medicine.disease ,Metastasis ,Nasopharyngeal carcinoma ,Internal medicine ,medicine ,Stage (cooking) ,business - Abstract
Background We aim at subdividing M1 stage to better predict survival of metastatic nasopharyngeal carcinoma (NPC) patients whose outcomes could vary greatly. Methods Patients with previously untreated metastatic NPC (training cohort) were recruited prospectively from 2007 to 2018 and were re-staged based on 8th edition of American Joint Committee on Cancer system. All patients had baseline plasma EBV DNA at diagnosis of metastasis. Characteristics of metastases (site, number and size of metastatic lesions) were confirmed by MRI and PET-CT. We used recursive partitioning analysis (RPA) incorporating baseline plasma EBV DNA and/or metastatic characteristics with internal validations to subdivide M1 stage. The two models were externally validated using an independent data set of 67 NPC patients who were non-metastatic at diagnosis but later developed distant metastases after radical treatment (validation cohort). Performance of survival prediction between the two models was compared with paired t-test under 1000 bootstrapping samples. Results The training cohort of 69 patients had a median follow-up of 40.8 months and 3-year overall survival (OS) of 36%. Model 1 incorporating pre-treatment plasma EBV DNA subdivided M1 stage into two groups: M1a (EBV DNA ≤2500 copies/ml; OS 74%) and M1b (EBV DNA >2500 copies/ml; OS 17%) (P 2500 copies/ml) (HR 4.7 (95% CI 1.9-11.5); P=.001) and metastatic site (coexisting liver and bone metastasis) (HR 2.2 (1.0-4.7); P=.046) were prognostic of OS. Model 1 demonstrated better model fit in predicting OS (Model 1: mean AIC 246.9 (95% CI 187.8-303.6) vs Model 2: mean AIC 257.7 (200.6-313.2); P Conclusions A novel RPA-based M1 stage set incorporating baseline plasma EBV DNA had a significantly better survival prediction, providing important values on prognosis and treatment decision making. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.
- Published
- 2019
43. Leukocyte telomere length associates with nasopharyngeal carcinoma risk and survival in Hong Kong Chinese
- Author
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Josephine Mun-Yee, Ko, Kay Hiu-Ki, Tsang, Wei, Dai, Sheyne Sta Ana, Choi, Merrin Man-Long, Leong, Roger Kai-Cheong, Ngan, Dora Lai-Wan, Kwong, Ashley, Cheng, Anne Wing-Mui, Lee, Wai Tong, Ng, Stewart, Tung, Victor Ho-Fun, Lee, Ka-On, Lam, Candy King-Chi, Chan, and Maria Li, Lung
- Subjects
Adult ,Aged, 80 and over ,Male ,Nasopharyngeal Carcinoma ,Adolescent ,Middle Aged ,Prognosis ,Survival Rate ,Young Adult ,Asian People ,Risk Factors ,Case-Control Studies ,Leukocytes ,Hong Kong ,Humans ,Female ,Child ,Telomere Shortening ,Aged ,Follow-Up Studies ,Retrospective Studies - Abstract
Telomere shortening occurs as an early event in tumorigenesis. The TERT-CLPTM1L locus associates with nasopharyngeal carcinoma (NPC) risk. It remains unknown if leukocyte telomere length (LTL) associates with NPC risk and survival. The relative LTL (rLTL) was measured by quantitative-PCR in 2,996 individuals comprised of 1,284 NPC cases and 1712 matched controls. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistic regression. The hazard ratio (HR) and 95% CI were calculated by Cox regression for survival analysis with rLTL and other clinical parameters in 1,243 NPC with a minimum follow-up period of 25 months. NPC patients had significantly shorter telomere length than controls. Shorter rLTL significantly associated with increased NPC risk, when the individuals were dichotomized into long and short telomeres based on median-split rLTL in the control group (OR = 2.317; 95% CI = 1.989-2.700, p = 4.10 × 10
- Published
- 2018
44. The Wnt modulator ICG‑001 mediates the inhibition of nasopharyngeal carcinoma cell migration in vitro via the miR‑150/CD44 axis
- Author
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On Ying Man, Michael Kahn, Kwok Wai Lo, LS Chan, George S.W. Tsao, Hong Lok Lung, Ricky N S Wong, Nai Ki Mak, King Chi Chan, Roger Kai Cheong Ngan, Anne Wing Mui Lee, Maria Li Lung, HH Kwok, and Luo Chen
