检索结果-南通市图书馆

Targeting stroma and tumor,silencing galectin 1 treats orthotopic mouse hepatocellular carcinoma

在线全文

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2024年第1期14卷 292-303页

作者： Tahereh Setayesh Ying Hu Farzam Vaziri Xin Chen Jinping Lai Dongguang Wei Yu-Jui Yvonne Wan Department of Medical Pathology and Laboratory Medicine University of CaliforniaDavisSacramentoCA 95817USA cancer Biology program the University of Hawaii Cancer CenterHonoluluHI 96813USA Department of Pathology and Laboratory Medicine Kaiser Permanente Sacramento Medical CenterSacramentoCA 95825USA

This study examines inhibiting galectin 1(Gal1)as a treatment option for hepatocellular carcinoma(HCC).Gal1 has immunosuppressive and cancer-promoting roles.Our data showed that Gal1 was highly expressed in human and mouse HCC.The levels of Gal1 positively correlated with the stages of human HCC and negatively with survival.The roles of Gal1 in HCC were studied using overexpression(OE)or silencing using Igals1 siRNA delivered by AAV9.Prior to HCC initiation induced by RAS and AKT mutations,lgals1-OE and silencing had opposite impacts on tumor load.The treatment effect of lgals1 siRNAwas further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9%or even 42%of the body weight.Comparing spatial transcriptomic profiles of Gal1 silenced and OE HCC,inhibiting matrix formation and recognition of foreign antigen in CD45t cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 silencing.Within the tumors,silencing Gal1 inhibited translational initiation,elongation,and termination.Furthermore,Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor,and the anti-HCC effect of lgals1 siRNAwas CD8-dependent.Overall,Gal1 silencing has a promising potential for HCC treatment.

关键词： Liver Hepatocellular carcinoma Carbohydrate-binding lectin Galectin 1 Extracellular matrix Translation Spatial transcriptomics Tumor-margin

CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of PKM supports antitumor immunity

在线全文

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand P.Sharda Mackenzie M.Lieberman Caitlin M.James Shivana M.Lightman Jason H.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi Hou Andrew M.Intlekofer Richard M.Higashi Teresa W.M.Fan Andrew N.Lane Kevin H.Eng Brahm H.Segal Elizabeth A.Repasky Kelvin P.Lee Scott H.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and Pathogenesis program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Present address:University of Colorado Boulder BoulderCO 80309USA Present address:Dana Farber cancer Institute BostonMA 02215USA Present address:Massachusetts Institute of Technology BostonMA 02139USA Present address:Melvin and Bren Simon Comprehensive cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been determined.In this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T cells.In doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose catabolism.ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events.Among these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector function.Importantly,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 PKM2

Somatic CDKN2A copy number variations are associated with the prognosis of esophageal squamous cell dysplasia

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

中华医学杂志(英文版) 2024年第8期137卷 980-989页

作者： Fan Zhiyuan Zhou Jing Tian Yuan Qin Yu Liu Zhaojun Gu Liankun Dawsey Sanford M. Wei Wenqiang Deng Dajun Division of cancer Epidemiology and Genetics National cancer Institute Bethesda MD USA National Central cancer Registry National cancer Center/National Clinical Research Center for cancer/cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 China Key Laboratory of Carcinogenesis and Translational Research (MOE/Beijing) Division of Etiology Peking University cancer Hospital and Institute Beijing 100142

Background: Somatic copy number variations (SCNVs) in theCDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whetherCDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value ofCDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys.Methods: This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detectCDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models.Results: A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in theCDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69]vs. 35.0% [28/80]vs. 51.8% [29/56],P <0.001). In the univariable competing risk analysis, the cumulative regression rate was statistically significantly lower (P = 0.008), while the cumulative progression rate was higher (P = 0.017) in ESCdys patients withCDKN2A deletion than in those withoutCDKN2A deletion.CDKN2A deletion was also an independent predictor of prognosis in ESCdys (P = 0.004) in the multivariable analysis.Conclusion: The results indicated thatCDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.

