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Sample records for amifostine

  1. Amifostine Injection

    Science.gov (United States)

    Amifostine is used protect the kidneys from harmful effects of the chemotherapy drug cisplatin in patients that ... this medication for the treatment of ovarian cancer. Amifostine is also used to decrease dryness in the ...

  2. Amifostine and hematologic effects.

    Science.gov (United States)

    Sriswasdi, C; Jootar, S; Giles, F J

    2000-04-01

    Amifostine is a protective agent of normal tissue from adverse effects of radiochemotherapy. It is the prodrug that is dephosphorylated by alkaline phosphatase on plasma membrane into the active form named WR-1065. More than 90 per cent of the drug is cleared from plasma in 6 minutes and the peak tissue concentration is 10-30 minutes after intravenous administration. Amifostine has the selective property to protect normal tissue but not cancer cells by mainly scavenging free radicals induced by radiation and chemocytotoxic agents. Both preclinical and clinical studies of this drug provide the significant protection of hematopoietic progentitors from a broad range of cytotoxic agents such as cyclophosphamide, cisplatin, vinblastine, carboplatin, mitomycin-C, fotemustine, doxorubicin, daunorubicin and radiation as well. Moreover, this drug can protect other normal organs or tissues including kidney, salivary gland, liver, heart, lung and small intestine. Amifostine is quite safe, the two major side effects are vomiting and hypotension, and the minor effects are flushing, sneezing, dizziness, chills, metallic taste etc. The drug was approved by the FDA of U.S.A. for use as a cytoprotectant in cyclophosphamide and cisplatin treatment for advanced ovarian cancer and non small cell lung cancer. PMID:10808697

  3. Radioprotection of human endothelial cells with amifostine

    Energy Technology Data Exchange (ETDEWEB)

    Andreopoulos, D.; Schleicher, U.M.; Ammon, J. [Technische Hochschule Aachen (Germany). Klinik fuer Radiotherapie - Onkologie; Cotarelo, C.L.; Hand, S. [Technische Hochschule Aachen (Germany). Inst. fuer Pathologie

    1999-11-01

    Materials and methods: We studied the effect of amifostine on radiation sensitivity of human endothelial cells and several tumor cell lines (HeLa, MIA PaCa-2 and BxPC-3). The cells were incubated in medium with a concentration of 1 {mu}g/{mu}l amifostine and after 1 hour irradiated with 10 or 20 Gy single dose. Proliferation index was measured by BrdU assay after another 8 and 24 hours. Results: The results show a higher proliferation rate of endothelial cells following radiation plus amifostine, compared with radiation alone. Amifostine induced an increase of proliferation in the control-non-irradiated human endothelial cells. After irradiation with 10 Gy single dose the proliferation of amifostine treated human endothelial cells was still higher. Amifostine exerts no apparent proliferative effect on the tumor cells. Conclusions: The results presented indicate that amifostine acts as an activation of proliferation of the human endothelial cells in a simple in-vitro system and indicate that amifostine supplementation prior to radiation therapy might exert a radioprotective effect to healthy tissue without spurring tumor growth. (orig.) [German] Material und Methode: Humane Endothelzellen und verschiedene Tumorzellinien (HeLa, MIA PaCa-2 and BxPC-3) wurden fuer eine Stunde mit 1 {mu}g/{mu}l Amifostin inkubiert und dann mit Dosen von 10 und 20 Gy bestrahlt. Die Proliferationsaktivitaet wurde mittels BrdU-Assay nach acht und 24 Stunden gemessen. Ergebnisse: Amifostin fuehrt zu einer verstaerkten Proliferation der unbestrahlten Endothelzellen. Nach der Bestrahlung mit 10 Gy Einzeitdosis zeigen die Endothelzellen mit Amifostin-Zusatz eine staerkere Proliferation als die Zellen ohne Amifostin. Ein protektiver Effekt auf die Tumorzellinien war nicht feststellbar. Schlussfolgerung: Die bisherigen Ergebnisse zeigen, dass Amifostin einen radioprotektiven Effekt auf humane Endothelzellen ausuebt und deren Proliferation stimuliert, ohne jedoch die Proliferation der Tumorzellen

  4. Clinical use of radioprotector amifostine (YM-08310)

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    Takahashi, Iku; Mitsuhashi, Norio; Itoh, Jun (Gunma Univ., Maebashi (Japan). School of Medicine)

    1984-11-01

    Radiotherapy was conducted at the Department of Radiology, Gunma University Hospital using amifostine (YM-08310) as a radioprotective agent. The subjects were patients suffering malignant tumors between 1978 and 1980, and comprised 52 with tumors in the head and neck region, 39 in the abdomino-pelvic region and 16 miscellaneous, totalling 107 in all. Amifostine was administered intravenously in a dose on principle, of 100 mg, 30 minutes prior to irradiation; the radioprotection provided by amifostine against reaction of the dermatomucosa caused by irradiation of head and neck region and against diarrhea caused by irradiation of the abdomino-pelvic region was investigated. 1. Side effects were observed in 10%, but there were no cases in which radiotherapy was interrupted for that reason. Most side effects were manifested as digestive organ symptoms and were most frequently observed in cases with drop infusion. 2. Clinical efficacy was evaluated at 80% or higher in cases with irradiation of the head and neck region, and deterioration in balanced diet content, which is an index of mucositis, was curbed in 70%. In the group administered amifostine thoses cases which required parenteral alimentation were significantly lower than the control group at 30 Gy or higher. 3. Control of diarrhea was feasible in 60% of patients irradiated in the abdomino-pelvic region. Moreover, despite the occurrence of diarrhea, the administration is considered to have adequate efficacy.

