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Recent advances in promising drugs for primary prevention of gastroesophageal variceal bleeding with cirrhotic portal hypertension

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hepatobiliary & pancreatic diseases International 2024年第1期23卷 4-13页

作者： Ji-Yao Sheng Zi-Fan Meng Qiao Li Yong-Sheng Yang Department of hepatobiliary and pancreatic Surgery the Second Hospital of Jilin UniversityChangchun 130041China jilin engineering laboratory for translational medicine of hepatobiliary and pancreatic diseases the Second Hospital of Jilin UniversityChangchun 130041China

Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with *** primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incidence of bleeding,their efficacy is limited due to side effects and related *** recent advances in precision medicine,precise drug treatment provides better treatment *** sources:Literature search was conducted in PubMed,MEDLINE and Web of Science for relevant articles published up to May *** on clinical trials was obtained from https://***/and http://***/.Results:The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising *** to the site of action,these drugs could be classified into four classes:intrahepatic,extrahepatic,both intrahepatic and extrahepatic targets and *** these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal ***:This review classified and summarized the promising drugs,which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension,demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.

关键词： Cirrhotic portal hypertension Target drug Primary prevention Bleeding

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Details determining the success in establishing a mouse orthotopic liver transplantation model

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World Journal of Gastroenterology 2020年第27期26卷 3889-3898页

作者： Ting Li Zheng Hu Lei Wang Guo-Yue Lv Department of hepatobiliary and pancreatic Surgery The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina Key laboratory of Organ Regeneration and Transplantation of Ministry of Education The First Hospital of Jilin UniversityChangchun 130061Jilin ProvinceChina National-Local Joint engineering laboratory of Animal Models for Human diseases Changchun 130061Jilin ProvinceChina Department of Gastrointestinal Surgery The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina

Liver transplantation(LT)is currently the only effective treatment option for endstage liver *** importance of animal models in transplantation is widely recognized among *** of the well-characterized mouse genome and the greater diversity and availability of both genetically modified animals and research reagents,mouse orthotopic LT(MOLT)has become an ideal model for the investigation of liver biology,tissue injury,regulation of alloimmunity and tolerance induction,and the pathogenesis of specific liver ***,due to its complicated and technically demanding procedure,the model has merely been used by only a few research groups in the world for *** a new learner,training lasting at least a couple of months or even years is *** of the investigators have emphasized the importance of elaborate techniques and dedicated instruments in establishing a MOLT model,but some details are often *** nontechnical details are also significant,especially for researchers who have little experience in mouse ***,we review and summarize the crucial technical and nontechnical details in establishing the model of MOLT based on scientific articles and our experience in six aspects:animal selection,anesthesia,perioperative management,organ procurement,back-table preparation,and implantation *** aim to enable research groups to shorten the learning curve and implement the mouse LT procedure with high technical success.

关键词： Mouse orthotopic liver transplantation Animal selection Anesthesia Perioperative management Organ procurement Back-table preparation Implantation surgery

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Safety and Efficacy of Physical Thermal Ablation Combined Sorafenib for Hepatocellular Carcinoma:A Meta-analysis

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Journal of Clinical and translational Hepatology 2021年第2期9卷 149-159页

作者： Mengdi Jin Qiong Yu Yahui Liu Weiling Xu Xueqi Fu Bai Ji Department of hepatobiliary and pancreatic Surgery the First Hospital of Jilin UniversityChangchunJilinChina Department of Epidemiology and Biostatistics School of Public HealthJilin UniversityChangchunJilinChina Edmond H.Fischer Signal Transduction laboratory College of Life SciencesJilin UniversityChangchunJilinChina

