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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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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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Laparoscopic appendectomy for acute appendicitis: How to discourage surgeons using inadequate therapy

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World Journal of Gastroenterology 2017年第32期23卷 5849-5859页

作者： tomohide hori takafumi machimoto yoshio kadokawa toshiyuki hata tatsuo ito shigeru kato daiki yasukawa yuki aisu yusuke kimura maho sasaki yuichi takamatsu taku kitano shigeo hisamori tsunehiro yoshimura department of gastrointestinal surgery tenriyorodusoudanjyo hospital

Acute appendicitis(AA) develops in a progressive and irreversible manner, even if the clinical course of AA can be temporarily modified by intentional medications. Reliable and real-time diagnosis of AA can be made based on findings of the white blood cell count and enhanced computed tomography. Emergent laparoscopic appendectomy(LA) is considered as the first therapeutic choice for AA. Interval/delayed appendectomy at 6-12 wk after disease onset is considered as unsafe with a high recurrent rate during the waiting time. However, this technique may have some advantages for avoiding unnecessary extended resection in patients with an appendiceal mass. Nonoperative management of AA may be tolerated only in children. Postoperative complications increase according to the patient's factors, and temporal avoidance of emergent general anesthesia may be beneficial for high-risk patients. The surgeon's skill and cooperation of the hospital are important for successful LA. Delaying appendectomy for less than 24 h from diagnosis is safe. Additionally, a semi-elective manner(i.e., LA within 24 h after onset of symptoms) may be paradoxically acceptable, according to the factors of the patient, physician, and institution. Prompt LA is mandatory for AA. Fortunately, the Japanese government uses a universal health insurance system, which covers LA.

关键词： Laparoscopic appendectomy Acute appendicitis Interval appendectomy surgery Delayed appendectomy

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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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The role of EPH receptors in cancer-related epithelial-mesenchymal transition

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Chinese Journal of Cancer 2014年第5期33卷 231-240页

作者： Rui-Xin Li Zi-Hua Chen Zhi-Kang Chen department of gastrointestinal surgery Xiangya HospitalCentral South University

Erythropoietin-producing hepatoma(EPH) receptors are considered the largest family of receptor tyrosine kinases and play key roles in physiological and pathologic processes in development and *** receptors are often overexpressed in human malignancies and are associated with poor ***,the functions of EPH receptors in epithelial-mesenchymal transition(EMT) remain largely *** review depicts the relationship between EPH receptors and the EMT marker E-cadherin as well as the crosstalk between EPH receptors and the signaling pathways involved *** discussion is focused on the clinical significance of EPH receptors as candidates for targeting in cancer ***,we summarize how targeted inhibition of both EPH receptors and EMT-related signaling pathways represents a novel strategy for cancer treatment.

关键词：受体酪氨酸激酶恶性肿瘤上皮转化间质促红细胞生成素信号通路癌症治疗

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Lymph node metastasis and lymphadenectomy of resectable adenocarcinoma of the esophagogastric junction

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Chinese Journal of Cancer Research 2014年第3期26卷 237-242页

作者： Xin-Zu Chen Wei-Han Zhang Jian-Kun Hu department of gastrointestinal surgery West China HospitalSichuan University

Based on Siewert classification, adenocarcinomas of the esophagogastric junction （AEGs） have different behaviors of perigastric-mediastinal nodal metastasis. Siewert type I AEGs have higher incidence of mediastinal nodal metastasis than those of type H or III, especially at middle-upper mediastinum. With regard to the necessity of mediastinal lymphadenectomy, theoretically, transthoracic esophagogastrectomy with complete mediastinal lymphadenectomy is suggested for Siewert type I AEGs, while transhiatal total gastrectomy with lower mediastinal and D2 perigastric lymphadenectomy is a standard surgery for type II-III AEGs. Nevertheless, the mediastinal nodal metastasis is an independent factor of poor prognosis for any type of AEG.

关键词： Adenocarcinomas of the esophagogastric junction (AEGs) surgery lymph node metastasis lymphadenectomy

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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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Prognostic significance of periostin in colorectal cancer

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Chinese Journal of Cancer Research 2019年第3期31卷 547-556页

作者： Xingming Deng Sheng Ao Jianing Hou Zhuofei Li Yunpeng Lei Guoqing Lyu department of gastrointestinal surgery Peking University Shenzhen Hospital

Accumulating evidence suggests that periostin is frequently upregulated in tissue injury, inflammation,fibrosis and tumor progression. Periostin expression in cancer cells can promote metastatic potential of colorectal cancer(CRC)via activating PI3 K/Akt signaling pathway. Moreover, periostin is observed mainly in tumor stroma and cytoplasm of cancer cells, which may facilitate aggressiveness of CRC. In this review, we summarize information regarding periostin to emphasize its role as a prognostic marker of CRC.

