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Targeting miRNA by CRISPR/Cas in cancer:advantages and challenges

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Military medical Research 2024年第3期11卷 345-373页

作者： Bashdar Mahmud Hussen Mohammed Fatih Rasul Snur Rasool Abdullah Hazha Jamal Hidayat Goran Sedeeq Hama Faraj Fattma Abodi Ali Abbas Salihi Aria Baniahmad Soudeh Ghafouri-Fard Milladur Rahman Mark C.Glassy Wojciech Branicki Mohammad Taheri Department of Biomedical Sciences Cihan University-ErbilErbilKurdistan Region 44001Iraq Department of Clinical Analysis College of PharmacyHawler Medical UniversityErbilKurdistan Region 44001Iraq Department of Pharmaceutical Basic Science Faculty of PharmacyTishk International UniversityErbilKurdistan Region 44001Iraq medical Laboratory Science Lebanese French UniversityErbilKurdistan Region 44001Iraq Department of Biology College of EducationSalahaddin University-ErbilErbilKurdistan Region 44001Iraq Department of medical Laboratory Science Komar University of Science and TechnologySulaymaniyah 46001Iraq Department of medical Microbiology College of Health SciencesHawler Medical UniversityErbilKurdistan Region 44001Iraq Department of Biology College of ScienceSalahaddin University-ErbilErbilKurdistan Region 44001Iraq Center of Research and Strategic Studies Lebanese French UniversityErbil 44001Iraq Institute of Human Genetics Jena University Hospital07747 JenaGermany Department of medical Genetics School of MedicineShahid Beheshti University of Medical SciencesTehran 374-37515Iran Department of Clinical Sciences MalmöSection for SurgeryLund University22100 MalmöSweden Translational Neuro-oncology Laboratory San Diego(UCSD)Moores Cancer CenterUniversity of CaliforniaSan DiegoCA 94720USA faculty of Biology Institute of Zoology and Biomedical ResearchJagiellonian University31-007 KrakówPoland Urology and Nephrology Research Center Shahid Beheshti University of Medical SciencesTehran 374-37515Iran

Clustered regulatory interspaced short palindromic repeats(CRISPR)has changed biomedical research and provided entirely new models to analyze every aspect of biomedical sciences during the last *** the study of cancer,the CRISPR/CRISPR-associated protein(Cas)system opens new avenues into issues that were once unknown in our knowledge of the non-coding genome,tumor heterogeneity,and precision ***/Cas-based geneediting technology now allows for the precise and permanent targeting of mutations and provides an opportunity to target small non-coding RNAs such as microRNAs(miRNAs).However,the development of effective and safe cancer gene editing therapy is highly dependent on proper design to be innocuous to normal cells and prevent introducing other *** study aims to highlight the cutting-edge approaches in cancer-gene editing therapy based on the CRISPR/Cas technology to target miRNAs in cancer ***,we highlight the potential challenges in CRISPR/Cas-mediated miRNA gene editing and offer advanced strategies to overcome them.

关键词： CRISPR CRISPR/Cas9 CRISPR/Cas12 Gene editing miRNAs Cancer therapy

Beamline design for multipurpose muon beams at CSNS EMuS

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Nuclear Science and Techniques 2024年第5期35卷 1-12页

作者： Yang Hong Ying-Peng Song Lu-Ping Zhou Jing-Yu Tang Zhi-Hao Zhou Nikolaos Vassilopoulos Institute of High Energy Physics Chinese Academy of Sciences(CAS)Beijing 100049China Spallation Neutron Source Science Center Dongguan 523803China University of Chinese Academy of Sciences Beijing 100049China radiotherapy Physics and Technology Center Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China Xi’an Jiaotong University Health Science Center Xi’an 710049China Department of Radiation oncology First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710049China School of Nuclear Science and Technology University of Science and Technology of ChinaHefei 230027China

A new muon beam facility,called the Experimental Muon Source(EMuS),was proposed for construction at the China Spallation Neutron Source(CSNS).The design of the complex muon beamlines for the EMuS baseline scheme,which is based on superconducting solenoids,superferric dipoles and room-temperature magnets,is presented *** muon beams,including surface muons,decay muons and low energy muons,have been developed for multipurpose *** optics design and simulation results of the trunk beamline and branch beamlines are *** a proton beam power of 25 kW at a standalone target station that consists of a conical graphite target and high-field superconducting solenoids,the muon beam intensity in the trunk beamline varies from 10^(7)/s for surface muons to 10^(10)/s for high-momentum decay *** at the endstations,these values vary from 10^(5)/s for surface muons to 10^(8)/s for decay muons.