Background and Aims:To compare the efficacy and safety of physical thermal ablation(PTA),including radiofrequency ablation(RFA)and microwave ablation(MWA),combined with sorafenib and physical thermal ablation alone for the control and treatment of hepatocellular carcinoma(HCC)according to the available ***:Comprehensive searches were performed on PubMed,Embase,CNKI,the Cochrane Library,China Biomedical Literature Database(known as CBM),Weipu Journal,and Wanfang ***-analysis was performed using Revman 5.3 ***:A total of 15 studies,consisting of 2,227 HCC patients,were selected and included in this *** with the RFA-alone group,the patients in the RFA+sorafenib group had longer 1-,2-,and 3-year overall survival(all p<0.05),better overall efficacy(p<0.0001),longer radiofrequency interval(p<0.001),and lower 2-year recurrence rate(p=0.02).The 1-year overall survival(p=0.003)and overall efficacy(p=0.002)of the MWA+sorafenib group were also higher than those of the MWA-alone *** incidences of adverse reactions in the RFA+sorafenib group,such as hand-foot skin reactions(p<0.001),diarrhea and constipation(p=0.0001),hypertension(p=0.009),and alopecia(p<0.001),were significantly higher than those in the RFA-alone ***:RFA or MWA combined with sorafenib has produced a better therapeutic effect on HCC than physical thermal ablation alone;however,adverse reactions have been *** is necessary to evaluate the safety of combination therapy,and pay close attention to the adverse reactions that develop in patients.

关键词： Physical thermal ablation Radiofrequency ablation Microwave ablation Sorafenib Hepatocellular carcinoma Meta-analysis

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Isolated anti-HBc is an independent risk factor for tumor recurrence in intrahepatic cholangiocarcinoma after curative resection

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hepatobiliary & pancreatic diseases International 2022年第5期21卷 472-478页

作者： Xiao-Bo Xu Chen Hu Han-Jin Yang Shu-Sen Zheng Department of hepatobiliary and pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key laboratory of Pulsed Power translational medicine of Zhejiang Province Hangzhou 310012China Department of Pathology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Lab of Combined Multi-Organ Transplantation Ministry of Public HealthHangzhou 310003China

Background:Intrahepatic cholangiocarcinoma(ICC)is a poorly understood and aggressive malignancy with increasing incidence and *** B virus(HBV)infection is recognized as one of the important risk factors of *** are few reports focusing on whether isolated antibody to hepatitis B core antigen(isolated anti-HBc,IAHBc)have prognostic role in ICC,while positive hepatitis B surface antigen(HBsAg)has been reported to be associated with the prognosis of *** aim of this study was to investigate the prognostic value of IAHBc in ICC patients after curative resection,in order to identify those who have the high risk of ICC recurrence in the early ***:We divided 209 ICC patients who underwent curative resection into 4 groups:groupⅠ(n=40),HBsAg(-)/antibody to hepatitis B surface antigen(anti-HBs)(-)/anti-HBc(+);groupⅡ(n=70),HBsAg(+)/anti-HBc(-);groupⅢ(n=55),HBsAg(-)/anti-HBs(+)/anti-HBc(+);and groupⅣ(n=44),HBsAg(-)/anti-HBc(-).We compared the recurrence-free survival(RFS)and overall survival(OS)among these four ***:The median follow-up time was 16.93 months(range 1-34.6 months).The 1-and 2-year RFS and OS rates were 60%and 42%,and 78%and 63%respectively in all *** to the whole non-IAHBc patients(groupⅡ+groupⅢ+groupⅣ),IAHBc patients(groupⅠ)showed significantly lower RFS at 1 year(39.8%vs.64.4%,P=0.001)and 2 years(20.7%vs.46.7%,P=0.001).When compared to other three individual groups,IAHBc patients(groupⅠ)also had the lowest *** did not find significant difference in OS among the four *** multivariate analysis revealed that IAHBc was an independent risk factor of ***:IAHBc is an independent poor prognostic factor for tumor recurrence in ICC patients after curative resection.

