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Mesenchymal-epithelial transition factor amplification correlates with adverse pathological features and poor clinical outcome in colorectal cancer

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1395-1406页

作者： Qiu-Xiao Yu Ping-Ying Fu Chi Zhang Li Li Wen-Ting Huang department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518116Guangdong ProvinceChina

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and the second most common cause of cancer-related mortality ***-epithelial transition factor(MET)gene participates in multiple tumor biology and shows clinical potential for pharmacological manipulation in tumor *** amplification has been reported in CRC,but data are very *** pathological values of MET in CRC may provide new therapeutic and genetic screening options in future clinical *** To determine the pathological significance of MET amplification in CRC and to propose a feasible screening *** A number of 205 newly diagnosed CRC patients undergoing surgical resection without any preoperative therapy at Shenzhen cancer Hospital of Chinese Academy of Medical Sciences were *** patients were without RAS/RAF mutation or microsatellite *** amplification and c-MET protein expression were analyzed using fluorescence in situ hybridization(FISH)and immunohistochemistry(IHC),*** between MET aberration and pathological features were detected using the chi-squared *** free survival(PFS)during the two-year follow-up was detected using the Kaplan-Meier method and log rank *** results of MET FISH and IHC were com pared using one-way *** Polysomy-induced MET amplification was observed in 14.4%of cases,and focal MET amplification was not ***-induced MET amplification was associated with a higher frequency of lymph node metastasis(LNM)(P<0.001)and higher tumor budding grade(P=0.02).In the survival analysis,significant difference was detected between patients with amplified-and non-amplified MET in a two-year follow-up after the first diagnosis(P=0.001).C-MET scores of 0,1+,2+,and 3+were observed in 1.4%,24.9%,54.7%,and 19.0%of tumors,respectively.C-MET overexpression correlated with higher frequency of LNM(P=0.002),but no significant difference of PFS was dete

关键词： Colorectal cancer MET Amplification Pathological features Prognosis Fluorescence in situ hybridization

Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China Life Sciences 2024年

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and Translational research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research Laboratory Peking University Cancer Hospital &Institute department of Gastrointestinal cancer Center Peking University Cancer Hospital & Institute department of Liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State Key Laboratory of Holistic Integrative Management of Gastrointestinal cancers Beijing Key Laboratory of Carcinogenesis and Translational Research Division of Gastrointestinal Cancer Translational Research Laboratory Peking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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Clinical benefit and safety profile of cross-line therapy with CDK4/6 inhibitors: a retrospective study of HR+/HER2–advanced breast cancer

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cancer Biology & Medicine 2024年第10期 934-950页

作者： Qi Zhao Mingxia Jiang Jiaxuan Liu Mengqi Zhang Maiyue He Shihan Zhou Jiani Wang Hongnan Mo Bo Lan Peng Yuan Pin Zhang Fei Ma Qiao Li Binghe Xu department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College

Objective: CDK4/6 inhibitors(CDK4/6is) in combination with endocrine therapy have secured a central role in the treatment of hormone receptor(HR)-positive advanced breast cancer(ABC) and have transformed the therapeutic landscape. Cross-line CDK4/6i therapy in which another CDK4/6i is continued after progression on a prior CDK4/6i may still offer advantageous therapeutic effects. Cross-line CDK4/6i therapy is an area of active investigation in the ongoing pursuit to improve outcomes for patients with HR+/human epidermal growth factor receptor 2(HER2)± ***: This retrospective study enrolled 82 patients with HR+/HER2± ABC who were treated with cross-line CDK4/6is(abemaciclib, palbociclib, ribociclib, and dalpiciclib) after progression with another CDK4/6i. The primary endpoint was progressionfree survival(PFS) according to version 1.1 of the Response Evaluation Criteria in Solid Tumors. Secondary endpoints included toxicity, objective response rate, disease control rate, and overall survival. Adverse events(AEs) were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events, as promulgated by the U.S. department of Health and Human ***: Eighty-two HR+/HER2± ABC patients who received cross-line CDK4/6i therapy from January 2022 to February 2024 were enrolled. The median age of the patients was 60 years. The median PFS of all patients was 7.6 months(95% CI, 5.9-9.2). Cox regression analysis identified lung metastasis and a switch to endocrine therapy following prior CDK4/6i therapy as independent predictive factors for PFS. Notably, patients who previously received abemaciclib and switched to palbociclib upon disease progression had a median PFS of 10.7 months. The strategy of transitioning to chemotherapy after progression on a prior CDK4/6i, then to a subsequent CDK4/6i merits further investigation. Hematologic toxicity was the most common grade ≥ 3 AEs. No instances of fatal safety events were ***: Cro

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PDCD2 as a prognostic biomarker in glioma correlates with malignant phenotype

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Genes & Diseases 2024年第5期11卷 390-406页

