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Journal of Veterinary Science May 2023Titanium is the most widely used metal for bone integration, especially for cancer patients receiving ionizing radiation. This study aimed to investigate the amifostine...
BACKGROUND
Titanium is the most widely used metal for bone integration, especially for cancer patients receiving ionizing radiation. This study aimed to investigate the amifostine administration that would reduce the effects of radiation on bone healing and osseointegration in rat models.
OBJECTIVES
It is aimed that the application of amifostine in rats receiving radiotherapy treatment will reduce the negative effects of ionizing radiation on the bone.
METHODS
Thirty-five adult male Wistar rats were randomly divided into one healthy and four experimental groups. In three consecutive days, two experimental groups of rats (AMF-RT-IMP and RT-IMP) were exposed to radiation (15 Gy/3 fractions of 5 Gy each). Then the titanium implants were inserted into the left tibia. Before the radiotherapy process, a 200 mg/kg dose of amifostine (AMF) was administered to the rats in the AMF-IMP and AMF-RT-IMP groups. Twenty-eight days after the screw implant, all rats were sacrificed, and their blood samples and tibia bones were collected for analysis.
RESULTS
The results indicated an accelerated bone formation and a more rapid healing process in the screw implants in the AMF-IMP, AMF-RT-IMP, and AMF-RT groups than in the RT-IMP group. Also, bone-implant contact area measurement and inflammation decreased with amifostine treatment in the implants subjected to irradiation ( < 0.05).
CONCLUSIONS
The results obtained in the present study suggested that amifostine prevents the losses of bone minerals, bone integrity, and implant position from ionizing-radiation when given before exposure.
Topics: Rats; Male; Animals; Amifostine; Tibia; Titanium; Radiation-Protective Agents; Rats, Wistar
PubMed: 37271503
DOI: 10.4142/jvs.23023 -
Journal of Clinical Oncology : Official... Jan 2011
Topics: Amifostine; Combined Modality Therapy; Head and Neck Neoplasms; Humans; Infusions, Intravenous; Infusions, Subcutaneous; Radiation-Protective Agents
PubMed: 21115854
DOI: 10.1200/JCO.2010.31.5051 -
Seminars in Radiation Oncology Jan 2003The use of chemical radioprotectors represents an obvious strategy to improve the therapeutic index in radiotherapy. Amofostine (WR-2721) has recently been approved for... (Review)
Review
The use of chemical radioprotectors represents an obvious strategy to improve the therapeutic index in radiotherapy. Amofostine (WR-2721) has recently been approved for use in head and neck cancer to protect against radiation-induced xerostomia. Currently, the question has arisen whether amifostine could be used for radioprotection in broader terms. Amifostine may have the potential to enable intensified treatment by ameliorating mucosal reactions that are often a limiting factor in accelerated fractionation or concomitant chemoradiation. However, it has as yet not been clarified whether sufficient amifostine to reduce mucositis can be administered before each radiation fraction without causing unacceptable toxicity. Also, the optimal dosage and schedule of amifostine in chemoradiation combinations have not yet been established. The major concern related to radioprotectiors is the potential hazard of collateral tumor protection. A number of clinical studies have concluded that amifostine does not reduce antitumor efficacy. However, not even the largest study conducted, with over 300 patients, has sufficient statistical power to detect a clinically significant reduction in tumor control rate. To put this issue ultimately to a rest, a clinical trial with a sufficient accrual to definitely rule out a tumor protective effect of amifostine needs to be conducted. Substances reducing radiation-induced toxicity by modulating the biological response to radiation injury may represent an alternative concept in radioprotection. However, such agents are still at a developmental stage.
Topics: Amifostine; Combined Modality Therapy; Dose-Response Relationship, Radiation; Europe; Humans; Neoplasms; Radiation-Protective Agents; Radiotherapy Dosage; Treatment Outcome; United States
PubMed: 12520465
DOI: 10.1053/srao.2003.50006 -
Annals of Plastic Surgery Oct 2020Indications for adjuvant radiation therapy (XRT) in breast cancer have expanded. Although highly effective, XRT damages surrounding tissues and vasculature, often...
