Radioresistance of Brain Tumors.
Ontology highlight
ABSTRACT:
SUBMITTER: Kelley K
PROVIDER: S-EPMC4846851 | biostudies-other | 2016 Mar
REPOSITORIES: biostudies-other
Publications
Radioresistance of Brain Tumors.
Kelley Kevin K Knisely Jonathan J Symons Marc M Ruggieri Rosamaria R
Cancers 20160330 4
Radiation therapy (RT) is frequently used as part of the standard of care treatment of the majority of brain tumors. The efficacy of RT is limited by radioresistance and by normal tissue radiation tolerance. This is highlighted in pediatric brain tumors where the use of radiation is limited by the excessive toxicity to the developing brain. For these reasons, radiosensitization of tumor cells would be beneficial. In this review, we focus on radioresistance mechanisms intrinsic to tumor cells. We ...[more]
Similar Datasets
Project description:BackgroundRadiation therapy is one of the most effective therapeutic tools for brain metastasis. However, it is inevitable that some cancer cells become resistant to radiation. This study is focused on the identification of genes associated with radioresistance in metastatic brain tumor from lung cancer and the functional examination of the selected genes with regards to altered sensitivity of cancer cells to radiation.MethodsAfter establishing radioresistant cells from the xenograft model, we explored the significant transcriptional changes by performing DNA microarray profiling. Functional analyses in vitro and in vivo performed to validate the gene responsible for radioresistance.ResultsTranscriptional changes induced by radiation therapy are much more extensive in H460 cells than in PC14PE6 cells. The expression levels of TopBP1 and Claspin were increased in the cancer cells that survived radiation therapy. Depletion of TopBP1 or Claspin using shRNA showed an enhancement of sensitivity to radiation in radioresistant lung cancer cells (PC14PE6). Moreover, increased levels of TopBP1 or Claspin endowed cells a higher resistance to radiation. In xenograft models, the knock-down of TopBP1 or Claspin significantly prolonged the median survival time post radiation therapy.ConclusionsWe analyzed the gene expression profiles of the radiosensitive cells and the radioresistant cells to define a set of genes that may be involved in endowing lung cancer cells radioresistance post brain metastasis. Functional analyses indicated that the expression TopBP1 and Claspin positively affects the survival of cancer cells and thus negatively the xenograft metastasis model animals in response to radiation. These results show that TopBP1 and Claspin can be potential targets for the enhanced efficacy of radiotherapy.
| S-EPMC4168047 | biostudies-literature
Project description:Familiality in brain tumors is not definitively substantiated.We used the Utah Population Data Base (UPDB), a genealogy representing the Utah pioneers and their descendants, record-linked to statewide cancer records, to describe the familial nature of primary brain cancer. We examined the familial clustering of primary brain tumors, including subgroups defined by histologic type and age at diagnosis. The UPDB includes 1,401 primary brain tumor cases defined as astrocytoma or glioblastoma, all with at least three generations of genealogy data. We tested the hypothesis of excess relatedness of brain tumor cases using the Genealogical Index of Familiality method. We estimated relative risks for brain tumors in relatives using rates of brain tumors estimated internally.Significant excess relatedness was observed for astrocytomas and glioblastomas considered as a group (n = 1,401), for astrocytomas considered separately (n = 744), but not for glioblastomas considered separately (n = 658). Significantly increased risks to first- and second-degree relatives for astrocytomas were identified for relatives of astrocytomas considered separately. Significantly increased risks to first-degree relatives, but not second degree, were observed for astrocytoma and glioblastoma cases considered together, and for glioblastoma cases considered separately.This study provides strong evidence for a familial contribution to primary brain cancer risk. There is evidence that this familial aspect includes not only shared environment, but also a heritable component. Extended high-risk brain tumor pedigrees identified in the UPDB may provide the opportunity to identify predisposition genes responsible for familial brain tumors.
| S-EPMC2676956 | biostudies-literature
Project description:Glioblastoma multiforme (GBM) requires radiotherapy (RT) as its definitive management. However, GBM still has a high local recurrence rate even after RT. Cancer stem-like cells (CSCs) might enable GBM to evade irradiation damage and cause therapeutic failure. The optimal RT plan should achieve a planning target volume (PTV) coverage of more than 95% but cannot always meet the requirements. Here, we demonstrate that irradiation with different tumor coverage rates to different brain areas has similar effects on GBM. To retrospectively analyze the relationship between PTV coverage and the survival rate in 26 malignant glioblastoma patients, we established primary cell lines from patient-derived malignant glioblastoma cells with the PTV95 (PTV coverage of more than 95%) program (GBM-MG1 cells) and the Non-PTV95 (poor PTV coverage of less than 95%) program (GBM-MG2 cells). The clinical results of PTV95 and Non-PTV95 showed no difference in the overall survival (OS) rate (P = .390) between the two different levels of PTV coverage. GBM-MG1 (PTV95 program) cells exhibited higher radioresistance than GBM-MG2 (Non-PTV95 program) cells. CD44 promotes radioresistance, CSC properties, angiogenesis and cell proliferation in GBM-MG1 (PTV95 program) cells. GBM patients receiving RT with the PTV95 program exhibited higher radioresistance, CSC properties, angiogenesis and cell proliferation than GBM patients receiving RT with the Non-PTV95 program. Moreover, CD44 plays a crucial role in these properties of GBM patients with the PTV95 program.
