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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

Science China Life Sciences 2025年第1期68卷 144-157页

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 LaboratoryPeking University Cancer Hospital & Institute Department of gastrointestinal Cancer center Peking University Cancer Hospital & Institute Department of Liver surgery & Transplantation Liver Cancer InstituteZhongshan HospitalFudan 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 ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking 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.

关键词： extrachromosomal DNA cancer therapy tumor heterogeneity drug resistance tumor evolution

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surgery for gastrointestinal malignant melanoma:Experience from surgical training center

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World Journal of Gastroenterology 2010年第6期16卷 745-748页

作者： Thawatchai Akaraviputh Satida Arunakul Varut Lohsiriwat Cherdsak Iramaneerat Atthaphorn Trakarnsanga Division of General surgery Department of SurgeryFaculty of Medicine Siriraj HospitalMahidol University

AIM:To characterize clinical features,surgery,outcome,and survival of malignant melanoma(MM) of the gastrointestinal(GI) tract in a surgical training center in Bangkok,Thailand. METHODS:A retrospective review was performed for all patients with MM of the GI tract treated at our institution between 1997 and 2007. RESULTS:Fourteen patients had GI involvement either in a metastatic form or as a primary melanoma. Thirteen patients with sufficient data were reviewed. The median age of the patients was 66 years(range:32-87 years) .Ten patients were female and three were *** patients had primary melanomas of the anal canal,stomach and the sigmoid colon(5,1 and 1 cases,respectively) .Seven patients underwent curative resections:three abdominoperineal resections,two wide local excisions,one total gastrectomy andone *** patients had distant metastatic lesions at the time of diagnosis,which made curative resection an inappropriate *** who underwent curative resection exhibited a longer mean survival time(29.7 mo,range:10-96 mo) than did patients in the palliative group(4.8 mo,P=0.0006) . CONCLUSION:GI MM had an unfavorable prognosis,except in patients who underwent curative resection(53.8%of cases) ,who had a mean survival of 29.7 mo.

关键词： Melanoma gastrointestinal tract Neoplasm metastasis

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First-line endoscopic treatment with over-the-scope clips significantly improves the primary failure and rebleeding rates in high-risk gastrointestinal bleeding: A single-center experience with 100 cases

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World Journal of Gastroenterology 2016年第41期22卷 9162-9171页

作者： Hans-Jürgen Richter-Schrag Torben Glatz Christine Walker Andreas Fischer Robert Thimme center of Interdisciplinary gastrointestinal Endoscopy Department of Medicine II Medical Center-University of Freiburg Faculty of Medicine University of Freiburg Department of General and Visceral surgery Medical Center-University of Freiburg Faculty of Medicine University of Freiburg

AIM To evaluate rebleeding, primary failure(PF) and mortality of patients in whom over-the-scope clips(OTSCs) were used as first-line and second-line endoscopic treatment(FLET, SLET) of upper and lower gastrointestinal bleeding(UGIB, LGIB).METHODS A retrospective analysis of a prospectively collected database identified all patients with UGIB and LGIB in a tertiary endoscopic referral center of the University of Freiburg, Germany, from 04-2012 to 05-2016(n= 93) who underwent FLET and SLET with OTSCs. The complete Rockall risk scores were calculated from patients with UGIB. The scores were categorized as gastrointestinal bleeding compared to SLET. The type of treatment determines the success of primary hemostasis or primary failure.

关键词： gastrointestinal bleeding Rockall risk score Over-the-scope clip First-line endoscopic treatment Second-line endoscopic treatment

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Hsa-miR-214-3p inhibits breast cancer cell growth and improves the tumor immune microenvironment by downregulating B7H3

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Oncology Research 2025年第1期33卷 103-121页

作者： YAN LU KANG WANG YUANHONG PENG MENG CHEN LIN ZHONG LUJI HUANG FU CHENG XINDAN SHENG XIN YANG MANZHAO OUYANG GEORGE A.CALIN ZHIWEI HE China-America Cancer Research Institute Guangdong Medical UniversityDongguan523808China GCP center Shunde HospitalSouthern Medical University(The First People’s Hospital of Shunde Foshan)Shunde528300China Department of gastrointestinal surgery Shunde HospitalSouthern Medical University(The First People’s Hospital of Shunde Foshan)Shunde528300China The Second School of Clinical Medicine Southern Medical UniversityGuangzhou510080China Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Department of Oncology Shunde HospitalSouthern Medical University(The First People’s Hospital of Shunde Foshan)Shunde528300China

Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),and cytotoxic T-lymphocyte antigen-4(CTLA-4)show limited clinical efficacy in many breast cancers.B7H3 has been widely reported as an immunosuppressive molecule,but its immunological function in breast cancer patients remains ***:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program(TCGA)and the Gene Expression Omnibus(GEO)*** were selected using the TarBase,miRTarBase,and miRBase *** regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays,which identified the specific action sites of *** expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR(qPCR).In vitro experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and ***,the regulatory impact of hsa-miR-214-3p on B7H3 was ***-linked immunosorbent assays(ELISA)and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells(PBMCs)on immune cells and associated ***:In breast cancer tissues,the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p,as well as with the regulatory effects on breast cancercell ***-miR-214-3p was found to inhibit breast cancer cell growth by downregulating ***,our research identified,for the first time,two binding sites for hsa-miR-214-3p on the 3’UTR of B7H3,both of which exert similar effects ***-culture experiments revealed that hsamiR-214-3p

关键词： Breast cancer B7H3 Hsa-miR-214-3p Immunotherapy

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Analysis of the delayed approach to the management of infected pancreatic necrosis

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World Journal of Gastroenterology 2011年第3期17卷 366-371页

作者： Nilesh Doctor Sujith Philip Vidhyachandra Gandhi Maharra Hussain Savio G Barreto Department of gastrointestinal surgery Jaslok Hospital and Research Center Department of surgery Bhatia Hospital Department of General and Digestive surgery Flinders Medical Center

AIM: To analyze outcomes of delayed single-stage necrosectomy after early conservative management of patients with infected pancreatic necrosis (IPN) associated with severe acute pancreatitis (SAP). METHODS: Between January 1998 and December 2009, data from patients with SAP who developed IPN and were managed by pancreatic necrosectomy were analyzed. RESULTS: Fifty-nine of 61 pancreatic necrosectomies were performed by open surgery and 2 laparoscopically. In 55 patients, single-stage necrosectomy could be performed (90.2%). Patients underwent surgery at a median of 29 d (range 13-46 d) after diagnosis of acute pancreatitis. Sepsis and multiple organ failure accounted for the 9.8% mortality rate. Pancreatic fistulae (50.8%) predominantly accounted for the morbidity. The median hospital stay was 23 d, and the median interval for return to regular activities was 110 ***: This series supports the concept of delayed single-stage open pancreatic necrosectomy for IPN. Advances in critical care, antibiotics and interventional radiology have played complementary role in improving the outcomes.

关键词： Necrosectomy Infected necrosis Pancreas Severe acute pancreatitis Inflammation

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Association between COX-2-1195G>A polymorphism and gastrointestinal cancer risk: A meta-analysis

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World Journal of Gastroenterology 2017年第12期23卷 2234-2245页

作者： Xiao-Wei Zhang Jun Li Yu-Xing Jiang Yu-Xiang Chen Department of gastrointestinal and Vascular surgery Deyang People's Hospital Department of General surgery and center for Minimal Invasive gastrointestinal surgery Southwest Hospital Third Military Medical University

