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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

Science China Life Sciences 2025年第1期 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.

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Baicalin Prevents Colon Cancer by Suppressing CDKN2A Protein Expression

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Chinese Journal of Integrative Medicine 2024年第11期30卷 1007-1017页

作者： LI Gang-gang CHU Xiu-feng XING Ya-min XUE Xia Ihtisham Bukhari LIANG Xin-feng XU Ji-xuan MI Yang ZHENG Peng-yuan Henan Key Laboratory of Helicobacter pylori Microbiota and Gastrointestinal CancersMarshall Medical Research CenterFifth Affiliated Hospital of Zhengzhou UniversityZhengzhou 400015China

Objective:To observe the therapeutic effects and underlying mechanism of baicalin against colon ***:The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and *** were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network ***,molecular docking and drug affinity responsive target stability(DARTS)analysis were performed to confirm the interaction between potential targets and ***,the mechanisms predicted by in silico analyses were experimentally verified in-vitro and ***:Baicalin significantly inhibited proliferation,invasion,migration,and induced apoptosis in MC38 and CT26 cells(all P<0.01).Additionally,baicalin caused cell cycle arrest at the S phase,while the G/G,phase was detected in the tiny portion of the *** network pharmacology analysis identified 6 therapeutic targets associated with baicalin,which potentially affect various pathways including 39 biological processes and 99 signaling *** addition,molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A(CDKN2A),protein kinase B(AKT),caspase 3,and mitogen-activated protein kinase(MAPK).In vitro,the expressions of CDKN2A,MAPK,and p-AKT were suppressed by baicalin in MC38 and CT26 *** vivo,baicalin significantly reduced the tumor size and weight(all P<0.01)in the colon cancer mouse model via inactivating p-AKT,CDKN2A,cyclin dependent kinase 4,cyclin dependent kinase 2,interleukin-1,tumor necrosis factorα,and activating caspase 3 and mouse double minute 2 homolog signaling(all P<0.05).Conclusion:Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.

关键词： colon cancer baicalin CDKN2A network pharmacology cell cycle apoptosis

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The promising role of poly（ADP-ribose） polymerase inhibitors in prostate cancer

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Asian Journal of Andrology 2016年第4期18卷 592-593页

作者： Jeanny B Aragon-Ching Clinical program Director of Genitourinary cancers INOVA Schar Cancer Institute 8505 Arlington Bird Suite 100 Faiffax VA USA

The TOPARP study showed the beneficial utility of olaparib in a heavily pretreatedpopulation of metastatic castration-resistant prostate cancer who were biomarker-positive for aberrations in DNA repair gene. A higher response rate to olaparib of 88% （14 out of 16 patients）, time to radiographic progression as well as overall survival, was seen in patients who were biomarker-positive compared to those who were not. This study showed a promising way of targeting prostate cancer with an enriched population of patients who harbor these deleterious genes. this paves the way for offering new therapeutic opportunities for men who have otherwise few remaining options.

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Update on the prevention of local recurrence and peritoneal metastases in patients with colorectal cancer

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World Journal of Gastroenterology 2014年第28期20卷 9286-9291页

作者： Paul H Sugarbaker Center for gastrointestinal Malignancies Program in Peritoneal Surface OncologyMedStar Washington Hospital Center

The prevention of a disease process has always been superior to the treatment of the same disease throughout the history of medicine and surgery. Local recurrence and peritoneal metastases occur in approximately 8% of colon cancer patients and 25% of rectal cancer patients and should be prevented. Strategies to prevent colon or rectal cancer local recurrence and peritoneal metastases include cytoreductive surgery and hyperthermic perioperative chemotherapy (HIPEC). These strategies can be used at the time of primary colon or rectal cancer resection if the HIPEC is available. At institutions where HIPEC is not available with the treatment of primary malignancy, a proactive second-look surgery is recommended. Several phase II studies strongly support the proactive approach. If peritoneal metastases were treated along with the primary colon resection, 5-year survival was seen and these results were superior to the results of treatment after peritoneal metastases had developed as recurrence. Also, prophylactic HIPEC improved survival with T3/T4 mucinous or signet ring colon cancers. A second-look has been shown to be effective in two published manuscripts. Unpublished data from MedStar Washington Cancer Institute also produced favorable date. Rectal cancer with peritoneal metastases may not be so effectively treated. There are both credits and debits of this proactive approach. Selection factors should be reviewed by the multidisciplinary team for individualized management of patients with or at high risk for peritoneal metastases.

