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Gut mucosal microbiota profiles linked to colorectal cancer recurrence

World Journal of Gastroenterology 2022年第18期28卷 1946-1964页

作者： Rui-Xue Huo Yi-Jia Wang Shao-Bin Hou Wei Wang Chun-Ze Zhang Xue-Hua Wan Department of Oncology Tianjin Union Medical CenterNankai UniversityTianjin 300121China Laboratory of Oncologic Molecular Medicine Tianjin Union Medical CenterNankai UniversityTianjin 300121China Advanced Studies in Genomics Proteomics and BioinformaticsUniversity of Hawaii at ManoaHonoluluHI 96822United States TEDA Institute of Biological Sciences and Biotechnology Nankai UniversityTianjin 300457China Department of Colorectal Surgery Tianjin Union Medical CenterNankai UniversityTianjin 300121China Tianjin Institute of Coloproctology Tianjin 300121China

BACKGROUND Emerging evidence links gut microbiota to various human diseases including colorectal cancer(CRC)initiation and ***,gut microbiota profiles associated with CRC recurrence and patient prognosis are not completely understood yet,especially in a Chinese *** To investigate the relationship between gut mucosal microbiota profiles and CRC recurrence and patient *** We obtained the composition and structure of gut microbiota collected from 75 patients diagnosed with CRC and 26 healthy *** patients were followed up by regular examination to determine whether tumors ***-paired samples from on-tumor,adjacent-tumor and off-tumor sites of patients diagnosed with/without CRC recurrence were analyzed to assess spatial-specific patterns of gut mucosal microbiota by 16S ribosomal RNA ***,we carried out bioinformatic analyses,Kaplan-Meier survival analyses and Cox regression analyses to determine the relationship between gut mucosal microbiota profiles and CRC recurrence and patient *** We observed spatial-specific patterns of gut mucosal microbiota profiles linked to CRC recurrence and patient prognosis.A total of 17 bacterial genera/families were identified as potential biomarkers for CRC recurrence and patient prognosis,including Anaerotruncus,Bacteroidales,Coriobacteriaceae,Dialister,Eubacterium,Fusobacterium,Filifactor,Gemella,Haemophilus,Mogibacteriazeae,Pyramidobacter,Parvimonas,Porphyromonadaceae,Slackia,Schwartzia,TG5 and *** Our work suggests that intestinal microbiota can serve as biomarkers to predict the risk of CRC recurrence and patient death.

关键词： Gut microbiota Colorectal cancer Prognosis Colorectal cancer recurrence Biomarker 16S rRNA sequencing analysis

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Proteome-Wide Analysis Using SOMAscan Identifies and Validates Epidermal Growth Factor as a Disease Marker of Collagenous Gastritis

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Gastro Hep Advances 2022年第5期1卷 689-702页

作者： Curci, Debora Dillon, Simon T. Gu, Xuesong Winter, Harland Libermann, Towia A. Institute for Maternal and Child Health - IRCCS “Burlo Garofolo” Advanced Diagnostic and Translational Medicine Laboratory Trieste Italy Division of Interdisciplinary Medicine and Biotechnology Beth Israel Deaconess Medical Center Boston MA United States Beth Israel Deaconess Medical Center Genomics Proteomics Bioinformatics and Systems Biology Center Boston MA United States Department of Medicine Harvard Medical School Boston MA United States Center for Pediatric Inflammatory Bowel Disease Massachusetts General Hospital Boston MA United States

Background and Aims: Collagenous gastritis (CG) is a rare disorder characterized by increased subepithelial collagen deposition and inflammatory infiltrates. The mechanisms involved in CG pathogenesis are poorly understood, and no CG-associated biomarkers have been identified. This proteomics study identified serum biomarkers and pathogenic pathways to provide new knowledge about the pathobiology of CG, a disease reported in less than 100 patients. Methods: Nine serum samples from pediatric patients diagnosed with CG were evaluated using novel aptamer-based proteomic technology and systems biology to generate new knowledge about the complex interactions between the differentially expressed proteins and candidate upstream regulators, using the Ingenuity Pathway Analysis in patients with non-CG and patients with normal gastric biopsies or nongastritis (NG). Results: SOMAscan analysis identified 63 proteins significantly dysregulated in CG as compared to non-CG or NG patients that converged around enhanced inflammatory response and immune cell migration but reduced vascular functions. Principal component analysis using 15 of those proteins accurately separated the CG cases from the 2 comparator control groups. Using immunoassays, serum epidermal growth factor concentrations in CG patients, a protein involved in collagen production, were confirmed to be significantly lower than those in gastritis/NG patients. Conclusion: This is the first comprehensive analysis of the proteome in CG patients that reveals metabolic pathways relating inflammation and fibrosis as well as a new potential role of epidermal growth factor as a disease biomarker. © 2022 The Authors

