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Dietary carbohydrate intake and risk of type 2 diabetes:a 16-year prospective cohort study

Science China Life Sciences 2025年

作者： Lu Gan Yi Yang Bin Zhao Kai Yu Kehua Guo Fang Fang Zhiguang Zhou Demetrius Albanes Jiaqi Huang Key Laboratory of Diabetes Immunology Ministry of Education and Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University CSU-Sinocare Research Center for Nutrition and Metabolic Health Xiangya School of Public Health Central South UniversityFurong Laboratory Division of cancer Epidemiology and genetics National Cancer Institute NIH Department of Health and Human Services School of Computer Science and Engineering Central South University Institute of Environmental Medicine Karolinska Institute National Clinical research center for Metabolic Diseases Key Laboratory of Diabetes Immunology Ministry of Education and Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University

Despite considerable research underscoring the importance of carbohydrate intake in relation to the risk of type 2 diabetes(T2D), a comprehensive assessment of this relationship is currently lacking. We aimed to examine the associations of various types and food sources of dietary carbohydrate intake with the risk of T2D, to evaluate potential effect modification by other factors, including genetic susceptibility,and to explore the potential mediators for such associations. The present study included 161,872 participants of the UK Biobank who were free of prevalent cancer, cardiovascular disease, or diabetes, and had at least one validated 24-h dietary recall assessment. Multivariableadjusted age-stratified Cox proportional hazard regression models were applied to estimate hazard ratios(HRs) and 95% confidence intervals(CI) for the associations of various types and food sources of dietary carbohydrate intake with risk of T2D. During a median follow-up of13.6 years, 4,176 incident cases of T2D were identified. In the multivariable-adjusted models, a greater intake of fiber, carbohydrates from whole grains, and carbohydrates from non-starchy vegetables was significantly associated with a lower risk of T2D(highest vs. lowest quantile, HR [95% CI]=0.70 [0.62–0.79], 0.74 [0.67–0.82], and 0.83 [0.75–0.92], respectively, all P for trend genetic susceptibility to T2D. Mediation analyses of the inverse association between T

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The impact of the TIM gene family on tumor immunity and i mmunosuppression

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Cellular & Molecular Immunology 2014年第1期11卷 41-48页

作者： Muhammad Baghdadi Masahisa Jinushi Hokkaido University Hokkaido Japan research center for Infection-Associated cancer Institute for Genetic Medicine Hokkaido UniversityHokkaido Japan

Tumor immunoevasion is an advanced phase of cancer immunosurveillance in which tumor cells acquire the ability to circumvent host immune systems and exploit protumorigenic inflammation. T-cell immunoglobulin mucin （TIM） gene family members have emerged as critical checkpoint proteins that regulate multiple immune response phases and maintain immune homeostasis. Accumulating evidence demonstrates that tumor cells exploit TIM gene family members to evade immunosurveillance, whereas TIM gene family members facilitate the prevention of inflammation-related tumor progression. Thus, a comprehensive analysis to clarify the relative contributions of TIM gene family members in tumor progression may elucidate immunosurveillance systems in cancer patients.

关键词： antitumor immunity immunoevasion immunosurveillance TIM tumorigenic inflammation

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Extra sex combs,chromatin,and cancer:Exploring epigenetic regulation and tumorigenesis in Drosophila

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Journal of genetics and Genomics 2011年第10期38卷 453-460页

作者： Can Zhang Bo Liu Guangyao Li Lei Zhou Department of Molecular genetics ＆ Microbiology Shands Cancer Center University of Florida 2033 Mowry Road Gainesville Florida 32610 USA