关键词： Cholangiocarcinoma Hepatitis B virus Isolated antibody to hepatitis B core antigen Occult hepatitis B infection

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Metal nanoparticles for cancer therapy:Precision targeting of DNA damage

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1132-1149页

作者： Qian Chen Chunyan Fang Fan Xia Qiyue Wang Fangyuan Li Daishun Ling Institute of Pharmaceutics Hangzhou Institute of Innovative MedicineCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Frontiers Science Center for Transformative Molecules School of Chemistry and Chemical EngineeringNational Center for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China World Laureates Association(WLA)Laboratories Shanghai 201203China Key laboratory of Precision Diagnosis and Treatment for hepatobiliary and pancreatic Tumor of Zhejiang Province Hangzhou 310009China

Cancer,a complex and heterogeneous disease,arises from genomic ***,DNA damage-based cancer treatments,including radiotherapy and chemotherapy,are employed in clinical ***,the efficacy and safety of these therapies are constrained by various factors,limiting their ability to meet current clinical *** nanoparticles present promising avenues for enhancing each critical aspect of DNA damage-based cancer *** customizable physicochemical properties enable the development of targeted and personalized treatment *** this review,we delve into the design principles and optimization strategies of metal *** shed light on the limitations of DNA damage-based therapy while highlighting the diverse strategies made possible by metal *** encompass targeted drug delivery,inhibition of DNA repair mechanisms,induction of cell death,and the cascading immune ***,we explore the pivotal role of physicochemical factors such as nanoparticle size,stimuli-responsiveness,and surface modification in shaping metal nanoparticle ***,we present insights into the challenges and future directions of metal nanoparticles in advancing DNA damage-based cancer therapy,paving the way for novel treatment paradigms.

关键词： DNA damage Metal nanoparticles Nucleus-targeting DNA repair inhibition Immune response Size optimization Stimuli-responsiveness Surface modification

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Tumor-responsive dynamic nanoassemblies for boosted photoimmunotherapy

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Nano Research 2023年第8期16卷 11125-11138页

作者： Dao Shi Nan Wang Jie Zhang Xi Hu Qiyue Wang Ruixue Xiao Baoyue Ding Fangyuan Li Daishun Ling Frontiers Science Center for Transformative Molecules School of Chemistry and Chemical EngineeringNational Center for Translational MedicineState Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong UniversityShanghai 200240China Institute of Pharmaceutics Hangzhou Institute of Innovative MedicineCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Pharmaceutics Jiaxing Key Laboratory for Photonanomedicine and Experimental TherapeuticsCollege of MedicineJiaxing UniversityJiaxing 314001China World Laureates Association(WLA)Laboratories Shanghai 201203China School of Pharmacy Anhui University of Chinese MedicineHefei 230012China Key laboratory of Precision Diagnosis and Treatment for hepatobiliary and pancreatic Tumor of Zhejiang Province Hangzhou 310009China

Photoimmunotherapy(PIT)is an emerging therapeutic approach that integrates phototherapy and immunotherapy to eliminate primary tumors under an appropriate dosage of local light irradiation,while simultaneously preventing tumor metastasis and recurrence by activating the host antitumor immune ***-responsive dynamic nanoassemblies(TDNs)have evolved from being a mere curiosity to a promising platform for high-performance ***,the dynamic nano-bio interaction between TDNs and tumor microenvironment remains poorly understood,which shall be critical for precise control of TDNs assembling/disassembling behavior and superior PIT *** deepen the understanding of the structure–function relationship of TDNs,this review introduces the rational design,nano-bio interactions,and controllable functionalities of cutting-edge TDNs for enhanced ***,the synergetic mechanism between TDNs-based PIT and immunomodulatory agents-mediated immunomodulation is particularly ***,the challenges and future perspectives in this emerging field are assessed.

