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MGMT promoter methylation is a strong prognostic factor for survival after progression in high-grade gliomas

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中华神经外科杂志(英文) 2024年第03期10卷 164-172页

作者： Zhang Jing Qiu Xiaoguang Feng Jin Yanwei Liu department of radiation oncology Beijing Tiantan Hospital Capital Medical University Beijing China

Background High-grade gliomas (HGGs) have a rapid relapse and short survival. Studies have identified many clinical characteristics and biomarkers associated with progression-free survival (PFS) and over-survival (OS). However, there has not yet a comprehensive study on survival after the first progression (SAP).Methods From CGGA and TCGA, 319 and 308 HGGs were confirmed as the first progression. The data on clinical characteristics and biomarkers were analyzed in accordance with OS, PFS, and *** Analysis of 319 patients from CGGA, significant predictors of improved OS/PFS/SAP were WHO grade, MGMT promoter methylation, and Ki-67 expression in univariate analysis. Further multivariate analysis showed MGMT promoter methylation and Ki-67 expression were independent predictors. However, an analysis of 308 patients from TCGA found MGMT promoter methylation is the only prognostic marker. A longer SAP was observed in patients with methylated MGMT promoter after standard chemoradiotherapy. In our data, HGGs could be divided into low, intermediate, and high-risk groups for SAP by MGMT methylation and Ki-67 *** Patients with MGMT promoter methylation have a prolonger SAP after standard chemoradiotherapy. HGGs could be divided into low, intermediate, and high-risk groups for SAP according to MGMT status and Ki-67 expression.

关键词： High-grade gliomas MGMT promoter methylation Survival after the first progression

Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks

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Science China(Life Sciences) 2024年第1期67卷 132-148页

作者： Ming Zhang Xiaoyang Wang Nan Yang Xu Zhu Zequn Lu Yimin Cai Bin Li Ying Zhu Xiangpan Li Yongchang Wei Shaokai Zhang Jianbo Tian Xiaoping Miao department of Epidemiology and Biostatistics School of Public HealthDepartment of Gastrointestinal OncologyZhongnan Hospital of Wuhan UniversityDepartment of Radiation OncologyRenmin Hospital of Wuhan UniversityTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430071China Research Center of Public Health Renmin hospital of Wuhan UniversityWuhan UniversityWuhan 430060China department of Cancer Epidemiology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Engineering Research Center of Cancer Prevention and ControlHenan International Joint Laboratory of Cancer PreventionZhengzhou 450008China department of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhan 430060China department of radiation oncology Renmin Hospital of Wuhan UniversityWuhan 430060China department of Gastrointestinal oncology Hubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430062China department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430073China Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China

Genome-wide association studies(GWASs)have identified over 140 colorectal cancer(CRC)-associated loci;however,target genes at the majority of loci and underlying molecular mechanisms are poorly ***,we utilized a Bayesian approach,integrative risk gene selector(iRIGS),to prioritize risk genes at CRC GWAS loci by integrating multi-omics *** a result,a total of 105 high-confidence risk genes(HRGs)were identified,which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in *** the 105 HRGs,CEBPB,located at the 20q13.13 locus,acted as a transcription factor playing critical roles in *** subsequent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK,PI3K-Akt,and Ras ***,by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls,we elucidated that rs1810503,a putative functional variant regulating CEBPB,was associated with CRC risk(OR=0.90,95%CI=0.86–0.93,P=1.07×10^(−7)).The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 ***,the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via longrange promoter-enhancer interactions,mediated by the transcription factor,REST,and thus decreased CRC *** summary,our study provides a genetic resource and a generalizable strategy for CRC etiology investigation,and highlights the biological implications of CEBPB in CRC tumorigenesis,shedding new light on the etiology of CRC.

