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Journal of Molecular Cell Biology 2022年第2期14卷 43-55页

作者： Fengyan Han Beibei Yang Mingyue Zhou Qiong Huang Minglang Mai Zhaohui Huang Maode Lai Enping Xu Honghe Zhang department of Pathology and Women’s Hospital Zhejiang University School of MedicineResearch Unit of Intelligence Classification of Tumor Pathology and Precision TherapyChinese Academy of Medical Sciences(2019RU042)Hangzhou 310058China Cancer Epigenetics Program Wuxi School of MedicineJiangnan UniversityWuxi 214122China Key Laboratory of Disease Proteomics of Zhejiang Province Zhejiang UniversityHangzhou 310058China Cancer Center Zhejiang UniversityHangzhou 310058China department of Pharmacology China Pharmaceutical UniversityNanjing 210009China

Alternative splicing(AS)and transcription elongation are vital biological processes,and their dysregulation causes multiple diseases,including ***,the coregulatory mechanism of AS and transcription elongation in tumors remains *** study demonstrates a novel AS pattern of tight junction protein 1(ZO1)regulated by the RNA polymerase II elongation rate in colorectal cancer(CRC).Glioma tumor suppressor candidate region gene 1(GLTSCR1)decreases the transcription elongation rate of ZO1 to provide a time window for binding of the splicing factor HuR to the specific motif in intron 22 of ZO1 and spliceosome recognition of the weak 3 and 5 splice sites in exon 23 to promote exon 23 *** exon 23 inclusion in ZO1 suppresses migration and invasion of CRC cells,our findings suggest a novel potential therapeutic target for CRC.

关键词： colorectal cancer alternative splicing transcription elongation GLTSCR1

Fabrication of multifunctional polydopamine-coated gold nanobones for PA/CT imaging and enhanced synergistic chemo-photothermal therapy

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Journal of Materials Science & Technology 2021年第4期63卷 97-105页

作者： Jingwei Xu Xiaju Cheng Fuxian Chen Weijie Li Xiaohui Xiao Puxiang Lai Guopeng Xu Li Xu Yue Pan department of Cardiothoralic Surgery Suzhou Municipal Hospital InstitutionSuzhou 215002China Jiangsu Key Laboratory of Infection and Immunity Institutes of Biology and Medical SciencesSoochow UniversitySuzhou 215123China Guangdong Provincial Key Laboratory of Malignant tumor Epigenetics and Gene Regulation Medical Research CenterSun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhou 510120China Center for precision medicine Sun Yat-Sen UniversityGuangzhou 510080China The Hong Kong Polytechnic University Department of Biomedical EngineeringHong Kong SARChina department of Respiratory medicine Suzhou Municipal Hospital InstitutionSuzhou 215002China

Multimodal imaging-guided chemo-photothermal therapy is an excellent cancer treatment,which can not only efficiently against tumor,but also can offer precise treatment window and real-time monitoring of the treatment *** our work,polydopamine(PDA)-coated gold nanobones(AuNBs@PDA nanocomplexes)were designed for this *** AuNBs@PDA nanocomplexes have strong absorbance in the near infrared(NIR)region and higher photothermal conversion efficiency(75.48%)than gold nanobones alone,which was facilitated for photoacoustic imaging and photothermal ***,the loading efficiency of doxorubicin(DOX)by AuNBs@PDA nanocomplexes could be up to about 70%and DOX release from AuNBs@PDA/DOX nanocomplexes sensitively response to the lower pH environment and NIR laser irradiation,which makes them become the excellent nano-carrier for the delivery of chemotherapy *** vitro and in vivo studies showed significant cytotoxicity and antitumor efficacy by the AuNBs@PDA/DOX nanoplatform with negligible side ***,the nanoplatform was also successfully employed for computed tomography(CT)imaging,attributing to the high atomic number and high X-ray attenuation coefficient of ***,we believed that the proposed PDA-coated gold nanobones would be a novel multifunctional theranostic nanoagent to realize the PA/CT imaging-guided chemo-photothermal therapy of cancer.