BACKGROUND
Indications for adjuvant radiation therapy (XRT) in breast cancer have expanded. Although highly effective, XRT damages surrounding tissues and vasculature, often resulting in delayed or compromised breast reconstruction. Thus, effective yet safe methods of radiation injury prophylaxis would be desirable. Amifostine is a Food and Drug Administration-approved radioprotectant; however, concerns about its potential to also protect cancer remain. The purpose of this study was to evaluate the oncologic safety of amifostine (AMF) in vitro and determine its effect on human breast cancer cells in the setting of XRT.
METHODS
One ER+/PR+/Her2- (MCF-7) and two ER-/PR-Her2- (MDA-MB-231, MDA-MB-468) breast cancer cell lines were investigated. Female fibroblasts were used as controls. Cells were treated with WR-1065, the active metabolite of AMF, 20 minutes before 0Gy, 10Gy, or 20Gy XRT. Live and dead cells were quantified; percent cell death was calculated.
RESULTS
WR-1065 treatment significantly preserved viability and reduced healthy female fibroblasts death after XRT compared with untreated controls. All three breast cancer cells lines exhibited radiosensitivity with substantial cell death. Cancer cells retained their radiosensitivity despite WR-1065 pretreatment, achieving the same degree of cell death as untreated controls.
CONCLUSIONS
This study demonstrated the proficiency of AMF to selectively protect healthy cells from XRT while breast cancer cells remained radiosensitive. These results support the oncologic safety of AMF in breast cancer in vitro. Further investigation is now warranted in vivo to ascertain the translational potential of using AMF as a radioprotectant to improve breast reconstruction after radiation treatment.
Topics: Amifostine; Animals; Breast Neoplasms; Female; Humans; Mammaplasty; Radiation Injuries; Radiation-Protective Agents; Rats; Rats, Sprague-Dawley
PubMed: 31850964
DOI: 10.1097/SAP.0000000000002110 -
Seminars in Oncology Apr 1999Amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) is a thiophosphate cytoprotectant agent with the potential to abrogate many... (Review)
Review
Amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) is a thiophosphate cytoprotectant agent with the potential to abrogate many chemotherapy-induced toxicities. In preclinical studies, amifostine protected against the cytotoxic effects of alkylating agents, platinum analogs, and radiation therapy in normal tissues, but preserved antineoplastic activity of these therapeutic modalities in tumor tissue. Most normal tissues were protected, including bone marrow, kidney, lung, and peripheral nerves. Recently, the protective effects of amifostine were confirmed by clinical studies, including a randomized trial demonstrating protection from cisplatin-induced myelosuppression, nephrotoxicity, and neurotoxicity. Many common chemotherapeutic agents, such as cisplatin, paclitaxel, and vinca alkaloids, cause dose-limiting neurotoxicity. Therefore, a neurologic protectant may help to reduce toxicity to patients, improve the tolerability of combination therapy with multiple neurotoxic agents, or allow investigators to intensify chemotherapy dose. This report reviews the potential role of amifostine as a neuroprotectant. Future clinical trials may expand the use of amifostine to abrogate neurotoxicity from multiple agents and combinations and compare amifostine with other neuroprotective agents.