关键词： CDKN2A Somatic copy number variations Esophageal squamous cell carcinoma Esophageal neoplasms Squamous intraepithelial lesions DNA copy number variations Prognosis Prospective study

Immune checkpoint inhibitors:breakthroughs in cancer treatment

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

cancer Biology & Medicine 2024年第6期21卷 451-472页

作者： Xueqing Kong Jinyi Zhang Shuwei Chen Xianyang Wang Qing Xi Han Shen Rongxin Zhang Laboratory of Immunology and inflammation School of Life Sciences and Biopharmaceutics Guangdong Pharmaceutical University Department of Biology School of Life Sciences and Biopharmaceutics Guangdong Pharmaceutical University

Over the past two decades, immunotherapies have increasingly been considered as first-line treatments for most cancers. One such treatment is immune checkpoint blockade(ICB), which has demonstrated promising results against various solid tumors in clinical trials. Monoclonal antibodies(mAbs) are currently available as immune checkpoint inhibitors(ICIs). These ICIs target specific immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4(CTLA-4) and programmed cell death protein 1(PD-1). Clinical trial results strongly support the feasibility of this immunotherapeutic approach. However, a substantial proportion of patients with cancer develop resistance or tolerance to treatment, owing to tumor immune evasion mechanisms that counteract the host immune response.Consequently, substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1, anti-programmed cell death ligand 1(anti-PD-L1), and anti-CTLA-4 treatments. Recently, several immune checkpoint molecular targets have been identified, such as T cell immunoreceptor with Ig and ITIM domains(TIGIT), mucin domain containing-3(TIM-3), lymphocyte activation gene-3(LAG-3), V-domain immunoglobulin suppressor of T cell activation(VISTA), B and T lymphocyte attenuator(BTLA), and signal-regulatory protein α(SIRPα). Functional m Abs targeting these molecules are under development. CTLA-4, PD-1/PD-L1, and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of research. This review discusses these structures, as well as clinical progress in m Abs targeting these immune checkpoint molecules and their potential applications.

关键词： CTLA-4 ICIs Immunotherapy PD-1 cancer

RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Military Medical Research 2024年第1期11卷 34-49页

作者： Yi-Qun Li Fang-Zhou Sun Chun-Xiao Li Hong-Nan Mo Yan-Tong Zhou Dan Lv Jing-Tong Zhai Hai-Li Qian Fei Ma Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

关键词： RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) Breast cancer

Magnetic resonance imaging-based lymph node radiomics for predicting the metastasis of evaluable lymph nodes in rectal cancer

在线全文

学校读者我要写书评

暂无评论

World Journal of Gastrointestinal Oncology 2024年第5期16卷 1849-1860页

作者： Yong-Xia Ye Liu Yang Zheng Kang Mei-Qin Wang Xiao-Dong Xie Ke-Xin Lou Jun Bao Mei Du Zhe-Xuan Li Department of Radiology The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210011Jiangsu ProvinceChina Department of Colorectal Surgery Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210000Jiangsu ProvinceChina1 Department of Pathology The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210011Jiangsu ProvinceChina Colorectal Center The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210011Jiangsu ProvinceChina

BACKGROUND Lymph node(LN)staging in rectal cancer(RC)affects treatment decisions and patient prognosis.For radiologists,the traditional preoperative assessment of LN metastasis(LNM)using magnetic resonance imaging(MRI)poses a challenge.AIM To explore the value of a nomogram model that combines Conventional MRI and radiomics features from the LNs of RC in assessing the preoperative metastasis of evaluable LNs.METHODS In this retrospective study,270 LNs(158 nonmetastatic,112 metastatic)were randomly split into training(n=189)and validation sets(n=81).LNs were classified based on pathology-MRI matching.Conventional MRI features[size,shape,margin,T2-weighted imaging(T2WI)appearance,and CE-T1-weighted imaging(T1WI)enhancement]were evaluated.Three radiomics models used 3D features from T1WI and T2WI images.Additionally,a nomogram model combining conventional MRI and radiomics features was developed.The model used univariate analysis and multivariable logistic regression.Evaluation employed the receiver operating characteristic curve,with DeLong test for comparing diagnostic performance.Nomogram performance was assessed using calibration and decision curve analysis.RESULTS The nomogram model outperformed conventional MRI and single radiomics models in evaluating LNM.In the training set,the nomogram model achieved an area under the curve(AUC)of 0.92,which was significantly higher than the AUCs of 0.82(P<0.001)and 0.89(P<0.001)of the conventional MRI and radiomics models,respectively.In the validation set,the nomogram model achieved an AUC of 0.91,significantly surpassing 0.80(P<0.001)and 0.86(P<0.001),respectively.CONCLUSION The nomogram model showed the best performance in predicting metastasis of evaluable LNs.