关键词： dopamine treatment bones

Designed fabrication of mesoporous silica-templated self-assembled theranostic nanomedicines

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Science China Chemistry 2021年第2期64卷 204-217页

作者： Fangyuan Li&Daishun Ling Yang Du Zheng Chen Ji Young Lee Peihua Lin Fan Xia Yunan Guan Fangyuan Li Daishun Ling Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Key Laboratory of Biomedical Engineering of the Ministry of Education College of Biomedical Engineering&Instrument ScienceZhejiang UniversityHangzhou 310027China Hangzhou Institute of Innovative medicine College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Key Laboratory of precision Diagnosis and Treatment for Hepatobiliary and Pancreatic tumor of Zhejiang Province Hangzhou 310009China

Theranostic nanosystems that integrate diagnosis and therapy have garnered increasing attention for personalized *** integration of the versatile nanoparticles to fabricate self-assembled theranostic nanomedicines becomes increasingly important in current medical *** silica nanoparticles(MSN)with their highly attractive physicochemical properties and favorable morphological attributes represent ideal templates for the controlled assembly and integration of functional nanomaterials to fabricate self-assembled theranostic *** rationally designed combination strategy and heterostructure will improve the overall bioavailability and preserve the unique property of each *** this review,the cutting-edge strategies for the designed fabrication of MSN-templated self-assembled nanomedicines are *** categorize MSN-based nanomedicines by their unique heterostructures,including core-shell,yolk-shell,core-satellite,heterodimer and core-shell-satellite structures,and discuss the controlled assembly approaches as well as the intriguing applications for disease ***,a perspective on the challenges in the clinical translation of self-assembled theranostic nanomedicines is highlighted.

关键词： self-assembly theranostics heterostructure mesoporous silica nanomedicines

Huge portal venous aneurysm incidentaloma caused by intrahepatic arterioportal fistula accompany with hepatobiliary stones and cholangitis

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Hepatobiliary Surgery and Nutrition 2021年第2期10卷 288-290页

作者： Zheng-Hao Liu Dong-Kai Zhou Yu-Cheng Xiang Cheng Zeng Wei-Lin Wang department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Key Laboratory of precision Diagnosis and Treatment for Hepatobiliary and Pancreatic tumor of Zhejiang Province HangzhouChina Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province HangzhouChina Clinical medicine Innovation Center of precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University HangzhouChina Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province HangzhouChina

A 64-year-old female was admitted to our department because of abdominal discomfort and recurrent fever for 1 month,she had attended her local hospital 10 days earlier,where the sign of fever was regarded as being due to the pulmonary infection,however,moxifloxacin and peramivir had no therapeutic *** admission,the physical examinations were showed an upper abdominal thrill and auscultation heard a blood vessel murmur at the same location,lab tests were not showed any remarkable results,the tumor marker levels were within normal *** portal color contrast ultrasonography was showed a 5.4 cm×3.3 cm bright spot in the left intrahepatic bile duct,and a 0.9 cm distal bright spot in,and 0.7 cm expansion of the right intrahepatic bile duct(Figure 1A).Contrast-enhanced computed tomography(CT)were showed intrahepatic cholangiectasis,tumor-like dilatation of the left portal ramus,and left liver atrophy and cirrhosis(Figure 1B).

关键词： intrahepatic admitted Figure

Mechanism of exosomal microRNA-224 in development of hepatocellular carcinoma and its diagnostic and prognostic value

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World Journal of Gastroenterology 2019年第15期25卷 1890-1898页

作者： Yao Cui Hai-Feng Xu Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Interventional Therapy department Peking University Cancer Hospital and Institute Ming-Yue Liu Yu-Jie Xu Jun-Chuang He Yun Zhou Shun-Dong Cang department of Oncology Henan Key Laboratory for Precision Medicine in Cancer Henan Provincial People's HospitalPeople's Hospital of Zhengzhou University School of Clinical Medicine Henan University department of Hepatobiliary Surgery Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou University School of Clinical Medicine Henan University

