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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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Mechanism of metastasis by membrane type 1-matrix metalloproteinase in hepatocellular carcinoma

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World Journal of Gastroenterology 2005年第40期11卷 6269-6276页

作者： Ying-Chi Ip Siu-Tim Cheung Ka-Ling Leung Sheung-Tat Fan Centre for the Study of liver disease and department of Surgery

AIM To investigate the precise role of membrane type 1-matrix metalloproteinase （NTI-NNP） in hepatocellular carcinoma （HCC） metastasis. METHODS- Human HCC cells Hep3B with overexpression of MTT-MMP were established by stable transfection, and compared with control cells carrying the empty vector. Cells were examined in vivo for their differences in the metastatic ability of athymic nude mice, and analyzed in vito for their differences in invasion ability by invasion chamber coated with Matrigel, adhesion towards collagen I and migration through culture chamber. Cell proliferation and apoptosis in adherent and suspension status were evaluated by MTr and flow cytometry analysis. RESULTS We found that overexpression of MT1-MMP could increase intrahepatic metastasis in nude mice with orthotopic implantation of HCC cells （incidence of 100% [MT1-MMP transfectants] vs 40% [vector control transfectants], P〈0.05）. NT1-MMP could also enhance cell invasion through Natrigel （107.7 vs 39.3 cells/field, P〈0.001）, adhesion towards matrix （0.30 vs 0.12 absorbance unit at 540 nm, P〈0.001）, cell migration （89.3 vs 39.0 cells/field, P〈0.001）, and cell proliferation （24.3 vs 40.5 h/doubling, P〈0.001）. We also observed that NTI-NNP supported cell survival （71.4% vs 23.9%, P〈0.001） with reduced apoptosis （43.7% vs51.0%, P〈0.05） in an attachment-free environment. CONCLUSION： MT1-MMP overexpression could enhance metastasis. In addition to its active role in matrix degradation during tumor invasion, MT1-MMP enhances tumor cell survival upon challenge of detachment, which is important during metastasis when cells enter the circulation.

关键词： MT1-MMPIMMP14 liver cancer Invasion Metastasis

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Optimization of dosage ratio of chlorogenic acid and gardenia glycosides in the treatment of rats with fatty liver disease induced by high-fat feed

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Journal of Traditional Chinese Medicine 2016年第5期36卷 683-688页

作者： Liang Huiqing Yang Jiaen Tang Jinmo Wu Chuncheng Li Hongshan Chen Shaodong department of liver disease Xiamen Hospital of Traditional Chinese Medicine department of liver disease Ningbo No. 2 Hospital department of Traditional Chinese Medicine Medical College of Xiamen University

OBJECTIVE: To investigate the optimal dosage ratio of chlorogenic acid and gardenia glycosides in treating the rates with fatty liver disease induced by high-fat ***: A rat model of non-alcoholic fatty liver disease(NAFLD) was established by using a high-fat diet. According to mathematical model "uniform design", varying doses of chlorogenic acid and gardenia glycosides have been combined to form 6 medications for the treatment of *** were then taken to observe pathological changes of the liver tissue(HE staining); changes in the fat metabolism pathway e.g. triglyceride(TG)and free fatty acid(FFA) content; alterations in liver function, i.e. serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST) activity; and differences in Malondialdehyde(MDA) and superoxide dismutase(SOD) content in the liver tissue. Multiple regression analysis was conducted to test the optimal dosage ratio of chlorogenic acid and gardenia ***: Fatty degeneration and vacuole-like changes of different degrees occurred in hepatic cells of the model group. Markers for fat metabolism, serum ALT and AST activities, and expression of MDA in liver tissue significantly increased, while SOD decreased. Combination of 90 mg chlorogenic acid and 90 mg Gardenia glycosides was the optimal dosage ratio of chlorogenic acid and gardenia glycosides in the treatment of rats with fatty liver induced by high-fat ***: Chlorogenic acid of 90 mg plus gardenia glycosides of 90 mg was the best combination in the treatment of fatty liver disease in rats induced by high-fat feed.