关键词： Biomarker Collagenous Gastritis Epidermal Growth Factor proteomics

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Targeting protein-protein interaction interfaces with antiviral N protein inhibitor in SARS-CoV-2

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Biophysical Journal 2024年第4期123卷 478-488页

作者： Hong, Jhen-Yi Lin, Shih-Chao Kehn-Hall, Kylene Zhang, Kai-Min Luo, Shun-Yuan Wu, Hung-Yi Chang, Sui-Yuan Hou, Ming-Hon Institute of Genomics and Bioinformatics and Department of Life Sciences National Chung Hsing University Taichung Taiwan Bachelor Degree Program in Marine Biotechnology College of Life Sciences National Taiwan Ocean University Keelung Taiwan Department of Biomedical Sciences and Pathobiology Virginia-Maryland College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg VA United States Center for Emerging Zoonotic and Arthropod-borne Pathogens Virginia Polytechnic Institute and State University Blacksburg VA United States Department of Chemistry National Chung Hsing University Taichung Taiwan Graduate Institute of Veterinary Pathobiology College of Veterinary Medicine National Chung Hsing University. Taichung Taiwan Department of Clinical Laboratory Sciences and Medical Biotechnology College of Medicine National Taiwan University Taipei Taiwan PhD Program in Medical Biotechnology National Chung Hsing University Taichung Taiwan Biotechnology Center National Chung Hsing University Taichung Taiwan

Coronaviruses not only pose significant global public health threats but also cause extensive damage to livestock-based industries. Previous studies have shown that 5-benzyloxygramine (P3) targets the Middle East respiratory syndrome coronavirus (MERS-CoV) nucleocapsid (N) protein N-terminal domain (N-NTD), inducing non-native protein-protein interactions (PPIs) that impair N protein function. Moreover, P3 exhibits broad-spectrum antiviral activity against CoVs. The sequence similarity of N proteins is relatively low among CoVs, further exhibiting notable variations in the hydrophobic residue responsible for non-native PPIs in the N-NTD. Therefore, to ascertain the mechanism by which P3 demonstrates broad-spectrum anti-CoV activity, we determined the crystal structure of the SARS-CoV-2 N-NTD:P3 complex. We found that P3 was positioned in the dimeric N-NTD via hydrophobic contacts. Compared with the interfaces in MERS-CoV N-NTD, P3 had a reversed orientation in SARS-CoV-2 N-NTD. The Phe residue in the MERS-CoV N-NTD:P3 complex stabilized both P3 moieties. However, in the SARS-CoV-2 N-NTD:P3 complex, the Ile residue formed only one interaction with the P3 benzene ring. Moreover, the pocket in the SARS-CoV-2 N-NTD:P3 complex was more hydrophobic, favoring the insertion of the P3 benzene ring into the complex. Nevertheless, hydrophobic interactions remained the primary stabilizing force in both complexes. These findings suggested that despite the differences in the sequence, P3 can accommodate a hydrophobic pocket in N-NTD to mediate a non-native PPI, enabling its effectiveness against various CoVs. © 2024 Biophysical Society

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BAG6 restricts pancreatic cancer progression by suppressing the release of IL33-presenting extracellular vesicles and the activation of mast cells

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Cellular & Molecular Immunology 2024年第8期21卷 918-931页

