Dexamethasone-Induced Enhancement of Resistance to Ionizing Radiation and Chemotherapeutic Agents in Human Tumor Cells

Mariotta, Manuel; Perewusnnyk, Gloria; Koechli, Ossi R.; Little, John B.; Doeberitz, Magnus von Knebel; Mirimanoff, René-Olivier; Rutz, Hans

doi:10.1007/s000660050027

Cited by 28 publications

(18 citation statements)

References 20 publications

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“…The mechanisms proposed for increased radioresistance include an effect on the cell cycle (26), a decrease in radio-induced apoptosis (27,28), and metabolic changes (29). However, this radioprotective effect was observed in few cell lines (31,32) and not in some others (32 -34). Here, we did not find any direct radiosensitization effect in vitro when the tumor cells were incubated in the presence of glucocorticoids (Fig.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoids Modulate Tumor Radiation Response through a Decrease in Tumor Oxygen Consumption

Crokart¹,

Jordan²,

Baudelet³

et al. 2007

Clinical Cancer Research

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Purpose: We hypothesized that glucocorticoids may enhance tumor radiosensitivity by increasing tumor oxygenation (pO 2 ) through inhibition of mitochondrial respiration. Experimental Design: The effect of three glucocorticoids (hydrocortisone, dexamethasone, and prednisolone) on pO 2 was studied in murine TLT liver tumors and FSaII fibrosarcomas. At the time of maximum pO 2 (t max , 30 min after administration), perfusion, oxygen consumption, and radiation sensitivity were studied. Local pO 2 measurements were done using electron paramagnetic resonance. The oxygen consumption rate of tumor cells after in vivo glucocorticoid administration was measured using high-frequency electron paramagnetic resonance. Tumor perfusion and permeability measurements were assessed by dynamic contrast-enhanced magnetic resonance imaging. Results: All glucocorticoids tested caused a rapid increase in pO 2 . At t max , tumor perfusion decreased, indicating that the increase in pO 2 was not caused by an increase in oxygen supply. Also at t max , global oxygen consumption decreased.When irradiation (25 Gy) was applied at t max , the tumor radiosensitivity was enhanced (regrowth delay increased by a factor of 1.7). Conclusion:These results show the potential usefulness of the administration of glucocorticoids before irradiation.Tumor hypoxia is a critical determinant of resistance to radiotherapy and chemotherapy (1, 2). To target this resistance, prodrugs have been developed that are activated in hypoxic regions (3). In addition to this approach, we may also consider that a transient increase in tumor oxygenation may be beneficial if combined with radiotherapy. Indeed, a number of tumor oxygenating treatments have been developed to improve the therapeutic outcome. Mechanistically, tumor hypoxia results from an imbalance between oxygen delivery and oxygen consumption, either of which may be potentially targeted by therapeutic interventions. On one hand, oxygen delivery may be increased by increasing tumor perfusion (4 -7) or by changing the hemoglobin saturation curve (8, 9). On the other hand, tumor hypoxia can be alleviated by decreasing the oxygen consumption. It has been predicted that modification of oxygen consumption is much more efficient at alleviating hypoxia than modification of oxygen delivery (10). Several drugs that inhibit mitochondrial respiration, such as metaiodobenzylguanidine (11), insulin (12, 13), and cyclooxygenase-2 inhibitors (14), have been characterized for their potential to increase tumor oxygenation and thereby enhance radiosensitivity.Here, we hypothesized that glucocorticoids could be other important modulators of tumor oxygenation. The rationale for this hypothesis is that glucocorticoids are known to inhibit oxidative phosphorylation of the respiratory chain, with important effect on respiration rate of cells (15,16). Using two different tumor models, we show that the administration of glucocorticoids (hydrocortisone, prednisolone, and dexamethasone) has a profound effect on tumor oxygenation....

