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Radiation therapy is an integral part of treatment for patients with glioblastoma. New technological advances in linear accelerators have made extra-high dose rate irradiation possible. This shortens patient treatment time significantly compared to standard dose rate irradiation, but the biologic effects of extra high dose rate irradiation are poorly understood. Glioma stem-like cells (GSCs) are resistant to standard radiation and contribute to tumor progression. Here, we assess the therapeutic effect of extra high dose rate vs. standard dose rate irradiation on GSCs. GSCs were exposed to 2, 4 and 6 Gy X-irradiation at dose rates of 4.2 Gy/min or 21.2 Gy/min (400 monitoring units (MU)/min or 2100 MU/min). We analyzed cell survival with cell growth assays, tumorsphere formation assays and colony formation assays. Cell kill and self-renewal were dependent on the total dose of radiation delivered. However, there was no difference in survival of GSCs or DNA damage repair in GSCs irradiated at different dose rates. GSCs exhibited significant G1 and G2/M phase arrest and increased apoptosis with higher doses of radiation but there was no difference between the two dose rates at each given dose. In a GSC-derived preclinical model of glioblastoma, radiation extended animal survival, but there was no difference in survival in mice receiving different dose rates of radiation. We conclude that GSCs respond to larger fractions of radiation, but extra high dose rate irradiation has no significant biologic advantage in comparison with standard dose rate irradiation.
This article was published in the following journal.
Name: PloS one
High-linear energy transfer (high LET) irradiation has significant cytotoxic effects on different cancerous stem-like cells (CSLCs) such as colorectal CSLCs. A review of the literature has indicated t...
It is believed that the dose-rate of radiation will have an influence on cell sensitivity. The dose-rate effects on cell survival can be expressed by the change of the β term in the linear quadratic ...
Glioma is one of the most common and aggressive tumors in the brain. Significant attention has been paid to the potential use of neural stem/progenitor cells (NSCs/NPCs) as delivery vehicles to cure g...
Many studies are focusing on the biological effects of gamma irradiation at low dose-rates. Studies have shown that chronic exposure to gamma irradiation at low dose-rates shortened the lifespan of mi...
The patterns of failure and long-term outcomes of patients with relapsed or refractory classical Hodgkin lymphoma (cHL) treated with total lymphoid irradiation (TLI) and high-dose chemotherapy (HDCT) ...
This pilot trial studies different high-dose chemotherapy regimens with or without total-body irradiation (TBI) to compare how well they work when given before autologous stem cell transpl...
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This phase I/II trial studies the side effects and best dose of melphalan and total marrow irradiation and how well they work with autologous stem cell transplantation in treating patients...
RATIONALE: Melphalan, a chemotherapeutic agent, has been found to be an effective treatment choice for destroying myeloma cells, especially when given at high (bone marrow ablative) doses....
A barbiturate with hypnotic and sedative properties (but not antianxiety). Adverse effects are mainly a consequence of dose-related CNS depression and the risk of dependence with continued use is high. (From Martindale, The Extra Pharmacopoeia, 30th ed, p565)
Biphasic dose responses of cells or organisms (including microorganisms) to an exogenous or intrinsic factor, in which the factor induces stimulatory or beneficial effects at low doses and inhibitory or adverse effects at high doses.
The highest dose of a biologically active agent given during a chronic study that will not reduce longevity from effects other than carcinogenicity. (from Lewis Dictionary of Toxicology, 1st ed)
Irradiation of one half or both halves of the body in the treatment of disseminated cancer or widespread metastases. It is used to treat diffuse metastases in one session as opposed to multiple fields over an extended period. The more frequent treatment modalities are upper hemibody irradiation (UHBI) or lower hemibody irradiation (LHBI). Less common is mid-body irradiation (MBI). In the treatment of both halves of the body sequentially, hemibody irradiation permits radiotherapy of the whole body with larger doses of radiation than could be accomplished with WHOLE-BODY IRRADIATION. It is sometimes called "systemic" hemibody irradiation with reference to its use in widespread cancer or metastases. (P. Rubin et al. Cancer, Vol 55, p2210, 1985)
Benign and malignant intra-axial tumors of the MESENCEPHALON; PONS; or MEDULLA OBLONGATA of the BRAIN STEM. Primary and metastatic neoplasms may occur in this location. Clinical features include ATAXIA, cranial neuropathies (see CRANIAL NERVE DISEASES), NAUSEA, hemiparesis (see HEMIPLEGIA), and quadriparesis. Primary brain stem neoplasms are more frequent in children. Histologic subtypes include GLIOMA; HEMANGIOBLASTOMA; GANGLIOGLIOMA; and EPENDYMOMA.
Immunoassay - ELISA
Immunoassays are quick and accurate tests to detect specific molecules. Immunoassays rely on an antibody to bind to the specific structure of a molecule. Antibodies are proteins generated by animals in response to the invasion of a foreign molecule (anti...