关键词： Surface muons Decay muons Muon beamline Superconducting solenoids Multi-channel electrostatic separator

Extended survival with metastatic pancreatic cancer under fruquintinib treatment after failed chemotherapy:Two case reports

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World Journal of Clinical Cases 2024年第7期12卷 1296-1304页

作者： Dan Wu Qiong Wang Shuai Yan Xia Sun Ya Qin Ming Yuan Nan-Yao Wang Xian-Ting Huang Department of oncology Jiangyin People's HospitalWuxi 214400Jiangsu ProvinceChina

BACKGROUND Pancreatic cancer is a highly malignant *** decades of treatment progress,the current five-year survival rate for patients is still less than 10%.For later-line treatment,the treatment options are even more ***-angiogenic drugs can improve progression-free survival in patients with advanced pancreatic *** data show that fruquintinib might improve the prognosis of advanced pancreatic cancer by targeting angiogenesis and lymphopoiesis,improving the abnormal vascular structure,and modulating the tumour immune *** SUMMARY We present two cases of third-line fruquintinib monotherapy that brought an extraprolonged progress-free survival(PFS)of 10 *** 1 took adjuvant gemcitabine-based and first-line nab-paclitaxel-based chemotherapy and then used local radiotherapy combined with programmed cell death 1 receptor(PD-1).Each line lasted approximately 7 ***,the patient took third-line fruquintinib,which was followed by stable disease for 10 months,during which no additional adverse effect was *** patient later refused to take fruquintinib due to difficulty urinating and lower abdominal pain after the coronavirus disease 2019(COVID-19)*** patient died in February *** 2 also took two prior lines of chemotherapy and then local radiotherapy combined with *** confirmed disease progression,the patient experienced a continuous partial response after using fruquintinib monotherapy in the third *** the patient had COVID-19 in December 2022,fruquintinib was *** patient died in January 2023 due to disease *** Both cases achieved a PFS benefit from later-line single-agent fruquintinib *** its better safety profile,fruquintinib may be worth exploring and studying in more depth as a later-line treatment for pancreatic cancer patients.

关键词： Pancreatic cancer Anti-vascular endothelial growth factor receptor Fruquintinib Case report

Application of radioactive iodine-125 microparticles in hepatocellular carcinoma with portal vein embolus

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2023-2030页

作者： Peng Meng Ji-Peng Ma Xiao-Fei Huang Kang-Le Zhang The Fourth Department of oncology Yantai Hospital of Traditional Chinese MedicineYantai 264001Shandong ProvinceChina Department of medical Services Yantai Hospital of Traditional Chinese MedicineYantai 264001Shandong ProvinceChina Department of Hepatobiliary Surgery The First Affiliated Hospital of Sun Yatsen UniversityGuangzhou 510062Guangdong ProvinceChina The Third Department of oncology Yantai Hospital of Traditional Chinese MedicineYantai 264001Shandong ProvinceChina

BACKGROUND Radioactive iodine-125(125I)microparticle therapy is a new type of internal radiation therapy that has shown unique advantages in the treatment of malignant tumors,especially hepatocellular *** with hepatocellular carcinoma frequently experience portal vein embolism,which exacerbates the difficulty and complexity of treatment.125I particles,used in local radiotherapy,can directly act on tumor tissue and reduce damage to surrounding healthy *** retrospective analysis,this study discussed the efficacy and safety of radioactive 125I particles in portal vein embolization patients with hepatocellular carcinoma in order to provide more powerful evidence supporting clinical *** To investigate the effect of transcatheter arterial chemoembolization combined with portal vein 125I particle implantation in the treatment of primary liver cancer patients with portal vein tumor thrombus and its influence on liver *** The clinical data of 96 patients with primary liver cancer combined with portal vein tumor thrombus admitted to our hospital between January 2020 and December 2023 were retrospectively ***-two patients received treatment with transcatheter arterial chemoembolization and implantation of 125I particles in the portal vein(combination group),while 44 patients received treatment with transcatheter arterial chemoembolization alone(control group).The therapeutic effects on tumor lesions,primary liver cancer,and portal vein tumor embolisms were compared between the two *** in relevant laboratory indexes before and after treatment were *** t test was used to compare the measurement data between the two groups,and the χ^(2) test was used to compare the counting data between *** The tumor lesion response rate in the combination group(59.62%vs 38.64%)and the response rate of patients with primary liver cancer complicated with portal vein tumor thrombus(80.77%vs 59.09%)were signi

