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Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance

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Chinese Medical Journal 2024年第7期137卷 859-870页

作者： Xianlong Wang Chuan Zhao Jincheng Lin Hongxing Liu Qiuhong Zeng Huadong Chen Ye Wang Dapeng Xu Wen Chen Moping Xu En Zhang Da Lin Zhixiong Lin Department of Bioinformatics School of Medical Technology and EngineeringKey Laboratory of Medical BioinformaticsKey Laboratory of Ministry of Education for Gastrointestinal CancerFujian Medical UniversityFuzhouFujian 350122China Department of Neurosurgery Sanbo Brain HospitalCapital Medical UniversityBeijing 100093China

Background:Adamantinomatous craniopharyngioma(ACP)is the commonest pediatric sellar *** effective drug is available and interpatient heterogeneity is *** study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles,imaging findings,and histological features,in order to predict the response to anti-inflammatory treatment and ***:Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled,including 119 ACPs and 23 papillary ***-exome sequencing(151 tumors,including recurrent ones),RNA sequencing(84 tumors),and DNA methylome profiling(95 tumors)were *** clustering and non-negative matrix factorization were used for subgrouping,and Cox regression were utilized for prognostic evaluation,***:Three distinct molecular subgroups were identified:WNT,ImA,and *** WNT subgroup showed higher Wnt/β-catenin pathway activity,with a greater number of epithelial cells and more predominantly solid *** ImA and ImB subgroups had activated inflammatory and interferon response pathways,with enhanced immune cell infiltration and more predominantly cystic ***-activated protein kinases(MEK/MAPK)signaling was activated only in ImA samples,while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group,mostly consisting of *** degree of astrogliosis was significantly elevated in the ImA group,with severe finger-like protrusions at the invasive front of the *** molecular subgrouping was an independent prognostic factor,with the WNT group having longer event-free survival than ImB(Cox,P=0.04).ImA/ImB cases were more likely to respond to immune checkpoint blockade(ICB)therapy than the WNT group(P<0.01).In the preliminary screening of subtyping markers,CD38 was significantly downregulated in WNT compared with ImA and ImB(P=0.01).Conclusions:ACP comprises three molecular subtypes with distinct

关键词： Craniopharyngioma Central nervous system tumor Precision medicine beta Catenin Proto-Oncogene Proteins B-raf

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Clinical efficacy and identification of factors confer resistance to afatinib(tyrosine kinase inhibitor)in EGFR-overexpressing esophageal squamous cell carcinoma

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3130-3140页

作者： Yanni Wang Chang Liu Huan Chen Xi Jiao Yujiao Wang Yanshuo Cao Jian Li Xiaotian Zhang Yu Sun Na Zhuo Fengxiao Dong Mengting Gao Fengyuan Wang Liyuan Dong Jifang Gong Tianqi Sun Wei Zhu Henghui Zhang Lin Shen Zhihao Lu Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital and InstituteBeijingChina Genecast Biotechnology Co. LtdWuxiPR China State Key laboratory of Holistic Integrative Management of gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital and InstituteBeijingChina Key laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of PathologyPeking University Cancer Hospital and InstituteBeijingChina Precision Scientific(Beijing)Co. Ltd.BeijingChina Generulor Company Bio-X Lab ZhuhaiGuangdongChina Biomedical Innovation Center Beijing Shijitan HospitalCapital Medical UniversityBeijingChina Beijing Key laboratory for Therapeutic Cancer Vaccines Beijing Shijitan HospitalCapital Medical UniversityBeijingChina

