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Synergistic anti-tumor therapy by a homotypic cell membranecloaked biomimetic nanocarrier with exceptionally potent activity against hepatic carcinoma

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Nano Research 2022年第9期15卷 8255-8269页

作者： Shini Feng Pinyue Ni Yan Gong Bijiang Geng Hui Li Chenlin Miao Ruyu Fan Levon Galstyan Dengyu Pan Fuxue Chen Huafei Li School of Lifesciences Shanghai UniversityShanghai 200444China School of Environmental and Chemical Engineering Shanghai UniversityShanghai 200444China SLAVMED Medical Center Manandyan st.9 bld.Yerevan 0037Republic of Armenia

hepatic carcinoma(HC)is the sixth most frequently occurring malignancies and the third leading cause of cancer death *** bromide(YM155)is a small molecule inhibitor of survivin,which has broad-spectrum anticancer therapeutic effects in various xenograft ***,several-day continuous infusion is required to achieve greater antitumor efficacy because of rapid elimination from the blood ***,a SMMC-7721 cancerous cyto-membrane-cloaked drug delivery system(DDS)(named as iM7721@GQD-YM),was developed for co-encapsulation of YM155 and graphene quantum dots(GQDs).Cytomembrane coating endowed iM7721@GQD-YM with effective targeting for homologous HC cells,excellent biocompatibility and favorable immunocompatibility for in vivo *** decoration of iRGD peptide further enhanced its tumor targeting activity by iRGD-integrin *** addition,under the irradiation of near-infrared ray(NIR),GQDs can directly kill tumors through photothermal effect and cause cell membrane rupture,accurately releasing YM155 at tumor *** physicochemical properties,in vivo and ex vivo anti-tumor efficacy,and mechanisms of iM7721@GQD-YM nanoparticles(NPs)were systematically investigated in this *** experimental results clearly indicate that the versatile biomimetic DDS holds great potential for the treatment of HC,which merits further investigation in both pre-clinical and clinical studies.

关键词： hepatic carcinoma sepantronium bromide(YM155) cancer cell membrane biomimetic drug delivery system graphene quantum dots photothermal effect

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Nanotechnology-based combinational strategies toward the regulation of myofibroblasts and diseased microenvironment in liver fibrosis and hepatic carcinoma

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Nano Research 2023年第12期16卷 13042-13055页

作者： Fenfen Li Ying Zhao Guangjun Nie School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China CAS Center for Excellence in Nanoscience National Center for Nanoscience and TechnologyBeijing 101408China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China GBA National Institute for Nanotechnology Innovation Guangzhou 510530China

Liver fibrosis and hepatic carcinoma(HCC)pose a huge challenge worldwide due to the lack of effective treatment options for end-stage liver *** to their functions and roles,hepatic myofibroblasts mainly include nontumoral fibroblasts(mainly activated hepatic stellate cells(HSCs)),which are involved in the wound-healing process of liver fibrosis,and cancer-associated fibroblasts(CAFs)in hepatic *** play a significant role in regulating extracellular matrix(ECM)deposition in progressive liver *** can be derived from activated HSCs and differentiate into ECM-producing ***,growing evidence shows that CAFs are the primary regulators of the HCC microenvironment,releasing growth factors and cytokines and suppressing the antitumor immune *** therapeutic strategies show reduced drug resistance and side ***-based combined strategies aim to improve the delivery efficiency of various therapeutic agents with reduced toxicity via multiple *** this review,we will discuss recent developments in combinational strategies based on nanotechnology that regulate myofibroblasts and the diseased microenvironment for liver fibrosis and HCC *** will also identify the major challenges that the field is facing and offer some insights for future drug discovery.

