Combinatorial effects of VEGFR kinase inhibitor axitinib and oncolytic virotherapy in mouse and human glioblastoma stem-like cell models.

CONCLUSIONS: Systemic TKI (axitinib) beneficially combines with G47Δ-mIL12 to enhance anti-tumor efficacy in both immune-deficient and immune-competent orthotopic Saha et al 4 GBM models. Our results support further investigation of TKIs in combination with oHSV for GBM treatment. PMID: 29599413 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research

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Alla S. Koltsova1,2, Anna A. Pendina1, Olga A. Efimova1*, Olga G. Chiryaeva1, Tatyana V. Kuznetzova1 and Vladislav S. Baranov1,2 1D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia 2Department of Genetics and Biotechnology, Saint Petersburg State University, Saint Petersburg, Russia In the present review, we focus on the phenomenon of chromothripsis, a new type of complex chromosomal rearrangements. We discuss the challenges of chromothripsis detection and its distinction from other chromoanagenesis events. Along with already known causes and mechanisms, we introdu...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
by Gertrud Rey Although cancer therapies have improved dramatically in recent years, the main options for treating cancer still consist of surgery, chemotherapy, and radiation therapy. This limitation is a problem for aggressive cancers like glioblastoma multiforme (GBM), brain cancers which are typically resistant to traditional therapies. GBM is a high grade glioma, an aggressive […]
Source: virology blog - Category: Virology Authors: Tags: Basic virology Gertrud Rey Information glioblastoma multiforme herpes simplex virus viral viral oncotherapy viruses Source Type: blogs
Chimeric HCMV/HSV-1 and Δγ134.5 oncolytic herpes simplex virus elicit immune mediated antigliomal effect and antitumor memory. Transl Oncol. 2017 Dec 04;11(1):86-93 Authors: Ghonime MG, Jackson J, Shah A, Roth J, Li M, Saunders U, Coleman J, Gillespie GY, Markert JM, Cassady KA Abstract Malignant gliomas are the most common primary brain tumor and are characterized by rapid and highly invasive growth. Because of their poor prognosis, new therapeutic strategies are needed. Oncolytic virotherapy (OV) is a promising strategy for treating cancer that incorporates both direct viral replication ...
Source: Translational Oncology - Category: Cancer & Oncology Authors: Tags: Transl Oncol Source Type: research
Publication date: 14 August 2017 Source:Cancer Cell, Volume 32, Issue 2 Author(s): Dipongkor Saha, Robert L. Martuza, Samuel D. Rabkin Glioblastoma is an immunosuppressive, fatal brain cancer that contains glioblastoma stem-like cells (GSCs). Oncolytic herpes simplex virus (oHSV) selectively replicates in cancer cells while inducing anti-tumor immunity. oHSV G47Δ expressing murine IL-12 (G47Δ-mIL12), antibodies to immune checkpoints (CTLA-4, PD-1, PD-L1), or dual combinations modestly extended survival of a mouse glioma model. However, the triple combination of anti-CTLA-4, anti-PD-1, and G47Δ-mIL12 cure...
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research
Enhancer of zeste homologue 2 (Ezh2), as the catalytically active component of the Polycomb Repressive Complex 2, is involved in transcriptional repression of certain genes by trimethylation of lysine 27 and lysine 9 of histone H3. A range of human tumors show overexpression of Ezh2, which is associated with poor prognosis. Ezh2 is involved in the biology of stem cells and is thought to be a stem cell specific oncogene. Oncolytic viruses are a novel family of anti-cancer agents capable of targeting cancer. Phase I-II clinical trials using conditionally-replicating Herpes Simplex Virus Type 1 (HSV-1) have provided prom...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: EXPERIMENTAL THERAPEUTICS - PRECLINICAL STUDIES (NON-IMMUNOLOGICAL) Source Type: research
Authors: Delwar ZM, Liu G, Kuo Y, Lee C, Bu L, Rennie PS, Jia WW Abstract Oncolytic herpes simplex virus type 1 (oHSV-1) therapy is an emerging treatment modality that selectively destroys cancer. Here we report use of a glioma specific HSV-1 amplicon virus (SU4-124 HSV-1) to selectively target tumour cells. To achieve transcriptional regulation of the SU4-124 HSV-1 virus, the promoter for the essential HSV-1 gene ICP4 was replaced with a tumour specific survivin promoter. Translational regulation was achieved by incorporating 5 copies of microRNA 124 target sequences into the 3'UTR of the ICP4 gene. Additionally, ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Authors: Yang FY, Chang WY, Lin WT, Hwang JJ, Chien YC, Wang HE, Tsai ML Abstract The ability to monitor the responses of and inhibit the growth of brain tumors during gene therapy has been severely limited due to the blood-brain barrier (BBB). A previous study has demonstrated the feasibility of noninvasive in vivo imaging with 123I-2'-fluoro-2'-deoxy-5-iodo-1-β-D-arabinofuranosyluracil (123I-FIAU) for monitoring herpes simplex virus type 1 thymidine kinase (HSV1-tk) cancer gene expression in an experimental animal model. Here, we tested the enhancement of SPECT with 123I-FIAU and ganciclovir (GCV) treatment ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Abstract Oncolytic virus (OV) is a genetically engineered virus that can selectively replicate in and kill tumor cells while not harming normal cells. OV therapy has been explored as a treatment for numerous cancers including glioblastoma, an aggressive and devastating brain tumor. Experiments show that extracellular matrix protein CCN1 limits OV therapy of glioma by orchestrating an antiviral response and enhancing the proinflammatory activation and migration of macrophages. Neutralizing CCN1 by antibody has been demonstrated to improve OV spread and tends to increase the time to disease progression. In this pape...
Source: Bulletin of Mathematical Biology - Category: Bioinformatics Authors: Tags: Bull Math Biol Source Type: research
Ylä-Herttuala S Abstract Malignant gliomas (MGs) are the most common malignant primary brain tumors with a short life estimate accompanied by a marked reduction in the quality of life. Herpes Simplex virus-1 thymidine kinase ganciclovir (HSV-TK/GCV) system is the best characterized enzyme prodrug therapy in use. However, lipophobicity of GCV and low enzymatic activity of HSV-TK reduce the treatment efficacy. Tomato TK (ToTK) has shown high activity in combination with its specific substrate azidothymidine (AZT). The aim of this study was to evaluate whether ToTK/AZT could be used as an alternative to HSV-TK/...
Source: Herpes - Category: Infectious Diseases Authors: Tags: Cancer Gene Ther Source Type: research
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