关键词： susceptibility genes gene screening models multi-omics GWAS CEBPB long-range promoter-enhancer interactions

New clinical trial design in precision medicine:discovery,development and direction

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1293-1321页

作者： Xiao-Peng Duan Bao-Dong Qin Xiao-Dong Jiao Ke Liu Zhan Wang Yuan-Sheng Zang department of Medical oncology Changzheng HospitalNaval Medical UniversityShanghaiChina

In the era of precision medicine,it has been increasingly recognized that individuals with a certain disease are complex and different from each *** to the underestimation of the significant heterogeneity across participants in traditional"one-sizefits-all"trials,patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket,umbrella,and platform trial designs under the master protocol *** recent years,the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous *** the rapid increase in the number of basket,umbrella,and platform trials,the current clinical and research understanding of these new trial designs,as compared with traditional trial designs,remains *** majority of the research focuses on methodologies,and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial ***,we provide this comprehensive review of the discovery and development of basket,umbrella,and platform trials and their underlying logic from the perspective of precision ***,we discuss future directions on the potential development of these new clinical design in view of the"Precision Pro","Dynamic Precision",and"Intelligent Precision".This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic,which be essential to accelerate the progression of precision medicine.

关键词： clinical approval successive

Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study

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Chinese Journal of Integrative Medicine 2024年第6期30卷 489-498页

作者： CAO Ni-da ZHU Xiao-hong MA Fang-qi XU Yan DONG Jia-huan QIN Meng-meng LIU Tian-shu ZHU Chun-chao GUO Wei-jian DING Hong-hua GUO Yuan-biao LIU Li-kun SONG Jin-jie WU Ji-ping CHENG Yue-lei ZENG Lin ZHAO Ai-guang oncology department I Longhua Hospital Shanghai University of Traditional Chinese MedicineShanghai200032China oncology department Zhongshan HospitalFudan UniversityShanghai200032China Gastrointestinal Surgery department Renji HospitalShanghai Jiaotong University School of MedicineShanghai200127China oncology department Fudan University Shanghai Cancer CenterShanghai200032China oncology department Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai200080China Traditional Chinese Medicine department Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China oncology department Shanxi Traditional Chinese Medicine HospitalTaiyuan030012China oncology department Xiyuan HospitalChina Academy of Chinese Medical ScienceBeijing102445China oncology department Yunnan Province Hospital of Traditional Chinese MedicineKunming650021China oncology department Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai201203China Shanghai NewCore Biotechnology Co. Ltd.Shanghai200240China

Objective To describe the treatment patterns and survival status of advanced gastric cancer(AGC)in China in the past two decades,and objectively evaluate the impact of standardized Chinese medicine(CM)treatment on the survival of AGC *** This multicenter registry designed and propensity score analysis study described the diagnosis characteristics,treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1,2000 and July 31,*** survival(OS)was evaluated between non-CM cohort(standard medical treatment)and CM cohort(integrated standard CM treatment≥3 months).Propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)were performed to adjust any difference in average outcomes for *** A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were *** them,1,607 received systemic chemotherapy,215(10.74%)accepted molecular targeted therapy,44(2.2%)received checkpoint inhibitor therapy,and 769(38.43%)received ***-drug regimen was the main choice for first-line treatment,with fluoropyrimidine plus platinum as the most common regimen(530 cases,60.09%).While 45.71%(16 cases)of patients with HER2 amplification received trastuzumab in *** application of apatinib increased(33.33%)in *** application of checkpoint inhibitors has increased since *** analysis showed that Lauren mixed type(P=0.017),cycles of first-line treatment>6(P=0.000),CM(P=0.000),palliative gastrectomy(P=0.000),trastuzumab(P=0.011),and apatinib(P=0.008)were independent prognostic factors for the OS of *** PSM and IPTW,the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months,respectively(P<0.001).Conclusions In real-world practice for AGC in China,therapy choices consisted with ***-drug regimen was the main first-line *** CM treatment was an independent

关键词： advancedgastriccancer real-world study treatment pattern survival analysis Chinese medicine

CA IX-targeted Ag_(2)S quantum dots bioprobe for NIR-II imaging-guided hypoxia tumor chemo-photothermal therapy