Epidermal growth factor receptor(EGFR)is reportedly overexpressed in most esophageal squamous cell carcinoma(ESCC)patients,but anti-EGFR treatments offer limited survival *** preclinical data showed the promising antitumor activity of afatinib in EGFR-overexpressing *** proof-of-concept,phase II trial assessed the efficacy and safety of afatinib in pretreated metastatic ESCC patients(n=41)with EGFR overexpression(NCT03940976).The study met its primary endpoint,with a confirmed objective response rate(ORR)of 39%in 38 efficacy-evaluable patients and a median overall survival of 7.8 months,with a manageable toxicity *** analysis of pretreatment tumors revealed that neurotrophic receptor tyrosine kinase 2(NTRK2)was negatively associated with afatinib sensitivity and might serve as a predictive biomarker,irrespective of EGFR ***,knocking down or inhibiting NTRK2 sensitized ESCC cells to afatinib *** study provides novel findings on the molecular factors underlying afatinib resistance and indicates that afatinib has the potential to become an important treatment for metastatic ESCC patients.

关键词： esophageal squamous expressing

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From macroautophagy to mitophagy:Unveiling the hidden role of mitophagy in gastrointestinal disorders

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World Journal of Gastroenterology 2024年第23期30卷 2934-2946页

作者： Duo-Lun Gao Meng-Ran Lin Nan Ge Jin-Tao Guo Fan Yang Si-Yu Sun Department of Gastroenterology Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic TechniquesShengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina

In this editorial,we comment on an article titled“Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases”,which was published in a recent issue of the World Journal of *** focused on the statement that“autophagy is closely related to the digestion,secretion,and regeneration of gastrointestinal cells”.With advancing research,autophagy,and particularly the pivotal role of the macroautophagy in maintaining cellular equilibrium and stress response in the gastrointestinal system,has garnered extensive ***,the significance of mitophagy,a unique selective autophagy pathway with ubiquitin-dependent and independent variants,should not be *** recent decades,mitophagy has been shown to be closely related to the occurrence and development of gastrointestinal diseases,especially inflammatory bowel disease,gastric cancer,and colorectal *** interplay between mitophagy and mitochondrial quality control is crucial for elucidating disease mechanisms,as well as for the development of novel treatment *** the pathogenesis behind gastrointestinal diseases and providing individualized and efficient treatment for patients are subjects we have been *** article reviews the potential mechanism of mitophagy in gastrointestinal diseases with the hope of providing new ideas for diagnosis and treatment.

关键词： Mitophagy gastrointestinal diseases Parkin Autophagic receptor Colorectal cancer Gastric cancer Inflammatory bowel disease

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Notoginsenoside Ft1 inhibits colorectal cancer growth by increasing CD8^(+)T cell proportion in tumor-bearing mice through the USP9X signaling pathway

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Chinese Journal of Natural Medicines 2024年第4期22卷 329-340页

作者： FENG Yutao LI Yuan MA Fen WU Enjiang CHENG Zewei ZHOU Shiling WANG Zhengtao YANG Li SUN Xun ZHANG Jiwei Shanghai Key laboratory of Compound Chinese Medicines The MOE Key Laboratory for Standardization of Chinese MedicinesInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China gastrointestinal surgery Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China

The management of colorectal cancer(CRC)poses a significant challenge,necessitating the development of innovative and effective *** research has shown that notoginsenoside Ft1(Ng-Ft1),a small molecule,markedly inhibits subcutaneous tumor formation in CRC and enhances the proportion of CD8^(+)T cells in tumor-bearing mice,thus restraining tumor *** into the mechanism revealed that Ng-Ft1 selectively targets the deubiquitination enzyme USP9X,undermining its role in shieldingβ-*** leads to a reduction in the expression of downstream effectors in the Wnt signaling *** findings indicate that Ng-Ft1 could be a promising small-molecule treatment for CRC,working by blocking tumor progression via the Wnt signaling pathway and augmenting CD8^(+)T cell prevalence within the tumor environment.