- Subjects
0301 basic medicine ,Cancer Research ,Pyrimidinones ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Cell Movement ,miR-150 ,Cell Line, Tumor ,Animals ,Humans ,RNA, Messenger ,RNA, Small Interfering ,Wnt Signaling Pathway ,Regulation of gene expression ,Nasopharyngeal Carcinoma ,biology ,Oncogene ,CD44 ,Wnt signaling pathway ,Cell migration ,Cell cycle ,Bridged Bicyclo Compounds, Heterocyclic ,Cell biology ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Hyaluronan Receptors ,Oncology ,030220 oncology & carcinogenesis ,Catenin ,biology.protein ,Female - Abstract
The Wnt signaling pathway is known to serve an important role in the control of cell migration. The present study analyzed the mechanisms underlying the in vitro modulation of the migration of nasopharyngeal carcinoma (NPC) cells by the CREB‑binding protein/catenin antagonist and Wnt modulator ICG‑001. The results revealed that ICG‑001‑mediated inhibition of tumor cell migration involved downregulated mRNA and protein expression of the Wnt target gene cluster of differentiation (CD)44. It was also demonstrated that ICG‑001 downregulated the expression of CD44, and this effect was accompanied by restored expression of microRNA (miRNA)‑150 in various NPC cell lines. Using a CD44 3'‑untranslated region luciferase reporter assay, miR‑150 was confirmed to be a novel CD44‑targeting miRNA, which could directly target CD44 and subsequently regulate the migration of NPC cells. The present study provides further insight into the inhibition of tumor cell migration through the modulation of miRNA expression by the Wnt modulator ICG‑001.
- Published
- 2018
45. Test-retest reliability of a computer-assisted self-administered questionnaire on early life exposure in a nasopharyngeal carcinoma case-control study
- Author
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Wai Tong Ng, Shing-Chun Chiang, Kam-Tong Yuen, Yap-Hang Chan, Sai Yin Ho, Roger Kai Cheong Ngan, Tai Hing Lam, Maria Li Lung, Zhi-Ming Mai, Kai-Ming Ip, Alice Wan-Ying Ng, Jia-Huang Lin, Dora Lai-Wan Kwong, and Anne Wing-Mui Lee
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Adolescent ,Science ,Online Systems ,Risk Assessment ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Surveys and Questionnaires ,Humans ,Medicine ,Public Health Surveillance ,Young adult ,Child ,Reliability (statistics) ,Nasopharyngeal Carcinoma ,Multidisciplinary ,business.industry ,Age Factors ,Case-control study ,Reproducibility of Results ,Environmental Exposure ,medicine.disease ,Early life ,Test (assessment) ,030104 developmental biology ,Nasopharyngeal carcinoma ,Case-Control Studies ,030220 oncology & carcinogenesis ,Physical therapy ,Etiology ,Hong Kong ,Female ,business ,Risk assessment - Abstract
We evaluated the reliability of early life nasopharyngeal carcinoma (NPC) aetiology factors in the questionnaire of an NPC case-control study in Hong Kong during 2014–2017. 140 subjects aged 18+ completed the same computer-assisted questionnaire twice, separated by at least 2 weeks. The questionnaire included most known NPC aetiology factors and the present analysis focused on early life exposure. Test-retest reliability of all the 285 questionnaire items was assessed in all subjects and in 5 subgroups defined by cases/controls, sex, time between 1st and 2nd questionnaire (2–29/≥30 weeks), education (secondary or less/postsecondary), and age (25–44/45–59/60+ years) at the first questionnaire. The reliability of items on dietary habits, body figure, skin tone and sun exposure in early life periods (age 6–12 and 13–18) was moderate-to-almost perfect, and most other items had fair-to-substantial reliability in all life periods (age 6–12, 13–18 and 19–30, and 10 years ago). Differences in reliability by strata of the 5 subgroups were only observed in a few items. This study is the first to report the reliability of an NPC questionnaire, and make the questionnaire available online. Overall, our questionnaire had acceptable reliability, suggesting that previous NPC study results on the same risk factors would have similar reliability.
