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Kavitha Ranganathan, Eric Simon, Jeremy Lynn, Alicia Snider, Yu Zhang, Noah Nelson, Alexis Donneys, Jose Rodriguez, Lauren Buchman, Dawn Reyna, Elke Lipka, Steven R Buchman
PURPOSE: Amifostine (AMF), a radioprotectant, is FDA-approved for intravenous administration in cancer patients receiving radiation therapy (XRT). Unfortunately, it remains clinically underutilized due to adverse side effects. The purpose of this study is to define the pharmacokinetic profile of an oral AMF formulation potentially capable of reducing side effects and increasing clinical feasibility. METHODS: Calvarial osteoblasts were radiated under three conditions: no drug, AMF, and WR-1065 (active metabolite)...
March 19, 2018: Pharmaceutical Research
Tolga Mercantepe, Deniz Unal, Levent Tümkaya, Zihni Acar Yazici
Cisplatin is an effective antineoplastic drug that is usually used to treat a number of different types of cancer in the clinic. One of the most notable side effects of cisplatin use is infertility. The present study was designed to determine the non-oxidative testicular effects caused by the use of cisplatin in rats. The rats were randomly allocated to the experimental groups. The untreated rats represented the control group (group I) and the treatment groups were as follows: cisplatin alone (group II), cisplatin+amifostine (group III), cisplatin+curcumin (group IV), and cisplatin+caffeic acid phenethyl ester (CAPE; group V)...
April 2018: Experimental and Therapeutic Medicine
John A Cook, Sarwat Naz, Miriam R Anver, Anastasia L Sowers, Kristin Fabre, Murali C Krishna, James B Mitchell
Amifostine is a potent antioxidant that protects against ionizing radiation effects. In this study, we evaluated the effect of Amifostine administered before total-body irradiation (TBI), at a drug dose that protects against TBI lethality, for potential protection against radiation-induced late effects such as a shortened lifespan and cancer. Three groups of mice were studied: 0 Gy control; 10.8 Gy TBI with Amifostine pretreatment; and 5.4 Gy TBI alone. Animals were monitored for their entire lifespan. The median survival times for mice receiving 0, 5...
March 12, 2018: Radiation Research
Jee-Youn Kim, Yong-Min An, Byeong Rok Yoo, Jin-Mo Kim, Song Yee Han, Younghwa Na, Yun-Sil Lee, Jaeho Cho
Radiation therapy has been used to treat over 70% of thoracic cancer; however, the method usually causes radiation pneumonitis. In the current study, we investigated the radioprotective effects of HSP27 inhibitor (J2) on radiation-induced lung inflammation in comparison to amifostine. In gross and histological findings, J2 treatment significantly inhibited immune cell infiltration in lung tissue, revealing anti-inflammatory potential of J2. Normal lung volume, evaluated by micro-CT analysis, in J2-treated mice was higher compared to that in irradiated mice...
March 8, 2018: Scientific Reports
Eric S Simon, Dawn Reyna, Richard J Lister, Cheryl Harteg, Elke Lipka
Hypotension is the dose-limiting side effect of the radio-protective drug Amifostine and results from relaxation of the vascular smooth muscle, which is directly mediated by the active metabolite, WR-1065, of Amifostine. The route of administration (currently FDA-approved only for intravenous administration) and the rapid metabolic conversion of Amifostine combine to yield high systemic levels of WR-1065 and facilitate the onset of hypotension. Research efforts aiming to optimize the delivery of WR-1065 to maintain efficacy while reducing its peak, systemic concentration below levels that induce hypotension are underway...
February 20, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
I Gurses, M Ozeren, M Serin, N Yucel, H S Erkal
OBJECTIVE: Amifositine is a phosphorylated thiol that holds its radioprotective actions by several indirect mechanisms. The purpose of this study was to evaluate histopathologically whether amifositine administration prior to irradiation would have a long‑term protective effect on heart tissue in an experimental rat model. METHODS: Single dose of 18 Gy radiation and sham radiation exposure were used in related groups. A dose of 200 mg/kg of amifostine was injected intraperitoneally 30 min prior to radiation exposure...
2018: Bratislavské Lekárske Listy
Theresa A Lawrie, John T Green, Mark Beresford, Linda Wedlake, Sorrel Burden, Susan E Davidson, Simon Lal, Caroline C Henson, H Jervoise N Andreyev
BACKGROUND: An increasing number of people survive cancer but a significant proportion have gastrointestinal side effects as a result of radiotherapy (RT), which impairs their quality of life (QoL). OBJECTIVES: To determine which prophylactic interventions reduce the incidence, severity or both of adverse gastrointestinal effects among adults receiving radiotherapy to treat primary pelvic cancers. SEARCH METHODS: We conducted searches of CENTRAL, MEDLINE, and Embase in September 2016 and updated them on 2 November 2017...