Developmental genetic studies in Drosophila unraveled the importance of Polycomb group （PcG） and Trithorax group （TrxG） genes in controlling cellular identity. PcG and TrxG proteins form histone modifying complexes that catalyze repressive or activating histone modifi- cations, respectively, and thus maintaining the expression status of homeotic genes. Human orthologs of PcG and TrxG genes are implicated in tumorigenesis as well as in determining the prognosis of individual cancers. Recent whole genome analyses of cancers also highlighted the importance of histone modifying proteins in controlling tumorigenesis. Comprehensive understanding of the mechanistic relationship between histone regulation and tumorigenesis holds the promise of significantly advancing our understanding and management of cancer. It is anticipated that Drosophila melanogaster, the model organism that contributed significantly to our understanding of the functional role of histone regulation in development, could also provide unique insight for our understanding of how histone dysregulation can lead to cancer. In this review, we will discuss several recent advances in this regard.

关键词： Polycomb Epigenetics Tumorigenesis Drosophila

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Highly Fluorescent Dye-Doped Silica Nanoparticles Increase Flow Cytometry Sensitivity for cancer Cell Monitoring

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Nano research 2009年第6期2卷 448-461页

作者： M.-Carmen Estévez Meghan B.OʼDonoghue Xiaolan Chen Weihong Tan center for research at the Bio/Nano Interface Departments of Chemistry and Department of Physiology and Functional GenomicsShands Cancer Center and UF Genetics InstituteMcKnight Brain InstituteUniversity of FloridaGainesvilleFlorida 32611-7200USA

Early and accurate diagnosis and treatment of cancer depend on rapid,sensitive,and selective detection of tumor *** diagnosis of cancers,especially leukemia,relies on histology and fl ow cytometry using single dye-labeled ***,this combination may not lead to high signal output,which can hinder detection,especially when the probes have relatively weak affi nities or when the receptor is expressed in a low concentration on the target cell *** solve these problems,we have developed a novel method for sensitive and rapid detection of cancer cells using dye-doped silica nanoparticles(NPs)which increases detection sensitivity in fl ow cytometry analyses between 10-and 100-fold compared to standard *** NPs are~60 nm in size and can encapsulate thousands of individual dye molecules within their *** have extensively investigated surface modifi cation strategies in order to make the NPs suitable for selective detection of cancer cells using fl ow *** NPs are functionalized with polyethylene glycol(PEG)to prevent nonspecifi c interactions and with neutravidin to allow universal binding with biotinylated *** virtue of their reliable and selective detection of target cancer cells,these NPs have demonstrated their promising usefulness in conventional fl ow ***,they have shown low background signal,high signal enhancement,and effi cient functionalization,either with antibody-or aptamer-targeting moieties.

关键词： Silica nanoparticle flow cytometry aptamer cell detection polyethylene glycol fl uorophore

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A neuron-immune circuit regulates neurodegeneration in the hindbrain and spinal cord of Arf1-ablated mice

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National Science Review 2023年第12期10卷 98-110页

作者： Guohao Wang Shuhan Jin Jiaqi Liu Xu Li Peng Dai Yuetong Wang Steven X.Hou The Basic research Laboratory Center for Cancer ResearchNational Cancer Institute at FrederickNational Institutes of Health Department of Cell and Developmental Biology at the School of Life Sciences State Key Laboratory of Genetic EngineeringInstitute of Metabolism and Integrative BiologyHuman Phenome Institute Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital Fudan University

Neuroimmune connections have been revealed to play a central role in neurodegenerative diseases(NDs).However, the mechanisms that link the central nervous system(CNS) and peripheral immune cells are still mostly unknown. We recently found that specific ablation of the Arf1 gene in hindbrain and spinal cord neurons promoted NDs through activating the NLRP3 inflammasome in microglia via peroxided lipids and adenosine triphosphate(ATP) releasing. Here, we demonstrate that IL-1β with elevated chemokines in the neuronal Arf1-ablated mouse hindbrain and spinal cord recruited and activated γ δ T cells in meninges. The activated γ δ T cells then secreted IFN-γ that entered into parenchyma to activate the microglia-A1astrocyte-C3-neuronal C3a R neurotoxic pathway. Remarkably, the neurodegenerative phenotypes of the neuronal Arf1-ablated mice were strongly ameliorated by IFN-γ or C3 knockout. Finally, we show that the Arf1-reduction-induced neuroimmune-IFN-γ-gliosis pathway exists in human NDs, particularly in amyotrophic lateral sclerosis and multiple sclerosis. Together, our results uncover a previously unknown mechanism that links the CNS and peripheral immune cells to promote neurodegeneration.