BACKGROUND Exosomes contain proteins, lipids, and biological molecules such as DNA and RNA. Nucleic acids in exosomes are a group of molecules that can act as biomarkers. Currently, there are many reports on exosomal microRNAs, which are ideal biomarkers for the early diagnosis of cancer. However, there are few reports on the role of exosomal microRNAs in the diagnosis and prognosis of hepatocellular carcinoma(HCC).AIM To understand the mechanism of exosomal microRNA-224(miR-224) in the development of HCC and evaluate its diagnostic and prognostic *** Cell culture and transfection of exosomal miRNA-224, real-time quantitative PCR, luciferase reporter assay, and other methods were used to find new biomarkers related to the development of HCC that can be used to diagnose HCC and predict HCC *** targeting glycine N-methyltransferase, incubating exosomes with miR-224 mimic resulted in a significant increase in cell proliferation compared to that of the control group, while incubation with the miR-224 inhibitor significantly reduced cell proliferation. The same results were obtained for the cell invasion assay. Serum exosomal miR-224 did have some ability to differentiate patients with HCC from healthy controls, with an area under the curve of 0.910, and HCC patients with higher serum exosomal miR-224 expression had lower overall *** Exosomal miR-224 is a tumor promotor and can be a marker of diagnosis and prognosis of HCC patients, however, its ability to distinguish liver diseases needs further verification.

关键词： Hepatocellular carcinoma Serum Exosome MicroRNA-224 Biomarker

Adrenal pheochromocytoma impacts three main pathways: cysteine-methionine, pyrimidine, and tyrosine metabolism

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第5期25卷 410-421页

作者： Chong LAI Qingling YANG Yunuo ZHANG Renjie GONG Majie WANG Jiankang LI Maode LAI Qingrong SUN department of Urology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China School of Basic Medical Sciences and Clinical Pharmacy China Pharmaceutical UniversityNanjing 210009China department of Laboratory medicine the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Laboratory of Behavioral Neuroscience Ningbo Kangning HospitalNingbo Institute of Microcirculation and HenbaneSchool of MedicineNingbo UniversityNingbo 315201China Xi'an Key Laboratory of Stem Celland Regenerative medicine Institute of Medical ResearchNorthwestern Polytechnical UniversityXi'an 710072China department of Pathology Research Unit of Intelligence Classification of Tumor Pathology and Precision TherapyChinese Academy of Medical Sciences Key Laboratory of Disease Proteomics of Zhejiang ProvinceZhejiang University School of MedicineHangzhou 310058China

Pheochromocytomas and paragangliomas(PPGLs)cause symptoms by altering the circulation levels of catecholamines and peptide ***,the diagnosis of PPGLs relies on diagnostic imaging and the detection of *** this study,we used ultra-performance liquid chromatography(UPLC)/quadrupole time-of-flight mass spectrometry(Q-TOF MS)analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma *** identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal *** conducting two steps of metabolomics analysis,we identified 111 differential metabolites between the healthy group and the patient group,among which 53 metabolites were *** integrating the information of differential metabolites and differentially expressed genes,we inferred that the cysteine-methionine,pyrimidine,and tyrosine metabolism pathways were the three main metabolic pathways altered by the *** analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma,whereas the pyrimidine pathway showed no significant ***,we developed an optimized diagnostic model of two metabolites,L-dihydroorotic acid and *** results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.

关键词： Pheochromocytoma and paraganglioma(PPGL) Metabolomics Gene set variation analysis L-Dihydroorotic acid Vanylglycol

Real-world clinical effectiveness of sorafenib among patients with unresectable hepatocellular carcinoma at two centers in the United States

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World Journal of Gastrointestinal Oncology 2023年第10期15卷 1796-1806页

作者： Daneng Li Stephen B Gruber Shrividya Iyer Sanjay Gupta Mohamedtaki Tejani department of Medical Oncology and therapeutics Research City of Hope Comprehensive Cancer CenterDuarteCA 91010United States Center for precision medicine City of Hope Comprehensive Cancer CenterDuarteCA 91010United States department of Oncology Worldwide Real-World EvidenceEisai Inc.NutleyNJ 07110United States department of Oncology and Hematology Advent Health Cancer InstituteOrlandoFL 32804United States