作者： Bilal Alashkar Alhamwe Viviane Ponath Fahd Alhamdan Bastian Dörsam Clara Landwehr Manuel Linder Kim Pauck Sarah Miethe Holger Garn Florian Finkernagel Anna Brichkina Matthias Lauth Dinesh Kumar Tiwari Malte Buchholz Daniel Bachurski Sabrina Elmshäuser Andrea Nist Thorsten Stiewe Lisa Pogge von Strandmann Witold Szymański Vanessa Beutgen Johannes Graumann Julia Teply-Szymanski Corinna Keber Carsten Denkert Ralf Jacob Christian Preußer Elke Pogge von Strandmann Institute for Tumor Immunology Philipps-University35043MarburgGermany Core Facility Extracellular Vesicles Philipps-University35043MarburgGermany Department of Anesthesiology Critical Careand Pain MedicineCardiac Anesthesia DivisionBoston Children’s HospitalBostonUSA Department of Immunology and Anaesthesia Harvard Medical SchoolBostonMAUSA Translational Inflammation Research Division&Core Facility for Single Cell Multiomics Philipps-University35043MarburgGermany Core Facility Bioinformatics Philipps-University35043MarburgGermany Clinic for Gastroenterology Endocrinology and MetabolismCenter for Tumor and Immune BiologyPhilipps-University35043MarburgGermany Institute of Systems Immunology Philipps-University35043MarburgGermany Cluster of Excellence on Cellular Stress Responses in Aging-Associated Diseases(CECAD) University of CologneCologneGermany Institute of Molecular Oncology and Genomics Core Facility Member of the German Center for Lung Research(DZL)Philipps-University35043MarburgGermany Institute of Lung Health Justus Liebig University35392GiessenGermany Institute of Translational Proteomics&Core Facility Translational Proteomics Biochemical/Pharmacological CentrePhilipps-University35043MarburgGermany Institute of Pathology Philipps-University Marburg and University Hospital Marburg(UKGM)MarburgGermany Department of Cell Biology and Cell Pathology Philipps-University35043MarburgGermany

Recent studies reveal a critical role of tumor cell-released extracellular vesicles(EVs)in pancreatic cancer(PC)***,driver genes that direct EV function,the EV-recipient cells,and their cellular response to EV uptake remain to be ***,we studied the role of Bcl-2-associated-anthanogene 6(BAG6),a regulator of EV biogenesis for cancer *** used a Cre recombinase/LoxP-based reporter system in combination with single-cell RNA sequencing to monitor in vivo EV uptake and tumor microenvironment(TME)changes in mouse models for pancreatic ductal adenocarcinoma(PDAC)in a Bag6 pro-or deficient *** vivo data were validated using mouse and human organoids and patient *** data demonstrated that Bag6-deficient subcutaneous and orthotopic PDAC tumors accelerated tumor growth dependent on EV ***,this was attributed to mast cell(MC)activation via EV-associated *** MCs promoted tumor cell proliferation and altered the composition of the TME affecting fibroblast polarization and immune cell *** cell proliferation and fibroblast polarization were mediated via the MC secretome containing high levels of PDGF and *** with high BAG6 gene expression and high protein plasma level have a longer overall survival indicating clinical *** current study revealed a so far unknown tumor-suppressing activity of BAG6 in ***6-deficiency allowed the release of EV-associated IL33 which modulate the TME via MC activation promoting aggressive tumor *** depletion using imatinib diminished tumor growth providing a scientific rationale to consider imatinib for patients stratified with low BAG6 expression and high MC infiltration.

关键词： Pancreatic cancer EVs BAG6 Mast cells

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Global epidemiology and antimicrobial resistance of Enterobacterales harbouring genes encoding OXA-48-like carbapenemases: insights from the results of the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme 2018-2021

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The Journal of antimicrobial chemotherapy 2024年第7期79卷 1581-1589页

作者： Yu-Lin Lee Wei-Yao Wang Wen-Chien Ko Po-Ren Hsueh Division of Infectious Disease Department of Internal Medicine Chung Shan Medical University Hospital Taichung Taiwan. PhD Program in Medical Biotechnology Institute of Genomics and Bioinformatics National Chung-Hsing University Taichung Taiwan. School of Medicine Chung Shan Medical University Taichung Taiwan. Department of Medicine College of Medicine National Cheng Kung University Tainan Taiwan. Departments of Laboratory Medicine and Internal Medicine China Medical University Hospital Chin Medical University Taichung Taiwan. School of Medicine China Medical University Taichung Taiwan. PhD Program for Ageing School of Medicine China Medical University Taichung Taiwan. Departments of Laboratory Medicine and Internal Medicine National Taiwan University Hospital National Taiwan University College of Medicine Taipei Taiwan.

