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Manganese enhances the antitumor function of CD8^(+)T cells by inducing type I interferon production

Cellular & Molecular Immunology 2021年第6期18卷 1571-1574页

作者： Yuan Song Yonghao Liu Huey Yee Teo Zuhairah Binte Hanafi Yu Mei Ying Zhu yen leong chua Mengze Lv Zhengfan Jiang Haiyan Liu Immunology Programme Life Sciences Institute and Department of Microbiology and ImmunologyYong Loo Lin School of MedicineNational University of SingaporeSingapore117456Singapore Jill Roberts Institute for Research in Inflammatory Bowel Disease(JRI) Weill Cornell MedicineCornell UniversityNew YorkNYUSA Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education School of Life SciencesPeking UniversityBeijing100871China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing100871China

The presence of cytosolic DNA at tumor sites and the activation of the cGAS-STING pathway have been implicated in the activation of antitumor immune responses.1,2,3 Manganese (Mn) is a necessary trace element for intracellular activities. It plays important roles in development, digestion, reproduction, antioxidant defense, energy production, immunity, and neuronal activity regulation.4 Mn was reported to enhance cGAS-STING activation through increased sensitivity to dsDNA during viral infections.5 However, it is unclear whether Mn can enhance antitumor immune functions. Here, we revealed that Mn2+ could inhibit the development of murine hepatocellular carcinoma (HCC) through immune modulations. It upregulated IFN-γ and TNF-α production in splenic and tumor-infiltrating CD8+ T cells. Moreover, Mn2+ significantly increased type I interferon (IFN) production and type I IFN-stimulated gene (ISG) expression in tumor-bearing mice. Further analysis revealed that myeloid cells could upregulate type I IFN production and increase costimulatory molecule expression upon Mn2+ stimulation. In vivo depletion of CD8+ T cells or treatment of IFNAR KO mice diminished the antitumor activity of Mn2+, suggesting that the antitumor function of Mn2+ is dependent on both CD8+ T cells and type I IFN signaling. Our results provide evidence to support Mn2+ as a novel agent that can be incorporated into cancer immunotherapy.

关键词： immunity interferon function

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A comparison of the clinical, demographic and psychiatric profiles among patients with erosive and non-erosive reflux disease in a multi-ethnic Asian country

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World Journal of Gastroenterology 2005年第23期11卷 3558-3561页

作者： Tiing-leong Ang Kwong-Ming Fock Tay-Meng Ng Eng-Kiong Teo Tju-Siang chua Jessica Tan Division of Gastroenterology

AIM:To examine the clinical spectrum of gastroesophageal reflux disease (GERD) and compare erosive (ERD) with non-erosive (NERD) in terms of clinical, demographic and psychiatric profiles. METHODS: Patients with reflux symptoms were enrolled and stratified to NERD and ERD after endoscopy (LA classification). Patients with ERD presenting with dyspepsia were included. Patients on proton pump inhibitors (PPI) or H2 receptor antagonists before endoscopy were excluded. Demographic data, Helicobacter pylori(H pylori) status and presence of minor psychiatric morbidity (based on General Health Questionnaire-28) were analyzed. RESULTS: Among 690 patients screened, 533 were eligible for analysis (male to female ratio: 3:2; Chinese: 75.4%; Malay: 9.8%; Indian: 14.8%). Clinical spectrum of GERD: N: 40.5%; A: 46%; B: 9.2%; C: 2.1%; D: 0.6%; Barrett's esophagus: 1.7%. Compared to patients with NERD, patients with ERD were significantly older (45 vs 39.4 years), more likely to be male (64.4% vs 53.7%), tended to smoke (19.6% vs 9.7%), less likely to have minor psychiatric morbidity (26.4 vs 46.7%) and were more likely to respond to PPI (79.7 vs 66.8%). There was also a trend towards a higher BMI (24.5 vs 23.5). Race, alcohol consumption and H pylori status were not significant. On multivariate analysis, age and presence of minor psychiatric morbidity remained with significant differences. CONCLUSION: The majority of patients who have typical symptoms of GERD have NERD or mild erosive reflux disease. Compared to patients with erosive reflux disease, patients with NERD were younger and had a higher prevalence of minor psychiatric morbidity.