关键词： Radioactive iodine-125 Hepatocellular carcinoma Transcatheter arterial chemoembolization Portal vein embolus Retrospective study

Circulating tumor cells shielded with extracellular vesicle-derived CD45 evade T cell attack to enable metastasis

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2114-2131页

作者： Chuan Yang Xueping Wang Kenneth K.W.To Caimei Cui Min Luo Shaocong Wu Lamei Huang Kai Fu Can Pan Zeyu Liu Teng Fan Caibo Yang Fang Wang Liwu Fu State Key Laboratory of oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060P.R.China School of Pharmacy Faculty of MedicineThe Chinese University of Hong KongHong KongChina LABVIV Technology(Shenzhen)Co. LtdShenzhen 518057China

Circulating tumor cells(CTCs)are precursors of distant metastasis in a subset of cancer patients.A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer *** remains elusive how CTCs evade immune surveillance and elimination by immune *** this study,we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle(EVs)-derived CD45(termed as CD45^(+)CTCs)that resisted T cell attack.A higher percentage of CD45^(+)CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer ***,CD45^(+)tumor cells orchestrated an immunosuppressive milieu and CD45^(+)CTCs exhibited remarkably stronger metastatic potential than CD45−CTCs in ***,CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells,thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune ***,these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis,providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.

关键词： CD45 metastasis prevention

5-Fluorouracil dose escalation generated desensitized colorectal cancer cells with reduced expression of protein methyltransferases and no epithelial-to-mesenchymal transition potential

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oncology Research 2024年第6期32卷 1047-1061页

作者： KIMBERLY FENECH ISAAC MICALLEF BYRON BARON Centre for Molecular Medicine and Biobanking University of MaltaMsidaMSD 2080Malta Department of Tumor Genetics and Biology Graduate School of Medical SciencesFaculty of Life SciencesKumamoto UniversityKumamoto860-8556Japan

Background:Colorectal cancer(CRC)is one of the most frequently diagnosed *** many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many *** study looked into the effect of 5-FU dose escalation on EMT and protein methylation in *** and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of *** motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion *** was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized *** blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation ***:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of *** 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental *** was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell ***,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU ***:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU

关键词： Chemoresistance Epithelial-to-mesenchymal transition Protein methylation Protein methyltransferases

Circulating tumor DNA and its role in detection, prognosis and therapeutics of hepatocellular carcinoma

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Chinese Journal of Cancer Research 2024年第2期36卷 195-214页

作者： Sana Rashid Yingchuan Sun Umair Ali Khan Saddozai Sikandar Hayyat Muhammad Usman Munir Muhammad Usman Akbar Muhammad Babar Khawar Zhiguang Ren Xinying Ji Malik Ihsan Ullah Khan Institute of Molecular Biology and Biotechnology University of LahoreLahore 54590Pakistan Department of Internal oncology(Section Ⅰ) Xuchang Municipal Central HospitalXuchang 461000China Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225001China Australian Institute for Bioengineering&Nanotechnology the University of QueenslandBrisbane 4072Australia Gomal Center of Biochemistry and Biotechnology Gomal UniversityDera Ismail Khan 29111Pakistan Applied Molecular Biology and Biomedicine Lab Department of ZoologyUniversity of NarowalNarowal Punjab 51600Pakistan Kaifeng Municipal Key Laboratory for Infection and Biosafety Henan International Joint Laboratory of Nuclear Protein RegulationSchool of Basic Medical SciencesHenan UniversityKaifeng 475004China faculty of Basic medical Subjects Shu-Qing Medical College of ZhengzhouZhengzhou 450064China Department of Medicine Huaxian County People's HospitalHuaxian 456400China

