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Nanocarrier drugs in the treatment of brain tumors

Journal of Cancer Metastasis and Treatment 2016年第1期2卷 407-416页

作者： Tereza Cerna Marie Stiborova Vojtech Adam Rene Kizek Tomas Eckschlager Department of Biochemistry Faculty of ScienceCharles UniversityAlbertov 2030CZ-12840 Prague 2Czech Republic Department of Chemistry and Biochemistry Laboratory metallomics and nanotechnologyMendel University in Brno and Central European Institute of TechnologyBrno University of TechnologyZemědělská1CZ-61300 BrnoCzech Republic Department of Human Pharmacology and Toxicology Faculty of PharmacologyUniversity of Veterinary and Pharmaceutical Sciences BrnoPalackeho 1CZ 61242 BrnoCzech Republic Department of Pediatric Hematology and Oncology 2nd Faculty of MedicineCharles Universityand University Hospital MotolV Uvalu 84CZ-15006 Prague 5Czech Republic

Nanoparticle-mediated targeted delivery of drugs might significantly reduce the dosage and optimize their release properties,increase specificity and bioavailability,improve shelf life,and reduce *** nanodrugs are able to overcome the blood-brain barrier that is an obstacle to treatment of brain *** in tumors have abnormal architecture and are highly permeable;moreover,tumors also have poor lymphatic drainage,allowing for accumulation of macromolecules greater than approximately 40 kDa within the tumor *** exploit this feature,known as the enhanced permeability and retention effect,to target solid *** targeting,*** modification of nanoparticles,is a way to decrease uptake in normal tissue and increase accumulation in a tumor,and it usually involves targeting surface membrane proteins that are upregulated in cancer *** targeting molecules are typically antibodies or their fragments;aptamers;oligopeptides or small *** are currently several FDA-approved nanomedicines,but none approved for brain tumor *** review,based both on the study of literature and on the authors own experimental work describes a comprehensive overview of preclinical and clinical research of nanodrugs in therapy of brain tumors.

关键词： brain tumors nanoparticles enhanced permeability and retention effect active targeting blood-brain barrier

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Clinical investigations of immunotherapy for human primary brain tumors

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Neuroimmunology and Neuroinflammation 2021年第3期8卷 154-173页

作者： Zahraa I.Khamis Nancy Al-Akkary Timothy Hua Sophia A.Draughon Yan Li Qing-Xiang Amy Sang Department of Chemistry and Biochemistry Florida State UniversityTallahasseeFL 32306USA Laboratory of Cancer Biology and Molecular Immunology Department of BiochemistryFaculty of Sciences-ILebanese UniversityBeirut 00000Lebanon Department of Chemical and Biomedical Engineering FAMU-FSU College of EngineeringFlorida State UniversityTallahasseeFL 32306USA Institute of Molecular Biophysics Florida State UniversityTallahasseeFL 32306USA

Human primary brain cancer is one of the most lethal and clinically challenging *** failure of conventional therapies to alleviate its poor outcome has prompted efforts to find innovative *** breakthroughs in immunotherapy across a variety of solid tumors have set immune-based therapeutics as a pillar for brain cancer ***,the unique features of brain malignancies including intratumoral heterogeneity,immunosuppressive microenvironment,and impervious blood-brain barrier,thwart the success of immunotherapeutic ***,seminal findings regarding tumor-driven enrichment of specific immune cells granted the field novel insights to harness the immune cells to fight *** review discusses the anatomical,microenvironmental,and immunobiological features of the human brain and presents an overview of immunotherapies tested for primary brain cancer patients with a special emphasis on registered phase 2,3,and combinatorial clinical *** checkpoint inhibitors,immune cell-based therapies,cancer vaccines,oncolytic viral therapy,and combination therapies are investigated in clinical settings for the treatment of human brain *** their occasional adverse effects,immune-targeted therapies provide a promising opportunity for primary brain cancer patients to enhance survival and improve prognosis.