关键词： Notoginsenoside Ft1 Colorectal cancer CD8^(+)T cell Ubiquitin-specific peptidase 9 X-linked β-Catenin Wnt

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Current status of early gastric cancer screening research

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Cancer Biology & Medicine 2024年第3期21卷 218-222页

作者： Can Hu Li Yuan Xiangdong Cheng Department of Gastric surgery Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiang 310022China Key laboratory of Prevention Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang ProvinceHangzhou 310022China Zhejiang Provincial Research Center for Upper gastrointestinal Tract Cancer Zhejiang Cancer HospitalHangzhou 310022China

Gastric cancer is a predominant threat to the health and well-being of China's residents. Data from the World Health Organization(WHO) in 2020 revealed that gastric cancer in China notably accounted for 44.0% of new c... 详细信息

关键词： cancer Gastric gastric

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Colonoscopy plays an important role in detecting colorectal neoplasms in patients with gastric neoplasms

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World Journal of gastrointestinal Oncology 2024年第1期16卷 133-143页

作者： Xu-Rui Liu Ze-Lin Wen Fei Liu Zi-Wei Li Xiao-Yu Liu Wei Zhang Dong Peng Department of gastrointestinal Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of gastrointestinal Surgery Yongchuan Hospital of Chongqing Medical UniversityChongqing 402160China

BACKGROUND Gastric cancer(GC)and colorectal cancer(CRC)are the fifth and third most common cancer worldwide,***,GC is reported to have a potential predictive value for CRC,especially for advanced *** To evaluate the necessity of colonoscopy for gastric neoplasm(GN)*** Four databases,including PubMed,EMBASE,the Cochrane Library,and Ovid,were used to perform the search strategy on May 2,*** prevalence of colorectal neoplasms(CRN)and baseline characteristics were compared between the neoplasm group and the control *** variables are expressed as the mean difference and standard *** of categorical variables in the two groups are expressed as odds ratios(OR)and 95%confidence intervals(95%CIs).Subgroup analysis according to different kinds of GNs was conducted for more in-depth *** results of this study are represented by forest *** bias was evaluated by a funnel *** data analyses were performed by STATA SE 16.0 *** A total of 3018 patients with GNs and 3905 healthy controls(age and sex matched)were enrolled for *** comparing the prevalence of CRNs between the two groups,CRNs were detected significantly more frequently in GN patients than in controls(OR=1.69,95%CI=1.28 to 2.23,I^(2)=85.12%,P=0.00),especially in patients with GC(OR=1.80,95%CI=1.49 to 2.18,I^(2)=25.55%,P<0.1).Moreover,other risk factors including age(OR=1.08,95%CI=1.00 to 1.17,I^(2)=90.13%,P=0.00)and male sex(OR=2.31,95%CI=1.26 to 4.22,I^(2)=87.35%,P=0.00),were related to the prevalence of *** patients in the GN group,body mass index(BMI,OR=0.88,95%CI=0.80 to 0.98,I^(2)=0.00%,P=0.92)and smoking(OR=1.03,95%CI=1.01 to 1.05,I^(2)=0.00%,P=0.57)were protective and risk factors for CRNs,*** Patients are recommended to undergo colonoscopy when diagnosed with GNs,especially GC patients with a low BMI and a history of smoking.

关键词： Gastric neoplasm Gastric cancer Colorectal neoplasm Colonoscopy

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Hypoxia-induced nuclear localization of ubiquinol-cytochrome-c reductase complex assembly factor 3(UQCC3)in hepatocellular carcinoma

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3173-3175页

作者： Yun Yang Yinhao Wei Yiying Sun Yong Zhou Hanshuo Yang Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Department of gastrointestinal Surgery West China HospitalSichuan UniversityChengdu 610041China

Dear Editor,The mitochondrion plays crucial roles in cellular energy generation and signaling *** studies have shown that nuclear-encoded mitochondrial proteins translocate into the nucleus to regulate cell function a... 详细信息

关键词： hepatocellular retrograde communicate

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Pylorus-preserving gastrectomy for early gastric cancer

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World Journal of gastrointestinal Oncology 2024年第3期16卷 653-658页