January 23, 2018: Cochrane Database of Systematic Reviews
Chen Yan, Lan Luo, Yoshishige Urata, Shinji Goto, Tao-Sheng Li
Radiotherapy for cancer patients damages normal tissues, thereby inducing an inflammatory response and promoting cancer metastasis. We investigated whether nicaraven, a compound with radioprotective and anti-inflammatory properties, could attenuate radiation-induced cancer metastasis to the lungs of mice. Nicaraven and amifostine, another commercial radioprotective agent, had limited effects on both the radiosensitivity of Lewis lung carcinoma cells in vitro and radiation-induced tumor growth inhibition in vivo...
January 12, 2018: Cancer Letters
Ehsan Malek, Vinita Gupta, Richard Creger, Paolo Caimi, Anant Vatsayan, Fahrettin Covut, Qaiser Bashir, Richard Champlin, Ruby Delgado, Gabriela Rondon, Brenda Cooper, Marcos de Lima, Hillard M Lazarus, Muzaffar Qazilbash
High-dose melphalan (HDM) followed by autologous hematopoietic cell transplantation (auto-HCT) remains the standard-of-care therapy for multiple myeloma (MM) even with the availability of proteasome inhibitors and immunomodulatory drugs. Gastrointestinal (GI) toxicity is the main cause of morbidity after HDM. Amifostine, a cytoprotective agent, may reduce HDM-associated GI toxicity. We conducted a case control study comparing HDM + auto-HCT with or without amifostine for MM patients. One hundred and seven patients treated at University Hospitals Cleveland Medical Center who received pre-transplant amifostine were compared to 114 patients treated at MD Anderson Cancer Center without use of this agent...
January 2, 2018: Leukemia & Lymphoma
Yabin Duan, Xingchen Yao, Junbo Zhu, Yongping Li, Juanling Zhang, Xuejiao Zhou, Yijie Qiao, Meng Yang, Xiangyang Li
The aim of the present study was to investigate the protective effects of yak-activated protein on hematopoiesis and cytokine function in radiation-induced injury in mice. A total of 180 Kunming mice were randomly divided into three groups (A, B and C). Of these, 60 were randomly divided into a normal control group, a radiation model group, a positive control group and 3 yak-activated protein groups (high, medium and low dose groups; 10, 5 and 2.5 mg/kg, respectively). The other 120 mice were used for the subsequent experiments on days 7 and 14 following radiation...
December 2017: Experimental and Therapeutic Medicine
Michael I Koukourakis, Alexandra Giatromanolaki, Konstantina Fylaktakidou, Maria Kouroupi, Efthimios Sivridis, Christos E Zois, Dimitra Kalamida, Achilleas Mitrakas, Stamatia Pouliliou, Ilias V Karagounis, Konstantinos Simopoulos, David J P Ferguson, Adrian L Harris
BACKGROUND/AIM: Amifostine is the only selective normal tissue cytoprotector, approved for the protection against platinum toxicities and radiotherapy-induced xerostomia. Free radical scavenger and DNA repair activities have been attributed to the drug. MATERIALS AND METHODS: We investigated the effect of amifostine on autophagy, lysosomal biogenesis and lipophagy of normal mouse liver exposed to clinically relevant doses of radiation. RESULTS: The study provides evidence that ionizing radiation blocks autophagy activity and lysosomal biogenesis in normal mouse liver...
January 2018: Anticancer Research
Koji Murono, Kazushige Kawai, Keisuke Hata, Shigenobu Emoto, Manabu Kaneko, Kazuhito Sasaki, Takeshi Nishikawa, Kensuke Otani, Toshiaki Tanaka, Hiroaki Nozawa
Although systemic chemotherapy has been improved, peritoneal carcinomatosis remains a factor of poor prognosis in patients with colorectal cancer. In order to achieve a higher drug concentration in the peritoneal cavity, intraperitoneal chemotherapy has been performed. However, the optimal regimen for intraperitoneal chemotherapy has not been determined. In this review of intraperitoneal chemotherapy for colorectal cancer, we summarize regimens of hyperthermic intraperitoneal chemotherapy (HIPEC) and other intraperitoneal chemotherapy modalities, such as early postoperative intraperitoneal chemotherapy (EPIC) and sequential postoperative intraperitoneal chemotherapy (SPIC)...
January 2018: Anticancer Research
Rakesh Raman Patyar, Sazal Patyar
As the use of radiation technology for nuclear warfare or for the benefits of mankind (e.g. in radiotherapy or radio-diagnosis) is increasing tremendously, the risk of associated side effects is becoming a cause of concern. These effects, ranging from nausea/vomiting to death, may result from accidental or deliberate exposure and begin in seconds. Through this review paper, efforts have been done to critically review different compounds which have been investigated as radioprotectors and radiation mitigators...