关键词： Peritoneal metastases Carcinomatosis Local recurrence Hyperthermic perioperative chemotherapy Secondary prevention Proactive treatment Mucinous colon cancer Signet ring colon cancer

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Use of early chemotherapy for hormone-sensitive prostate cancer： time for CHAARTED

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Asian Journal of Andrology 2016年第3期18卷 444-445页

作者： Jeanny B Aragon-Ching Clinical program Director of Genitourinary cancers INOVA Dwight and Martha gchar Cancer Institute8505 Arlington Boulevard Suite 100 Pairfax VAUSA.

CHAARTED was an ECOG-led phase III trial looking at early chemotherapy with the use of docetaxel in addition to androgen deprivation therapy （ADT） versus ADT alone in hormone-sensitive prostate cancer. The positive results of the trial showing marked improvement in overall survival in those who received chemotherapy with ADT have revolutionized the treatment of metastatic castration-sensitive prostate cancer.

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Double-tract reconstruction is superior to esophagogastrostomy in controlling reflux esophagitis and enhancing quality of life after proximal gastrectomy:Results from a prospective randomized controlled clinical trial in China

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Chinese Journal of Cancer Research 2023年第6期35卷 645-659页

作者： Yinan Zhang Hongtao Zhang Yan Yan Ke Ji Ziyu Jia Heli Yang Biao Fan Anqiang Wang Xiaojiang Wu Ji Zhang Jiafu Ji Xin Ji Zhaode Bu Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Guowen(Changchun)International Hospital Changchun 136199China State Key Laboratory of Holistic Integrative Management of gastrointestinal cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchEndoscopy CenterPeking University Cancer Hospital&InstituteBeijing 100142China State Key Laboratory of Holistic Integrative Management of gastrointestinal cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchGastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China

Objective:The aim of this study was to prospectively compare double-tract reconstruction(DTR)and esophagogastrostomy(EG)after proximal gastrectomy(PG)regarding the incidence of reflux esophagitis,quality of life(QOL),nutritional status and surgical ***:This study was a randomized controlled *** eligible for PG were enrolled and randomly assigned to the EG group and DTR *** characteristics of patients,parameters for surgical safety,incidence of reflux esophagitis,nutrition status and QOL were collected and compared between the two *** analysis and multivariate analysis were performed to determine the significant factors affecting the incidence of reflux esophagitis after ***:Thirty-seven patients of the EG group and 36 patients of the DTR group were *** incidence of reflux esophagitis was significantly lower in the DTR group than in the EG group(8.3%vs.32.4%,P=0.019).The DTR group demonstrated a more favorable QOL than the EG group after *** nutritional status was balanced within the EG group and the DTR *** operation time was longer in the DTR group than in the EG group(191 min vs.221 min,P=0.001),while surgical safety was similar in the two ***:Our research demonstrated that DTR is superior to EG after PG in terms of the incidence of reflux esophagitis and provides a more satisfactory QOL without increasing surgical complications or sacrificing nutritional status.

关键词： Double-tract reconstruction proximal gastrectomy quality of life reflux esophagitis

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Advances in MET tyrosine kinase inhibitors in gastric cancer

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Cancer Biology & Medicine 2024年第6期21卷 484-498页

作者： Yifan Zhang Lin Shen Zhi Peng Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China State Key Laboratory of Holistic Integrative Management of gastrointestinal cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China

Gastric cancer is among the most frequently occurring cancers and a leading cause of cancer-related deaths *** gastric cancer is highly heterogenous and comprised of different subtypes with distinct molecular and clinical characteristics,the management of gastric cancer calls for better-defined,biomarker-guided,molecular-based treatment *** is a receptor tyrosine kinase mediating important physiologic processes,such as embryogenesis,tissue regeneration,and wound ***,mounting evidence suggests that aberrant MET pathway activation contributes to tumour proliferation and metastasis in multiple cancer types,including gastric cancer,and is associated with poor patient *** such,MET-targeting therapies are being actively developed and promising progress has been demonstrated,especially with MET tyrosine kinase *** review aims to briefly introduce the role of MET alterations in gastric cancer and summarize in detail the current progress of MET tyrosine kinase inhibitors in this disease area with a focus on savolitinib,tepotinib,capmatinib,and *** on current knowledge,this review further discusses existing challenges in MET alterations testing,possible resistance mechanisms to MET inhibitors,and future directions of MET-targeting therapies.