关键词： Periostin prognostic functionality stromal cells colorectal cancer

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Impact of regular enteral feeding via jejunostomy during neo-adjuvant chemotherapy on body composition in patients with oesophageal cancer

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World Journal of gastrointestinal Oncology 2019年第12期11卷 1182-1192页

作者： Imran M Mohamed John Whiting Benjamin HL Tan department of Upper gastrointestinal surgery Queen Elizabeth Hospital

BACKGROUND Malnourishment and sarcopenia are well documented phenomena in oesophageal *** undergoing neo-adjuvant chemotherapy prior to oesophagectomy have complex nutritional *** To examine the effect of regular nutritional support via feeding jejunostomy on overall body composition in patients undergoing neo-adjuvant chemotherapy prior to oesophagectomy for oesophageal *** Retrospective data were collected for 15 patients before and after neo-adjuvant *** patients had feeding jejunostomies inserted at staging laparoscopy prior to neo-adjuvant chemotherapy and underwent regular jejunostomy *** in body composition were determined by analysis of computed tomography *** Patient age was 61.3±12.8 years,and 73%of patients were *** time between start of chemotherapy and surgery was 107±21.6 *** was no change in weight(74.5±14.1 kg to 74.8±13.1 kg)and body mass index(26.0±3.8 kg/m^2 to 26.1±3.4 kg/m^2).Body composition analysis revealed a statistically significant decrease in lumbar skeletal muscle index despite regular feeding(45.8±8.0 cm^2/m^2 to 43.5±7.3 cm^2/m^2;P=0.045).The proportion of sarcopenic patients increased(33.3% to 60%).Six patients(40%)experienced dose-limiting toxicity during *** Regular jejunostomy feeding during neo-adjuvant chemotherapy can maintain weight and adipose *** alone is not sufficient to maintain muscle *** insight into the underlying processes causing reduced muscle mass in cancer patients may help to provide targeted interventions.

关键词： Body composition Neo-adjuvant therapy Oesophageal cancer Enteral feeding

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Paeoniflorin inhibits human gastric carcinoma cell proliferation through up-regulation of microRNA-124 and suppression of PI3K/Akt and STAT3 signaling

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World Journal of Gastroenterology 2015年第23期21卷 7197-7207页

作者： Yong-Bin Zheng Gao-Chun Xiao Shi-Lun Tong Yu Ding Qiu-Shuang Wang Sheng-Bo Li Zhi-Nan Hao department of gastrointestinal surgery Renmin Hospital of Wuhan University

AIM: To examine the potential anti-tumor activity of paeoniflorin in the human gastric carcinoma cell line ***: Cell viability and cytotoxic effects in MGC-803 cells were analyzed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay, respectively. Cell apoptosis of MGC-803 cells was measured using flow cytometry,DAPI staining assay and caspase-3 activity *** reverse transcription-polymerase chain reaction(RT-PCR) was used to measure the expression of microRNA-124(miR-124) in response to *** expression of phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt), phospho-Akt(p-Akt) and phospho-signal transducer and activator of transcription3(p-STAT3) were also measured by quantitative RTPCR and Western blot analysis in normal, miR-124 and anti-miR-124 over-expressing MGC-803 cells, treated with ***: Paeoniflorin was found to inhibit MGC-803 cell viability in a dose-dependent manner. Paeoniflorin treatment was associated with the induction of apoptosis and caspase-3 activity in MGC-803 cells. Paeoniflorin treatment significantly increased miR-124 levels and inhibited the expression of PI3 K, Akt, p-Akt and p-STAT3 in MGC-803 cells. Interestingly, the over-expression of miR-124 inhibits PI3K/Akt and phospho-STAT3 expressions in MGC-803 cells. PI3 K agonist(IGF-1, 1μg/10 μL) or over-expression of STAT3 reversed the effect of paeoniflorin on the proliferation of MGC-803 cells. Over-expression of anti-miR-124 in MGC-803 cells reversed paeoniflorin-induced ***: In summary, the in vitro data suggest that paeoniflorin is a potential novel therapeutic agent against gastric carcinoma, which inhibits cell viability and induces apoptosis through the up-regulation of miR-124 and suppression of PI3K/Akt and STAT3 signaling.

关键词： Gastric cancer Paeoniflorin MicroRNA-124 Phosphatidylinositol 3-kinase Akt Signal transducerand activator of transcription 3

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