关键词： Immunotherapy brain tumors brain tumor microenvironment checkpoint inhibitors oncolytic viruses cancer vaccines immune cell-based therapies

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Fetal brain tumors:Prenatal diagnosis by ultrasound and magnetic resonance imaging

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World Journal of Radiology 2015年第1期7卷 17-21页

作者： Herbene Jose Milani Edward Araujo Junior Sergio Cavalheiro Patrícia Soares Oliveira Wagner Jou Hisaba Enoch Quindere Sa Barreto Maurício Mendes Barbosa Luciano Marcondes Nardozza Antonio Fernandes Moron Department of Obstetrics Paulista School of Medicine-Federal University of Sao Paulo(EPM-UNIFESP)Sao Paulo 05303-000Brazil Discipline of Neurosurgery Paulista School of Medicine-Federal University of Sao Paulo(EPM-UNIFESP)Sao Paulo 05303-000Brazil Department of Diagnostic Imaging Paulista School of Medicine-Federal University of Sao Paulo(EPM-UNIFESP)Sao Paulo 05303-000Brazil

Congenital central nervous system tumors diagnosed during pregnancy are rare, and often have a poor prognosis. The most frequent type is the teratoma. Use of ultrasound and magnetic resonance image allows the suspicion of brain tumors during pregnancy. However, the definitive diagnosis is only confirmed after birth by histology. The purpose of this mini-review article is to describe the general clinical aspects of intracranial tumors and describe the main fetal brain tumors.

关键词： Fetus brain tumors Teratoma Ultrasound Magnetic resonance imaging

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Quantitative Cerebral Blood Volume Image Synthesis from Conventional MRI Using Image-to-Image Translation Techniques in brain tumors

Quantitative Cerebral Blood Volume Image Synthesis from Conv...

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第十六届中国医师协会神经外科医师年会

作者： LIU Yingchao

Background:Cerebral blood volume(CBV) mapping is the most accepted and robust method to evaluate tumor perfusion conditions,but it is not a standard process and will be missing in some clinical *** study aimed to investigate the feasibility of image-to-image translation techniques in generating CBV maps from conventional MR images of brain tumors with the help of the Bookend perfusion ***:A total of 756 MRI scans,including quantitative CBV maps produced by Bookend perfusion,were included in this retrospective *** were randomly assigned to a training cohort and validation cohort at a ratio of 7:*** sense-consistency generative adversarial network(SGAN) and the 3D encoder-decoder with only mean absolute error loss(MAE-ED) were trained to synthesize the CBV *** evaluation(four metrics below) and qualitative evaluation(a subjective score that ranged from 0 to 3) were performed to evaluate the quality of the synthesized CBV ***:For the quantitative evaluations,MAE-ED using pre-and post-T1 weighted imaging and apparent diffusion coefficient maps achieved the highest performance,with a mean absolute error of 1.76,mean squared error of 0.34,structural similarity of 86.29 and peak signal-to-noise ratio of *** qualitative evaluations of synthesized CBV via MAE-ED,a weighted average value of 2.63 was reached,and the ratios of zero to one,one to two,and two to three were 3.6%,29.6% and 66.8%,***:With the help of the Bookend perfusion technique,the image-to-image translation technique could produce a qualified and convincing CBV map from conventional MR images for reliable clinical *** of the study:A dynamic susceptibility contrast perfusion-weighted imaging-derived cerebral blood volume(CBV) map is the most accepted and robust method to evaluate tumor perfusion *** synthesis of CBV maps has become urgent due to the lack of standardized CBV maps without interoperator divergenc

关键词： quantitative cerebral blood volume generative adversarial network image-to-image translation MRI brain tumors

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Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders:drug stability,targeting efficiency,and safety

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Neural Regeneration Research 2025年第7期20卷 1883-1899页

作者： Mingyu Zhang Chunyu Xiang Renrui Niu Xiaodong He Wenqi Luo Wanguo Liu Rui Gu Department of Orthopedic Surgery China-Japan Union Hospital of Jilin UniversityChangchunJilin ProvinceChina

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely ***,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic *** are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and ***,they can potentially treat traumatic and nontraumatic central nervous system *** this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics ***,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain *** studies related to liposomes are still in the laboratory stage and have not yet entered clinical ***,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and ***,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

关键词： Alzheimer's disease amyotrophic lateral sclerosis brain tumors central nervous system Huntington's disease liposome drug delivery neurological disorders Parkinson's disease spinal cord injury traumatic brain injury

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Remodeling the blood–brain barrier microenvironment by natural products for brain tumor therapy

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Acta Pharmaceutica Sinica B 2017年第5期7卷 541-553页