OBJECTIVES:The recent emergence of carbapenem-resistant Enterobacterales poses a major and escalating threat to global public health. This study aimed to analyse the global distribution and antimicrobial resistance of Enterobacterales harbouring variant OXA-48-like carbapenemase-related genes. METHODS:Enterobacterales isolates were collected from the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme during 2018-2021. Comprehensive antimicrobial susceptibility testing and β-lactamase gene detection were also conducted, along with statistical analysis of the collected data. RESULTS:Among the 72 244 isolates, 1934 Enterobacterales isolates were identified to harbour blaOXA-48-like genes, predominantly Klebsiella spp. (86.9%). High rates of multidrug resistance were observed, with only ceftazidime/avibactam and tigecycline showing favourable susceptibility. A discrepancy between the genotype and phenotype of carbapenem resistance was evident: 16.8% (233 out of 1384) of the Enterobacterales isolates with blaOXA-48-like genes exhibited susceptibility to meropenem. Specifically, 37.4% (64/95) of Escherichia coli strains with blaOXA-48-like genes displayed meropenem susceptibility, while the corresponding percentages for Klebsiella pneumoniae and Enterobacter cloacae complex were 25.2% (160/1184) and 0% (0/36), respectively (P < 0.05). Geographical analysis revealed that the highest prevalence of blaOXA-48-like genes occurred in Asia, the Middle East and Eastern Europe. The proportion of K. pneumoniae isolates harbouring blaOXA-232 increased from 23.9% in 2018 to 56.0% in 2021. By contrast, the proportion of blaOXA-48 decreased among K. pneumoniae isolates during 2018-2021. CONCLUSIONS:This study underscores the widespread and increasing prevalence of blaOXA-48-like genes in Enterobacterales and emphasizes the need for enhanced surveillance, improved diagnostic methods and tailored antibiotic stewardship to combat the spread of these resistant pathogens.

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Bile acid synthesis impedes tumor-specific T cell responses during liver cancer

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Science (New York, N.Y.) 2025年第6730期387卷 192-201页

作者： Varanasi, Siva Karthik Chen, Dan Liu, Yingluo Johnson, Melissa A. Miller, Cayla M. Ganguly, Souradipta Lande, Kathryn LaPorta, Michael A. Hoffmann, Filipe Araujo Mann, Thomas H. Teneche, Marcos G. Casillas, Eduardo Mangalhara, Kailash C. Mathew, Varsha Sun, Ming Jensen, Isaac J. Farsakoglu, Yagmur Chen, Timothy Parisi, Bianca Deota, Shaunak Havas, Aaron Lee, Jin Chung, H Kay Schietinger, Andrea Panda, Satchidananda Williams, April E. Farber, Donna L. Dhar, Debanjan Adams, Peter D. Feng, Gen-Sheng Shadel, Gerald S. Sundrud, Mark S. Kaech, Susan M. NOMIS Center for Immunobiology and Microbial Pathogenesis Salk Institute for Biological Studies La Jolla CA United States Department of Pathology School of Medicine University of California San Diego La Jolla CA United States Sanford Burnham Prebys Medical Discovery Institute La Jolla CA United States Department of Medicine School of Medicine University of California San Diego CA United States Razavi Newman Integrative Genomics and Bioinformatics Core Facility Salk Institute for Biological Studies La Jolla CA United States Department of Microbiology and Immunology Columbia University Irving Medical Center New York NY USA Department of Surgery Columbia University Irving Medical Center New York NY USA Regulatory Biology Laboratory Salk Institute for Biological Studies La Jolla CA United States Immunology Program Memorial Sloan Kettering Cancer Center New York NY USA Immunology and Microbial Pathogenesis Program Weill Cornell Graduate School of Medical Sciences New York NY USA Parker Institute for Cancer Immunotherapy New York NY USA Department of Microbiology and Immunology Geisel School of Medicine at Dartmouth Hanover NH USA Department of Medicine Geisel School of Medicine at Dartmouth Hanover NH USA Center for Digestive Health Dartmouth Health NH United States Dartmouth Cancer Center Dartmouth Health NH United States

The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid N-acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy. Furthermore, different BAs regulated CD8+ T cells differently;primary BAs induced oxidative stress, whereas the secondary BA lithocholic acid inhibited T cell function through endoplasmic reticulum stress, which was countered by ursodeoxycholic acid. We demonstrate that modifying BA synthesis or dietary intake of ursodeoxycholic acid could improve tumor immunotherapy in liver cancer model systems.