关键词： fibroblasts liver fibrosis hepatic carcinoma nanotechnology

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An Intelligent Prediction Model for Target Protein Identification in hepatic carcinoma Using Novel Graph Theory and ANN Model

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Computer Modeling in Engineering & Sciences 2022年第10期133卷 31-46页

作者： G.Naveen Sundar Stalin Selvaraj D.Narmadha K.Martin Sagayam A.Amir Anton Jone Ayman A.Aly Dac-Nhuong Le Computer Science and Engineering Karunya Institute of Technology and SciencesCoimbatore641114India Centre for Nanotechnology&Advanced Biomaterials(CeNTAB) School of Chemical&BiotechnologySASTRA Deemed to be UniversityThanjavur613401India Department of ECE Karunya Institute of Technology and SciencesCoimbatore641114India Department of Mechanical Engineering College of EngineeringTaif UniversityTaif21944Saudi Arabia Institute of Research and Development Duy Tan UniversityDanang550000Vietnam Faculty of Information Technology Duy Tan UniversityDanang550000Vietnam

Hepatocellular carcinoma(HCC)is one major cause of cancer-related mortality around the ***,at advanced stages of HCC,systematic treatment options are currently *** a result,new pharmacological targetsmust be discovered regularly,and then tailored medicines against HCC must be *** this research,we used biomarkers of HCC to collect the protein interaction network related to ***,DC(Degree Centrality)was employed to assess the importance of each *** an improved Graph Coloring algorithm was used to rank the target proteins according to the interaction with the primary target protein after assessing the top ranked proteins related to ***,physio-chemical proteins are used to evaluate the outcome of the top ranked *** proposed graph theory and machine learning techniques have been compared with six existing *** the proposed approach,16 proteins have been identified as potential therapeutic drug targets for hepatic *** is observable that the proposed method gives remarkable performance than the existing centrality measures in terms of Accuracy,Precision,Recall,Sensitivity,Specificity and F-measure.

关键词： Drug target detection hepatic carcinoma degree centrality graph coloring artificial neural network model

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Correlation between blood circulation grading and angiogenesis using ultrasonic contrast of rabbit VX2 hepatic carcinoma

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Asian Pacific Journal of Tropical Medicine 2016年第2期9卷 148-153页

作者： Chang-Song Xu Yi-Jin Su Ming Xu Wei Liu Peng Hao Lian-Fang Du Department of Ultrasound Huai'an First People's Hospital Nanjing Medical University Department of Ultrasound Shanghai General Hospital of Nanjing Medical University

Objective: To build the rabbit model of VX2 hepatic carcinoma, examine the tumor body using the ultrasonic contrast and study the correlation between the blood circulation grading and angiogenesis. Methods: The VX2 tumor strain was prepared in the lateral muscle of the hind legs of 40 male New Zealand rabbits (which were purchased from Nanjing Senbao Biotech Co., Ltd.). The tumor block was embedded in the center of left liver lobe directly to build the rabbit model of VX2 hepatic carcinoma. The ultrasonic contrast was performed 14 d after implanting the tumor body. The semi-quantitative classification (0-IV level) was taken according to the blood flow of tumor vessel. Animals were executed using the air embolism method. The liver was separated to extract RNA and total protein respectively. The real-time PCR and western blotting method were employed to detect the expression of angiogenesis-related factors of VEGF, bFGF and TNP-alpha, while the ultrasonic contrast to detect the correlation with blood circulation grading. The Pearson product moment correlation coefficient was used to measure the linear relationship between these two variables and analyze the correlation between the blood circulation grading and angiogenesis using the ultrasonic contrast. Results: Thirty-three rabbits had the successful model of VX2 hepatic carcinoma. The blood circulation grading by ultrasonic contrast was: 2 cases at level 0 (6.60%), 5 cases at level I (16.7%), 12 cases at level 11 (40.0%), 6 cases at level III (20.0%) (local dense or clustered blood flow) and 5 cases at level IV (16.7%). The results showed that there was positive correlation between three angiogenesis-related factors and the blood circulation grading. The correlation coefficient between three angiogenesis-related factors and the blood circulation grading was over 0.9, which indicated the relatively high correlation. Conclusions: The ultrasound blood circulation grading for the hepatic carcinoma can clearly reflect th

