scholarly journals Influential Factors and Synergies for Radiation-Gene Therapy on Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Mei Lin ◽  
Junxing Huang ◽  
Yujuan Shi ◽  
Yanhong Xiao ◽  
Ting Guo
Keyword(s):  
Gene Therapy ◽  
Target Gene ◽  
Radiation Sensitivity ◽  
Regulatory Elements ◽  
Influential Factors ◽  
Regulatory Sequence ◽  
Therapeutic Gene ◽  
Radiation Induced ◽  
Application Potential ◽  
Low Activity

Radiation-gene therapy, a dual anticancer strategy of radiation therapy and gene therapy through connecting radiation-inducible regulatory sequence to therapeutic gene, leading to the gene being induced to express by radiation while radiotherapy is performed and finally resulting in a double synergistic antitumor effect of radiation and gene, has become one of hotspots in the field of cancer treatment in recent years. But under routine dose of radiation, especially in the hypoxia environment of solid tumor, it is difficult for this therapy to achieve desired effect because of low activity of radiation-inducible regulatory elements, low level and transient expression of target gene induced by radiation, inferior target specificity and poor biosecurity, and so on. Based on the problems existing in radiation-gene therapy, many efforts have been devoted to the curative effect improvement of radiation-gene therapy by various means to increase radiation sensitivity or enhance target gene expression and the expression’s controllability. Among these synergistic techniques, gene circuit, hypoxic sensitization, and optimization of radiation-induced sequence exhibit a good application potential. This review provides the main influential factors to radiation-gene therapy on cancer and the synergistic techniques to improve the anticancer effect of radiation-gene therapy.

scholarly journals Glucocorticoid receptor wields chromatin interactions to tune transcription for cytoskeleton stabilization in podocytes

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hong Wang ◽  
Aiping Duan ◽  
Jing Zhang ◽  
Qi Wang ◽  
Yuexian Xing ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Glucocorticoid Receptor ◽  
Protective Effect ◽  
Histone Modification ◽  
Regulatory Networks ◽  
Target Gene ◽  
Regulatory Elements ◽  
Chromatin Interactions ◽  
Super Enhancer

AbstractElucidating transcription mediated by the glucocorticoid receptor (GR) is crucial for understanding the role of glucocorticoids (GCs) in the treatment of diseases. Podocyte is a useful model for studying GR regulation because GCs are the primary medication for podocytopathy. In this study, we integrated data from transcriptome, transcription factor binding, histone modification, and genome topology. Our data reveals that the GR binds and activates selective regulatory elements in podocyte. The 3D interactome captured by HiChIP facilitates the identification of remote targets of GR. We found that GR in podocyte is enriched at transcriptional interaction hubs and super-enhancers. We further demonstrate that the target gene of the top GR-associated super-enhancer is indispensable to the effective functioning of GC in podocyte. Our findings provided insights into the mechanisms underlying the protective effect of GCs on podocyte, and demonstrate the importance of considering transcriptional interactions in order to fine-map regulatory networks of GR.

scholarly journals Immunotherapy and Gene Therapy for Oncoviruses Infections: A Review

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 822
Author(s):  
Nathália Alves Araújo de Almeida ◽  
Camilla Rodrigues de Almeida Ribeiro ◽  
Jéssica Vasques Raposo ◽  
Vanessa Salete de Paula
Keyword(s):  
Gene Therapy ◽  
Checkpoint Inhibitors ◽  
Gene Replacement ◽  
Gene Products ◽  
Transcription Activator ◽  
Therapeutic Gene ◽  
T Lymphotropic Virus ◽  
Barr Virus ◽  
B Virus ◽  
Epstein Barr

Immunotherapy has been shown to be highly effective in some types of cancer caused by viruses. Gene therapy involves insertion or modification of a therapeutic gene, to correct for inappropriate gene products that cause/may cause diseases. Both these types of therapy have been used as alternative ways to avoid cancers caused by oncoviruses. In this review, we summarize recent studies on immunotherapy and gene therapy including the topics of oncolytic immunotherapy, immune checkpoint inhibitors, gene replacement, antisense oligonucleotides, RNA interference, clustered regularly interspaced short palindromic repeats Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based gene editing, transcription activator-like effector nucleases (TALENs) and custom treatment for Epstein–Barr virus, human T-lymphotropic virus 1, hepatitis B virus, human papillomavirus, hepatitis C virus, herpesvirus associated with Kaposi’s sarcoma, Merkel cell polyomavirus, and cytomegalovirus.

Arf6-mediated macropinocytosis enhanced suicide gene therapy of C16TAB-condensed Tat/pDNA nanoparticles in ovarian cancer

Nanoscale ◽  
2021 ◽  
Author(s):  
Zhe Sun ◽  
Jinhai Huang ◽  
Linjia Su ◽  
Jing Li ◽  
Fangzheng Qi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gene Therapy ◽  
Cancer Treatment ◽  
Plasmid Dna ◽  
Suicide Gene ◽  
Cell Penetrating Peptides ◽  
Therapeutic Gene ◽  
Hiv Tat ◽  
Efficient Delivery ◽  
Cell Penetrating

Using cell-penetrating peptides (CPPs), typically HIV-Tat, to deliver the therapeutic gene for cancer treatment has being hampered by low efficient delivery and complicated uptake route of plasmid DNA (pDNA). On...