Topics: Amifostine; Antineoplastic Agents; Clinical Trials as Topic; Cytoprotection; Humans; Nervous System; Nervous System Diseases; Protective Agents
PubMed: 10348265
DOI: No ID Found -
European Journal of Cancer Care Mar 2009Although head and neck cancer is not one of the most common cancers, it is a debilitating disease with poor prognosis and considerable post-treatment normal tissue... (Review)
Review
Although head and neck cancer is not one of the most common cancers, it is a debilitating disease with poor prognosis and considerable post-treatment normal tissue toxicity. The unremitting search to increase the therapeutic ratio between tumour control and late normal tissue injury led to the adoption of altered fractionation schedules. While the increase in acute toxicity can be managed with appropriate medical support, damage produced to late responding tissues is usually irreversible, therefore clinically unacceptable. By altering the conventionally fractionated radiotherapy both loco-regional control and overall survival are increased. Moreover, phase III randomized trials indicated that the combined administration of cisplatin and radiotherapy further improves treatment outcome. Although the uptake of cisplatin in normal cells is not amplified by the combined modality treatment, cisplatin, by itself is a highly cytotoxic agent. Therefore, the need for normal tissue protection has arisen. Amifostine is a selective, radio-protective drug used in both radiotherapy and chemotherapy to reduce normal tissue toxicity. This paper provides an overview of clinical trials employing cisplatin-radiotherapy treatment for advanced head and neck cancer with specific focus on normal tissue toxicity. The emerging role of radioprotectors and furthermore, the effectiveness of amifostine in combined cisplatin-radiotherapy trials are presented.
Topics: Amifostine; Antineoplastic Agents; Cisplatin; Combined Modality Therapy; Head and Neck Neoplasms; Humans; Radiation-Protective Agents; Radiotherapy, Adjuvant
PubMed: 19267726
DOI: 10.1111/j.1365-2354.2008.01032.x -
Plastic and Reconstructive Surgery Oct 2014Immediate expander-based breast reconstruction after mastectomy is a prevalent option for many women with breast cancer. When coupled with adjuvant radiation therapy,...
BACKGROUND
Immediate expander-based breast reconstruction after mastectomy is a prevalent option for many women with breast cancer. When coupled with adjuvant radiation therapy, however, radiation-induced skin and soft-tissue injury diminish the success of this reconstructive technique. The authors hypothesize that prophylactic administration of the cytoprotectant amifostine will reduce soft-tissue complications from irradiation, aiding expander-based reconstruction.
METHODS
Sprague-Dawley rats were divided into two groups: operative expander placement (expander group) and operative sham (sham group). Expander specimens received a sublatissimus tissue expander with a 15-cc fill volume; shams underwent identical procedures without expanders. Experimental groups were further divided into control specimens receiving no further intervention, radiation therapy-only specimens receiving human-equivalent irradiation, and amifostine plus radiation therapy specimens receiving both amifostine and human-equivalent irradiation. After a 45-day recovery period, animals were evaluated grossly and with ImageJ analysis for skin and soft-tissue complications.
RESULTS
None of the control, radiation therapy-alone, or amifostine plus radiation therapy sham specimens showed skin and soft-tissue complications. For expander animals, significantly fewer amifostine plus radiation therapy specimens [four of 13 (30 percent)] demonstrated skin and soft-tissue complications compared with radiation therapy-alone specimens [nine of 13 (69 percent); p = 0.041]. ImageJ evaluation of expander specimens demonstrated a significant increase in skin and soft-tissue necrosis for radiation therapy-alone specimens (12.94 percent) compared with animals receiving amifostine plus radiation therapy (6.96 percent) (p = 0.019).
CONCLUSIONS
Amifostine pretreatment significantly reduced skin and soft-tissue complications. These findings demonstrate that amifostine prophylaxis provides protection against radiation-induced skin and soft-tissue injury in a murine model of expander-based breast reconstruction.