作者： Fengsheng Dai Yixiao Yuan Jiaqi Hao Xing Cheng Xiangyi Zhou Li Zhou Rui Tian Yi Zhao Tingxiu Xiang department of Oncology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China Chongqing Key Laboratory of Translational research for cancer Metastasis and Individualized Treatment Chongqing University Cancer HospitalChongqing 400030China department of Neurosurgery Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan International Scientific and Technological Cooperation Base of Brain Tumor research Xiangya HospitalCentral South UniversityChangshaHunan 410008China department of Neuro-Oncology Chongqing University Cancer HospitalChongqing 400030China

Programmed cell death 2(PDCD2)is related to cancer progression and chemotherapy *** role of PDCD2 in solid cancers(excluding hematopoietic malignancies)and their diagnosis and prognosis remains *** TCGA,CGGA,GEPIA,cBioPortal,and GTEx databases were analyzed for expression,prognostic value,and genetic modifications of PDCD2 in cancer *** enrichment analysis,CCK8,colony formation assay,transwell assay,and xenograft tumor model were undertaken to study the PDCD2’s biological function in glioma(GBMLGG).The PDCD2 gene was associated with solid cancer *** the functional enrichment analysis results,PDCD2 was shown to participate in several important GBMLGG biological *** cells may be inhibited in their proliferation,migration,invasion,and xenograft tumor growth by knocking down *** research can provide new insights into solid cancer prognostic biomarkers of PDCD2.

关键词： Biomarker Glioma Programmed cell death 2 Progression Solid cancer

A Blood Hepatocellular Carcinoma Signature Recognizes Very Small Tumor Nodules with Metastatic Traits

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Journal of Clinical and Translational Hepatology 2024年第6期12卷 551-561页

作者： Kun Chen Junxiao Wang Liping Jiang Fei Zhao Ruochan Zhang Zhiyuan Wu Dongmei Wang Yuchen Jiao Hui Xie Chunfeng Qu State Key Lab of Molecular Oncology Department of ImmunologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Senior department of Oncology Fifth Medical Center of Chinese PLA General HospitalBeijingChina Aerospace Medical Center/Aerospace Center Hospital Peking University Aerospace Clinical CollegeBeijingChina State Key Lab of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Background and Aims:Hepatocellular carcinoma(HCC)cases with small nodules are commonly treated with radi-ofrequency ablation(RFA),but the recurrence rate remains *** study aimed to establish a blood signature for identifying HCC with metastatic traits ***:Data from HCC patients treated between 2010 and 2017 were retrospectively collected.A blood signature for meta-static HCC was established based on blood levels of alpha-fetoprotein and des-γ-carboxy-prothrombin,cell-free DNA(cfDNA)mutations,and methylation changes in target genes in frozen-stored plasma samples that were collected before RFA *** HCC blood signature was validated in patients prospectively enrolled ***:Of 251 HCC patients in the retrospective study,33.9% experienced recurrence within 1 year *** HCC blood signature identified from these patients included des-γ-carboxy-prothrombin≥40mAU/mL with cfDNA mutation score,where cfDNA mutations occurred in the genes of TP53,CTNNB1,and TERT *** signature effectively predicted 1-year post-RFArecurrence of HCC with 92% specificity and 91% sensitivity in the retrospective dataset,and with 87% specificity and 76% sensitivity in the prospective dataset(n=32 patients).Among 14 cases in the prospective study with biopsy tissues available,positivity for the HCC blood signature was associated with a higher HCC tissue score and shorter distance between HCC cells and ***:This study established an HCC blood signature in pre-RFA blood that potentially reflects HCC with metastatic traits and may be valuable for predicting the disease’s early recurrence post-RFA.

关键词： Liquid biopsy Liver dysplastic nodules Radiofrequency ablation Hepatocellular carcinoma Recurrence prediction Metastatic nodules

Nab-paclitaxel plus capecitabine as first-line treatment for advanced biliary tract cancers:An open-label,non-randomized,phase II clinical trial

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World Journal of Gastroenterology 2024年第30期30卷 3564-3573页

作者： Ling-Xiao Xu Jia-Jia Yuan Ran Xue Jun Zhou department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing)Peking University Cancer Hospital and InstituteBeijing 100142China

BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment *** To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic *** This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing cancer Hospital and the First Hospital of China Medical *** patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease *** primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and *** A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were *** response assessment was impeded for one patient due to premature demise from tumor *** the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were *** Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.

关键词： Nab-paclitaxel Capecitabine Biliary tract cancer Objective response rate Phase II clinical trial

Surgical management of metastatic neuroendocrine tumors:beyond the realm of evidence-based medicine

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Hepatobiliary Surgery and Nutrition 2024年第3期13卷 551-553页

作者： Jonathan R.Strosberg Taymeyah Al-Toubah department of Gastrointestinal Oncology Moffitt Cancer Center&Research InstituteUniversity of South FloridaTampaFLUSA

How strong is the evidence supporting surgery for patients with metastatic neuroendocrine tumors(NETs)?This is the chief question from ***’comprehensive and balanced literature analysis on the surgical treatment of metastatic pancreatic NETs(1).No matter how many non-randomized studies demonstrate a survival advantage for patients undergoing cytoreductive hepatic surgery or resection of the primary pancreatic tumor,the methodological biases remain constant(2-9).Patients undergoing surgery tend to be younger and healthier,and their tumors tend to be lower grade,less aggressive,and fewer in number than patients undergoing other systemic or liver-directed *** other words,the survival advantage begins when the patient is selected as a surgical candidate and before the scalpel even touches the *** multivariate analyses can control for some confounding variables,it is impossible to control for *** a simple concept such as tumor burden is challenging to standardize:a patient with a few large tumors confined to a single hepatic lobe may have a vastly different prognosis than a patient with a similar burden of miliary tumors scattered throughout the liver(2).