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Journal of Pharmaceutical Analysis 2024年第6期14卷 878-888页

作者： Xinyue Cui Zhuang Hu Ruihan Li Peng Jiang Yongchang Wei Zilin Chen department of radiation and Medical oncology Zhongnan Hospital of Wuhan University and School of Pharmaceutical SciencesWuhan UniversityWuhan430071China Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of EducationHubei Province Engineering and Technology Research Center for Fluorinated PharmaceuticalsWuhan430071China

Hypoxia is the common characteristic of almost all solid tumors,which prevents therapeutic drugs from reaching the ***,the development of new targeted agents for the accurate diagnosis of hypoxia tumors is widely *** carbonic anhydrase IX(CA IX)is abundantly distributed on the hypoxia tumor cells,it is considered as a potential tumor biomarker.4-(2-Aminoethyl)benzenesulfonamide(ABS)as a CA IX inhibitor has inherent inhibitory activity and good targeting *** this study,Ag_(2)S quantum dots(QDs)were used as the carrier to prepare a novel diagnostic and therapeutic bioprobe(Ag_(2)S@polyethylene glycol(PEG)-ABS)through ligand exchange and amide condensation ***_(2)S@PEG-ABS can selectively target tumors by surface-modified ABS and achieve accurate tumor imaging by the near infrared-II(NIR-II)fluorescence characteristics of Ag_(2)S *** modification of Ag_(2)S QDs greatly improves its water solubility and stability,and therefore achieves high photothermal stability and high photothermal conversion efficiency(PCE)of 45.17%.Under laser irradiation,Ag_(2)S@PEG-ABS has powerful photothermal and inherent antitumor combinations on colon cancer cells(CT-26)in *** also has been proved that Ag_(2)S@PEG-ABS can realize the effective treatment of hypoxia tumors in vivo and show good ***,it is a new efficient integrated platform for the diagnosis and treatment of hypoxia tumors.

关键词： CA IX-targeted Hypoxia tumor combination therapy NIR-II imaging Photothermal effect

Predicting the Prognosis and Immunotherapeutic Response of Triple-Negative Breast Cancer by Constructing a Prognostic Model Based on CD8+T Cell-Related Immune Genes

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Biomedical and Environmental Sciences 2024年第6期37卷 581-593页

作者： Nani Li Xiaoting Qiu Jingsong Xue Limu Yi Mulan Chen Zhijian Huang department of Medical oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014FujianChina department of Breast Surgical oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014FujianChina Departmen of Pathology Shenzhen Longhua Maternity and Child Healthcare HospitalShenzhen 518109GuangdongChina

Objective Triple-negative breast cancer(TNBC)poses a significant challenge for treatment ***8+T cells,which are pivotal immune cells,can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing *** leveraging these genes,our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to *** Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC *** the initial stage,we identified 67 differentially expressed genes associated with immune response in CD8+T ***,we narrowed our focus to three key genes,namely CXCL13,GBP2,and GZMB,which were used to construct a prognostic *** accuracy of the model was assessed using the validation set data and receiver operating characteristic(ROC)***,we employed various methods,including Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway,immune infiltration,and correlation analyses with CD274(PD-L1)to explore the model's predictive efficacy in immunotherapeutic ***,we investigated the potential underlying biological pathways that contribute to divergent treatment *** We successfully developed a model capable of predicting the prognosis of patients with *** areas under the curve(AUC)values for the 1-,3-,and 5-year survival predictions were 0.618,0.652,and 0.826,*** this risk model,we stratified the samples into high-and low-risk *** KEGG enrichment analysis,we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism,whereas the low-risk group demonstrated significant enrichment in cytokine ***,immune landscape analysis revealed noteworthy variations between(PD-L1)expression and risk scores,indicating that o

关键词： Breast Cancer Immunotherapy Prognosis CD8+T cells PD-L1

Vitamin D and prostate cancer prevention

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World Journal of Clinical oncology 2024年第6期15卷 691-694页