- Published
- 2018
46. The addition of pretreatment plasma Epstein-Barr virus DNA into the eighth edition of nasopharyngeal cancer TNM stage classification
- Author
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Lai-San Wong, Dora L.W. Kwong, Patty Pui-Ying Ho, Pek-Lan Khong, Sum-Yin Chan, Sik-Kwan Chan, Wing-Lok Chan, Brian O'Sullivan, Victor Ho-Fun Lee, Anne Wing-Mui Lee, Chor-Yi Ng, Vincent Lai, Cheuk-Wai Choi, Dennis K.C. Leung, Mai-Yee Luk, To-Wai Leung, Ka-On Lam, Chi-Chung Tong, and Tsz-Him So
- Subjects
Stage classification ,Male ,Cancer Research ,medicine.medical_specialty ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,medicine.medical_treatment ,Recursive partitioning ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Drug Therapy ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Stage (cooking) ,Neoplasm Staging ,Chemotherapy ,Nasopharyngeal Carcinoma ,business.industry ,Hazard ratio ,Cancer ,Nasopharyngeal Neoplasms ,Middle Aged ,medicine.disease ,Prognosis ,Survival Analysis ,Radiation therapy ,Treatment Outcome ,Oncology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,DNA, Viral ,Female ,Radiotherapy, Intensity-Modulated ,business - Abstract
The eighth edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage classification (TNM) for nasopharyngeal carcinoma (NPC) was launched. It remains unknown if incorporation of nonanatomic factors into the stage classification would better predict survival. We prospectively recruited 518 patients with nonmetastatic NPC treated with radical intensity-modulated radiation therapy ± chemotherapy based on the eighth edition TNM. Recursive partitioning analysis (RPA) incorporating pretreatment plasma Epstein-Barr virus (EBV) DNA derived new stage groups. Multivariable analyses to calculate adjusted hazard ratios (AHRs) derived another set of stage groups. Five-year progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS) were: Stage I (PFS 100%, OS 90%, CSS 100%), II (PFS 88%, OS 84%, CSS 95%), III (PFS 84%, OS 84%, CSS 90%) and IVA (PFS 71%, OS 75%, CSS 80%) (p < 0.001, p = 0.066 and p = 0.002, respectively). RPA derived four new stages: RPA-I (T1-T4 N0-N2 & EBV DNA
- Published
- 2018
47. Analysis of Radiotherapy to Recurrent Nasopharyngeal Carcinoma (NPC) in Hong Kong
- Author
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James C.H. Chow, Anne Wing-Mui Lee, Chi-Leung Chiang, Wai Tong Ng, J. Lai, T.C. Fung, M.C.H. Lee, D.M. Poon, A. Cheung, Victor Ho-Fun Lee, Kwok-Hung Au, and C.Y. Wong
- Subjects
Oncology ,Radiation therapy ,Cancer Research ,medicine.medical_specialty ,Radiation ,business.industry ,Internal medicine ,medicine.medical_treatment ,medicine ,Radiology, Nuclear Medicine and imaging ,Recurrent Nasopharyngeal Carcinoma ,business - Published
- 2019
48. The impact of palliative care training for oncologists and integrative palliative service in a public-funded hospital cluster-a retrospective cohort study
- Author
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Pak-Lun Lam, Kwok-Keung Yuen, To-Wai Leung, Tai-Chung Lam, Anne Wing-Mui Lee, and Cheuk-Wai Choi
- Subjects
Male ,medicine.medical_specialty ,Palliative care ,Referral ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,medicine ,Humans ,030212 general & internal medicine ,Aged ,Retrospective Studies ,Oncologists ,business.industry ,Hospitals, Public ,Nursing research ,Palliative Care ,Retrospective cohort study ,Odds ratio ,medicine.disease ,Patient Outcome Assessment ,Oncology ,030220 oncology & carcinogenesis ,Family medicine ,Public hospital ,Emergency medicine ,Female ,business ,Cohort study - Abstract
Oncological care of advanced cancer patients was provided by multiple departments in Hong Kong. One of these departments, the clinical oncology department (COD), introduced systematic palliative care training for its oncologists since 2002. The COD was recognized as a European Society for Medical Oncology (ESMO) Designated Centre of Integrated Oncology and Palliative Care since 2009. This retrospective cohort study aims to review the impact of integrative training and service on palliative care coverage and outcome. Clinical information, palliative service provision, and end-of-life outcomes of patients who passed away from lung, colorectal, liver, stomach, or breast cancer in the Hong Kong West public hospital network during July 2015 to December 2015 were collected. A total of 307 patients were analyzed. Around half (49.2%) were attended primarily by COD, and 68.9% received palliative service. There are significantly fewer patients referred to palliative care from other departments (p