BACKGROUND In the United States,sorafenib monotherapy was approved in 2007 for first-line(1L)treatment of patients with unresectable hepatocellular carcinoma(uHCC).As other therapies have been approved in recent years for hepatocellular carcinoma treatment in later lines,it is essential to assess clinical effectiveness of older therapies in actual clinical practice to inform healthcare practitioners’decisions for better patient *** To assess patient characteristics/clinical effectiveness of 1L sorafenib in uHCC patients treated in United States academic and community practice *** A retrospective observational study was conducted among adult patients(≥18 years)in the United States initiating sorafenib monotherapy as 1L systemic therapy for uHCC with Eastern Cooperative Oncology Group status of 0 or 1 between January 2016 and December 2019 at City of Hope and Advent *** were extracted by trained abstractionists from individual patients’electronic health records and captured in electronic case report *** Review Board approvals were obtained prior to study *** were captured from the time of sorafenib initiation until death or the end of *** data were de-identified prior to *** outcomes assessed included provider-reported best response,progression-free survival(PFS),and overall survival(OS).PFS and OS were estimated using Kaplan-Meier *** Among 134 uHCC patients treated with 1L sorafenib,majority were male(75%),and most were Caucasian(62%)or Asian(19%).Median patient age was 64 *** most common etiologies of liver disease were hepatitis C(54%),alcohol-related liver disease(16%),and hepatitis B(11%).Most patients were reported to have Barcelona Clinic Liver Cancer stage B(19%)or stage C(70%)*** 134 patients,110(82%)were reported to have discontinued treatment or died during *** reasons for sorafenib discontinuation were reported as progression(35%)and toxici

关键词： Retrospective observational study Sorafenib Hepatocellular carcinoma Clinical effectiveness

Leukocyte cell-derived chemotaxin 2(LECT2)regulates liver ischemia-reperfusion injury

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Liver Research 2024年第3期8卷 165-171页

作者： Meng-Qi Dong Yuan Xie Zhi-Liang Tang Xue-Wen Zhao Fu-Zhen Lin Guang-Yu Zhang Zhi-Hao Huang Zhi-Min Liu Yuan Lin Feng-Yong Liu Wei-Jie Zhou State Key Laboratory of Organ Failure Research Department of General SurgeryGuangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal TumorNanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina department of Hepato-Biliary-Pancreatic and Hernia Surgery The First People's Hospital of ZhaoqingZhaoqingGuangdongChina department of Interventional Radiology Senior Department of OncologyFifth Medical Center of PLA General HospitalBeijingChina

Background and aim Hepatic ischemia–reperfusion injury(IRI)is a significant challenge in liver transplantation,trauma,hypovolemic shock,and hepatectomy,with limited effective interventions *** study aimed to investigate the role of leukocyte cell-derived chemotaxin 2(LECT2)in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA(shRNA)delivered through adeno-associated virus(AAV)*** and methods This study analyzed human liver and serum samples from five patients undergoing the Pringle ***2-knockout and C57BL/6J mice were *** IRI was induced by clamping the hepatic *** included recombinant human LECT2(rLECT2)and ***2 expression levels and serum biomarkers including alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine,and blood urea nitrogen(BUN)were *** analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were *** Serum and liver LECT2 levels were elevated during hepatic *** LECT2 protein and mRNA levels increased post ***2-knockout mice had reduced weight loss;hepatic necrosis;and serum ALT,AST,creatinine,and BUN ***2 treatment exacerbated weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN).AAV-Lect2-shRNA treatment significantly reduced weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN),indicating therapeutic *** Elevated LECT2 levels during hepatic IRI increased liver *** knockout or shRNA-mediated knockdown of Lect2 reduced liver damage,indicating its therapeutic ***-mediated Lect2-shRNA delivery mitigated hepatic IRI,offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

关键词： Hepatic ischemia-reperfusion injury(IRI) Leukocyte cell-derived chemotaxin 2 (LECT2) Adeno-associated virus(AAV)

Inhibition of focal adhesion kinase enhances antitumor response of radiation therapy in pancreatic cancer through CD8+ T cells

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Cancer Biology & medicine 2021年第1期18卷 206-214页