关键词： neurodegenerative diseases disease-associated microglia γδ T cells reactive astrocyte IFN-γ C3

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The evolution of cancer genomic medicine in Japan and the role of the National cancer center Japan

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cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National cancer center research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National cancer center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

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Four outstanding young Chinese scientists received the 2013 Scholar Award from the US Chinese Anti-cancer Association and the National Foundation for cancer research

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Chinese Journal of cancer 2013年第12期32卷 631-635页

作者： Lifang Hou Li Yan Wei Zhang Michael Yi Wang Shi-Yuan Cheng Department of Preventive Medicine Center of Genetic Medicine The Robert H.Lurie Comprehensive Cancer Center Northwestern University US Chinese Anti-cancer Association Los Angeles Department of Pathology University of Texas MD Anderson Cancer Center National Foundation for cancer research Department of Neurology & Northwestern Brain Tumor Institute Center of Genetic Medicine The Robert H.Lurie Comprehensive Cancer Center Northwestern University

To facilitate and strengthen collaborations among cancer researchers and physicians in the United States and China,the US Chinese Anticancer Association(USCACA)and the National Foundation for cancer research(NFCR)have established the Scholar Excellence Award for the USCACA-NFCR Scholar Exchange and Fellowship Program in Basic,Translational,and Clinical *** 2010,10 young Chinese researchers and physicians have received the award for their outstanding achievements in cancer research accomplished while in the

关键词：中国科学家基金会癌症美国协会抗癌学者学术交流

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Benefit of everolimus as a monotherapy for a refractory breast cancer patient bearing multiple genetic mutations in the PI3K/AKT/mTOR signaling pathway

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cancer Biology & Medicine 2018年第3期15卷 314-321页

作者： Yehui Shi Wenwen Zhang Yingnan Ye Yanan Cheng Lei Han Pengpeng Liu Weipeng Zhao Zhongsheng Tong Jinpu Yu Medical Oncology Department of Breast cancer Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerKey Laboratory of Cancer Immunology and BiotherapyTianjin 300060China cancer Molecular Diagnostics Core Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerKey Laboratory of Cancer Immunology and BiotherapyTianjin 300060China Department of Immunology Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerKey Laboratory of Cancer Immunology and BiotherapyTianjin 300060China

A postmenopausal patient with a diagnosis of estrogen receptor(ER)(+), progesterone receptor(PR)(+), and human epidermal growth factor receptor-2(HER2)(-) breast cancer was reported. The patient refused surgery and was resistant to conventional chemotherapy regimens. Computed tomography and the circulating tumor cell test indicated that the patient's tumor burden increased rapidly even after several chemotherapy sessions. Multiple genetic aberrances in the phosphatidylinositol3-kinases(PI3 K) signaling pathway were detected via next-generation sequencing(NGS)-based liquid biopsy, including a p. G1007 R missense mutation in exon 21 of PIK3 CA(33.61%), a p.L70 fs frameshift mutation in exon 3 of phosphatase and tension homolog deleted on chromosome ten(PTEN)(49.14%), and a p. D1542 Y missense mutation in exon 32 of mammalian target of rapamycin(m TOR)(1.66%). Therefore, only the m TOR inhibitor everolimus was administered to the patient. Partial remission(PR) was observed after 2 months, and sustained stable disease(SD) was observed after a year and a half. Subsequent sequencing showed that the mutation ratio of PIK3 CA decreased to 4.17%, and that the PTEN and m TOR mutations disappeared, which revealed the significant curative effect of everolimus. We report the first case of successful monotherapy treatment using everolimus in a patient with advanced breast cancer bearing mutations in genes involved in the PI3 K/ARK/m TOR signaling pathway. The success of this case highlights the invaluable clinical contribution of NGS-based liquid biopsy, as it successfully provided an optimal therapeutic target for the patient with advanced breast cancer.