AIM To perform a meta-analysis to investigate the association between cyclooxygenase-2(COX-2)-1195G>A gene polymorphism and gastrointestinal cancers. METHODS Publications related to the COX-2-1195G>A gene polymorphism and gastrointestinal cancers published before July 2016 were retrieved from Pub Med, EMBASE, Web of Science, China Biological Medicine Database, China National Knowledge Infrastructure, and CQVIP Database. Meta-analysis was performed using Stata11.0 software. The strength of the association was evaluated by calculating the combined odds ratios(ORs) and the corresponding 95%CIs. The retrieved publications were excluded or included one by one for sensitivity analysis. In addition, the funnel plot, Begg's rank correlation test, and Egger's linear regression method were applied to analyse whether the included publications had publication bias. RESULTS A total of 24 publications related to the COX-2-1195G>A gene polymorphism were included, including 28 studies involving 11043 cases and 18008 controls. The meta-analysis results showed that the COX-2-1195G>A gene polymorphism significantly correlated with an increased risk of gastrointestinal cancers, particularly gastric cancer(A vs G: OR = 1.35; AA/AG vs GG: OR = 1.54; AA vs GG/AG: OR = 1.43; AA vs GG: OR = 1.80; AG vs GG: OR = 1.35). Compared to the Caucasian population in America and Europe, the COX-2-1195G>A gene polymorphism in the Asian population(A vs G: OR = 1.30; AA/AG vs GG: OR= 1.50; AA vs GG/AG: OR = 1.35; AA vs GG: OR = 1.71; AG vs GG: OR = 1.37) significantly increased gastrointestinal cancer risk. The sensitivity analysis(P A gene polymorphism might be a potential risk factor for gastrointestinal cancers. Further validation by a large homogeneous study is warranted.

关键词： COX-2 -1195G>A Polymorphism Meta-analysis gastrointestinal cancer

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Depression and anxiety levels in therapy-nave patients with inflammatory bowel disease and cancer of the colon

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World Journal of Gastroenterology 2007年第3期13卷 438-443页

作者： Branislav R Filipovi Branka F Filipovi Mirko Kerkez Nikola Milini Tomislav Ran■elovi Institute of Anatomy School of Medicine Belgrade Clinical and Hospital center "Be■anijska Kosa" Department of Gastroenterology Belgrade Serbia Department of gastrointestinal surgery Clinical Center of Serbia Serbia Department of gastrointestinal surgery Clinical and Hospital Center "Be■anijska Kosa" Belgrade Serbia

AIM: To assess whether depression and anxiety are more expressed in patients with the first episode of inflammatory bowel disease (IBD) than in individuals with newly discovered cancer of the colon (CCa). METHODS: A total of 32 patients with IBD including 13 males and 19 females, aged 27 to 74, and 30 patients with CCa including 20 males and 10 females, aged 39-78, underwent a structured interview, which comprised Hamilton’s Depression Rating Inventory, Hamilton’s Anxiety Rating Inventory and Paykel’s Stressful Events Rating Scale. RESULTS: Patients of the IBD group expressed both depression and anxiety. Depressive mood, sense of guilt, psychomotor retardation and somatic anxiety were also more pronounced in IBD patients. The discriminant function analysis revealed the total depressive score was of high importance for the classification of a newly diagnosed patient into one of the groups. CONCLUSION: Newly diagnosed patients with IBD have higher levels of depression and anxiety. Moreover, a psychiatrist in the treatment team is advisable from the beginning.

关键词： Crohn's disease Ulcerative colitis Colon cancer Mood disorder

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Management of splenic artery aneurysm associated with extrahepatic portal vein obstruction

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Hepatobiliary & Pancreatic Diseases International 2012年第3期11卷 330-333页

作者： Pramod Kumar Mishra Sundeep Singh Saluja Ashok K Sharma Premanand Pattnaik Department of gastrointestinal surgery surgery GB Pant Hospital Department of gastrointestinal surgery and Department of Radiology surgery GB Pant Hospital Department of gastrointestinal surgery GB Pant Hospital

BACKGROUND: Splenic artery aneurysms although rare are clinically significant in view of their propensity for spontaneous rupture and life-threatening bleeding. While portal hypertension is an important etiological factor, the majority of reported cases are secondary to cirrhosis of the liver. We report three cases of splenic artery aneurysms associated with extrahepatic portal vein obstruction and discuss their management. METHODS: The records of three patients of splenic artery aneurysm associated with extrahepatic portal vein obstruction managed from 2003 to 2010 were reviewed retrospectively. The clinical presentation, surgical treatment and outcome were analyzed. RESULTS: The aneurysm was >3 cm in all patients. The clinical symptoms were secondary to extrahepatic portal vein obstruction (hematemesis in two, portal biliopathy in two) while the aneurysm was asymptomatic. Doppler ultrasound demonstrated aneurysms in all patients. A proximal splenorenal shunt was performed in two patients with excision of the aneurysm in one patient and ligation of the aneurysm in another one. The third patient had the splenic vein replaced by collaterals and hence underwent splenectomy with aneurysmectomy. All patients had an uneventful post-operative course. CONCLUSIONS: Splenic artery aneurysms are associated with extrahepatic portal vein obstruction. surgery is the mainstay of treatment. Although technically difficult, it can be safely performed in an experienced center with minimal morbidity and good outcome.