关键词： hepatic carcinoma VX2 Ultrasonic contrast Angiogenesis bFGF TNF-alpha

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COLOR FLOW IMAGING OF hepatic carcinoma

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Chinese Journal of Cancer Research 1994年第1期6卷 45-50页

作者： Xu Zhizhang Wang Wenping(Department of Diagnostic Ultrasound,Zhongshan Hospital,Shanghai Medical University,Shanghai 200032) 1. Department of Diagnostic Ultrasound Zhongshan Hospital Shanghai Medical University 200032 Shanghai

Color flow imaging(CFI)ultrasound technique can discover the tumor vascularity and superimposed it to convontional B-mode ultrasonogram in real-time. The flow velocity on spectral Doppler sonogram can be measured by setting the sample volume to any selected *** hundred and thirty-six patients with solid hepatic space-occupied lesions had been admitted and 113 cases were confirmed by operation and pathology,23 patients were strongly suspected by hepatic angiography (HAA).Ninety nine patients with 109 nodules were finally diagnosed as hepatic cellular carcinoma(HCC).According to color flow distribution pattern,3 kinds of color configuation had been *** vascularity discovered by CFI,especially the arterial blood flow was easy to be recognized,and its emerge rate was quite different between HCC group(94.5%)and hemangioma(HCH)group(17.07%)(P0. 50 and >0.80 respectively)from HCH (P0.6m/s).The detection rate of A-P shunt was 64% in HCC group,but no case could be detected in HCH group.

关键词： hepatic carcinoma Color flow imaging(CFI) Spectral Doppler sonogram Resistant index(RI) Pulsatile index(PI) hepatic artery angiography(HAA).

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Anti-hepatic carcinoma mechanisms of calycosin through targeting ferroptosis

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Intelligent Medicine 2023年第3期3卷 173-179页

作者： Litao Nie Yimei Liao Rui Zhou Xiao Liang Xiaowei Wan Xin Li Min Su Key Laboratory of Environmental Pollution and Integrative Omics Guilin Medical UniversityGuilinGuangxi Zhuang Autonomous Region 541004China Department of Clinical Pharmacy Guigang City People's HospitalThe Eighth Affiliated Hospital of Guangxi Medical UniversityGuigangGuangxi Zhuang Autonomous Region 537100China Department of Hepatobiliary Surgery Guigang City People's HospitalThe Eighth Affiliated Hospital of Guangxi Medical UniversityGuigangGuangxi Zhuang Autonomous Region 537199China Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation Guilin Medical UniversityGuilinGuangxi Zhuang Autonomous Region 541004China

Background Ferroptosis,a pathologic state induced by lipid-driven oxidative stress,is associated with the development of human ***,a natural compound with antioxidant and anti-inflammatory activities,has promising antitumor ***,the ferroptosis-related mechanism of calycosin in the treatment of hepatic carcinoma has not been *** This study applied network pharmacology and bioinformatic approaches(including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis)to investigate the pharmacologic targets and mechanism of action of calycosin in the treatment of hepatic carcinoma through targeting *** searching online databases including The Cancer Genome Atlas,FerrDb,GeneCards,SwissTargetPrediction,SuperPred,BindingDB,TargetNet,BATMAN-TCM,and Drugbank,we identified 13 ferroptosis-related putative target genes of calycosin against hepatic carcinoma including IL-6,PTGS2,SRC,HRAS,NQO1,NOX4,PGK1,G6PD,GPI,MIF,NOS2,ALDOA,and *** Molecular docking analysis revealed that calycosin potentially binded directly with the target proteins IL-6,PTGS2,and *** enrichment analysis of these proteins indicated that they were involved in gluconeogenesis and apoptosis through regulation of ERK1,ERK2,and MAPK activities(Phepatic carcinoma by targeting ferroptosis through regulation of IL-6,PTGS2,and SRC.