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Early-Life Risks of Central Precocious Puberty

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Endocrine Practice 2025年

作者： Yin, Wei-Jou Hsu, Jhih-Wei Chen, Chun-Chang Su, Emily Chia-Yu Wang, San-Yuan Chen, Yan-Jen Chen, Yang-Ching College of Medicine Taipei Medical University Taipei Taiwan Department of Family Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Biomedical Informatics Taipei Medical University Taipei Taiwan Master Program in Clinical Genomics and Proteomics Department of Pharmaceutical Sciences Taipei Medical University Taipei Taiwan Department of Family Medicine Wan Fang Hospital Taipei Medical University Taipei Taiwan Nutrition Research Center Taipei Medical University Hospital Taipei Taiwan

Objectives: To investigate the factors in early life that may contribute to central precocious puberty (CPP). Methods: The study utilized data from the Taiwan Puberty Longitudinal Study, including 2241 children under pubertal assessment and a questionnaire of risk factors. We analyzed associations using the Fitting Generalized Linear Models in R (R Core Team, 2023), with R studio (Posit, 2023) version 4.3.1. Results: Among the 2241 children examined, 745 had CPP. Overall, higher gestational weight gain (GWG) increased the risk of CPP (odds ratio [OR]: 1.03, 95% CI: 1.01-1.05);while higher GWG served as a protective factor in females (OR: 0.97, 95% CI: 0.95-0.99). Maternal gestational diabetes mellitus (GDM) also increased the CPP risk, particularly in males (OR: 2.66, 95% CI: 1.00-7.25). Longer exclusive breastfeeding was linked to lower CPP risk overall (OR: 0.96, 95% CI: 0.93-1.00) but was not significant when analyzed by gender. Conclusions: Higher maternal GWG was associated with an increased risk of CPP overall, while GWG became negatively associated with CPP, only in females. Maternal GDM was linked to a higher risk of CPP, particularly in males. The duration of exclusive breastfeeding was inversely correlated with CPP risk, but this effect was not significant when analyzed by gender. © 2025 AACE

关键词： central precocious puberty early-life risk factors pediatrics

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Metformin escape in prostate cancer by activating the PTGR1 transcriptional program through a novel super-enhancer

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Signal Transduction and Targeted Therapy 2023年第9期8卷 4365-4379页

作者： Jianheng Ye Shanghua Cai Yuanfa Feng Jinchuang Li Zhiduan Cai Yulin Deng Ren Liu Xuejin Zhu Jianming Lu Yangjia Zhuo Yingke Liang Jianjiang Xie Yanqiong Zhang Huichan He Zhaodong Han Zhenyu Jia Weide Zhong Department of Urology Guangzhou First People’s HospitalSouth China University of Technology510180 GuangzhouGuangdongChina Urology Key Laboratory of Guangdong Province The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical University510230 GuangzhouGuangdongChina Guangzhou National Laboratory No.9 XingDaoHuanBei RoadGuangzhou International Bio Island510005 GuangzhouGuangdongChina Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences100700 BeijingChina Department of Botany and Plant Sciences University of CaliforniaRiversideCA 92507USA Graduate Program in Genetics Genomics&BioinformaticsUniversity of CaliforniaRiversideCA 92507USA State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyTaipa999078 MacaoChina

The therapeutic efficacy of metformin in prostate cancer(PCa)appears uncertain based on various clinical *** treatment failure may be attributed to the high frequency of transcriptional dysregulation,which leads to drug ***,the underlying mechanism is still *** this study,we found evidences that metformin resistance in PCa cells may be linked to cell cycle ***-enhancers(SEs),crucial regulatory elements,have been shown to be associated with drug resistance in various *** analysis of SEs in metformin-resistant(MetR)PCa cells revealed a correlation with Prostaglandin Reductase 1(PTGR1)expression,which was identified as significantly increased in a cluster of cells with metformin resistance through single-cell transcriptome *** functional experiments showed that PTGR1 overexpression accelerated cell cycle progression by promoting progression from the G0/G1 to the S and G2/M phases,resulting in reduced sensitivity to ***,we identified key transcription factors that significantly increase PTGR1 expression,such as SRF and RUNX3,providing potential new targets to address metformin resistance in *** conclusion,our study sheds new light on the cellular mechanism underlying metformin resistance and the regulation of the SE-TFs-PTGR1 axis,offering potential avenues to enhance metformin’s therapeutic efficacy in PCa.