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Section: Discussionmentioning

confidence: 99%

Glucocorticoids Modulate Tumor Radiation Response through a Decrease in Tumor Oxygen Consumption

Crokart¹,

Jordan²,

Baudelet³

et al. 2007

Clinical Cancer Research

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“…Therefore, Dex might compromise the responsiveness of tumor cells to DNA damaging agents such as chemo and/or radio-therapies by slowing down tumor cell replication. Indeed, the use of corticosteroid has shown to increase tumor's radioresistance, however, this effect seems to be cell type dependent [37]. Perhaps the upregulation of steroid receptors following ionizing radiation therapy is the mechanism responsible for Dex-induced radioresistance [38].…”

Section: Possible Effects Of Corticosteroids On Gliomamentioning

confidence: 99%

“…However, cancer therapeutics often target rapidly dividing cells, it becomes quite possible that Dex might compromise the responsiveness of tumor cells to chemotherapy and/or radio-therapy by slowing down tumor cell replication. Indeed, the use of corticosteroids was shown to increase tumor's radioresistance and chemoresistance [37,92,93]. GBM and fibroblast cell lines did not acquire resistance to ionizing radiation, whereas some of the carcinoma cell lines did [37,94].…”

Section: The Anti-proliferation Properties Of Dexmentioning

confidence: 99%

“…Indeed, the use of corticosteroids was shown to increase tumor's radioresistance and chemoresistance [37,92,93]. GBM and fibroblast cell lines did not acquire resistance to ionizing radiation, whereas some of the carcinoma cell lines did [37,94]. Upregulation of steroids receptors following ionizing radiation therapy may be a potential mechanism responsible for Dex-induced radioresistance [38].…”

Section: The Anti-proliferation Properties Of Dexmentioning

confidence: 99%

“…Since cancer therapeutics often target rapidly growing cells, it is quite possible that Dex might compromise the responsiveness of tumor cells to chemotherapy and/or radiotherapy via inhibiting tumor cell growth. Indeed, several studies suggested that Dex might compromise the responsiveness of tumor cells to chemotherapy and/or radiotherapy [37,92,93]. Pre-treatment with Dex induces Bcl-xL expression and inhibited cell death induced by staurosporine, camptothecin and etoposide in astrocytoma cultures [93].…”

Section: Corticosteroids Might Reduce the Efficacy Of Chemotherapy Anmentioning

confidence: 99%

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Glioma: A Tale of Corticosteroids, Thiopurines and Proposed Novel AntiGlioma Small Molecules

Ahmed¹

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Analysis of concordance with antiemetic guidelines in pediatric, adolescent, and young adult patients with cancer using a large‐scale administrative database

et al. 2019

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ObjectThe appropriate use of antiemetics is important for the prevention of chemotherapy‐induced nausea and vomiting (CINV); however, little is known about the rate of concordance with antiemetic guidelines for CINV in the field of pediatric, adolescent, and young adult.MethodsUsing the Diagnosis Procedure Combination system in Japan, we identified patients <30 years of age who were diagnosed with cancer between July 2010 and March 2016. We have assessed concordance with the ASCO antiemetic guidelines for each emetic risk category of chemotherapeutic drugs. Furthermore, we have assessed the risk factors of discordance with the antiemetic guidelines using a logistic regression.ResultsIn total, 21 106 patients who underwent chemotherapy were included. The rates of concordance with the guidelines in each emetic risk category of chemotherapeutic drugs were 51.1% in high risk, ≥18 years of age; 21.5% in high risk, <18 years of age; 32.1% in moderate risk; 52.0% in low risk; and 51.6% in minimal risk. The main reason for the discordance was underuse of antiemetics, especially steroids. The factors for discordance were younger age, use of moderate and high emetic risk chemotherapeutic drugs, hematological malignancy, and brain tumor.ConclusionThere is substantial scope to improve the antiemetic practice and reduce the risk of discordance with the antiemetic guidelines in pediatric, adolescent, and young adult patients. The risk factors are different from those in adults. Further investigations to evaluate the causes of discordance are warranted.

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Dexamethasone-Induced Enhancement of Resistance to Ionizing Radiation and Chemotherapeutic Agents in Human Tumor Cells

Cited by 28 publications

References 20 publications

Glucocorticoids Modulate Tumor Radiation Response through a Decrease in Tumor Oxygen Consumption

Glucocorticoids Modulate Tumor Radiation Response through a Decrease in Tumor Oxygen Consumption

Glioma: A Tale of Corticosteroids, Thiopurines and Proposed Novel AntiGlioma Small Molecules

Analysis of concordance with antiemetic guidelines in pediatric, adolescent, and young adult patients with cancer using a large‐scale administrative database

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