作者： Xiao Zhao Rujing Chen Mei Liu Jianfang Feng Jun Chen Kaili Hu Murad Research Center for Modernized Chinese Medicine Institute of Interdisciplinary Integrative Medicine ResearchShanghai University of Traditional Chinese Medicine Key Laboratory of Smart Drug Delivery Fudan University Ministry of Education

brain tumor incidence shows an upward trend in recent years; brain tumors account for 5% of adult tumors, while in children, this figure has increased to 70%. Moreover, 20%–30% of malignant tumors will eventually metastasize into the brain. Both benign and malignant tumors can cause an increase in intracranial pressure and brain tissue compression, leading to central nervous system(CNS) damage which endangers the patients' lives. Despite the many approaches to treating brain tumors and the progress that has been made, only modest gains in survival time of brain tumor patients have been achieved. At present, chemotherapy is the treatment of choice for many cancers, but the special structure of the blood–brain barrier(BBB) limits most chemotherapeutic agents from passing through the BBB and penetrating into tumors in the brain. The BBB microenvironment contains numerous cell types, including endothelial cells, astrocytes, peripheral cells and microglia, and extracellular matrix(ECM). Many chemical components of natural products are reported to regulate the BBB microenvironment near brain tumors and assist in their treatment. This review focuses on the composition and function of the BBB microenvironment under both physiological and pathological conditions, and the current research progress in regulating the BBB microenvironment by natural products to promote the treatment of brain tumors.

关键词： Blood–brain barrier Microenvironment Natural products brain tumors Glioma Extracellular matrix

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Targeting the glucocorticoid receptor-CCR8 axis mediated bone marrow T cell sequestration enhances infiltration of anti-tumor T cells in intracranial cancers

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Cellular & Molecular Immunology 2024年第10期21卷 1145-1157页

作者： Jia Zhang Yuzhu Shi Xiaotong Xue Wenqing Bu Yanan Li Tingting Yang Lijuan Cao Jiankai Fang Peishan Li Yongjing Chen Zhen Li Changshun Shao Yufang Shi The Third Affiliated Hospital of Soochow University Institutes for Translational MedicineState Key Laboratory of Radiation Medicine and ProtectionSoochow University Suzhou Medical CollegeSuzhouJiangsuChina Department of Experimental Medicine and Biochemical Sciences TORUniversity of Rome“Tor Vergata”RomeItaly Center for Molecular Imaging and Nuclear Medicine State Key Laboratory of Radiation Medicine and ProtectionSchool for Radiological and Interdisciplinary Sciences(RAD-X)Soochow UniversityCollaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education InstitutionsSuzhouJiangsuChina

brain tumors such as glioblastomas are resistant to immune checkpoint blockade therapy,largely due to limited T cell infiltration in the ***,we show that mice bearing intracranial tumors exhibit systemic immunosuppression and T cell sequestration in bone marrow,leading to reduced T cell infiltration in brain *** plasma corticosterone drives the T cell sequestration via glucocorticoid receptors in tumor-bearing *** mediated by glucocorticoid-induced T cell dynamics and the subsequent tumor growth promotion can be abrogated by adrenalectomy,the administration of glucocorticoid activation inhibitors or glucocorticoid receptor antagonists,and in mice with T cell-specific deletion of glucocorticoid ***8 expression in T cells is increased in tumor-bearing mice in a glucocorticoid receptor-dependent ***,chemokines CCL1 and CCL8,the ligands for CCR8,are highly expressed in bone marrow immune cells in tumor-bearing mice to recruit T *** findings suggested that brain tumor-induced glucocorticoid surge and CCR8 upregulation in T cells lead to T cell sequestration in bone marrow,impairing the anti-tumor immune *** the glucocorticoid receptor-CCR8 axis may offer a promising immunotherapeutic approach for the treatment of intracranial tumors.

关键词： brain tumors Anti-tumor immunity T cell redistribution Glucocorticoid receptor CCR8

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PROBING THE IMPACT OF GAMMA-IRRADIATION ON THE METABOLIC STATE OF NEURAL STEM AND PRECURSOR CELLS USING DUAL-WAVELENGTH INTRINSIC SIGNAL TWO-PHOTON EXCITED FLUORESCENCE

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Journal of Innovative Optical Health Sciences 2011年第3期4卷 289-300页

作者： TATIANA B.KRASIEVA ERICH GIEDZINSKI KATHERINE TRAN MARY LAN CHARLES L.LIMOLI BRUCE J.TROMBERG Laser Microbeam and Medical Program Beckman Laser Institute University of California Irvine1002 Health Sciences Road EastIrvineCA 92612USA Department of Radiation Oncology University of California IrvineCalifornia 92697USA

Two-photon excitedfluorescence(TPEF)spectroscopy and imaging were used to investigate the effects of gamma-irradiation on neural stem and precursor cells(NSPCs).While the observed signal from reduced nicotinamide adenine dinucleotide(NADH)was localized to the mitochondria,the signal typically associated with oxidizedflavoproteins(Fp)was distributed diffusely throughout the *** measured TPEF emission and excitation spectra were similar to the established spectra of NAD(P)H and *** intensity was markedly increased by addition of the electron transport chain(ETC)modulator menadione to the medium,along with a concomitant decrease in the NAD(P)H ***-dimensional(3D)neurospheres were imaged to obtain the cellular metabolic index(CMI),calculated as the ratio of Fp to NAD(P)Hfluorescence *** effects were found to differ between low-dose(50 cGy)and high-dose(50 cGy)***-dose irradiation caused a marked drop in CMI values accompanied by increased cellular *** higher doses,both NAD(P)H and Fp signals increased,leading to an overall elevation in CMI *** underscore the complex relationship between radiation dose,metabolic state,and proliferation status in NSPCs and highlight the ability of TPEF spectroscopy and imaging to characterize metabolism in 3D spheroids.