Retrovirus-Mediated Gene Therapy for Hepatocellular Carcinoma with Reversely Oriented Therapeutic Gene Expression Regulated by α-Fetoprotein Enhancer/Promoter

2001 ◽  
Vol 287 (4) ◽  
pp. 1034-1040 ◽  
Author(s):  
Hiroki Ishikawa ◽  
Keisuke Nakata ◽  
Fumihiro Mawatari ◽  
Toshihito Ueki ◽  
Shotaro Tsuruta ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Gene Therapy ◽  
Therapeutic Gene

scholarly journals Identification of key genes and associated pathways in neuroendocrine tumors through bioinformatics analysis and predictions of small drug molecules

2020 ◽  
Author(s):  
Praveenkumar Devarbhavi ◽  
Basavaraj Vastrad ◽  
Anandkumar Tengli ◽  
Chanabasayya Vastrad ◽  
Iranna Kotturshetti
Keyword(s):  
Drug Target ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Regulatory Elements ◽  
Future Research ◽  
High Morbidity ◽  
Hub Genes ◽  
Go Enrichment ◽  
Significant Difference

AbstractNeuroendocrine tumor (NET) is one of malignant cancer and is identified with high morbidity and mortality rates around the world. With indigent clinical outcomes, potential biomarkers for diagnosis, prognosis and drug target are crucial to explore. The aim of this study is to examine the gene expression module of NET and to identify potential diagnostic and prognostic biomarkers as well as to find out new drug target. The differentially expressed genes (DEGs) identified from GSE65286 dataset was used for pathway enrichment analyses and gene ontology (GO) enrichment analyses and protein - protein interaction (PPI) analysis and module analysis. Moreover, miRNAs and transcription factors (TFs) that regulated the up and down regulated genes were predicted. Furthermore, validation of hub genes was performed. Finally, molecular docking studies were performed. DEGs were identified, including 453 down regulated and 459 up regulated genes. Pathway and GO enrichment analysis revealed that DEGs were enriched in sucrose degradation, creatine biosynthesis, anion transport and modulation of chemical synaptic transmission. Important hub genes and target genes were identified through PPI network, modules, target gene - miRNA network and target gene - TF network. Finally, survival analyses, receiver operating characteristic (ROC) curve and RT-PCR validated the significant difference of ATP1A1, LGALS3, LDHA, SYK, VDR, OBSL1, KRT40, WWOX, NINL and PPP2R2B between metastatic NET and normal controls. In conclusion, the DEGs and hub genes with their regulatory elements identified in this study will help us understand the molecular mechanisms underlying NET and provide candidate targets for future research.

scholarly journals The dopamine receptor antagonist trifluoperazine prevents phenotype conversion and improves survival in mouse models of glioblastoma

2020 ◽  
Vol 117 (20) ◽  
pp. 11085-11096 ◽  
Author(s):  
Kruttika Bhat ◽  
Mohammad Saki ◽  
Erina Vlashi ◽  
Fei Cheng ◽  
Sara Duhachek-Muggy ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Dopamine Receptor ◽  
Mouse Models ◽  
Radiation Sensitivity ◽  
Adult Brain ◽  
Continuous Treatment ◽  
Cell Phenotype ◽  
Dopamine Receptor Antagonist ◽  
Radiation Induced

Glioblastoma (GBM) is the deadliest adult brain cancer, and all patients ultimately succumb to the disease. Radiation therapy (RT) provides survival benefit of 6 mo over surgery alone, but these results have not improved in decades. We report that radiation induces a glioma-initiating cell phenotype, and we have identified trifluoperazine (TFP) as a compound that interferes with this phenotype conversion. TFP causes loss of radiation-induced Nanog mRNA expression, and activation of GSK3 with consecutive posttranslational reduction in p-Akt, Sox2, and β-catenin protein levels. TFP did not alter the intrinsic radiation sensitivity of glioma-initiating cells (GICs). Continuous treatment with TFP and a single dose of radiation reduced the number of GICs in vivo and prolonged survival in syngeneic and patient-derived orthotopic xenograft (PDOX) mouse models of GBM. Our findings suggest that the combination of a dopamine receptor antagonist with radiation enhances the efficacy of RT in GBM by preventing radiation-induced phenotype conversion of radiosensitive non-GICs into treatment-resistant, induced GICs (iGICs).

A correlation between radiation sensitivity and initial chromatid breaks in cancer cell lines revealed by Calyculin A-induced premature condensation

2006 ◽  
Vol 1 (3) ◽  
pp. 451-462 ◽  
Author(s):  
Jianshe Yang ◽  
Xigang Jing ◽  
Zhuanzi Wang ◽  
Wenjian Li
Keyword(s):  
Cell Lines ◽  
Radiation Sensitivity ◽  
Calyculin A ◽  
Linear Quadratic ◽  
Technique Survival ◽  
Positive Linear Correlation ◽  
Radiation Induced ◽  
Clinical Radiotherapy

AbstractThree human malignancy cell lines were irradiated with 60Co γ-rays. Initial chromatid breaks were measured by using the chemically induced premature chromosome condensation technique. Survival curves of cells exposed to gamma rays was linear-quadratic while the efficiency of Calyculin A in inducing PCC of G2 PCC was about five times more than G1 PCC. A dose-dependent increase in radiation-induced chromatid/isochromatid breaks was observed in G1 and G2 phase PCC and a nearly positive linear correlation was found between cell survival and chromatin breaks. This study implies that low LET radiation-induced chromatid/isochromatid breaks can potentially be used to predict the radiosensitivity of tumor cells either in in vitro experimentation or in in vivo clinical radiotherapy.

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