作者： Ke-Kang Sun Yong-You Wu Department of gastrointestinal Surgery The Affiliated Kunshan Hospital to Jiangsu UniversitySuzhou 215300Jiangsu ProvinceChina Department of gastrointestinal Surgery The Second Affiliated Hospital of Soochow UniversitySuzhou 215008Jiangsu ProvinceChina

Pylorus-preserving gastrectomy(PPG)has been widely accepted as a function-preserving gastrectomy for middle-third early gastric cancer(EGC)with a distal tumor border at least 4 cm proximal to the *** procedure essentially preserves the function of the pyloric sphincter,which requires to preserve the upper third of the stomach and a pyloric cuff at least 2.5 *** suprapyloric and infrapyloric vessels are usually preserved,as are the hepatic and pyloric branches of the vagus *** with distal gastrectomy,PPG has significant advantages in preventing dumping syndrome,body weight loss and bile reflux *** postoperative complications after PPG have reached an acceptable *** can be considered a safe,effective,and superior choice in EGC,and is expected to be extensively performed in the future.

关键词： Gastric cancer Pylorus-preserving gastrectomy Oncological safety Gastric stasis

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Role of oncogenic long noncoding RNA KCNQ1OT1 in colon cancer

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Oncology Research 2024年第3期32卷 585-596页

作者： GANG LIU LEI SHI BIN WANG ZEHUI WU HAIYUAN ZHAO TIANYU ZHAO LIANGHUI SHI Department of gastrointestinal Surgery First ffiliated Hospital of Wannan Medical CollegeWuhu241001China Chongqing Key laboratory of Oral Diseases and Biomedical Sciences Stomatological Hospital of Chongqing Medical UniversityChongqing401147China

The role of lncRNA KCNQ1 opposite strand/antisense transcript 1(KCNQ1OT1)in colon cancer involves various tumorigenic processes and has been studed ***,the mechanism by which it promotes colon cancer remains *** vector pSEB61 was retroftted in established HCT116 siKCN and SW480-siKCN cells to silence KCNQ1 *** proliferation was measured using CCK8 assay,and flow cytometry(FCM)detected cell cydle *** sequencing(RNA Seq)analysis showed differentially expressed genes(DEGs).Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were carried out to analyze enriched functions and signaling ***-qPCR,immunofluorescence,and western blotting were carried out to validate downstream gene *** effects of tumorigenesis were evaluated in BALB/c nude mice by tumor *** data revealed that the silencing of KONQ1OT1 in HCT116 and SW480 cells slowed cell growth and decreased the number of cells in the G2/M ***-Seq analysis showed the data of DEGs enriched in various GO and KEGG pathways such as DNA replication and cell *** qPCR,immunofluorescence,and western blotting confirmed downstream CCNE2 and PCNA gene ***116 siKCN cells signifcantly suppressed tumorigenesis in BALB/c nude *** study suggests that lncRNA KCNQ1OT1 may provide a promising therapeutic strategy for colon cancer.

关键词： lncRNA KCNQ1OT1 Colon cancer HCT116 cells Tumorigenesis

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RP11-789C1.1 inhibits gastric cancer cell proliferation and accelerates apoptosis via the ATR/CHK1 signaling pathway

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中华医学杂志(英文版) 2024年第15期137卷 1835-1843页

作者： Liu Wenwei Feng Wei Zhang Yongxin Lei Tianxiang Wang Xiaofeng Qiao Tang Chen Zehong Song Wu Digestive Diseases Center The Seventh Affiliated Hospital of Sun Yat-sen University Shenzhen Guangdong China Department of gastrointestinal Surgery The First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China laboratory of General Surgery The First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China Department of gastrointestinal Surgery The Third Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong China

Background: Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully ***: We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC *** vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of ***: Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxiatelangiectasia mutated and Rad3 related (ATR), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin ***: In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.

关键词： Long non-coding RNA RP11-789C1.1 Stomach neoplasms ATR CHK1 Oxaliplatin

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