关键词： hepatic carcinoma Ferroptosis Calycosin Bioinformatics Pharmacologic target

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Intraoperative ultrasonography during radiofrequency ablation for hepatic carcinoma

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The Chinese-German Journal of Clinical Oncology 2008年第5期7卷 263-265页

作者： Wentao Kong Weiwei Zhang Ningyi Shao Hanzi Xu Department of Hepato-biliary Surgery Nanjing Drum Tower Hospital Affiliated to Medical School Nanjing University Nanjing 210008 China

Objective： To explore the feasibility and efficiency of intraoperative ultrasonography （IOUS） in the cool-tip ra- diofrequency ablation （RFA） of hepatic carcinoma. Methods： Thirty-one patients of hepatic carcinoma were enrolled in this study. In the process of open-surgical cool-tip radiofrequency ablations, IOUS was applied to assess the hepatic lesions, guide and monitor the process of RFA in real-time. Results： Under the guidance of intraoperative ultrasonography, the open surgical RFA in all patients proceed smoothly. Seven additional hepatic lesions were found that were not detected in preoperative imaging. A false positive focal lesion reported by preoperative MRI was accurately ruled out by IOUS. Conclusion： Intraoperative ultrasonography is superior to ordinary imaging techniques in finding missed lesions, avoiding complications such as injuries of bile ducts and vessels. Monitoring the real-time RFA process thereby obviously optimizing the treatment of hepatic carcinoma.

关键词： intraoperative ultrasonography radiofrequency ablation hepatic carcinoma

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The expression of TGF-β_1,ADAM12 and HB-EGF in primary hepatic carcinoma

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The Chinese-German Journal of Clinical Oncology 2008年第12期7卷 686-689页

作者： Hailin Cheng De＇an Tian Xudong Hu Mei Liu Zili Dan Bo Wang Peiyuan Li Xiaoping Chen Department of Gastroenterology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Department of Liver Disease Wuhan Medical Treatment Center Whan 430022 China

Objective: To detect the expression and location of TGF-β1, ADAM12 and HB-EGF in primary hepatic carcinoma and study their effect on the growth and metastasis of hepatoma carcinoma cell. Methods: TGF-β1, ADAM12 and HB-EGF were detected by RT-PCR and immunohistochemistry in 30 cases of hepatic carcinoma tissues, 30 cases of adjacent carci- noma tissues and 5 cases of normal hepatic tissues. Results: RT-PCR analyses showed that the mRNA expression of TGF-β1, ADAM12 and HB-EGF were markedly increased in each hepatic carcinoma tissue compared with its adjacent tissue (P hepatic tissue. Immunohistochemistry showed the same outcome on the expression of above three factors in hepatic tissues as RT-PCR. Proteins location analyses showed the proteins of TGF-β1, ADAM12 and HB-EGF all distributed in the stroma of hepatic carcinoma tissues. The positive correlation was found between TGF-β1 and ADAM12 (r = 0.6137, P carcinoma cells, portal vein thrombus and the metastasis of absorbent glands, especially with hepatic cirrhosis caused by hepatitis B virus. Conclu- sion: TGF-β1, ADAM12 and HB-EGF possibly play an important role in the process of growth, invasion and metastasis of hepatoma carcinoma cell, meanwhile, the above three factors may collectively participate in the transition from hepatic cirrhosis caused by hepatitis B virus to hepatocellular carcinoma.

关键词： transforming growth factor-beta1 a disintegrin and metalloprotease-12 heparin-binding EGF-like growth factor hepatic carcinoma metastasis

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Inorganic drug as a part of nanocarries: delivery of arsenic trioxide for enhanced anti-cancer therapy of hepatic carcinoma

Inorganic drug as a part of nanocarries: delivery of arsenic...