- Published
- 2017
49. Shorter Half-Life Clearance of Plasma EBV DNA Is a Significant Prognostic Factor of Non-Metastatic Nasopharyngeal Carcinoma Treated with Radical Intensity-Modulated Radiation Therapy
- Author
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Victor Ho-Fun Lee, TW Leung, Mai-Yee Luk, Sy Chan, S.K. Chan, Dora L.W. Kwong, Ka-On Lam, Chi-Chung Tong, Anne Wing-Mui Lee, and Horace C.W. Choi
- Subjects
Cancer Research ,Prognostic factor ,Radiation ,business.industry ,Half-life ,Intensity-modulated radiation therapy ,medicine.disease ,Oncology ,Nasopharyngeal carcinoma ,medicine ,Cancer research ,Non metastatic ,Radiology, Nuclear Medicine and imaging ,business - Published
- 2019
50. Whole-exome sequencing identifies MST1R as a genetic susceptibility gene in nasopharyngeal carcinoma
- Author
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Mingfang Ji, Roger Kai Cheong Ngan, Josephine Mun Yee Ko, Pak C. Sham, Harry Ho-Yin Yiu, Anne Wing-Mui Lee, Dora L.W. Kwong, Maria Li Lung, Arthur Kwok Leung Cheung, Clara S. Tang, Kwok Hung Au, Bonnie W.Y. Wong, Ka-On Lam, Florence Cheung, Alan K. S. Chiang, Jianji Pan, Zengfeng Zhang, Merrin Man Long Leong, Xun Peng, Chun Chung Yau, Hoi Ching Cheng, Stewart Tung, Hong Zheng, Wai Tong Ng, Victor Ho-Fun Lee, and Wei Dai
- Subjects
0301 basic medicine ,Adult ,Male ,Adolescent ,Nasopharyngeal neoplasm ,Biology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Germline mutation ,MST1R ,medicine ,Genetic predisposition ,otorhinolaryngologic diseases ,Missense mutation ,Cancer susceptibility genes ,Humans ,Exome ,Genetic Predisposition to Disease ,Exome sequencing ,Multidisciplinary ,Nasopharyngeal Carcinoma ,Carcinoma ,Receptor Protein-Tyrosine Kinases ,Nasopharyngeal Neoplasms ,Middle Aged ,Biological Sciences ,medicine.disease ,stomatognathic diseases ,030104 developmental biology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Whole-exome sequencing ,Case-Control Studies ,Cancer research ,Female ,Sequence Analysis ,Early-age onset - Abstract
Multiple factors, including host genetics, environmental factors, and Epstein-Barr virus (EBV) infection, contribute to nasopharyngeal carcinoma (NPC) development. To identify genetic susceptibility genes for NPC, a whole-exome sequencing (WES) study was performed in 161 NPC cases and 895 controls of Southern Chinese descent. The gene-based burden test discovered an association between macrophage-stimulating 1 receptor (MST1R) and NPC. We identified 13 independent cases carrying the MST1R pathogenic heterozygous germ-line variants, and 53.8% of these cases were diagnosed with NPC aged at or even younger than 20 y, indicating that MST1R germline variants are relevant to disease early-age onset (EAO) (age of ≤20 y). In total, five MST1R missense variants were found in EAO cases but were rare in controls (EAO vs. control, 17.9% vs. 1.2%, P = 7.94 × 10(-12)). The validation study, including 2,160 cases and 2,433 controls, showed that the MST1R variant c.G917A:p.R306H is highly associated with NPC (odds ratio of 9.0). MST1R is predominantly expressed in the tissue-resident macrophages and is critical for innate immunity that protects organs from tissue damage and inflammation. Importantly, MST1R expression is detected in the ciliated epithelial cells in normal nasopharyngeal mucosa and plays a role in the cilia motility important for host defense. Although no somatic mutation of MST1R was identified in the sporadic NPC tumors, copy number alterations and promoter hypermethylation at MST1R were often observed. Our findings provide new insights into the pathogenesis of NPC by highlighting the involvement of the MST1R-mediated signaling pathways.
- Published
- 2016
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