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Mitochondria-targeted atovaquone promotes anti-lung cancer immunity by reshaping tumor microenvironment and enhancing energy metabolism of anti-tumor immune cells

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Cancer Communications 2024年第3期44卷 448-452页

作者： Donghai Xiong Zheng yin Mofei Huang yian Wang Micael Hardy Balaraman Kalyanaraman Stephen t wong Ming you Center for Cancer Prevention Houston Methodist Neal Cancer CenterHouston Methodist HospitalWeill Cornell MedicineHoustonTexasUSA Department of Systems Medicine and Bioengineering Houston Methodist Cancer CenterHouston Methodist HospitalWeill Cornell MedicineHoustonTexasUSA Aix Marseille Univ Centre Nationaldela Recherche Scientifique(CNRS)Institut de Chimie Radicalaire(ICR)UnitéMixte de Recherche(UMR)7273MarseilleFrance Department of Biophysics Medical College of WisconsinMilwaukeeWisconsinUSA

Dear Editor,Atovaquone(AtO),a mitochondrial inhibitor,has anti-cancer effects[1].Based on AtO,we developed mitochondria-targeted atovaquone(Mito-AtO)that had even stronger anti-tumor efficacy than AtO[2].We syn-thesized Mito-AtO by attaching the bulky triphenylphos-phonium(tPP)group to AtO via a ten-carbon alkyl chain(Supplementary file of methods;Supplementary Figure S1).

关键词： metabolism immunity targeted

Superior antibody and membrane protein‑specific t‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime S.Rosa Duque Samuel M.S.Cheng Carolyn A.Cohen Daniel Leung Xiwei Wang Xiaofeng Mu yuet Chung tsun Ming Lau Manni Wang Wenyue Zhang yanmei Zhang Howard H.W.wong Leo C.H.tsang Sara Chaothai tsz Chun Kwan John K.C.Li Karl C.K.Chan Leo L.H.Luk Jenson C.H.Ho Wing yan Li Amos M.t.Lee Jennifer H.y.Lam Sau Man Chan Wilfred H.S.wong Issan y.S.tam Masashi Mori Sophie A.Valkenburg Malik Peiris Wenwei tu yu Lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina HKU‑Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina Research Institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and Infection C2i Hong KongChina

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is *** dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is *** study(NCt04800133)investigated the superiority of antibody and t-cell responses of full-dose CoronaVac by ID over IM administration in *** Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days *** and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,*** Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4^(+),SNM-specific IL-2^(+)CD8^(+),S-specific IL-2^(+)CD8^(+),N-specific IL-2^(+)CD4^(+),N-specific IL-2^(+)CD8^(+)and M-specific IL-2^(+)CD4^(+)responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was *** ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNt90),PRNt50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2^(+)CD4^(+),interferon-γ+CD8^(+)and IL-2^(+)CD8^(+)responses were superior and non-inferior to *** estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,*** ID groups reported more local,mild adverse *** this is the first study to demonstrate superior antibody and M-specific t-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the

关键词： CoronaVac Coronavirus disease 2019 Immunity Intradermal Vaccine

Inhibition of Heterogeneous Nucleation in Water by Hydrogel Coating

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Research 2024年第2期2023卷 139-147页

作者： Siyang Li Panpan Zhu yaoting Xue Lei Wangg tuck-Whye wong Xuxu yang Haoei Zhou tiefeng Li We yang Department of Engineering Mechanics Zhejiang UniversityHangzhou 310027China Key Laboratory of Soft Machines and Smart Devices of Zhejiang Province Zhejiang UniversityHangzhou 310027China Center for X-Mechanics Department of Engineering MechanicsZhejiang UniversityHangzhou 310027China School of Biomedical Engineering and Health Sciences and Advanced Membrane technology Research Centre Universiti Teknologi MalaysiaSkudai 81310Malaysia

Heterogeneous nucleation plays a critical role in the phase transition of water,which can cause damage in various ***,we report that heterogeneous nucleation can be inhibited by utilizing hydrogel coatings to isolate solid surfaces and ***,which contain over 90%water when fully swelled,exhibit a high degree of similarity to *** to this similarity,there is a great energy barrier for heterogeneous nucleation along the water-hydrogel ***,hydrogel coatings,which possess polymer networks,exhibit higher fracture energy and more robust adhesion to solid surfaces compared to *** high fracture and adhesion energy acts as a deterrent for fracture nucleation within the hydrogel or along the hydrogel-solid *** a hydrogel layer approximately 100μm thick,the boiling temperature of water under atmospheric pressure can be raised from 100 to 108℃.Notably,hydrogel coatings also result in remarkable reductions in cavitation pressure on multiple solid *** have demonstrated the efficacy of hydrogel coatings in preventing damages resulting from acceleration-induced *** coatings have the potential to alter the energy landscape of heterogeneous nucleation on the water-solid interface,making them an exciting avenue for innovation in heat transfer and fluidic systems.