Topics: Amifostine; Animals; Male; Mammaplasty; Models, Animal; Radiation Injuries; Radiation-Protective Agents; Rats; Rats, Sprague-Dawley; Tissue Expansion
PubMed: 25357049
DOI: 10.1097/PRS.0000000000000543 -
Seminars in Oncology Aug 1996Amifostine selectively protects normal, but not tumor, tissue from the cytotoxic damage induced by radiation therapy and chemotherapy. In a broad range of preclinical... (Review)
Review
Amifostine selectively protects normal, but not tumor, tissue from the cytotoxic damage induced by radiation therapy and chemotherapy. In a broad range of preclinical and phase II and III clinical studies, amifostine has been shown to substantially reduce anticancer drug-induced neutropenia, thrombocytopenia, nephrotoxicity, neurotoxicity (including ototoxicity and peripheral neuropathy), musculoskeletal toxicity, cardiotoxicity, and mutagenicity. Based on the rapidly expanding clinical trials database, there is strong rationale to design phase II and III studies of amifostine as a cytoprotective agent in patients with early and/or advanced breast, bladder, cervix, head and neck, small cell and non-small cell lung, ovarian, and rectal cancers, as well as melanoma, pediatric sarcomas, and lymphomas, including Hodgkin's disease. In this article, we have attempted to survey recently completed and ongoing phase II and III clinical studies and suggest specific designs for future clinical trials to establish the ultimate role of amifostine as a broad-spectrum cytoprotective agent.
Topics: Adult; Amifostine; Antineoplastic Agents; Child; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Humans; Neoplasms
PubMed: 8783674
DOI: No ID Found -
Seminars in Oncology Apr 1999Effective radiotherapy for patients with cancer should include maximal tumor cell killing with minimal injury to normal tissue. However, current radiation doses that can... (Review)
Review
Effective radiotherapy for patients with cancer should include maximal tumor cell killing with minimal injury to normal tissue. However, current radiation doses that can be delivered without causing severe damage to surrounding normal tissues are often insufficient to eradicate a tumor. Recently, a number of agents have been developed to protect normal tissue from the harmful effects of antitumor therapies. The aminothiol amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) has been the subject of extensive research as a prospective protector. While this drug has been approved for use to reduce toxicities associated with cisplatin, several studies also have demonstrated that amifostine protects normal tissues from both acute and late radiation damage without protecting the tumor. Consequently, higher radiation doses could be used with less than or equal risk to surrounding normal tissues. This report reviews the physicochemical basis of radiation therapy on biologic tissues and the mechanisms responsible for the cytoprotective effects of amifostine. The increasing body of biochemical, preclinical, and clinical data could justify the use of protectors such as amifostine with radiotherapy to provide improved therapeutic efficacy and quality of life for the patient.
Topics: Amifostine; Clinical Trials as Topic; Cytoprotection; Humans; Neoplasms; Radiation-Protective Agents; Radiotherapy
PubMed: 10348266
DOI: No ID Found -
Oxidative Medicine and Cellular... 2017The present study was aimed at investigating the effect of amifostine on myocardial ischemia/reperfusion (I/R) injury of mice and H9c2 cells cultured with TBHP...
The present study was aimed at investigating the effect of amifostine on myocardial ischemia/reperfusion (I/R) injury of mice and H9c2 cells cultured with TBHP (tert-butyl hydroperoxide). The results showed that pretreatment with amifostine significantly attenuated cell apoptosis and death, accompanied by decreased reactive oxygen species (ROS) production and lower mitochondrial potential (ΔΨm). In vivo, amifostine pretreatment alleviated I/R injury and decreased myocardial apoptosis and infarct area, which was paralleled by increased superoxide dismutase (SOD) and reduced malondialdehyde (MDA) in myocardial tissues, increased Bcl2 expression, decreased Bax expression, lower cleaved caspase-3 level, fewer TUNEL positive cells, and fewer DHE-positive cells in heart. Our results indicate that amifostine pretreatment has a protective effect against myocardial I/R injury via scavenging ROS.
Topics: Amifostine; Animals; Apoptosis; Cell Survival; Cells, Cultured; Disease Models, Animal; Mice; Mitochondria; Myocardial Reperfusion Injury; Oxidative Stress; Pre-Exposure Prophylaxis; Radiation-Protective Agents
PubMed: 28392886
DOI: 10.1155/2017/4130824