关键词： photoimmunotherapy tumor-responsive dynamic nanoassemblies immunosuppressive tumor microenvironment

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A tumor-targeting nano-adjuvant for in situ vaccine based on ultrasound therapy

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Aggregate 2024年第3期5卷 290-298页

作者： Linjie Cui Haochen Yao Fuxin Xue Jiali Sun Xitong Ren Mengfei Zheng Zhilin Liu Zhaohui Tang Key laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchunChina School of Applied Chemistry and engineering University of Science and Technology of ChinaHefeiChina Department of hepatobiliary and pancreatic Surgery The First Hospital of Jilin UniversityChangchunChina Key laboratory of UV Emitting Materials and Technology Northeast Normal UniversityChangchunChina

Ultrasound-generated antigens combined with TLR7/8 agonists as adjuvants have demonstrated signiﬁcant anti-tumor efﬁcacy as an in-situ ***,the use of TLR7/8 agonists can cause severe inﬂammatory *** this study,we present a novel tumor-targeting nano-adjuvant termed aPDL1-PLG/R848 NPs,which are composed of aPDL1 antibody,Fc-III-4C peptide linker(Fc-linker)and poly(L-glutamic acid)-*** ultrasound irradiation,antigen-presenting cells activate immune mechanisms in vivo under dual stimulation of in situ antigens and immune *** strategy inhibits primary tumor growth and induces a strong antigen-speciﬁc immune memory effect to prevent tumor recurrence in *** work offers a safe and potent platform for an in situ cancer vaccine based on ultrasound therapy.

关键词： immunotherapy in situ vaccine R848 nanoparticles tumor-targeting ultrasound therapy

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E3 ligase MG53 suppresses tumor growth by degrading cyclin D1

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3768-3779页

作者： Meng Fang Hong-Kun Wu Yumeng Pei Yan Zhang Xiangyu Gao Yanyun He Gengjia Chen Fengxiang Lv Peng Jiang Yumei Li Wenwen Li Peng Jiang Lin Wang Jiafu Ji Xinli Hu Rui-Ping Xiao State Key laboratory of Membrane Biology Institute of Molecular MedicineCollege of Future TechnologyPeking University100871 BeijingChina Peking-Tsinghua Center for Life Sciences 100871 BeijingChina Department of hepatobiliary and pancreatic Surgery the First Affiliated HospitalZhejiang University School of Medicine310003 HangzhouChina Zhejiang Provincial Key laboratory of pancreatic Disease 310003 HangzhouChina Beijing City Key laboratory of Cardiometabolic Molecular medicine Peking University100871 BeijingChina Key laboratory of Carcinogenesis and translational Research(Ministry of Education/Beijing) Gastrointestinal Tumor CenterPeking University Cancer Hospital&Institute100142 BeijingChina School of Life Sciences Tsinghua University100084 BeijingChina Research Center for Tissue engineering and Regenerative medicine Union HospitalTongji Medical CollegeHuazhong University of Science and Technology430022 WuhanChina

Due to the essential role of cyclin D1 in regulating transition from G1 to S phase in cell cycle,aberrant cyclin D1 expression is a major oncogenic event in many types of *** particular,the dysregulation of ubiquitination-dependent degradation of cyclin D1 contributes to not only the pathogenesis of malignancies but also the refractory to cancer treatment regiments with CDK4/6 *** we show that in colorectal and gastric cancer patients,MG53 is downregulated in more than 80%of tumors compared to the normal gastrointestinal tissues from the same patient,and the reduced MG53 expression is correlated with increased cyclin D1 abundance and inferior ***,MG53 catalyzes the K48-linked ubiquitination and subsequent degradation of cyclin ***,increased expression of MG53 leads to cell cycle arrest at G1,and thereby markedly suppresses cancer cell proliferation in vitro as well as tumor growth in mice with xenograft tumors or AOM/DSS induced-colorectal ***,MG53 deficiency results in accumulation of cyclin D1 protein and accelerates cancer cell growth both in culture and in animal *** findings define MG53 as a tumor suppressor via facilitating cyclin D1 degradation,highlighting the therapeutic potential of targeting MG53 in treating cancers with dysregulated cyclin D1 turnover.