关键词： Chlorogenic acid Gardenia glycosides Non-alcoholic fatty liver disease Uniform design method Dose optimization

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^(14)C-urea breath test in patients undergoing anti-tuberculosis therapy

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World Journal of Gastroenterology 2005年第11期11卷 1712-1714页

作者： Sayed Amir Mirbagheri Amir Ali Sohrabpour Mehrdad Hasibi Babak Moghimi Mehdi Mohamadnejad department of Gastroenterology Digestive disease Research Center department of Infectious diseases GI and liver disease Research Center

AIM: Urea breath test (UBT) is a non-invasive diagnostic test for detecting the presence of Helicobacter pylori(H pylori).In this study we evaluated the effect of anti-tuberculosis therapy on the results of ***: Patients, with the diagnosis of tuberculosis (TB) who had a positive UBT at the point of starting antiTB therapy, were included. None had a history of peptic ulcer disease or had taken antibiotics, bismuth compounds and/or PPI in the previous month, 14C-UBT was repeated at the end of the second month and the end of treatment period and one month after completion of treatment ***: Thirty-five patients (23 males) were enrolled.14C-UBT was negative in all 35 patients (100%) at the end of the second month and remained negative in 30cases (85.7%) at the end of the treatment course. One month after completion of treatment course, UBT remained negative in 13 patients (37.1%).CONCLUSION: Our report underscores the need for caution while interpreting urea breath test results in patients undergoing anti-TB therapy. Furthermore, the combination of drugs used in this study resulted in H pylori eradication in a minority of patients.

关键词： Urea breath test (UBT) Helicobacter pylori Tuberculosis

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Integration of perioperative features and intragraft TCF7L2 expression to predict lipid metabolic disorder in liver transplant recipients

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Science China Life Sciences 2025年第1期68卷 297-299页

作者： Junbin Zhou Rongli Wei Guanghan Fan Zhengxing Lian Xuanyu Zhang Linsong Tang Zhetuo Qi Haiyang Xie Shusen Zheng Qiang Wei Xiao Xu department of Hepatobiliary and Pancreatic Surgery People's Hospital of LishuiAffiliated Lishui Hospital of Wenzhou Medical UniversityThe First Affiliated Hospital of Lishui University NHFPC Key Laboratory of Combined Multi-Organ Transplantation Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryHangzhou First People's Hospital department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of Medicine department of Urology The Second Affiliated HospitalZhejiang University School of Medicine department of Hepatobiliary and Pancreatic Surgery Department of Liver TransplantationShulan (Hangzhou) Hospital Hangzhou Medical College Zhejiang University School of Medicine

Dear Editor, liver transplantation(LT) is the only curative therapy for patients with endstage liver disease(He et al., 2023; Ling et al., 2022). Post-transplant hypertriglyceridemia(PTHT), which has an incidence of up to 32.8% in 6 months after LT, is one of the major post-transplant complications(Toshima et al., 2020).

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Influenza virus H1N1 induced apoptosis of mouse astrocytes and the effect on protein expression

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Asian Pacific Journal of Tropical Medicine 2014年第7期7卷 572-575页

作者： Xu-Dong Pei Yu-Feng Zhai Huai-Hong Zhang department of Infection and liver disease Nanyang Central Hospital

Objective:To investigate the effects of influenza A virus H1N1 infection on the proliferation and apoptosis of mouse astrocytes cells and its protein ***:After mouse astrocytes was infected with purified influenza A virus H1N1 in vitro,viral integration and replication status of the cells were detected by RT-PCR assay,cell proliferation and apoptosis was determined by MTT method and flow cytometry,*** protein expression was delected by Western ***:Agarose gel electrophoresis showed H1N1 virus can infect astrocytes and can be *** staining showed H1N1 virus infection can inhibit the proliferation of mouse astrocytes,which makes cell viability decreased *** cytometry showed that the proportion of Annein V staining positive vascular endothelial cells in the influenza A virus group was significantly higher than that in the control *** blot analysis showed after24 h and 32 h of infection,there were cells caspase-3 protein and the expression of its active form(lysed caspase-3 protein)*** proportion of Bax/Bcl-2 also ***:Influenza A virus can infect human vascular endothelial cells and proliferation and it can induce apoptosis of endothelial cells.

关键词： Influenze virus H1N1 Apoptosis

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Estimating liver weight of adults by body weight and gender

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World Journal of Gastroenterology 2006年第14期12卷 2217-2222页

作者： See Ching Chan Chi Leung Liu Chung Mau Lo Banny K Lam Evelyn W Lee Yik Wong Sheung Tat Fan Centre for the Study of liver disease Department of Surgery The University of Hong Kong Pokfulam Hong Kong China Centre for the Study of liver disease Department of Radiology The University of Hong Kong Pokfulam Hong Kong China