关键词： fracture cavitation similarity

Cost effectiveness of nonpharmacological prevention programs for diabetes:A systematic review of trial-based studies

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Chronic Diseases and translational Medicine 2024年第1期10卷 12-21页

作者： yongyi Xiong Zhaohua Huo Samuel y.S.wong Benjamin H.K.yip Jockey Club School of Public Health and Primary Care Prince of Wales HospitalThe Chinese University of Hong KongShatinHong KongChina

trial-based economic value of prevention programs for diabetes is *** aimed to review the cost-effectiveness of nonpharmacological interventions to prevent type-2 diabetes mellitus(t2DM)for high-risk *** electronic databases were searched up to March *** assessing both the cost and health outcomes of nonpharmacological interventions for people at high-risk of t2DM were *** quality of the study was assessed by the Consolidated Health Economic Evaluation Reporting Standards 2022 *** primary outcome for synthesis was incremental cost-effectiveness ratios(ICER)for quality-adjusted life years(QALys),and costs were standardized in 2022 US *** synthesis was performed,considering different types and delivery methods of *** studies included five based on the US diabetes prevention program(DPP),six on non-DPP-based lifestyle interventions,four on health education,and one on screening plus lifestyle *** with usual care,lifestyle interventions showed higher potential of cost-effectiveness than educational *** lifestyle interventions,DPP-based programs were less cost-effective(median of ICERs:$27,077/QALy)than non-DPP-based programs(median of ICERs:$1395/QALy)from healthcare perspectives,but with larger decreases in diabetes ***,the cost-effectiveness of interventions was more possibly realized through the combination of different delivery *** interventions to prevent t2DM in high-risk populations are both cost-effective and feasible in various ***,economic evidence from low-and middle-income countries is still lacking,and interventions delivered by trained laypersons and combined with peer support sessions or mobile technologies could be potentially a cost-effective solution in such settings with limited resources.

关键词： economic evaluation nonpharmacological interventions pre-diabetes prevention

Feasibility and safety of minimally invasive multivisceral resection for t4b rectal cancer:A 9-year review

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 777-789页

作者： Kai Siang Chan Biquan Liu Ming Ngan Aloysius tan Kwang yeong How Kar yong wong Department of General Surgery Tan Tock Seng HospitalSingapore 308433Singapore

BACKGROUND Colorectal cancer is the third most common cancer and the second highest cause of cancer-related mortality *** 5%-10%of patients are diagnosed with locally advanced rectal cancer(LARC)on *** LARC invading into other structures(i.e.t4b),multivisceral resection(MVR)and/or pelvic ex-enteration(PE)remains the only potential curative surgical *** and/or PE is a major and complex surgery with high post-operative *** invasive surgery(MIS)has been shown to improve short-term post-operative outcomes in other gastrointestinal malignancies,but there is little evi-dence on its use in MVR,especially so for robotic *** is a single-center retrospective cohort study from 1st January 2015 to 31st March *** criteria were patients diagnosed with ct4b rectal cancer and underwent MVR,or stage 4 disease with resectable systemic ***-tients who underwent curative MVR for locally recurrent rectal cancer,or me-tachronous rectal cancer were also *** criteria were patients with systemic metastases with non-resectable *** patients planned for elective surgery were enrolled into the standard enhanced recovery after surgery pathway with standard peri-operative management for colorectal *** sur-gery was defined based on technical difficulty of surgery(*** PE,bladder-sparing prostatectomy,pelvic lymph node dissection or need for flap creation).Our primary outcomes were the margin status,and complication ***-gorical values were described as percentages and analysed by the chi-square *** variables were expressed as median(range)and analysed by Mann-Whitney U *** overall survival(OS)and recurrence-free survival(RFS)were analysed using Kaplan-Meier estimates with life table ***-rank test was performed to determine statistical significance between cumulative *** significance was defined as Ptimates with li