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2018年第十二届中国药物制剂大会

作者：姚文栋 Tao Jiaoyang Zhu Jingjing Li Fanzhu Zhejiang Chinese Medical University

The aim of our study was to construct a FA and PEG-modified lipid coated nanoparticle（NP） for targeting delivery and controlled release of arsenic trioxide（ATO）, using a reverse microemulsion method. Herein, ATO, an inorganic drug, was used as a major material to construct nanocarries. Taking advantage of reaction of ATO and Calcium ion, we have developed a novel method for synthesizing the nanoparticle with uniform size（121.2±0.93 nm）, high drug loading capacity（18.52±0.69%）, and pH-dependent drug release in pH 5.5, 6.8 and 7.4, respectively. The formulation was done in two steps. The pure ATO and Calcium ion were first stabilized for dispersion in an organic solvent by coating with 1, 2-dioleoylsn-glycero-3-phosphate（DOPA）. After purification, additional lipids were added to stabilize the NPs for dispersion in an aqueous solution. The final NPs contain a lipid bilayer coating. At the same time, hemolytic toxicity and the cytotoxicity, cell cycle analysis, cellular uptake of the drug delivery system were examined based on HepG2 and LO2, showing good biosafety, nice uptake and in vitro anti-tumor ability of nanocarriers by HepG2. In summary, this suggested that the NPs in this synthetic strategy provided a promising way for hepatic carcinoma therapy.

关键词： Nanocarries Arsenic trioxide Calcium ion Two steps hepatic carcinoma

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Ultrasound-guided fine needle biopsy of intra- hepatic nodules and low elevation of AFP in early diagnosis of hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2005年第1期4卷 50-54页

作者： Yi-Mi He, Xiao-Yan Wang, Shang-Da Gao, Li-Yun Yu, Xiao-Dong Lin and Li-Wu Lin Fuzhou, China Department of Ultrasonography, Union Hospital of Fujian Medical University, Fujian Provincial Ultrasonic Medical Institute, Fuzhou 350001, China Department of Ultrasonography Union Hospital of Fujian Medical University Fujian Provincial Ultrasonic Medical Institute Fuzhou 350001 China. rosehe5893@***

BACKGROUND: With the progress in early clinical treat- ment of hepatocellular carcinoma (HCC), early detection and diagnosis of HCC have been increasingly pressing. Combined alpha-fetoprotein ( AFP) determination and ul- trasonography has become the main method for the detec- tion of small HCC; but the relationship between low eleva- tion of AFP and pathologic findings of small HCC has not been well defined. The aim of this study was to assess the value of ultrasound-guided fine needle biopsy of intrahe- patic nodules and low elevation of serum AFP in the early diagnosis of HCC. METHODS; Fifty-nine patients with serum AFP exceeding 20 ng/ml and intrahepatic nodules varying from 0.8 cm to 5.0 cm in diameter who had been detected by ultrasonogra- phy underwent ultrasound-guided percutaneous fine needle biopsy, and cytological staining and histological sectioning were performed at the same time. RESULTS: Among the 59 patients, 11 patients (18.6%) showed AFP level above 400 ng/ml, 5 (8. 5%) from 200 ng/ml to 400 ng/ml, 18 (30. 5%) from 50 ng/ml to 200 ng/ml and 25 (42. 4% ) from 20 ng/ml to 50 ng/ml. Fol- low-up demonstrated that 53 patients (89.8%) had a pro- gressive increase of AFP level. In 58 patients (98.3%) cancer cells were found by cytological staining and/or his- tological sectioning. CONCLUSIONS: In those patients with slightly increased or continuously positive AFP, hepatic carcinoma should be highly suspected when AFP increases gradually and intrahe- patic nodules are detected by ultrasonography in follow-up. Once intrahepatic carcinoma nodules are suspected, ultra- sound-guided fine needle biopsy should be performed as early as possible for early diagnosis and treatment.

关键词： ultrasonography hepatic carcinoma alpha-fetoprotein fine needle biopsy

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