| S-EPMC6943151 | biostudies-literature
Project description:Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation. Replicate DNA array experiments identified 52 genes differentially expressed in nu61 tumors compared with SCC-61 tumors. Of these, 19 genes were in the IFN-signaling pathway and moreover, 25 of the 52 genes were inducible by IFN in the nu61 cell line. Among the genes involved in IFN signaling, STAT1alpha and STAT1beta were the most highly overexpressed in nu61 compared to SCC-61. STAT1alpha and STAT1beta cDNAs were cloned and stably transfected into SCC-61 tumor cells. Clones of SCC-61 tumor cells transfected with vectors expressing STAT1alpha and STAT1beta demonstrated radioprotection after exposure to 3 Gy (P < 0.038). The results indicate that radioresistance acquired during radiotherapy treatment may account for some treatment failures and demonstrate an association of acquired tumor radioresistance with up-regulation of components of the IFN-related signaling pathway.
| S-EPMC341831 | biostudies-literature
Project description:Mutations in TP53 and RB1 have been shown to participate in the development of malignant brain tumors. Emerging evidence shows that mutations are involved in LGI1 in brain tumor progression. Herein we present data from the sequencing of a series of high- and low-grade gliomas with matched normal DNA. We report on 35 unique missense mutations in TP53, RB1 and LGI1 genes and use available information for each mutation in order to classify them as likely to be 'driver' or 'passenger' mutations. The identification of putatively deleterious mutations in LGI1 supports the notion that this locus may play a role in brain cancer development.
| S-EPMC3933973 | biostudies-literature
Project description:The 2016 World Health Organization (WHO) classification of primary central nervous system (CNS) tumors includes numerous uncommon (representing ?1% of tumors) low-grade (grades I-II) brain neoplasms with varying clinical behaviors and outcomes. Generally, gross tumor or maximal safe resection is the primary treatment. Adjuvant treatments, though their exact role is unknown, may be considered individually based on pathological subtypes and a proper assessment of risks and benefits. Targetable mutations such as BRAF (proto-oncogene B-Raf), TRAIL (tumor necrosis factor apoptosis inducing ligand), and PDGFR (platelet derived growth factor receptor) have promising roles in future management.
| S-EPMC6374757 | biostudies-literature
Project description:Altered metabolism is a hallmark of cancer cells. Tumor cells rewire their metabolism to support their uncontrolled proliferation by taking up nutrients from the microenvironment. The amino acid glutamine is a key nutrient that fuels biosynthetic processes including ATP generation, redox homeostasis, nucleotide, protein, and lipid synthesis. Glutamine as a precursor for the neurotransmitter glutamate, and plays a critical role in the normal functioning of the brain. Brain tumors that grow in this glutamine/glutamate rich microenvironment can make synaptic connections with glutamatergic neurons and reprogram glutamine metabolism to enable their growth. In this review, we examine the functions of glutamate/glutamine in the brain and how brain tumor cells reprogram glutamine metabolism. Altered glutamine metabolism can be leveraged to develop non-invasive imaging strategies and we review these imaging modalities. Finally, we examine if targeting glutamine metabolism could serve as a therapeutic strategy in brain tumors.
| S-EPMC6893651 | biostudies-literature
Project description:Malignant brain tumors are the most common cause of solid cancer death in children. New targeted therapies are vital to improve treatment outcomes, but must be developed to enable trafficking across the blood brain barrier (BBB). Since activated T cells cross the BBB, cancer immunotherapy can be harnessed to unlock the cytotoxic potential of the immune system. However, standard of care treatments (i.e., chemotherapy and radiation) applied concomitant to pediatric brain tumor immunotherapy may abrogate induction of immunotherapeutic responses. This review will discuss the development of immunotherapies within this paradigm using emerging approaches being investigated in phase I/II trials in children with refractory brain tumors, including checkpoint inhibitors, vaccine immunotherapy, and adoptive cell therapy.
| S-EPMC5664064 | biostudies-literature
Project description:Improvements in brain tumor treatments have led to an increase in the number of young women with brain tumors who are now considering pregnancy. The aim of this study is to evaluate the influence of pregnancy on brain tumor biology.In this institutional review board-approved retrospective study, we searched the institution's database for patients with glial brain tumors who were pregnant at the time of diagnosis or became pregnant during the course of their illness. We identified 34 such patients and reviewed their charts to determine each patient's clinical course and pregnancy outcome.Fifteen patients were diagnosed with a primary brain tumor during pregnancy: 3 with glioblastomas, 6 with grade III gliomas, and 6 with grade II gliomas. Pregnancy was terminated in only 2 of these patients, and the remainder delivered healthy babies. Twenty-three patients became pregnant after diagnosis (4 patients were pregnant at diagnosis and again after diagnosis). Of the patients who became pregnant after diagnosis, the 5 with grade I tumors had stable disease during and after pregnancy. However, of the 18 patients with grade II or III gliomas, 8 (44%) had confirmed tumor progression during pregnancy or within 8 weeks of delivery.In contrast to grade I gliomas, the tumor biology of grades II and III gliomas may be altered during pregnancy, leading to an increased risk of tumor progression. These findings support the need for increased tumor surveillance and patient counseling and for additional data collection to further refine these results.
| S-EPMC4136891 | biostudies-other
Project description:Brain tumors in neonatal age group is uncommon comparing with older children and adults. In older children brain tumors are commonly infratentorial, where as in neonates, they are supratentorial. Though extracranial tumors are commoner in neonates, brain tumors cause 5-20% deaths approximately. We are presenting a review on brain tumors in neonates.
| S-EPMC5538596 | biostudies-other