作者： Arsen Osipov Alex B.Blair Juliane Liberto Jianxin Wang Keyu Li Brian Herbst Yao Xu Shiqi Li Nan Niu Rufiaat Rashid Ding Ding Yanan Liu Zaiqi Wang Christopher L.Wolfgang Richard A.Burkhart Daniel Laheru Lei Zheng The Sydney Kimmel Comprehensive Cancer Center Johns Hopkins University School of MedicineBaltimore 21287MDUSA The Pancreatic Cancer precision medicine Center of Excellence Program Johns Hopkins University School of MedicineBaltimore 21287MDUSA department of Oncology Johns Hopkins University School of MedicineBaltimore 21287MDUSA department of Surgery Johns Hopkins University School of MedicineBaltimore 21287MDUSA Inx Med Shanghai Shanghai 201202China

Objective:Pancreatic ductal adenocarcinoma(PDAC)is a deadly malignancy,due in large part to its resistance to conventional therapies,including radiotherapy(RT).Despite RT exerting a modest antitumor response,it has also been shown to promote an immunosuppressive tumor *** studies demonstrated that focal adhesion kinase inhibitors(FAKi)in clinical development inhibit the infiltration of suppressive myeloid cells and T regulatory(T regs)cells,and subsequently enhance effector T cell *** inhibitors in clinical development have not been investigated in combination with RT in preclinical murine models or clinical ***,we investigated the impact of FAK inhibition on RT,its potential as an RT sensitizer and immunomodulator in a murine model of ***:We used a syngeneic orthotopic murine model to study the effect of FAKi on hypofractionated ***:In this study we showed that IN10018,a small molecular FAKi,enhanced antitumor response to *** activity of the combination of FAKi and RT is T cell *** in combination with RT enhanced CD8+T cell infiltration significantly in comparison to the radiation or FAKi treatment alone(Ptumor microenvironment of PDAC for immunotherapy.

关键词： Focal adhesion protein-tyrosine kinases radiotherapy pancreatic neoplasms immunomodulation

MicroRNAs as novel predictive biomarkers and therapeutic targets in colorectal cancer

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World Journal of Gastroenterology 2014年第33期20卷 11727-11735页

作者： Verena Stiegelbauer Samantha Perakis Alexander Deutsch Hui Ling Armin Gerger Martin Pichler Division of Clinical Oncology Department of Internal Medicine Medical University of Graz 8036 Graz Austria Division of Hematology Department of Internal Medicine Medical University of Graz 8036 Graz Austria department of Experimental therapeutics University of Texas MD Anderson Cancer Center Houston TX 77030 United States

Colorectal cancer(CRC) is the third most common cancer in western countries. Despite significant improvement in available treatment options, CRC still remains the second leading cause of cancer-related death. Traditionally, 5-fluorouracil has been used as the main chemotherapy drug for treatment of metastatic CRC(mCRC). However, during the last two decades more effective chemotherapeutic agents such as oxaliplatin, irinotecan and the monoclonal antibodies cetuximab, panitumumab and bevacizumab have been used in clinical practice. More recently, the therapeutic armamentarium has been supplemented by the monoclonal antibodies bevacizumab, cetuximab and panitumumab as well as the protein-trap aflibercept and the smallmolecule multi-kinase inhibitor regorafenib. One of the major problems for the management of CRC is the inherent or acquired resistance to therapeutic approaches. The discovery of microRNAs(miRNAs), a class of small, endogenous, non-coding, single-stranded RNAs that play a role as post-transcriptional regulators, has added new dimensions to the diagnosis and treatment of cancer. Because miRNAs are important regulators of carcinogenesis, progression, invasion, angiogenesis and metastases in CRC, they might serve as potential predictive and prognostic factors and even as therapeutic targets themselves. Several miRNAs are already known to be dysregulated in CRCs and have been linked to biological processes involved in tumor progression and response to anti-cancer therapies. This review summarizes current therapeutic approaches for treating CRC and highlights the role of miRNAs as novel predictive biomarkers and potential drug targets in CRC patients.

关键词： Colorectal cancer MicroRNAs 5-fluorouracil Epidermal growth factor receptor Targeted therapy