关键词： Laparoscopy Minimally invasive surgical procedures Multivisceral resection Pelvic Exenteration Rectal neoplasms Robotic surgical procedures

Chemosensitizing Effect of Monk Fruit Extract on Human Bladder Cancer Cells

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Journal of Cancer therapy 2024年第6期15卷 250-264页

作者： Sensuke Konno Jonathan wong Andrew Penunuri Kelvin Zheng Muhammad Choudhury Department of Urology New York Medical College Valhalla New York USA

the outcomes of chemotherapy have been unsatisfactory with the palpable side effects. We hypothesized that natural products might help improve chemotherapy with few side effects. Recently, we came across the bioactive extracts of monk fruit (Siraitia grosvenori) with anticancer activity. We then investigated if these extracts might have chemosensitizing effect to improve the efficacy of drugs clinically used today. Four different drugs, cisplatin (CPL), carboplatin (CBL), mitomycin C (MMC), and gemcitabine (GEM), were used in this study. Human bladder cancer t24 cells were treated with each drug itself or drug combined with either LLE or MOG (two types of monk fruit extracts). Cell viability was determined to assess anticancer effect and also explored the anticancer mechanism of such combinations, focusing on the status of glycolysis, cell cycle, and chromatin structure. Cell viability test showed that all drugs had anticancer activity, reducing cell viability, but only CPL showed the enhanced anticancer effect when combined with LLE (not with MOG). the rest of three drugs had no such effects with LLE or MOG. the CPL/LLE combination was found to disrupt glycolysis, by inhibiting hexokinase activity, resulted in the decreased AtP synthesis. this combination also blocked the cell cycle progression, due to a G1 cell cycle arrest. Moreover, the two epigenetic regulators, DNA methyltransferase and histone deacetylase, were inactivated with the combination, indicating chromatin modifications. Ultimately, these treated cells were found to undergo apoptosis. In conclusion, anticancer activity of CPL can be significantly enhanced with LLE. this chemosensitizing effect is attributed to the glycolysis inhibition, a G1 cell cycle arrest, and chromatin modifications, ultimately leading to apoptosis. thus, certain natural products such as LLE could be used as an adjuvant agent in current chemotherapy, improving the drug efficacy but minimizing side effects.

关键词： Monk Fruit Anticancer Bladder Cancer Chemosensitization Lakanto

the risk of prostate cancer on incidental finding of an avid prostate uptake on 2-deoxy-2-[^(18)F]fluoro-D-glucose positron emission tomography/computed tomography for non-prostate cancer-related pathology:A single centre retrospective study

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Asian Journal of Urology 2024年第1期11卷 33-41页

作者： Anthony Franklin troy Gianduzzo Boon Kua David wong Louise McEwan James Walters Rachel Esler Matthew J.Roberts Geoff Coughlina John W.yaxley Department of Urology The Wesley HospitalBrisbaneQLDAustralia Wesley Medical Research BrisbaneQLDAustralia School of Medicine The University of QueenslandBrisbaneQLDAustralia Department of Radiology Wesley Medical ImagingBrisbaneQLDAustralia Department of Urology Royal Brisbane and Women's HospitalBrisbaneQLDAustralia

Objective:to review the risk of prostate cancer(PCa)in men with incidentally reported increased intraprostatic uptake at 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography(18F-FDG PEt/Ct)ordered at Department of Urology,the Wesley Hospital,Brisbane,QLD,Australia for non-PCa related ***:Retrospective analysis of consecutive men between August 2014 and August 2019 presenting to a single institution for 18F-FDG PEt/Ct for non-prostate related conditions was *** were classified as benign,indeterminate,or malignant depending of the results of prostate-specific antigen(PSA),PSA velocity,biopsy histopathology,and three-tesla(3 t)multiparametric MRI(mpMRI)Prostate Imaging Reporting and Data System score,or gallium-68-prostate-specific membrane antigen(68Ga-PSMA)PEt/Ct ***:three percent(273/9122)of men demonstrated 18F-FDG avidity within the ***-five percent(231/273)were further investigated,including with PSA tests(227/231,98.3%),3 t mpMRI(68/231,29.4%),68Ga-PSMA PEt/Ct(33/231,14.3%),and prostate biopsy(57/231,24.7%).Results were considered benign in 130/231(56.3%),indeterminate in 31/231(13.4%),and malignant in 70/231(30.3%).PCa was identified in 51/57(89.5%)of the men who proceeded to biopsy,including 26/27(96.3%)men with Prostate Imaging Reporting and Data System scores 4-5 mpMRI and six men with a positive 68Ga-PSMA PEt/*** most common Gleason score on biopsy was greater than or equal to 4+5(14/51,27.5%).68Ga-PSMA PEt/Ct was concordant with the 18F-FDG findings in 26/33(78.8%).All 13 men with a positive concordant 18F-FDG,3 t mpMRI,and 68Ga-PSMA PEt/Ct had PCa on *** was no statistically significant difference in the 18F-FDG maximum standardized uptake value between the benign or malignant groups(5.7 vs.6.1;p=0.580).Conclusion:In this study,after an incidental finding of an avid intraprostatic lesion on 18F-FDG PEt/Ct,70 of the 231 cases(30.3%;0.8%of the entire cohort)had results c