关键词： splenic artery aneurysm extrahepatic portal vein obstruction portal hypertension proximal splenorenal shunt

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Minilaparotomy to rectal cancer has higher overall survival rate and earlier short-term recovery

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World Journal of Gastroenterology 2012年第37期18卷 5289-5294页

作者： Xiao-Dong Wang Ming-Jun Huang Chuan-Hua Yang Ka Li Li Li gastrointestinal surgery center West China Hospital in Sichuan University Chengdu 610041 Sichuan Province China

AIM： To report our experience using mini-laparotomy for the resection of rectal cancer using the total meso- rectal excision （TME） technique, METHODS： Consecutive patients with rectal cancer who underwent anal-colorectal surgery at the authors＇ hospital between March 2001 and June 2009 were included, In total, 1415 patients were included in the study, The cases were divided into two surgical proce- dure groups （traditional open laparotomy or mini-lap- arotomy）, The mini-laparotomy group was defined as having an incision length ≤ 12 cm. Every patient un- derwent the TME technique with a standard operation performed by the same clinical team. The multimodal preoperative evaluation system and postoperative fast track were used. To assess the short-term outcomes, data on the postoperative complications and recovery functions of these cases were collected and analysed. The study included a plan for patient follow-up, to ob- tain the long-term outcomes related to 5-year survival and local recurrence. RESULTS： The mini-laparotomy group had 410 pati- ents, and 1015 cases underwent traditional laparoto- my. There were no differences in baseline characteris- tics between the two surgical procedure groups. The overall 5-year survival rate was not different between the rnini-laparotorny and traditional laparotorny groups （80.6% vs 79.4%, P = 0.333）, nor was the 5-year local recurrence （1.4% vs 1.5%, P = 0.544）. However, 1-year mortality was decreased in the rnini-laparotorny group compared with the traditional laparotorny group （0% vs 4.2%, P 〈 0.0001）. Overall 1-year survival rates were 100% for Stage Ⅰ, 98.4% for Stage Ⅱ, 97.1% for Stage Ⅲ, and 86.6% for Stage Ⅳ. Local recurrence did not differ between the surgical groups at 1 or 5 years. Local recurrence at 1 year was 0.5% （2 cases） for mini-laparotorny and 0.5% （5 cases） for traditional laparotorny （P = 0.670）. Local recurrence at 5 years was 1.5% （6 cases） for mini-laparotorny and 1.4% （14 cases） for traditional laparotorn

关键词： Rectal neoplasm Mini-laparotomy Survival Total mesorectal excision

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Diagnosis and management of choledochal cyst: 20 years of single center experience

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World Journal of Gastroenterology 2014年第22期20卷 7061-7066页

作者： Nabil Gadelhak Ahmed Shehta Hosam Hamed Department of surgery Gastrointestinal Surgical CenterMansoura UniversityManoura 35516DakahleyyaEgypt

We report the first case series from Africa and the Middle East on choledochal cyst, a disease which shows significant geographical distribution with high incidence in the Asian population. In this study, the epidemiological data of the patients are presented and analyzed. Attention was paid to diagnostic imaging and its accuracy in the diagnosis and classification of choledochal cyst. Most cases of choledochal cyst disease have type I and IV-A cysts according to the Todani classification system, which support the etiological theories of choledochal cyst, especially Babbitt’s theory of the anomalous pancreaticobiliary duct junction, which are clearly stated. The difficulties and hazards of surgical management and methods used to avoid operative complications are clarified. Early and late postoperative complications are also included. This study should be followed by multicenter studies throughout Egypt to help assess the incidence of choledochal cysts in one of the largest populations in Africa and the Middle East.

关键词： Choledochal cyst Hepatic cyst Hepaticojejunostomy Caroli disease Hepatectomy

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