关键词： Gastric cancer MET alterations MET tyrosine kinase inhibitors savolitinib MET testing

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Neoadjuvant chemotherapy with capecitabine combined with oxaliplatin for mid-low locally advanced rectal cancer with negative mesorectal fascia:Long-term outcomes of a prospective trial(PKUCH-R03 trial)

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Chinese Journal of Cancer Research 2024年第4期36卷 410-420页

作者： Nan Chen Minghe Zhao Yunfeng Yao Lin Wang Yifan Peng Tingting Sun Tiancheng Zhan Jun Zhao Aiwen Wu Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterUnit IIIPeking University Cancer Hospital&InstituteBeijing 100142China State Key Laboratory of Holistic Integrative Management of gastrointestinal cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchGastrointestinal Cancer CenterUnit IIIPeking University Cancer Hospital&InstituteBeijing 100142China

Objective:To evaluate the safety and efficacy of neoadjuvant chemotherapy(NCT)in mid-low locally advanced rectal cancer with negative mesorectal fascia(MRF).Methods:This prospective,single-arm phaseⅡtrial was designed and conducted at Peking University Cancer *** patients who provided consent received 3 months of NCT(capecitabine and oxaliplatin,CapOX)followed by total mesorectal excision(TME).The primary endpoint was the rate of pathological complete response(pCR).Results:From January 2019 through December 2021,a total of 53 patients were enrolled,7.5%of whom experienced grade 3-4 adverse events during *** pCR rate was 17.0%for the entire cohort,and the overall rate of postoperative complications was 37.7%(1.9%of gradeⅢa patients).The 3-year disease-free survival rate was 91.4%,and 23.5%(12/51)of the patients suffered from major low anterior resection syndrome(LARS).Postoperative complications were independently associated with major ***:For patients with mid-low rectal cancer with negative MRF,3 months of NCT were found to yield a favorable tumor response with acceptable *** fair long-term survival,the NCT regimen could be associated with low rates of perioperative complications as well as acceptable anal function.

关键词： Neoadjuvant chemotherapy rectal cancer mesorectal fascia disease-free survival anal function

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Inhibition of METTL3 in macrophages provides protection against intestinal inflammation

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Cellular & Molecular Immunology 2024年第6期21卷 589-603页

作者： Huilong Yin Zhuan Ju Xiang Zhang Wenjie Zuo Yuhang Yang Minhua Zheng Xiaofang Zhang Yuning Liu Yingran Peng Ying Xing Angang Yang Rui Zhang Henan Key Laboratory of Immunology and Targeted Therapy School of Medical TechnologyXinxiang Medical UniversityXinxiangHenan453003China Molecular Immunology and Immunotherapy Laboratory School of Medical TechnologyXinxiang Medical UniversityXinxiangHenan453003China Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine School of Medical TechnologyXinxiang Medical UniversityXinxiangHenan453003China State Key Laboratory of Holistic Integrative Management of gastrointestinal cancers and Department of Immunology Fourth Military Medical UniversityXi’anShaanxi710032China State Key Laboratory of Holistic Integrative Management of gastrointestinal cancers and Department of Biochemistry and Molecular Biology Fourth Military Medical UniversityXi’anShaanxi710032China State Key Laboratory of Holistic Integrative Management of gastrointestinal cancers and Department of Medical Genetics and Developmental Biology Fourth Military Medical UniversityXi’anShaanxi710032China Department of Endocrinology Xi’an Daxing HospitalXi’anShaanxi710000China

Inflammatory bowel disease(IBD)is prevalent,and no satisfactory therapeutic options are available because the mechanisms underlying its development are poorly *** this study,we discovered that increased expression of methyltransferase-like 3(METTL3)in macrophages was correlated with the development of colitis and that depletion of METTL3 in macrophages protected mice against dextran sodium sulfate(DSS)-induced *** characterization indicated that METTL3 depletion increased the YTHDF3-mediated expression of phosphoglycolate phosphatase(PGP),which resulted in glucose metabolism reprogramming and the suppression of CD4+T helper 1(Th1)cell *** analysis revealed that glucose metabolism contributed to the ability of METTL3 depletion to ameliorate colitis *** addition,we developed two potent small molecule METTL3 inhibitors,namely,F039-0002 and 7460-0250,that strongly ameliorated DSS-induced ***,our study suggests that METTL3 plays crucial roles in the progression of colitis and highlights the potential of targeting METTL3 to attenuate intestinal inflammation for the treatment of colitis.

关键词： Colitis Glucose metabolism Macrophage N6-methyladenosine modification

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Circulating cell-free mtDNA as a new biomarker for cancer detection and management

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Cancer Biology & Medicine 2024年第2期21卷 105-110页

作者： Fan Peng Siyuan Wang Zehui Feng Kaixiang Zhou Huanqin Zhang Xu Guo Jinliang Xing Yang Liu State Key Laboratory of Holistic Integrative Management of gastrointestinal cancers and Xijing Hospital of Digestive Diseases Fourth Military Medical UniversityXi’an 710032China Department of Clinical Diagnosis Tangdu HospitalFourth Military Medical UniversityXi’an 710038China

Cancer is a major cause of death worldwide,and was responsible for 19.29 million new cases and 9.96 million deaths in 2020 *** total number of patients with cancer worldwide is estimated to reach 28 million by *** Ame... 详细信息

关键词： Cancer cancer death

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