关键词： Radiomics Lymph node metastasis Rectal cancer Magnetic resonance imaging

TGF-βsignaling in health,disease,and therapeutics

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Signal Transduction and Targeted Therapy 2024年第4期9卷 1466-1505页

作者： Ziqin Deng Tao Fan Chu Xiao He Tian Yujia Zheng Chunxiang Li Jie He Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

ransforming growth factor(TGF)-βis a multifunctional cytokine expressed by almost every tissue and cell type.The signal transduction of TGF-βcan stimulate diverse cellular responses and is particularly critical to embryonic development,wound healing,tissue homeostasis,and immune homeostasis in health.The dysfunction of TGF-βcan play key roles in many diseases,and numerous targeted therapies have been developed to rectify its pathogenic activity.In the past decades,a large number of studies on TGF-βsignaling have been carried out,covering a broad spectrum of topics in health,disease,and therapeutics.Thus,a comprehensive overview of TGF-βsignaling is required for a general picture of the studies in this field.In this review,we retrace the research history of TGF-βand introduce the molecular mechanisms regarding its biosynthesis,activation,and signal transduction.We also provide deep insights into the functions of TGF-βsignaling in physiological conditions as well as in pathological processes.TGF-β-targeting therapies which have brought fresh hope to the treatment of relevant diseases are highlighted.Through the summary of previous knowledge and recent updates,this review aims to provide a systematic understanding of TGF-βsignaling and to attract more attention and interest to this research area.

关键词： homeostasis healing wound

Ferroptosis:a critical mechanism of N^(6)-methyladenosine modification involved in carcinogenesis and tumor progression

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Science China(Life Sciences) 2024年第6期67卷 1119-1132页

作者： Qingqing Wei Changning Xue Mengna Li Jianxia Wei Lemei Zheng Shipeng Chen Yumei Duan Hongyu Deng Faqing Tang Wei Xiong Ming Zhou NHC Key Laboratory of Carcinogenesis Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China cancer Research Institute and School of Basic Medical Sciences Central South UniversityChangsha 410078China The Key Laboratory of Carcinogenesis and cancer Invasion of the Chinese Ministry of Education Central South UniversityChangsha 410078China Hunan Key Laboratory of Oncotarget Gene Hunan Key Laboratory of Cancer MetabolismHunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China

Ferroptosis is an iron-dependent regulatory cell necrosis induced by iron overload and lipid peroxidation.It occurs when multiple redoxactive enzymes are ectopically expressed or show abnormal function.Hence,the precise regulation of ferroptosis-related molecules is mediated across multiple levels,including transcriptional,posttranscriptional,translational,and epigenetic levels.N^(6)-methyladenosine(m^(6)A)is a highly evolutionarily conserved epigenetic modification in mammals.The m^(6)A modification is commonly linked to tumor proliferation,progression,and therapy resistance because it is involved in RNA metabolic processes.Intriguingly,accumulating evidence suggests that dysregulated ferroptosis caused by the m^(6)A modification drives tumor development.In this review,we summarized the roles of m^(6)A regulators in ferroptosis-mediated malignant tumor progression and outlined the m^(6)A regulatory mechanism involved in ferroptosis pathways.We also analyzed the potential value and application strategies of targeting m^(6)A/ferroptosis pathway in the clinical diagnosis and therapy of tumors.

关键词： ferroptosis m6A modification RNA methylation m^(6)A regulator tumor progression

Plant-based dietary patterns and risk of esophageal cancer:A prospective cohort study spanning 17 years

在线全文

学校读者我要写书评

暂无评论

Chinese Journal of cancer Research 2024年第1期36卷 36-45页

作者： Xiaorui Zhang Feifan He Jiayue Li Ru Chen Xinqing Li Li Li Fen Liu Shaoming Wang Wenqiang Wei Department of Epidemiology and Health Statistics School of Public HealthBeijing Municipal Key Laboratory of Clinical EpidemiologyCapital Medical UniversityBeijing 100069China National Central cancer Registry office National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of cancer Epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Objective: Plant-based diets have multiple health benefits for cancers;however, little is known about the association between plant-based dietary patterns and esophageal cancer(EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC.Methods: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index(PDI), healthful plant-based diet index(h PDI), and unhealthful plant-based diet index(u PDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios(HRs) and 95% confidence intervals(95% CIs) of EC across 3plant-based diet indices and further stratified the analysis by subgroups.Results: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50(95% CI, 0.32-0.77) for h PDI. In addition, the HR per 10-point increase in the h PDI score was 0.42(95% CI, 0.27-0.66) for ECs. Conversely, u PDI was positively associated with the risk of EC, and the HR was 1.80(95% CI, 1.16-2.82). The HR per 10-point increase in the u PDI score was 1.90(95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses.Conclusions: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

关键词： Esophageal cancer diet dietary pattern epidemiology nutrition prospective cohort study