关键词： Reflux disease Clinical spectrum Psychiatric morbidity

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Epinephrine injection therapy versus a combination of epinepnrine injection and endoscopic hemoclip in the treatment of bleeding ulcers

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World Journal of Gastroenterology 2005年第7期11卷 1044-1047页

作者： Tju-Siang chua Kwong-Ming Fock Tay-Meng Ng Eng-Kiong Teo Jessica Yi-Lyn Tan Tiing-leong Ang Division of Gastroenterology

AIM: To assess the efficacy of hemoclip application in combination with epinephrine injection in the treatment of bleeding peptic ulcers and to compare the clinical outcomes between patients treated with such a combination therapy and those treated with epinephrine injection ***: A total of 293 patients (211 males, 82females) underwent endoscopic therapy for bleeding peptic ulcers. Of these, 202 patients (152 males, 50females) received epinephrine injection therapy while 91patients (59 males, 32 females) received combination therapy. The choice of endoscopic therapy was made by the endoscopist. Hemostatic rates, rebleeding rates, need for emergency surgery and 30-d mortality were the outcome measures ***: Patients who received combination therapy were significantly older (mean age 66±16 years, range24-90 years) and more suffered from chronic renal failure compared to those who received epinephrine injection therapy alone (mean age 61±17 years, range 21-89 years).Failure to achieve permanent hemostasis was 4% in the group who received epinephrine injection alone and 11%in the group who received combination therapy. When the differences in age and renal function between the two treatment groups were taken into account by multivariate analysis, the rates of initial hemostasis,rebleeding rates, need for surgery and 30-d mortality for both treatment options were not significantly ***: Combination therapy of epinephrine injection with endoscopic hemoclip application is an effective method of achieving hemostasis in bleeding peptic ulcer diseases. However, superiority of combination therapy over epinephrine injection alone, could not be demonstrated.

关键词： Bleeding peptic ulcer Epinephrine Endoscopic hemoclip Combination therapy

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Spontaneous superior mesenteric artery dissection following upper gastrointestinal panendoscopy: A case report and literature review

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World Journal of Clinical Cases 2019年第20期7卷 3276-3281页

作者： Chih-Ming Ou Yang Yu-Tong yen Chai-Hock chua Chin-Chu Wu Kuan-En Chu Tsung-I Hung Department of General Surgery Shin Kong Wu Ho-Su Memorial HospitalTaipei 111Taiwan Department of Cardiovascular Surgery Shin Kong Wu Ho-Su Memorial HospitalTaipei 111Taiwan Department of Radiology Shin Kong Wu Ho-Su Memorial HospitalTaipei 111Taiwan Department of Internal Medicine Division of GastroenterologyShin Kong Wu Ho-Su Memorial HospitalTaipei 111Taiwan

BACKGROUND Complications associated with upper gastrointestinal(UGI)endoscopy are uncommon,and rarely involve those of cardiovascular *** report herein a unique case of spontaneous superior mesenteric artery dissection(SMAD)after UGI *** SUMMARY A 45-year-old man who had previously undergone UGI panendoscopy and colonoscopy during a voluntary health check-up at our facility was admitted to the emergency room(ER)at the same facility due to persistent epigastric pain with radiation to the *** the ER,the patient did not present notable abnormalities upon physical,conscious,or laboratory examinations apart from mild tenderness in the epigastric *** abdominal aortic dissection was suspected,and abdominal contrast-enhanced computed tomography confirmed *** was then transferred to the cardiovascular ward and treated conservatively with fasting,prostaglandin E1,and *** patient recovered and returned home soon after,and was symptom-free 6 months after discharge from the *** SMAD after UGI panendoscopic procedure is a previously unreported *** of this complication and associated sequela is warranted.

关键词： Upper gastrointestinal panendoscopy Spontaneous superior mesenteric artery dissection Case report

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快速成型原理与应用

快速成型原理与应用

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2004年

作者：原chua leong Lim

来源：畅想之星图书光盘版（南... 评论

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Long-term albumin infusion in decompensated cirrhosis:A review of current literature

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World Journal of Hepatology 2021年第4期13卷 421-432页

作者： Yu Jun Wong Rahul Kumar Yu Jing Jonathan chua Tiing leong Ang Department ofGastroenterology and Hepatology Changi General HospitalSingapore 529889Singapore Department of Internal Medicine Yong Loo Lin School of MedicineSingapore 117597Singapore

Decompensated cirrhosis is characterized by chronic inflammation and severe portal hypertension leading to systemic circulatory *** infusion has been widely used in decompensated cirrhosis in patients with spontaneous bacterial peritonitis,large-volume paracentesis and hepatorenal *** data suggest long-term albumin infusion has both oncotic and non-oncotic properties which may improve the clinical outcomes in decompensated cirrhosis *** review the current literature on both the established and potential role of albumin,and specifically address the controversies of long-term albumin infusion in decompensated cirrhosis patients.