January 15, 2018: European Journal of Pharmacology
Fatemeh Ghane Sharbaf, Hamid Farhangi, Farahnak Assadi
Children with cancer treated with cytotoxic drugs are frequently at risk of developing renal dysfunction. The cytotoxic drugs that are widely used for cancer treatment in children are cisplatin (CPL), ifosfamide (IFO), carboplatin, and methotrexate (MTX). Mechanisms of anticancer drug-induced renal disorders are different and include acute kidney injury (AKI), tubulointerstitial disease, vascular damage, hemolytic uremic syndrome (HUS), and intrarenal obstruction. CPL nephrotoxicity is dose-related and is often demonstrated with hypomagnesemia, hypokalemia, and impaired renal function with rising serum creatinine and blood urea nitrogen levels...
2017: International Journal of Preventive Medicine
Sean S Davies, Linda S Zhang
PURPOSE OF THE REVIEW: To summarize recent evidence supporting the use of reactive carbonyl species scavengers in the prevention and treatment of disease. RECENT FINDINGS: The newly developed 2-aminomethylphenol class of scavengers shows great promise in preclinical trials for a number of diverse conditions including neurodegenerative diseases and cardiovascular disease. In addition, new studies with the thiol-based and imidazole-based scavengers have found new applications outside of adjunctive therapy for chemotherapeutics...
April 2017: Current Pharmacology Reports
Güleser Saylam, Ömer Bayır, Salih Sinan Gültekin, Ferda Alparslan Pınarlı, Ünsal Han, Mehmet Hakan Korkmaz, Mehmet Eser Sancaktar, İlkan Tatar, Mustafa Fevzi Sargon, Emel Çadallı Tatar
BACKGROUND: To analyze protective/regenerative effects of adipose tissue-derived mesenchymal stem cells (ADMSC) on (131)I-Radioiodine (RAI)-induced salivary gland damage in rats. MATERIALS AND METHODS: Study population consisted of controls (n:6) and study groups (n:54): RAI (Group 1), ADMSC (Group 2), amifostine (Group 3), RAI+amifostine (Group 4), concomitant RAI+ADMSC (Group 5) and RAI+ADMSC after 48 h (Group 6). We used light microscopy (LM), transmission electron microscopy (TEM), and salivary gland scintigraphy (SGS), and analyzed data statistically...
September 2017: Radiology and Oncology
Catherine N Tchanque-Fossuo, Alexis Donneys, Sagar S Deshpande, Deniz Sarhaddi, Noah S Nelson, Laura A Monson, Sara E Dahle, Steve A Goldstein, Steven R Buchman
BACKGROUND: Using distraction osteogenesis (DO) to regenerate robust endogenous bone could greatly enhance postoncologic reconstruction of head and neck cancer. However, radiation (XRT) corrosive effects still preclude DO's immense potential. We posit that adjunctive pretreatment with the radioprotectant amifostine (AMF) can optimize wound healing and allow for successful DO with quantifiable enhancements in bony union and strength despite previous surgical bed irradiation. METHODS: Two groups of murine left hemimandibles were exposed to a human equivalent radiation dosage fractionated over 5 daily doses of 7 Gy...
September 19, 2017: Annals of Plastic Surgery
Lang-Yue Hu, Wen-Li Mi, Gen-Cheng Wu, Yan-Qing Wang, Qi-Liang Mao-Ying
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a progressive, enduring, and often irreversible adverse effect of many antineoplastic agents, among which sensory abnormities are common and the most suffering issues. The pathogenesis of CIPN has not been completely understood, and strategies for CIPN prevention and treatment are still open problems for medicine. OBJECTIVES: The objective of this paper is to review the mechanism-based therapies against sensory abnormities in CIPN...
September 15, 2017: Current Neuropharmacology
Krishnanand Mishra, Ghazi Alsbeih
The search for efficient radioprotective agents to protect from radiation-induced toxicity, due to planned or accidental radiation exposure, is still ongoing worldwide. Despite decades of research and development of widely different biochemical classes of natural and derivative compounds, a safe and effective radioprotector is largely unmet. In this comprehensive review, we evaluated the evidence for the radioprotective performance of classical thiols, vitamins, minerals, dietary antioxidants, phytochemicals, botanical and bacterial preparations, DNA-binding agents, cytokines, and chelators including adaptogens...
October 2017: 3 Biotech
Martin Czejka, Johannes Schüller, Heidemarie Kletzl
The cytoprotective agent amifostine (AMI) is capable to protect healthy cells (contrary to tumor cells) due to higher activity of alkaline phosphatase at the membrane site of normal cells. In seven clinical trials the influence of AMI on the pharmacokinetics of different cytostatics was investigated. Preadministration of AMI increased Cmax of doxorubicin (+ 44 %, p < 0.06), epirubicin (+ 31 %, P < 0.08), mitomycin C (+ 41 %, p < 0.01) and docetaxel (+ 31 % and + 17 %, not significant). In contrary, the peak concentration of pirarubicin , the tetrahydropyranyl-prodrug of doxorubicin was decreased (- 50 %, P < 0...
August 25, 2017: Scientia Pharmaceutica
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