Hepatocellular carcinoma(HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers;the most prominent is circulating tumor DNA(ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction(PCR) [emulsion PCR(ePCR), digital PCR(dPCR), and bead, emulsion, amplification, magnetic(BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection,treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations(either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1;2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF;3) DNA methylation(RASSF1A, SEPT9, KMT2C and CCNA2);4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1;and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful ***, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that f

关键词： Hepatocellular carcinoma circulating tumor DNA biomarkers single nucleotide variations diagnosis prognosis

Metabologenomics and network pharmacology to understand the molecular mechanism of cancer research

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World Journal of Clinical Cases 2024年第3期12卷 474-478页

作者： Yusuf Tutar Department of Basic Pharmaceutical Sciences Faculty of PharmacyDivision of BiochemistryUniversity of Health SciencesIstanbul 34668Turkey Health Sciences faculty Recep Tayyip Erdogan UniversityRize 53350Turkey Molecular oncology Division Health Sciences InstitutesUniversity of Health SciencesIstanbul 34668Turkey Molecular Medicine Division Health Sciences InstitutesUniversity of Health SciencesIstanbul 34668Turkey

In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cases 2023 November 6;11(31):*** all living forms are able to manufacture particular chemicals-metabolites that enable them to differentiate themselves from one another and to overcome the unique obstacles they encounter in their natural *** methods for chemical warfare,communication,nutrition acquisition,and stress prevention are made possible by these specialized *** is a popular technique for collecting direct mea-surements of metabolic activity from many biological ***,con-fusing metabolite identification is a typical issue,and biochemical interpretation is frequently constrained by imprecise and erroneous genome-based estimates of enzyme *** annotation and gene integration uses a biochemical reaction network to obtain a metabolite-gene association so called *** network uses an approach that emphasizes metabolite-gene consensus via biochemical *** metabolomics and genomics data is ***,computer networking proposes that using meta-bolomics data may improve annotations in sequenced species and provide testable hypotheses for specific biochemical *** The genome and metabolites of biological organisms are not fully characterized with current ***,increasing high-throughput metabolomics and genomics data provide promising generation of paired data sets to understand the molecular mechanism of biochemical processes as well as determining targets for pharmaceutical drug *** network infrastructures to integrate omics analysis can provide molecular mechanism of biochemical ***,clinical data may be integrated to gene expression–metabolite expression by system genetics appr

关键词： Network pharmacology Metabologenomics Genome Pathways Cancer

Engineering nanomedicines for immunogenic eradication of cancer cells:Recent trends and synergistic approaches

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2475-2504页

作者： Ahmed O.Elzoghby Omar Samir Hagar E.Emam Ahmed Soliman Riham M.Abdelgalil Yomna M.Elmorshedy Kadria A.Elkhodairy Mahmoud L.Nasr Division of Engineering in Medicine and Division of Renal Medicine Department of MedicineBrigham and Women's HospitalHarvard Medical SchoolBoston 02115MAUSA Cancer Nanotechnology Research Laboratory(CNRL) Faculty of PharmacyAlexandria UniversityAlexandria 21521Egypt

Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment(TME)leading to failure of immune *** therapeutic strategies including chemotherapy,radiotherapy,photodynamic,photothermal,magnetic,chemodynamic,sonodynamic and oncolytic therapy,have been developed to induce immunogenic cell death(ICD)of cancer cells and thereby elicit immunogenicity and boost the antitumor immune ***,many challenges hamper the clinical application of ICD inducers resulting in modest immunogenic ***,we outline the current state of using nanomedicines for boosting ICD of cancer ***,synergistic approaches used in combination with ICD inducing nanomedicines for remodeling the TME via targeting immune checkpoints,phagocytosis,macrophage polarization,tumor hypoxia,autophagy and stromal modulation to enhance immunogenicity of dying cancer cells were *** further highlight the emerging trends of using nanomaterials for triggering amplified ICD-mediated antitumor immune *** reticulum localized ICD,focused ultrasound hyperthermia,cell membrane camouflaged nanomedicines,amplified reactive oxygen species(ROS)generation,metallo-immunotherapy,ion modulators and engineered bacteria are among the most innovative *** challenges,merits and demerits of ICD inducer nanomedicines were also discussed with shedding light on the future role of this technology in improving the outcomes of cancer immunotherapy.

关键词： Immunogenic cell death Immunogenic eradication Nanomedicines Drug delivery Cancer immunotherapy Antitumor immunity T cells Tumor associated antigens Synergistic immune response