关键词： Albumin Cirrhosis Hepatic encephalopathy Hepatorenal syndrome Acuteon-chronic liver failure Spontaneous bacterial peritonitis Large-volume paracentesis

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Analysis of core protein clusters identifies candidate variable sites conferring metronidazole resistance in Helicobacter pylori

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Gastroenterology Report 2019年第1期7卷 42-49,I0002页

作者： Eng-Guan chua Aleksandra W.Debowski KMary Webberley Fanny Peters Binit Lamichhane Mun-Fai Loke Jamuna Vadivelu Chin-yen Tay Barry J.Marshall Michael J.Wise The Marshall Centre for Infectious Diseases Research and Training University of Western AustraliaPerthWestern AustraliaAustralia School of Biomedical Sciences Faculty of Health and Medical SciencesUniversity of Western AustraliaPerthWestern AustraliaAustralia Department of Medical Microbiology University of MalayaKuala LumpurWilayah PersekutuanMalaysia Shenzhen Dapeng New District Kuichong People Hospital ShenzhenGuangdongChina UM Marshall Centre University of MalayaKuala LumpurWilayah PersekutuanMalaysia School of Computer Science and Software Engineering University of Western AustraliaPerthWestern AustraliaAustralia

Background:Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate Helicobacter pylori ***,the global emergence of metronidazole resistance in Hp poses a major challenge to health *** of RdxA is known to be a major mechanism of conferring metronidazole resistance in ***,metronidazole resistance can also arise in *** strains expressing functional RdxA protein,suggesting that there are other mechanisms that may confer resistance to this ***:We performed whole-genome sequencing on 121 *** clinical strains,among which 73 were ***-alignment analysis of core protein clusters derived from clinical strains containing full-length RdxA was *** sites in each alignment were statistically compared between the resistant and susceptible groups to determine candidate genes along with their respective amino-acid changes that may account for the development of metronidazole resistance in ***:Resistance due to RdxA truncation was identified in 34%of metronidazole-resistant *** of core protein clusters derived from the remaining 48 metronidazole-resistant strains and 48 metronidazole-susceptible identified four variable sites significantly associated with metronidazole *** sites included R16H/C in RdxA,D85N in the inner-membrane protein RclC(HP0565),V265I in a biotin carboxylase protein(HP0370)and A51V/T in a putative threonylcarbamoyl–AMP synthase(HP0918).Conclusions:Our approach identified new potential mechanisms for metronidazole resistance in *** that merit further investigation.

关键词： Helicobacter pylori metronidazole antibiotic resistance whole-genome sequencing core protein clusters sequence alignment

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Gastric peritoneal carcinomatosis-a retrospective review

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World Journal of Gastrointestinal Oncology 2017年第3期9卷 121-128页

作者： Hwee leong Tan Claramae Shulyn Chia Grace Hwei Ching Tan Su Pin Choo David Wai-Meng Tai Clarinda Wei Ling chua Matthew Chau Hsien Ng Khee Chee Soo Melissa Ching Ching Teo Division of Surgical Oncology National Cancer Centre Singapore Dvision of Medical Oncology National Cancer Centre Singapore