关键词： RUNX3 cancer offering

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Inhibition of ADAM9 promotes the selective degradation of KRAS and sensitizes pancreatic cancers to chemotherapy

Nature Cancer

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Nature Cancer 2024年第3期5卷 400-419页

作者： Huang, Yu-Kai Cheng, Wei-Chung Kuo, Ting-Ting Yang, Juan-Cheng Wu, Yang-Chang Wu, Heng-Hsiung Lo, Chia-Chien Hsieh, Chih-Ying Wong, Sze-Ching Lu, Chih-Hao Wu, Wan-Ling Liu, Shih-Jen Li, Yi-Chuan Lin, Ching-Chan Shen, Chia-Ning Hung, Mien-Chie Lin, Jaw-Town Yeh, Chun-Chieh Sher, Yuh-Pyng Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Cancer Biology and Precision Therapeutics Center China Medical University Taichung Taiwan Ph.D. Program for Cancer Biology and Drug Discovery China Medical University and Academia Sinica Taichung Taiwan School of Chinese Medicine College of Chinese Medicine China Medical University Taichung Taiwan Graduate Institute of Integrated Medicine College of Chinese Medicine China Medical University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology College of Medical and Health Science Asia University Taichung Taiwan Center for Molecular Medicine China Medical University Hospital Taichung Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Taipei Taiwan National Institute of Infectious Diseases and Vaccinology National Health Research Institutes Miaoli Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Biological Science and Technology China Medical University Taichung Taiwan Division of Hematology and Oncology China Medical University Hospital Taichung Taiwan Genomics Research Center Academia Sinica Taipei Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine E-Da Hospital Kaohsiung Taiwan Department of Medicine School of Medicine China Medical University Taichung Taiwan Department of Surgery Organ Transplantation Center China Medical University Hospital Taichung Taiwan Institute of Biochemistry and Molecular Biology China Medical University Taichung Taiwan

Kirsten rat sarcoma virus (KRAS) signaling drives pancreatic ductal adenocarcinoma (PDAC) malignancy, which is an unmet clinical need. Here, we identify a disintegrin and metalloproteinase domain (ADAM)9 as a modulator of PDAC progression via stabilization of wild-type and mutant KRAS proteins. Mechanistically, ADAM9 loss increases the interaction of KRAS with plasminogen activator inhibitor 1 (PAI-1), which functions as a selective autophagy receptor in conjunction with light chain 3 (LC3), triggering lysosomal degradation of KRAS. Suppression of ADAM9 by a small-molecule inhibitor restricts disease progression in spontaneous models, and combination with gemcitabine elicits dramatic regression of patient-derived tumors. Our findings provide a promising strategy to target the KRAS signaling cascade and demonstrate a potential modality to enhance sensitivity to chemotherapy in PDAC. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.

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Double negative T cells,a potential biomarker for systemic lupus erythematosus

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Precision Clinical medicine 2020年第1期3卷 34-43页

作者： Jessy J.Alexander Alexander Jacob Anthony Chang Richard J.Quigg James N.Jarvis Department of Pathology University of ChicagoChicagoIL 60637USA Departments of Medicine PediatricsJacobs School of Medicine and Biomedical Sciences and GeneticsGenomics&Bioinformatics ProgramUniversity at BuffaloBuffaloNY 14203USA

Systemic lupus erythematosus(SLE)is an autoimmune disease that is a challenge to diagnose and *** is an urgent need for biomarkers to help define organ involvement,and more effective therapies.A unique population of T cells,the CD3^(+)CD4^(−)CD8^(−)(DNeg)cells,is significantly increased in lupus *** cases(53%)of pediatric SLE patients had elevated DNeg cells in their peripheral blood,which correlated with kidney function(R^(2)=0.54).Significant infiltration of DNeg cells was observed in both adult and pediatric lupus kidneys by *** the first time,this study provides direct evidence that DNeg cells facilitate kidney injury in preclinical 8-week-old MRL/lpr lupus *** lupus mice,the increase in DNeg cells tracked with worsening disease and correlated with kidney function(R^(2)=0.85).Our results show that DNeg cells per se can cause kidney dysfunction,increase in number with increase in disease pathology,and could serve as a potential biomarker.

关键词： CD3^(+)CD4^(−)CD8^(−)T cells glomerulonephritis inflammation lupus

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