作者： Evita Krumina Abrahams Ocanto Felipe Couñago department of radiation oncology GenesisCare GuadalajaraGuadalajara 19004Spain department of radiation oncology San Francisco de Asís University HospitalGenesisCare MadridMadrid 28002Spain department of radiation oncology Vithas La Milagrosa University HospitalGenesisCare MadridMadrid 28010Spain National Director GenesisCare Spain

Vitamin D is a hot topic nowadays,especially its relationship with cancer ***,vitamin D is associated with bone health principally,but the new research has discovered an impact on immune function and cellular sig-naling,even in same studies talk about a hormone,however,the most important relationship is its implication in cellular processes,inhibiting cancer *** now,the recent studies are oriented about a benefit and a cause-effect relationship between prostate cancer and normal levels of vitamin *** premise opens a lot of questions in this *** editorial highlighted the most important studies in this area.

关键词： Prostate cancer Vitamin D Screening Cancer Prevention

Gastric metastasis of small cell lung carcinoma:A rare but noteworthy entity to consider

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World Journal of Clinical oncology 2024年第10期15卷 1379-1382页

作者： Cemal Ugur Dursun Ahmet Oguz Tugcu Galip Dogukan Dogru department of radiation oncology Kartal Dr.Lutfi Kirdar City Hospitalİstanbul 34865Türkiye department of radiation oncology Gulhane Training and Research HospitalAnkara 06010Türkiye

Small cell lung carcinoma(SCLC)is an aggressive malignancy known for its propensity for early and extensive metastatic *** metastasis,where cancer cells disseminate from the lung to the stomach,is a rare but increasingly recognized complication of *** review provides a comprehensive overview of gastric metastasis in SCLC,addressing its clinical significance,diagnostic challenges,management strategies,and ***,it examines the broader metastatic patterns of SCLC and compares them with other malignancies known for gastric *** metastasis in SCLC,though infrequent,is clinically significant and often indicates advanced disease with a poor *** typically metastasizes to the liver,brain,bones,and adrenal glands,with the stomach being an unusual *** incidence of gastric meta-stasis ranges from 1%to 5%in autopsy studies,although this may be underes-timated due to diagnostic difficulties and asymptomatic early *** gastric metastasis presents several challenges,including the asymptomatic nature of many cases,limitations of conventional imaging techniques,and difficulties in distinguishing metastatic lesions from primary gastric cancer via *** diagnosis requires careful examination to identify SCLC cells through their characteristic small cell morphology and neuroendocrine *** of gastric metastasis in SCLC typically involves a multidisciplinary *** therapy,pri-marily chemotherapy,remains the cornerstone of treatment,with palliative care addressing symptoms and *** intervention is usually reserved for specific cases requiring symptomatic *** prognosis for patients with gastric metastasis from SCLC is generally poor,reflecting the advanced stage of the *** survival is significantly re-duced compared to patients without gastric *** review emphasizes the need for enhanced awareness and early detection to

关键词： Lung cancer Small cell lung cancer Gastric metastasis Metastasis Rare metastasis

Role of cancer stem cell ecosystem on breast cancer metastasis and related mouse models

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Zoological Research 2024年第3期45卷 506-517页

作者： Xilei Peng Haonan Dong Lixing Zhang Suling Liu Fudan University Shanghai Cancer Center&Institutes of Biomedical Sciences/State Key Laboratory of Genetic Engineering/Cancer Institutes/department of oncology/Key Laboratory of Breast Cancer in Shanghai/Shanghai Key Laboratory of Medical Epigenetics/Shanghai Key Laboratory of radiation oncology/International Co-laboratory of Medical Epigenetics and Metabolism Ministry of Science and Technology/Shanghai Medical College/Fudan UniversityShanghai 200032China

Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and *** cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and *** have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast *** tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ***,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer *** this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory ***,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during ***,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.

关键词： Breast cancer Metastasis Cancer stem cell Ecosystem Tumor microenvironment Mouse model