AIM To characterize patients with gastric peritoneal carcinomatosis(PC) and their typical clinical and treatment course with palliative systemic chemotherapy as the current standard of *** We performed a retrospective electronic chart review of all patients with gastric adenocarcinoma with PC diagnosed at initial metastatic presentation between January 2010 and December 2014 in a single tertiary referral *** We studied a total of 271 patients with a median age of 63.8 years and median follow-up duration of 5.1 mo. The majority(n = 217, 80.1%) had the peritoneum as the only site of metastasis at initial presentation. Palliative systemic chemotherapy was eventually planned for 175(64.6%) of our patients at initial presentation, of which 171 were initiated on it. Choice of first-line regime was in accordance with the National Comprehensive Cancer Network Guidelines for Gastric Cancer Treatment. Thesepatients underwent a median of one line of chemotherapy, completing a median of six cycles in total. Chemotherapy disruption due to unplanned hospitalizations occurred in 114(66.7%), while cessation of chemotherapy occurred in 157(91.8%), with 42 cessations primarily attributable to PC-related complications. Patients who had initiation of systemic chemotherapy had a significantly better median overall survival than those who did not(10.9 mo vs 1.6 mo, P < 0.001). Of patients who had initiation of systemic chemotherapy, those who experienced any disruptions to chemotherapy due to unplanned hospitalizations had a significantly worse median overall survival compared to those who did not(8.7 mo vs 14.6 mo, P < 0.001).CONCLUSION Gastric PC carries a grim prognosis with a clinical course fraught with disease-related complications which may attenuate any survival benefit which palliative systemic chemotherapy may have to offer. As such, investigational use of regional therapies is warranted and required validation in patients with isolated PC to maximize their

关键词： Peritoneal carcinomatosis Gastric cancer

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^(68)Gallium-labelled PSMA-PET/CT as a diagnostic and clinical decision-making tool in Asian prostate cancer patients following prostatectomy

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Cancer Biology & Medicine 2019年第1期16卷 157-165页

作者： Janice S.H.Tan Charles X.Y.Goh yen Sin Koh Youquan Li Jeffrey K.L.Tuan Eu Tiong chua Terence W.K.Tan Michael L.C.Wang Lui Shiong Lee Kae Jack Tay Ravindran Kanesvaran Chee Keong Toh Aaron K.T.Tong Winnie W.C.Lam Melvin L.K.chua Division of Radiation Oncology National Cancer Centre Singapore Department of Nuclear Medicine and Molecular Imaging Singapore General Hospital Radiological Sciences Academic Clinical Programme Duke-NUS Medical School Oncology Academic Clinical Programme Duke-NUS Medical School Department of Urology Singapore General Hospital Department of Surgery Sengkang General Hospital Division of Medical Oncology National Cancer Centre Singapore Division of Medical Sciences National Cancer Centre Singapore

Objective: Prostate cancers(PCa) in Asian individuals are molecularly distinct from those found in their Caucasian *** is no risk stratification tool for Asian men with rapid biochemical recurrence(BCR) following radical prostatectomy(Rad P). This study aims to assess the detection rate of ^(68)Ga-prostate-specific membrane antigen-positron emission tomography/computed tomography(PSMA-PET/CT) for diagnosis of clinical recurrence and as a treatment decision making tool in Asian patients with BCR post-Rad ***: ^(68)Ga PSMA-PET and CT body with/without bone scan [conventional workup(CWU)] were performed in 55 Asian patients with BCR within 36 months post-Rad P. Two blinded reviewers assessed the images. Detection rates of ^(68)Ga PSMAPET/CT were evaluated, and impact on management was reviewed by comparison with ***: Median time to BCR post-Rad P was 8.1 months. Detection rate for ^(68)Ga PSMA-PET/CT was 80%(44/55). A positive scan was significantly associated with increasing prostate-specific antigen(PSA) level [odds ratio(OR) = 1.13(95% CI 1.05–1.30), P =0.017], but not with higher Gleason grade or shorter PSA doubling time. Compared to CWU, ^(68)Ga PSMA-PET/CT detected an additional 106 lesions in 33/44 patients with a positive scan, resulting in a change in management in 25/44(56.8%) patients: 10 to hormonal therapy(HT) and whole pelvis radiotherapy(RT) in addition to bed RT, and 15 to palliative HT ***: In the present report, we demonstrated the diagnostic and treatment decision utility of ^(68)Ga PSMA-PET/CT in Asian men with rapid BCR. Detection of small volume nodal and systemic recurrences at low PSA levels(< 1.0 ng/mL) highlights the role of the tool in assigning patients to treatment intensification with HT-RT or palliative HT in polymetastatic disease.

关键词： ^68Ga PSMA PET/CT prostate cancer Asian diagnostic recurrence prostatectomy salvage radiotherapy

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Rapid prototyping: principles and applications 3rd ed.

引用

2010年

作者： C.K. chua K.F.leong C.S.Lim.

Includes bibliographical references and index.

ISBN: (纸本)9789812778970;9812778977

Includes bibliographical references and index.

关键词： Rapid prototyping CAD/CAM systems Solid freeform fabrication

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