关键词： Neuroendocrine tumor(NET) cytoreduction debulking surgery transplantation

On fractional discrete financial system:Bifurcation,chaos,and control

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Chinese Physics B 2024年第10期33卷 129-140页

作者： Louiza Diabi Adel Ouannas Amel Hioual Shaher Momani Abderrahmane Abbes Laboratory of Dynamical Systems and Control University of Larbi Ben M’hidiOum El Bouaghi 04000Algeria department of Mathematics and Computer Science University of Larbi Ben M’hidiOum El Bouaghi 04000Algeria Nonlinear Dynamics research Center Ajman UniversityAjman 346United Arab Emirates department of Mathematics The University of JordanAmman 11942Jordan Laboratory of Mathematics Dynamics and ModelizationUniversity Badji MokhtarAnnaba 23000Algeria

The dynamic analysis of financial systems is a developing field that combines mathematics and economics to understand and explain fluctuations in financial *** paper introduces a new three-dimensional(3D)fractional financial map and we dissect its nonlinear dynamics system under commensurate and incommensurate *** such,we evaluate when the equilibrium points are stable or unstable at various fractional *** use many numerical methods,phase plots in 2D and 3D projections,bifurcation diagrams and the maximum Lyapunov *** techniques reveal that financial maps exhibit chaotic attractor *** study is grounded on the Caputo-like discrete operator,which is specifically influenced by the variance of the commensurate and incommensurate ***,we confirm the presence and measure the complexity of chaos in financial maps by the 0-1 test and the approximate entropy ***,we offer nonlinear-type controllers to stabilize the fractional financial *** numerical results of this study are obtained using MATLAB.

关键词： financial model stability chaos commensurate and incommensurate orders complexity

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Beyond clinical trials:CDK4/6 inhibitor efficacy predictors and nomogram model from real‐world evidence in metastatic breast cancer

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cancer Innovation 2024年第6期3卷 58-75页

作者： Binliang Liu Zhe‐Yu Hu Ning Xie Liping Liu Jing Li Xiaohong Yang Huawu Xiao Xuran Zhao Can Tian Hui Wu Jun Lu Jianxiang Gao Xuming Hu Min Cao Zhengrong Shui Yu Tang Quchang Ouyang department of Breast cancer Medical Oncology Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaHunanChina department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina department of Gastroenterology The Third Xiangya Hospital of Central South UniversityChangshaHunanChina

Background:CDK4/6 inhibitors(CDK4/6i)have shown promising results in the treatment of hormone receptor‐positive(HR+)metastatic breast cancer(MBC)when combined with endocrine therapy(ET).It is crucial to evaluate the actual effectiveness and safety of CDK4/6i in clinical practice,as well as to analyze the factors that can predict their ***:Patients with HR+MBC who received CDK4/6i‐based therapy between may 2016 and may 2023 at Hunan cancer Hospital were evaluated for progression‐free survival(PFS).Adverse reactions were assessed based on the National cancer Institute Common Toxicity Criteria(version 5.0).Results:This study included 344 patients,with a median PFS(mPFS)of 12.8 months(range:10.4–15.2 months).After adjustment,Cox multivariate regression analysis revealed that visceral metastasis(specifically liver and brain metastases),Eastern Cooperative Oncology Group Performance Status(ECOG PS)≥1,estrogen receptor≤80%,progesterone receptor≤10%,Ki‐67>30%,and treatment in later stages were significant factors associated with reduced *** on this,we created a prognostic nomogram and validated its performance,obtaining a C‐index of 0.714(95%confidence interval:0.640–0.787)as well as reliable calibration and clinical *** mPFS of CDK4/6i rechallenge was 7.7 months;for patients who initially discontinued CDK4/6i for reasons other than disease progression,CDK4/6i rechallenge still provided a mPFS of 11.4 *** tolerability and safety of combining CDK4/6is with ET were *** events led to treatment discontinuation in 3.8%of ***(29.1%),leukopenia(13.7%),and anemia(4.1%)were the primary grade 3/4 adverse ***:This real‐world study highlights the ample efficacy and reasonable safety of combined CDK4/6i and ET in patients with HR+*** treatment decisions and ongoing safety monitoring are important to optimize the therapeutic benefit of CDK4/6i treatment.

关键词： breast cancer CDK4/6 inhibitor efficacy predictive factors real‐word study