关键词： Multiphoton microscopy cellular metabolic index gamma radiation brain tumors NAD(P)H flavoproteins

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Advancing brain Tumor Analysis through Dynamic Hierarchical Attention for Improved Segmentation and Survival Prognosis

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Computers, Materials & Continua 2023年第12期77卷 3835-3851页

作者： S.Kannan S.Anusuya Department of Computer Science and Engineering Malla Reddy College of EngineeringSecunderabadTelunganaIndia Department of Information Technology Saveetha School of EngineeringSaveetha Institute of Medical and Technical SciencesSIMATSChennaiTamil Nadu602117India

Gliomas,the most prevalent primary brain tumors,require accurate segmentation for diagnosis and risk *** this paper,we develop a novel deep learning-based method,the Dynamic Hierarchical Attention for Improved Segmentation and Survival Prognosis(DHA-ISSP)*** DHA-ISSP model combines a three-band 3D convolutional neural network(CNN)U-Net architecture with dynamic hierarchical attention mechanisms,enabling precise tumor segmentation and survival *** DHA-ISSP model captures fine-grained details and contextual information by leveraging attention mechanisms at multiple levels,enhancing segmentation *** achieving remarkable results,our approach surpasses 369 competing teams in the 2020 Multimodal brain Tumor Segmentation *** a Dice similarity coefficient of 0.89 and a Hausdorff distance of 4.8 mm,the DHA-ISSP model demonstrates its effectiveness in accurately segmenting brain *** also extract radio mic characteristics from the segmented tumor areas using the DHA-ISSP *** applying cross-validation of decision trees to the selected features,we identify crucial predictors for glioma survival,enabling personalized treatment *** the DHA-ISSP model and the desired features,we assess patients’overall survival and categorize survivors into short,mid,in addition to long *** proposed work achieved impressive performance metrics,including the highest accuracy of 0.91,precision of 0.84,recall of 0.92,F1 score of 0.88,specificity of 0.94,sensitivity of 0.92,area under the curve(AUC)value of 0.96,and the lowest mean absolute error value of 0.09 and mean squared error value of *** results clearly demonstrate the superiority of the proposed system in accurately segmenting brain tumors and predicting survival outcomes,highlighting its significant merit and potential for clinical applications.

关键词： Survival prediction 3D multimodal MRI brain tumors segmentation CNN U-Net deep learning

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Epigenetic modulators for brain cancer stem cells: Implications for anticancer treatment

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World Journal of Stem Cells 2021年第7期13卷 670-684页

作者： Luana Abballe Evelina Miele Department of Pediatric Hematology/Oncology and Cellular and Gene Therapy Bambino GesùChildren's HospitalIRCCSRome 00165Italy

Primary malignant brain tumors are a major cause of morbidity and mortality in both adults and children,with a dismal prognosis despite multimodal therapeutic *** the last years,a specific subpopulation of cells within the tumor bulk,named cancer stem cells(CSCs)or tumor-initiating cells,have been identified in brain tumors as responsible for cancer growth and disease *** features of tumor cells strongly affect treatment response,leading to the escape from conventional therapeutic approaches and subsequently causing tumor *** research efforts have focused at identifying new therapeutic strategies capable of specifically targeting CSCs in cancers by taking into consideration their complex *** epigenetic machinery plays a key role in the genesis and progression of brain tumors as well as inducing CSC reprogramming and preserving CSC ***,reverting the cancer epigenome can be considered a promising therapeutic *** main epigenetic mechanisms have been described:DNA methylation,histone modifications,and non-coding RNA,particularly *** of these mechanisms has been proven to be targetable by chemical compounds,known as epigeneticbased drugs or epidrugs,that specifically target epigenetic *** review here recent advances in the study of epigenetic modulators promoting and sustaining brain tumor stem-like *** focus on their potential role in cancer therapy.

关键词： Cancer stem cells Epigenetics brain tumors Epigenetic drugs Histone deacetylase inhibitors DNA methyltransferase inhibitors

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