关键词： Prostatecancer Positionemission tomography Multiparametric magneticresonance imaging Prostatebiopsy

Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 t-cell killing

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Cellular & Molecular Immunology 2024年第4期21卷 362-373页

作者： Zeguang Wu Qiezhong Lamao Meichao Gu Xuanxuan Jin ying Liu Feng tian ying yu Pengfei yuan Shuaixin Gao thomas S.Fulford Adam P.Uldrich Catherine C.L wong Wensheng Wei Biomedical Pioneering Innovation Center Peking-Tsinghua Center for Life SciencesPeking University Genome Editing Research CenterState Key Laboratory of Protein and Plant Gene ResearchSchool of Life SciencesPeking University100871BeijingChina EdiGene Inc. Life Science ParkChangping District102206BeijingChina Center for Precision Medicine Multi-Omics Research Peking University Health Science CenterPeking University100191BeijingChina Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity The University of MelbourneParkvilleVIC3010Australia Cancer Immunology Program Peter MacCallum Cancer CentreMelbourneVICAustralia State Key Laboratory for Complex Severe and Rare DiseasesClinical Research InstitutePeking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegePeking-Tsinghua Center for Life Sciences100871BeijingChina

Vγ9Vδ2 t cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate *** our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 t cells,we performed a comprehensive genome-scale CRISPR screening of cancer *** found that four molecules belonging to the butyrophilin(BtN)family,specifically BtN2A1,BtN3A1,BtN3A2,and BtN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 t *** coordinated function of these BtN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX ***,an enzyme called QPCtL was shown to play a key role in modifying the N-terminal glutamine of these BtN proteins and was found to be a crucial factor in Vγ9Vδ2 t cell killing of cancer *** our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 t ***,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating t-cell activity.

关键词： Butyrophilin Vγ9Vδ2 t-cell Cancer-specific immune evasion Glutaminyl-peptide cyclotransferase-like Pyrophosphate metabolite Immunotherapy

Immunoregulatory and Anti-cancer Activities of Combination treatment of Novel Four-Herb Formula and Doxorubicin in 4t1-Breast Cancer Bearing Mice

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Chinese Journal of Integrative Medicine 2024年第4期30卷 311-321页

作者： Lea Ling-yu Kan Ben Chung-Lap Chan Grace Gar-Lee yue LI Pei-ting Sharon Sze-Man Hon HUANG Dan-qi Miranda Sin-Man tsang Clara Bik-San Lau Ping-Chung Leung Chun-Kwok wong Institute of Chinese Medicine The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Chemical Pathology The Chinese University of Hong KongHong Kong SARChina China-Australia International Research Centre for Chinese Medicine School of Health and Biomedical SciencesSTEM CollegeRMIT UniversityBundooraVictoriaAustralia Li Dak Sum yip yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong Kong SARHong KongChina

Objective to investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(tNBC).Methods Murine-derived triple-negative mammary carcinoma cell line,4t1 cells,was cultured and inoculated into mouse mammary ***-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4t1 cells resuspended in 100µL of normal saline in the mammary fat *** from the day of tumor cell inoculation,tumors were grown for 6 *** LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,*** LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).the D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).the treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a *** control group received daily oral gavage of 0.2 mL double-distilled *** treatment period was 30 *** the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota *** Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(Ptered the hypoxia and overall immune lymphocyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological ***,immunosuppressive genes,cytokines,and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(Ption treatment demonstrated synergetic activities and was most effective

关键词： adjunctivetherapy breast cancer cytokines Chinese medicine tumor microenvironment