关键词： MG53 markedly thereby

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Genetic engineering drives the breakthrough of pig models in liver disease research

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Liver Research 2024年第3期8卷 131-140页

作者： Chenhao Xu Xixi Fang Xiao Xu Xuyong Wei Zhejiang University School of medicine HangzhouZhejiangChina Department of hepatobiliary and pancreatic Surgery Hangzhou First People’s HospitalHangzhouZhejiangChina Key laboratory of Integrated Oncology and Intelligent medicine of Zhejiang Province HangzhouZhejiangChina Hangzhou Normal University HangzhouZhejiangChina School of Clinical medicine Hangzhou Medical CollegeHangzhouZhejiangChina NHC Key laboratory of Combined Multi-organ Transplantation HangzhouZhejiangChina Institute of translational medicine Zhejiang UniversityHangzhouZhejiangChina

Compared with the widely used rodents,pigs are anatomically,physiologically,and genetically more similar to humans,making them high-quality models for the study of liver ***,we review the latest research progress on pigs as a model of human liver disease,including methods for establishing them and their advantages in studying cystic fibrosis liver disease,acute liver failure,liver regeneration,non-alcoholic fatty liver disease,liver tumors,and *** also emphasize the importance of genetic engineering techniques,mainly the CRISPR/Cas9 system,which has greatly enhanced the utility of porcine models as a tool for substantially advancing liver disease *** engineering is expected to propel the pig as one of the irreplaceable animal models for future biomedical research.

关键词： Animal model Liver disease Genetic engineering CRISPR/Cas9 Xenogeneic liver transplantation Pig

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MiR-27a Promotes Hepatocellular Carcinoma Cell Proliferation Through Suppression of its Target Gene Peroxisome Proliferator-activated Receptor γ

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Chinese Medical Journal 2015年第7期128卷 941-947页

作者： Shuo Li Jing Li Bing-Yuan Fei Dan Shao Yue Pan Zhan-Hao MO Bao-Zhen Sun Dan Zhang Xiao Zheng Ming Zhang Xue-Wen Zhang Li Chen Department of hepatobiliary and pancreatic Surgery China-Japan Union Hospital Jilin University Changchun Jilin 130021 China Department of Pharmacology Nanomedicine Engineering Laboratory of Jilin Province College of Basic Medical Sciences Jilin University Changchun Jilin 130021 China Department of General Surgery China-Japan Union Hospital Jilin University Changchun Jilin 130021 China Endoscopy Center China-Japan Union Hospital Jilin University Changchun Jilin 130021 China

Background： MicroRNAs （miRNAs） function as essential posttranscriptional modulators ofgene expression, and are involved in a wide range of physiologic and pathologic states, including cancer. Numerous miRNAs are deregulated in hepatocellular carcinoma （HCC）. This study aimed to investigate the role of miR-27a in the development of HCC. Methods： The expression of MiR-27a was measured by quantitative real-time polymerase chain reaction （qRT-PCR）. 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide was used to examine changes in the viability of HepG2, Bel-7402, Bel-7404 hepatoma cell lines associated with up-regulation or down-regulation of miR-27a. A dual-luciferase activity assay was used to verily a target gene ofmiR-27a, lmmunohistochemistry, qRT-PCR, Western blotting analysis, and cell cycle and apoptosis flow cytometric assays were used to elucidate the mechanism by which miR-27a modulates liver cancer cell proliferation. Results： The expression of miR-27a was significantly increased in HCC tissues and HepG2, Bel-7402, Bel-7404 hepatoma cell lines （P 〈 0.05）. We also found that the down-regulation of miR-27a in HepG2 cells dramatically inhibited proliferation, blocked the G1 to S cell cycle transition and induced apoptosis （P 〈 0.05）. In addition, miR-27a directly targeted the 3＇-untranslated region of peroxisonae proliferator-activated receptor y （PPAR-γ）, and ectopic miR-27a expression suppressed PPAR-γ expression on the mRNA and protein levels. The rosiglitazone-induced overexpression of PPAR-γ attenuated the effect of miR-27a in HCC cells. Conclusions： Our findings suggested that miRNA-27a promoted HCC cell proliferation by regulating PPAR-γ expression. MiR-27a may provide a potential therapeutic strategy for HCC treatment.

关键词： Cell Proliferation Hepatocellular Carcinoma: MiR-27a: Peroxisonle Proliferator-activated Receptor γ

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