AIM： To estimate the standard liver weight for assessing adequacies of graft size in live donor liver transplantation and remnant liver in major hepatectomy for cancer. METHODS： In this study, anthropometric data of body weight and body height were tested for a correlation with liver weight in 159 live liver donors who underwent donor right hepatectomy including the middle hepatic vein. liver weights were calculated from the right lobe graft weight obtained at the back table, divided by the proportion of the right lobe on the computed tomography. RESULTS： The subjects, all Chinese, had a mean age of 35.8 ± 10.5 years, and a female to male ratio of 118：41. The mean volume of the right lobe was 710.14 ±131.46 mL and occupied 64.55%±4.47% of the whole liver on computed tomography. Right lobe weighed 598.90±117.39 g and the estimated liver weight was 927.54 ± 168.78 g. When body weight and body height were subjected to multiple stepwise linear regression analysis, body height was found to be insignificant. Females of the same body weight had a slightly lower liver weight. A formula based on body weight and gender was derived： Estimated standard liver weight （g）=218＋BW （kg）× 12.3＋gender×51 （R^2 = 0.48）（female=0, male= 1）. Based on the anthropometric data of these 159 subjects, liver weights were calculated using previously published formulae derived from studies on Caucasian, .lapanese, Korean, and Chinese. All formulae overestimated liver weights compared to this formula. The Japanese formula overestimated the estimated standard liver weight （ESLW） for adults less than 60 ***： A formula applicable to Chinese males and females is available. A formula for individual races appears necessary.

关键词： Estimated standard liver weight liver tranplantation

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Skeletal muscle-specific Bambi deletion induces hypertrophy and oxidative switching coupling with adipocyte thermogenesis against metabolic disorders

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Science China Life Sciences 2025年

作者： Xiangping Yao Xudong Mai Ye Tian Yifan Liu Guanghui Jin Ze Li Shujie Chen Xiaoshuang Dai Liujing Huang Zijing Fan Guihua Pan Xiaohan Pan Xiangmin Li Michael C Yu Jia Sun Jingxing Ou Hong Chen Liwei Xie College of Life and Health Sciences Guangdong Industry Polytechnic department of Endocrinology and Metabolism Zhujiang Hospital Southern Medical University State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied MicrobiologyInstitute of Microbiology Guangdong Academy of Sciences Institute of Aging Research Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics School of Medical Technology Guangdong Medical University department of Hepatic Surgery and liver transplantation Center of the Third Affiliated Hospital Organ Transplantation Institute Sun Yat-sen University Organ Transplantation Research Center of Guangdong ProvinceGuangdong province engineering laboratory for transplantation medicine Guangdong Provincial Key Laboratory of Liver Disease Research School of Public Health Xinxiang Medical University BGI Institute of Applied Agriculture BGI-Shenzhen department of Applied Biology and Chemical Technology The Hong Kong Polytechnic University department of Biological Sciences State University of New York at Buffalo department of Internal Medicine Shunde Women and Children's Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan) Guangdong Medical University

Skeletal muscle plays a significant role in both local and systemic energy metabolism. The current investigation aims to explore the role of the Bambi gene in skeletal muscle, focusing on its implications for muscle hypertrophy and systemic metabolism. We hypothesize that skeletal muscle-specific deletion of Bambi induces muscle hypertrophy, improves metabolic performance, and activates thermogenic adipocytes via the reprogramming of progenitor of i WAT, offering potential therapeutic strategies for metabolic syndromes. Leveraging the Chromatin immunoprecipitation(ChIP)-seq and bioinformatics analysis, Bambi gene is shown to be a direct target of HIF2α, which is further confirmed by ChIP-qPCR and promoter luciferase assay. Skeletal muscle-specific Bambi deletion led to significant muscle hypertrophy and improved metabolic parameters, even under high-fat diet conditions. This deletion induced metabolic reprogramming of stromal vascular fractions(SVFs) into thermogenic adipocytes, contributing to systemic metabolic improvements, potentially through the secretory ***, mice with skeletal muscle-specific Bambi deletion demonstrate resistance to high-fat diet-induced metabolic disorders, highlighting a potential therapeutic pathway for metabolic syndrome management. Thus, skeletal muscle-specific deletion of Bambi triggers muscle growth, enhances metabolic performance, and activates thermogenic adipocytes. These findings suggest Bambi as a novel therapeutic target for metabolic syndromes, providing new insights into the interaction between muscle hypertrophy and systemic metabolic improvement. The study underscores the potential of manipulating muscle physiology to regulate whole-body metabolism, offering a novel perspective on treating metabolic disorders.

