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Functional Assays for Specific Targeting and Delivery of RNA Nanoparticles to Brain Tumor

Cumulative progress in nanoparticle development has opened a new era of targeted delivery of therapeutics to cancer cells and tissue. However, developing proper detection methods has lagged behind resulting in the lack of precise evaluation and monitoring of the systemically administered nanoparticles. RNA nanoparticles derived from the bacteriophage phi29 DNA packaging motor pRNA have emerged as a new generation of drugs for cancer therapy. Multifunctional RNA nanoparticles can be fabricated by bottom-up self-assembly of engineered RNA fragments harboring targeting (RNA aptamer or chemical ligand), therapeutic (siRNA, miRNA, ribozymes, and small molecule drugs), and imaging (fluorophore, radiolabels) modules. We have recently demonstrated that RNA nanoparticles can reach and target intracranial brain tumors in mice upon systemic injection with little or no accumulation in adjacent healthy brain tissues or in major healthy internal organs. Herein, we describe various functional imaging methods (fluorescence confocal microscopy, flow cytometry, fluorescence whole body imaging, and magnetic resonance imaging) to evaluate and monitor RNA nanoparticle targeting to intracranial brain tumors in mice. Such imaging techniques will allow in-depth evaluation of specifically delivered RNA therapeutics to brain tumors.
Source: Springer protocols feed by Biotechnology - Category: Biotechnology Source Type: news

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Publication date: Available online 1 May 2018 Source:Trends in Pharmacological Sciences Author(s): Theodora Vasilogiannakopoulou, Christina Piperi, Athanasios G. Papavassiliou High-grade gliomas are primary brain tumors with a highly aggressive, invasive phenotype and dismal outcome. Targeting cell metabolism and cancer bioenergetics has emerged as a potential effective therapeutic approach. Selective aldehyde dehydrogenase isoenzyme activity regulates glioma tumor growth, invasiveness, and resistance to current treatments, and has potential as a therapeutic target.
Source: Trends in Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research
We report on two sisters originally suspected of having CMMRD syndrome due to their history of colonic polyps and NF1 associated skin findings, both were subsequently found to have biallelicMSH6 mutations. After years of CMMRD syndrome follow-up, the proband was diagnosed with breast cancer at age 29, while her sister was diagnosed with a glioblastoma at age 27. Immunohistochemistry analysis on the breast tumor tissue revealed weak MSH6 protein staining. Exome sequencing revealed a hypermutated breast tumor and an ultra-hypermutated brain tumor. Multi-gene panel testing was also performed and revealed no additional mutatio...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
Glioblastoma multiform (GBM) is the most common and devastating type of primary brain tumor, being considered the deadliest of human cancers. In this context, extensive efforts have been undertaken to develop new drugs that exhibit both antiproliferation and antimetastasis effects on GBM. 1,4-Naphthoquinone (1,4-NQ) scaffold has been found in compounds able to inhibit important biological targets associated with cancer, which includes DNA topoisomerase, Hsp90 and monoamine oxidase. Among potential antineoplastic 1,4-NQs is the plant-derived lapachol (2-hydroxy-3-prenyl-1,4-naphthoquinone) that was found to be active agains...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research
Source: Clinical Trials And Noteworthy Treatments For Brain Tumors - Category: Cancer & Oncology Source Type: clinical trials
Authors: Sárközy M, Kahán Z, Csont T Abstract Small non-coding RNAs including microRNAs (miRNAs) have been recently recognized as important regulators of gene expression. MicroRNAs play myriads of roles in physiological processes as well as in the pathogenesis of a number of diseases by translational repression or mRNA destabilization of numerous target genes. The miR-106b-25 cluster is highly conserved in vertebrates and consists of three members including miR-106b, miR-93 and miR-25. MiR-106b and miR-93 share the same seed sequences; however, miR-25 has only a similar seed sequence resulting in...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
In conclusion, these results indicate that in cocultured MSC/U87 cells EcTI impairs the metabolic activity, proliferation, and reduced invasion, possibly associated with observed cytokines secretion. In this context, we confirmed that the plant derived protein potentiated the anticancer effects, induced by MSC, as represented by GBM U87 cell line. PMID: 29765540 [PubMed]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
In this study, our findings demonstrated that protein and mRNA levels of HDAC1 were increased in glioma cell lines and glioma tissues compared to normal glial cell lines and non-neoplastic brain tissues, respectively. Furthermore, HDAC1 knockdown cells displayed decreased proliferation and invasion capabilities, whereas HDAC1 overexpressing glioblastoma cells displayed more proliferation and invasion capabilities in vitro. These novel outcomes suggested that knockdown of HDAC1 possibly suppressed the expression of phosphorylated AKT (p-AKT) and phosphorylated ERK (p-ERK) proteins, while overexpression of HDAC1 significantl...
Source: Brain Research - Category: Neurology Authors: Tags: Brain Res Source Type: research
Abstract Diffuse gliomas comprise the bulk of "brain cancer" in adults. The recent update to the 4th edition of the World Health Organization's classification of tumors of the central nervous system reflects an unprecedented change in the landscape of the diagnosis and management of diffuse gliomas that will affect all those involved in the management and care of patients. Of the recently discovered gene alterations, mutations in the Krebs cycle enzymes isocitrate dehydrogenases (IDHs) 1 and 2 have fundamentally changed the way the gliomas are understood and classified. Incorporating information on a few...
Source: Archives of Pathology and Laboratory Medicine - Category: Laboratory Medicine Authors: Tags: Arch Pathol Lab Med Source Type: research
Holden Mullen, 14 months, from Naperville, Illinois, is fighting for his life after he was diagnosed with a rare form of brain cancer that affects only about 30 children in the US annually.
Source: the Mail online | Health - Category: Consumer Health News Source Type: news
Abstract Medulloblastoma (MB) is the most common malignant brain tumor occurring in children, and although high long-term survival rates have been reached with current therapeutic protocols, several neurological injuries are still observed among survivors. It has been shown that the development of MB is highly dependent on the microenvironment surrounding it and that the CXCL12 chemokine and its receptor, CXCR4 and the Sonic Hedgehog (SHH) pathway are crucial for cerebellar development, coordinating proliferation and migration of embryonic cells and malfunctions in these axes can lead to MB development. Indeed, th...
Source: Acta Oncologica - Category: Cancer & Oncology Authors: Tags: Acta Oncol Source Type: research
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