scholarly journals Improved Killing of Human High-Grade Glioma Cells by Combining Ionizing Radiation with Oncolytic Parvovirus H-1 Infection

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Karsten Geletneky ◽  
Andreas D. Hartkopf ◽  
Robert Krempien ◽  
Jean Rommelaere ◽  
Joerg R. Schlehofer

Purpose. To elucidate the influence of ionizing radiation (IR) on the oncolytic activity of Parvovirus H-1 (H-1PV) in human high-grade glioma cells.Methods. Short term cultures of human high-grade gliomas were irradiated at different doses and infected with H-1PV. Cell viability was assessed by determining relative numbers of surviving cells. Replication of H-1PV was measured by RT-PCR of viral RNA, fluorescence-activated cell sorter (FACS) analysis and the synthesis of infectious virus particles. To identify a possible mechanism for radiation induced change in the oncolytic activity of H-1PV we performed cell cycle analyses.Results. Previous irradiation rendered glioma cells fully permissive to H-1PV infection. Irradiation 24 hours prior to H-1PV infection led to increased cell killing most notably in radioresistant glioma cells. Intracellular levels of NS-1, the main effector of H-1PV induced cytotoxicity, were elevated after irradiation. S-phase levels were increased one day after irradiation improving S-phase dependent viral replication and cytotoxicity.Conclusion. This study demonstrates intact susceptibility of previously irradiated glioma-cells for H-1PV induced oncolysis. The combination of ionizing radiation followed by H-1PV infection increased viral cytotoxicity, especially in radioresistant gliomas. These findings support the ongoing development of a clinical trial of H-1PV in patients with recurrent glioblastomas.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Terziev ◽  
Dimitri Psimaras ◽  
Yannick Marie ◽  
Loic Feuvret ◽  
Giulia Berzero ◽  
...  

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.


Cell Cycle ◽  
2018 ◽  
Vol 17 (18) ◽  
pp. 2256-2267
Author(s):  
Fanghua Song ◽  
Dong Li ◽  
Yajie Wang ◽  
Xiaolin Bi

2018 ◽  
Author(s):  
Jinzhou Yuan ◽  
Hanna Mendes Levitin ◽  
Veronique Frattini ◽  
Erin C. Bush ◽  
Deborah M. Boyett ◽  
...  

ABSTRACTBackgroundDespite extensive molecular characterization, we lack a comprehensive understanding of lineage identity, differentiation, and proliferation in high-grade gliomas (HGGs). We sampled the cellular milieu of HGGs with massively-parallel single-cell RNA-Seq.ResultsWhile HGG cells can resemble glia or even immature neurons and form branched lineage structures, mesenchymal transformation results in unstructured populations. Glioma cells in a subset of mesenchymal tumors lose their neural lineage identity, express inflammatory genes, and co-exist with marked myeloid infiltration, reminiscent of molecular interactions between glioma and immune cells established in animal models. Additionally, we discovered a tight coupling between lineage resemblance and proliferation among malignantly transformed cells. Glioma cells that resemble oligodendrocyte progenitors, which proliferate in the brain, are often found in the cell cycle. Conversely, glioma cells that resemble astrocytes, neuroblasts, and oligodendrocytes, which are non-proliferative in the brain, are generally non-cycling in tumors.ConclusionsThese studies reveal a relationship between cellular identity and proliferation in HGG and distinct population structures that reflects the extent of neural and non-neural lineage resemblance among malignantly transformed cells.


Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 49
Author(s):  
Bimal Prasad Jit ◽  
Biswajita Pradhan ◽  
Rutumbara Dash ◽  
Prajna Paramita Bhuyan ◽  
Chhandashree Behera ◽  
...  

Ionizing radiation results in extensive damage to biological systems. The massive amount of ionizing radiation from nuclear accidents, radiation therapy (RT), space exploration, and the nuclear battlefield leads to damage to biological systems. Radiation injuries, such as inflammation, fibrosis, and atrophy, are characterized by genomic instability, apoptosis, necrosis, and oncogenic transformation, mediated by the activation or inhibition of specific signaling pathways. Exposure of tumors or normal cells to different doses of ionizing radiation could lead to the generation of free radical species, which can release signal mediators and lead to harmful effects. Although previous FDA-approved agents effectively mitigate radiation-associated toxicities, their use is limited due to their high cellular toxicities. Preclinical and clinical findings reveal that phytochemicals derived from plants that exhibit potent antioxidant activities efficiently target several signaling pathways. This review examined the prospective roles played by some phytochemicals in altering signal pathways associated with radiation response.


1996 ◽  
Vol 19 (6) ◽  
pp. 601-608 ◽  
Author(s):  
Jacqueline G. Emrich ◽  
Hans Bender ◽  
Reiner Class ◽  
Jeffrey Eshleman ◽  
Curtis Miyamoto ◽  
...  

1982 ◽  
Vol 24 (5) ◽  
pp. 505-519 ◽  
Author(s):  
Leslie A. Lewis

The temporal frequencies of different stages of prophase I were determined cytologically in Sordaria brevicollis (Olive and Fantini) as the basis for ascertaining the degree of synchrony in meiosis in this ascomycete. Croziers, karyogamy-zygotene and pachytene asci were shown to be in significant majorities at three distinct periods of the meiotic cycle. The response of recombination frequency to ionizing radiation was examined for the entire meiotic cycle. Three radiosensitive periods were determined. This response, which correlated temporally with each of the three peaks in ascal frequency, is interpreted as showing that the meiotic cycle of this organism is divided into periods of recombination commitment (radiation reduced frequencies) during the pre-meiotic S phase and recombination consummation (radiation induced frequencies) during zygotene and pachytene. The results are discussed in the context of the time at which recombination is consummated in eukaryotes such as yeast and Drosophila.


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