关键词： Breast cancer everolimus next-generation sequencing liquid biopsy PI3K/AKT/mTOR

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Gallbladder carcinoma: prognostic factors and therapeutic options

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World Journal of Gastroenterology 2015年第43期21卷 12211-12217页

作者： Thorsten Oliver Goetze Institut of Clinical cancer research UCT-University Cancer Center Frankfurt

The outcome of gallbladder carcinoma is poor,and the overall 5-year survival rate is less than 5%. In early-stage disease,a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma,which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection,primary sclerosing cholangitis,an anomalous junction of the pancreaticobiliary duct,and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However,despite theoretical risk factors,only a third of gallbladder carcinomas are recognized preoperatively. In most patients,the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ‘‘incidental or occult gallbladder carcinoma''(IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore,the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However,the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry(GR),which records the largest number of incidental gallbladder carcinomas in Europe,indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature,a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1 b and T2 carcinomas. The reason for a

关键词： Gallbladder carcinoma Stage-adjusted therapy Radic

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Predictive value of K-ras and PIK3CA in non-small cell lung cancer patients treated with EGFR-TKIs: a systemic review and meta-analysis

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cancer Biology & Medicine 2015年第2期12卷 126-139页

作者： Jie-Ying Chen Ya-Nan Cheng Lei Han Feng Wei Wen-Wen Yu Xin-Wei Zhang Shui Cao Jin-Pu Yu Department of Immunology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin Key Laboratory of Cancer Immunology and Biotherapy cancer Molecular Diagnostic Core Laboratory Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin Key Laboratory of Cancer Immunology and Biotherapy Biotherapy center Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin Key Laboratory of Cancer Immunology and Biotherapy

Objective： A meta-analysis was performed to augment the insufficient data on the impact of mutative EGFR downstream phosphatidylinositol-3-kinase （PI3K） and mitogen-activated protein kinase （MAPK） pathways on the clinical efficiency of epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI） treatment of non-small cell lung cancer （NSCLC） patients. Methods： Network databases were explored in April, 2015. Papers that investigated the clinical outcomes of NSCLC patients treated with EGFR-TKIs according to the status of K-ras and/or PIK3CA gene mutation were included. A quantitative meta-analysis was conducted using standard statistical methods. Odds ratios （ORs） for objective response rate （ORR） and hazard ratios （HRs） for progression-free survival （PFS） and overall survival （OS） were calculated. Results： Mutation in K-ras significantly predicted poor ORR [OR =0.22; 95% confidence interval （CI）, 0.13-0.35], shorter PFS （HR =1.56; 95% CI, 1.27-1.92）, and shorter OS （HR =1.59; 95% CI, 1.33-1.91） in NSCLC patients treated with EGFR-TKIs. Mutant PIK3CA significantly predicted shorter OS （HR =1.83; 95% CI, 1.05-3.20）, showed poor ORR （OK =0.70; 95% CI, 0.22-2.18）, and shorter PFS （HR = 1.79; 95% CI, 0.91-3.53） in NSCLC patients treated with EGFR-TKIs. Conclusion： K-ras mutation adversely affected the clinical response and survival of NSCLC patients treated with EGFR- TKIs. PIK3CA mutation showed similar trends. In addition to EGFR, adding K-ras and PIK3CA as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will benefit from EGFR-TKI treatment.

关键词： Non-small cell lung cancer (NSCLC) tyrosine kinase inhibitor (TKI) targeted therapy K-ras PIK3CA meta-analysis

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