Chemical radioprotection: A critical review of amifostine as a cytoprotector in radiotherapy

Andreassen, Christian Nicolaj; Grau, Cai; Lindegaard, Jacob Christian

doi:10.1053/srao.2003.50006

Cited by 169 publications

(118 citation statements)

References 77 publications

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“…[9][10][11][12][25][26][27][28][29][30][31] With the availability of sophisticated computer-controlled modification systems for clinical radiotherapy dose distribution by modern linear accelerators including intensity-modulated radiation therapy, 1,2,7 many physical barriers to dose optimization in complex tumor volumes have been overcome. Unfortunately, effective high dose delivery to complex tumor volumes in the thoracic cavity, which has been developed for patients with lung cancer, esophagus cancer, and other thoracic malignancies, has necessitated often large lung transit volumes and associated toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Pharmacologic interventions and biologic response modifiers have recently been focused on pulmonary radiation protection. Intravenous or systemic delivery of compounds such as WR2721 (Amifostine), [9][10][11][26][27][28][29]32 colony stimulating factors, 31 or other antioxidant molecules 30,33,34 has the potential problem of distribution to tumor vasculature within the target volume. 27,29 Simultaneous tumor and normal tissue radiation protection would not alter the therapeutic ratio or shift to a desirable effect of normal tissue radiation protection.…”

Section: Discussionmentioning

confidence: 99%

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Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes protects the murine lung from irradiation damage

et al. 2005

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Intratracheal injection of manganese superoxide dismutaseplasmid/liposome (MnSOD-PL) complexes has been demonstrated to delay the onset and reduce the extent of ionizing irradiation-induced murine pulmonary organizing alveolitis/ fibrosis. To facilitate translation of this modality to clinical fractionated radiotherapy, inhalation delivery of MnSOD-PL was developed using an ultrasonic nebulizer. Transgene product was quantitated by immunohistochemical quantitation and pulmonary tissue levels of MnSOD biochemical activity. C57BL/6NHsd female mice demonstrated a plasmid dose-dependent increased expression of MnSOD transgene product over the range of 250 mg-2.5 mg of MnSOD-PL administered over a constant 5 min interval. Delivery of a constant concentration of 500 mg of MnSOD-PL with varying times of administration ranging from 0.5 to 10 min demonstrated optimal MnSOD expression at 5 min. Mice pretreated by inhalation delivery of MnSOD-PL demonstrated significantly improved survival after 20 Gy single fraction irradiation to both lungs compared to LacZ-PL inhalation-treated or irradiated control mice. Mice receiving 10 fractions of 3.5 cGy demonstrated increased pulmonary MnSOD transgene product activity by a protocol of every Monday-Wednesday or daily inhalation of MnSOD-PL. Thus, inhalation radioprotective gene therapy using MnSOD-PL provides a practical and effective method for delivery of lung-specific radioprotection during fractionated radiotherapy protocols in a mouse model. Gene Therapy (2005) 12, 685-693.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes protects the murine lung from irradiation damage

et al. 2005

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“…In addition to its high efficacy in ameliorating xerostomia resulting from irradiation (4,5), high frequencies of deleterious side effects (nausea, cutaneous reactions, hypotension, etc.) and even tumor radioprotection have been reported, which limit its use (6)(7)(8)(9). Therefore, the search for other radioprotectors with high potency and low toxicity should be the primary subject of further research.…”

Section: Introductionmentioning

confidence: 99%

Research progress in the radioprotective effect of superoxide dismutase

et al. 2012

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Irradiation from diverse sources is ubiquitous and closely associated with human activity. Radiation therapy (RT), an important component of the multiple radiation origins, contributes significantly to oncotherapy by killing tumor cells. On the other hand, RT can also cause some undesired normal tissue injuries that afflict numerous cancer patients. Although many promising radioprotective agents are emerging, few of them have entered the market successfully due to various limitations. At present, the most accepted hypothesis for the radiation-caused injury involves reactive oxygen species (ROS) generation. Superoxide dismutase (SOD), the unique enzyme responsible for the dismutation of superoxide radicals, is expected to occupy an indispensable position in the treatment of ROS-mediated tissue injuries originating from exposure to radiation. This review focuses on the mechanism of radioprotection by SOD at the tissue or organ level, cellular level, and molecular level, respectively, in order to provide references for further investigation of radiation injury and development of new radioprotectors.

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“…The protective effects on both tumor and normal tissue of any radioprotector should be quantatively known and a therapeutic gain can be calculated. Ideally the dose-response effect of the compound should be evaluated both in the normal and the tumor tissue and ideal dose be determined (Andreassen et al, 2003). At both physiological and pharmacological concentrations, melatonin acts as a differentiating agent in some cancer cells and lowers their invasive and metastatic status through alterations in adhesion molecules and maintenance of gap junctional intercellular communication.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Melatonine Against Radiation Induced Nephrotoxicity in Rats

Küçüktülü¹,

Yavuz²,

Çobanoğlu³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Protective Effect of Melatonine Against Radiation Induced Nephrotoxicity in Rats 13, 4101-4105 IntroductionKidneys are frequently included into the therapy area during radiotherapy applications. The extent of radiation damage depends on both dose and volume of radiation (Perez et al., 2008). Renal tolerance dose is 20 Gy in bilateral irradiation, while in unilateral exposure renal dysfunction starts in 15 Gy and renal function is completely lost in doses of 25-30 Gy. Concomitant use of cisplatin some chemicals such as BCNU and actinomycin further lowers the tolerance dose. When renal tolerance dose is exceeded after a latent period of 6 mounts acute nephritis develops, after 18 mounts on chronic nephritis and hiperreninemic hypertension is observed. In histopathologic examination interstial edema secondary to increased capillary permeability is evident in acute phase, (Zaki et al., 2003).Rapid multiplication of the tumoral cell leaves hypoxia and necrotic areas at the center of the tumors. Since radiation is ineffective at these regions, higher radiation doses are usually required at the tumor center to control tumoral multiplication. The normal tissue surrounding the tumor is rich in blood vessels and well oxygenated, AbstractPurpose: The degree of radiation injury to kidneys which are located within the limits of radiotherapy area is determined by the volume and the dose of radiation to which the organ is exposed. When the tolerance dose of the kidney is exceeded after a latent period of 6 months acute nephritis develops and after 18 months chronic nephritis ensues. Melatonin is known to prevent the oxidative injury of toxins and radiotherapy with its free radical scavenging capacity. Methods and materials: In this study 8 weeks old 24 Sprague -Dawley rats were allocated into 4 groups: Control group; Radiotherapy group (20 Gy bilaterally in 5 fractions); Melatonin group (10 mg/kg intraperitoneally), and Melatonin+radiotherapy group (20 Gy Radiotherapy in 5 fractions+ melatonin 10 mg/kg intraperitoneally). After a follow-up period of 6 months BUN was determined in all groups. After rats were euthanized the kidneys were removed for histopathological examination under both light and electron microscopes. Results: After 6 months follow-up, both at light and electron microscopy levels, the radiotherapy group (p<0.05). Conclusion: It was shown in this experimental model that melatonin has protective effects against radiation injury to kidneys.

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Chemical radioprotection: A critical review of amifostine as a cytoprotector in radiotherapy

Cited by 169 publications

References 77 publications

Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes protects the murine lung from irradiation damage

Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes protects the murine lung from irradiation damage

Research progress in the radioprotective effect of superoxide dismutase

Protective Effect of Melatonine Against Radiation Induced Nephrotoxicity in Rats

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