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Pre-endoscopic screening for Helicobacter pylori and celiac disease in young anemic women

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World Journal of Gastroenterology 2009年第22期15卷 2748-2753页

作者： Lucy Vannella Debora Gianni Edith Lahner Antonio Amato Enzo Grossi Gianfranco Delle Fave Bruno Annibale department of Digestive and liver disease Hospital Sant'AndreaII School of Medicine University Sapienza Center for Thalassemic disease of Rome department of Medical Affair Italian Diagnostic Center department of Digestive and liver disease Hospital Sant’AndreaII School of Medicine University Sapienza

AIM： To evaluate the usefulness of pre-endoscopic serological screening for He//cobacter py/or/ （H py/or/} infection and celiac disease in women aged 〈 50 years affected by iron-deficiency anemia （IDA）. METHODS： One hundred and fifteen women aged 〈 50 years with IDA were tested by human recombinant tissue transglutaminase IgA antibodies （tTG） and anti-H pylori IgG antibodies, tTG and H pylori IgG antibody were assessed using an enzyme-linked immunosorbent assay （ELISA）. All women were invited to undergo upper GI endoscopy. During gastroscopy, biopsies were collected from antrum （n = 3）, gastric body （n = 3） and duodenum （n = 4） in all patients, irrespective of test results. The assessment of gastritis was performed according to the Sydney system and celiac disease was classified by Marsh＇s System. RESULTS： 45.2% women were test-positive： 41 patients positive for H pylori antibodies, 9 patients for tTG and 2 patients for both. The gastroscopy compliance rate of test-positive women was significantly increased with respect to those test- negative （65.4% vs 42.8%; Fisher test P = 0.0239）. The serological results were confirmed by gastroscopy in 100% of those with positive H pylori antibodies, in 50% of those with positive tTG and in 81.5% of test- negative patient. Sensitivity and specificity were 84.8% and 100%, respectively for Hpylori infection and, 80% and 92.8% for tTG. Twenty-eight patients had positive H pylori antibodies and in all the patients, an active Hpylori infection was found. In particular, in 23 out of 28 （82%） patients with positive H pylori antibodies, a likely cause of IDA was found because of the active inflammation involving the gastric body. CONCLUSION： Anti-H pylori IgG antibody and tTG IgA antibody testing is able to select women with IDA to submit for gastroscopy to identify H pylori pangastritis and/or celiac disease, likely causes of IDA.

关键词： Iron deficiency anemia Women Celiac disease Helicobacter pylori gastritis

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Efficacy of Early Treatment on 52 Patients with Preneoplastic Hepatitis B Virus-Associated Hepatocellular Carcinoma by Compound Phyllanthus Urinaria L.

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Chinese Journal of Integrative Medicine 2014年第4期20卷 263-271页

作者：童光东张希周大桥魏春山贺劲松肖春玲刘心亮郑颖俊陈思暖唐海鸿 department of liver disease Shenzhen Hospital Affiliated to Guangzhou University of Chinese Medicine

Objective:To observe the change in the number of antibodies of preneoplastic hepatocellular carcinoma(HCC) using early treatment by Compound Phyllanthus Urinaria L.(CPUL) on patients with preneoplastic hepatitis B virus(HBV)-associated ***:A total of 102 cirrhosis patients with regenerative or dysplastic nodules whose sera were tested positive for at least one of these six proteins(five up-regulated genes URG4,URG7,URG11,URG12 and URG19,and one down-regulated gene DRG2) were assigned randomly to two groups using continual random codes by SPSS ***-two patients were in the treatment group and 50 patients were in the control *** was used in the treatment group for 3 years,while the control group did not receive any *** changes in HBV-DNA level,number of antibodies,and hepatocarcinogenesis occurred were *** who did not develop HCC were followed up for another 2 ***:HBV-DNA levels decreased >2log in 22.2%(10/45) of patients in the treatment group in contrast to only 5.0%(2/40) of patients in the control group(P=0.0228).The number of antibodies that were tested positive in the treatment group(1.08± 1.01)was significantly lower compared with the control group(2.11 ±1.12) after 24 months of drug treatment(P<0.01).Both the positive rates of anti-URG11(33/52) and anti-URG19(31/52) were over 60%at baseline in the two groups,and were decreased to 48.1%(25/52) and 46.2%(24/52) respectively at 36 months of drug treatment,while the rates increased to 68.0%(34/50) and 66.0%(33/50) respectively(P=0.0417,P=0.0436) in the control *** positive rate of anti-DRG2 was increased to 55.8%(29/52) at 36 months of drug treatment,while in the control group was decreased to 36.0%(18/50,P=0.0452).Among the 102 patients who developed HCC,2 were in the treatment group and 9 were in the control group,meaning that a significant difference between the two groups(P=0.0212).In11 patients who developed HCC,anti-URG11 and anti-URG19 were al

关键词： carcinoma hepatic cell serologic preneoplastic markers of hepatocellular carcinoma compound phyllanthus urinaria L.

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