Assessment of cytotoxic damage induced by irradiation combined with hyperthermia and Gemcitabine on cultured glioblastoma spheroid cells

Asayesh, T.; Changizi, Vahid; Eyvazzadeh, Nazila

doi:10.1016/j.radphyschem.2015.11.031

Cited by 7 publications

(3 citation statements)

References 15 publications

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“…In some studies, gemcitabine has been shown to selectively remove B lymphocytes, myeloid-derived suppressor cells, and Tregs, and may avoid Q4 cross-resistance to TMZ by working through an MGMT-independent mechanism of action. As a powerful chemotherapeutic and radiosensitizing drug, gemcitabine has been evaluated in clinical trials, demonstrating its ability to enhance the efficacy of radiation therapy for GBM and to act as a radiation sensitizer. − …”

Section: Combination Of Therapies Related To Metabolic Regulation In ...mentioning

confidence: 99%

Tumor Metabolism: A New Field for the Treatment of Glioma

Chai,

Zhang,

Zhang

et al. 2024

Bioconjugate Chem.

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The clinical treatment of glioma remains relatively immature. Commonly used clinical treatments for gliomas are surgery combined with chemotherapy and radiotherapy, but there is a problem of drug resistance. In addition, immunotherapy and targeted therapies also suffer from the problem of immune evasion. The advent of metabolic therapy holds immense potential for advancing more efficacious and tolerable therapies against this aggressive disease. Metabolic therapy alters the metabolic processes of tumor cells at the molecular level to inhibit tumor growth and spread, and lead to better outcomes for patients with glioma that are insensitive to conventional treatments. Moreover, compared with conventional therapy, it has less impact on normal cells, less toxicity and side effects, and higher safety. The objective of this review is to examine the changes in metabolic characteristics throughout the development of glioma, enumerate the current methodologies employed for studying tumor metabolism, and highlight the metabolic reprogramming pathways of glioma along with their potential molecular mechanisms. Importantly, it seeks to elucidate potential metabolic targets for glioblastoma (GBM) therapy and summarize effective combination treatment strategies based on various studies.

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Section: Combination Of Therapies Related To Metabolic Regulation In ...mentioning

confidence: 99%

Tumor Metabolism: A New Field for the Treatment of Glioma

Chai,

Zhang,

Zhang

et al. 2024

Bioconjugate Chem.

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“…Relevant pre-clinical and clinical endpoints to be reflected in MCTS assays are growth delay (non-curative) and long-term control probability (curative). From the less than one dozen studies using HT + RT in spheroid cultures [18][19][20][21][22][23][24][25][26][27][28], a few have indeed analyzed spheroid volume growth delay as a response to therapy [27,28]. However, therapeutic read-outs as pendants to TCP and TCD 50 were not considered.…”

Section: Introductionmentioning

confidence: 99%

Efficient Heat Shock Response Affects Hyperthermia-Induced Radiosensitization in a Tumor Spheroid Control Probability Assay

Chen

Michlíková

Eckhardt

et al. 2021

Cancers

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Hyperthermia (HT) combined with irradiation is a well-known concept to improve the curative potential of radiotherapy. Technological progress has opened new avenues for thermoradiotherapy, even for recurrent head and neck squamous cell carcinomas (HNSCC). Preclinical evaluation of the curative radiosensitizing potential of various HT regimens remains ethically, economically, and technically challenging. One key objective of our study was to refine an advanced 3-D assay setup for HT + RT research and treatment testing. For the first time, HT-induced radiosensitization was systematically examined in two differently radioresponsive HNSCC spheroid models using the unique in vitro “curative” analytical endpoint of spheroid control probability. We further investigated the cellular stress response mechanisms underlying the HT-related radiosensitization process with the aim to unravel the impact of HT-induced proteotoxic stress on the overall radioresponse. HT disrupted the proteome’s thermal stability, causing severe proteotoxic stress. It strongly enhanced radiation efficacy and affected paramount survival and stress response signaling networks. Transcriptomics, q-PCR, and western blotting data revealed that HT + RT co-treatment critically triggers the heat shock response (HSR). Pre-treatment with chemical chaperones intensified the radiosensitizing effect, thereby suppressing HT-induced Hsp27 expression. Our data suggest that HT-induced radiosensitization is adversely affected by the proteotoxic stress response. Hence, we propose the inhibition of particular heat shock proteins as a targeting strategy to improve the outcome of combinatorial HT + RT.

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“…Experimental studies have shown that high temperatures can directly induce damage to glioma cells and result in radio-or chemosensitization [39][40][41][42][43]. Unlike healthy tissues, tumors have an increased thermal sensitivity, which is caused by biophysical differences between healthy and tumor cells associated with a low efficiency of ATP production in tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Concurrent Thermochemoradiotherapy in Glioblastoma Treatment: Preliminary Results

Ryabova¹,

Novikov²,

Gribova³

et al. 2019

Glioma - Contemporary Diagnostic and Therapeutic Approaches

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Glioblastoma is the most frequent and aggressive primary brain tumor. The patient can be alive with this pathology using the modern standard of intensive combined treatment less than 2 years. Between December 2013 and August 2017, 30 patients with newly diagnosed supratentorial glioblastoma had received concomitant chemoradiotherapy with transcranial radiofrequency hyperthermia. The gross total or the subtotal resection of the tumor was made previously in all cases. The median follow-up time after operation achieved 12 months (95% confidence interval (CI): 8.5-23 months) in this study. The median disease-free survival time was 9.6 months (95% CI: 7.2-19.0 months). The median overall survival time of patients included in the study was 23.4 months. No increase in the systemic side effects of chemotherapy was found compared with the frequency described in the population. Preliminary results had shown that the usage of concomitant thermochemoradiotherapy with transcranial radiofrequency hyperthermia improves progression-free survival rates. Overall survival rates also tended to increase. Given the absence of severe complications, it is necessary to continue research to achieve statistically significant results.

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Assessment of cytotoxic damage induced by irradiation combined with hyperthermia and Gemcitabine on cultured glioblastoma spheroid cells

Cited by 7 publications

References 15 publications

Tumor Metabolism: A New Field for the Treatment of Glioma

Tumor Metabolism: A New Field for the Treatment of Glioma

Efficient Heat Shock Response Affects Hyperthermia-Induced Radiosensitization in a Tumor Spheroid Control Probability Assay

Concurrent Thermochemoradiotherapy in Glioblastoma Treatment: Preliminary Results

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