  5. Binding of amifostine to human serum albumin: a biophysical study.

    Science.gov (United States)

    Sun, Yifu; Wu, Han; Zhao, Guoqing; Shi, Ying

    2015-02-01

    The aim of this present work is to investigate the interaction between amifostine and human serum albumin (HSA) in simulated physiological conditions by spectroscopic methods to reveal potential toxic effects of the drug. The results reflected that amifostine caused fluorescence quenching of HSA through a static quenching process, which was further confirmed by the electrochemical experiments. The binding constants at 290, 297 and 304 K were obtained as 2.53 × 10(5) /M, 8.13 × 10(4) /M and 3.59 × 10(4) /M, respectively. There may be one binding site of amifostine on HSA. The thermodynamic parameters indicated that the interaction between amifostine and HSA was driven mainly by hydrogen bonding and electrostatic forces. Synchronous fluorescence spectra, circular dichroism and Fourier transform infrared spectroscopy results showed amifostine binding slightly changed the conformation of HSA with secondary structural content changes. Förster resonance energy transfer study revealed high possibility of energy transfer with amifostine-Trp-214 distance of 3.48 nm. The results of the present study may provide valuable information for studying the distribution, toxicological and pharmacological mechanisms of amifostine in vivo. PMID:24962599

  6. Amifostine - a radioprotector in locally advanced head and neck tumors

    Energy Technology Data Exchange (ETDEWEB)

    Schoenekaes, K.G.; Wagner, W. [Paracelsus-Strahlenklinik, Osnabrueck (Germany); Prott, F.J. [Muenster Univ. (Germany). Inst. fuer Strahlenonkologie

    1999-11-01

    Purpose: There are some preliminary informations about the beneficial use of amifostine in avoiding side effects in patients with head and neck tumors who underwent radiotherapy. Patients and method: Amifostine was given as daily intravenous application (500 mg) 10 to 15 minutes prior to radiotherapy in 20 patients. The results were compared with another collective of patients which was similar. Results: According to the WHO score mucositis became manifest in 10 patients (Grade I) and 4 patients (Grade II) in the amifostine group vs 9 patients (Grade II), 6 patients (Grade III) and 1 patient (Grade IV) in the control group. Xerostomia has been seen in 15 patients (Grade I) and 5 patients (Grade II) after administration of amifostine. Without the drug 2 patients suffered from xerostomia (Grade I), 8 patients (Grade II) and 8 patients (Grade III), respectively. Administering amifostine had been feasible and non problematic. Only a small rate of toxic side effects like nausea (11%) or emesis (4%) was documented. Conclusions: Amifostine is an effective radioprotector decreasing acute and late side effects in patients with head and neck tumors. (orig.) [German] Zielsetzung: Bisher gibt es nur wenige Informationen ueber den Nutzen von Amifostin bezueglich der Verminderung oder Vermeidung von Nebenwirkungen einer Radiatio bei Patienten mit Tumoren im HNO-Trakt. Patienten und Methode: Amifostin wurde als intravenoese Kurzinfusion mit einer Dosis von 500 mg zehn bis 15 Minuten vor der Bestrahlung bei 20 Patienten appliziert. Die unter Radiatio aufgetretenen Nebenwirkungen wurden nach WHO bzw. nach dem Oral Assessment Guide nach Eilers ausgewertet und mit einem entsprechenden historischen Kollektiv der Klinik verglichen. Ergebnisse: In der Amifostin-Gruppe wurde bei zehn Patienten eine Mukositis Grad I und bei vier Patienten eine Mukositis Grad II nach WHO beobachtet. Grad-III- und Grad-IV-Nebenwirkungen traten nicht auf. In der Kontrollgruppe waren dagegen bei neun

  7. Efficacy and tolerability of amifostine in elderly cancer patients

    OpenAIRE

    Barutca, Sabri; Meydan, Nezih; Akar, Harun; Yavasoglu, Irfan; Kadikoylu, Gurhan; Bolaman, Zahit

    2004-01-01

    Background: Amifostine is a cytoprotective agent used to prevent cisplatin nephrotoxicity. It is associated with dose-limiting acute toxicities of emetic symptoms (nausea and vomiting) and transient hypotension.

  8. Radioprotection of hematopoietic progenitors by low dose amifostine prophylaxis

    OpenAIRE

    Seed, Thomas M.; Inal, Cynthia E.; Singh, Vijay K

    2014-01-01

    Purpose Amifostine is a highly efficacious cytoprotectant when administered in vivo at high doses. However, at elevated doses, drug toxicity manifests for general, non-clinical radioprotective purposes. Various strategies have been developed to avoid toxic side-effects: The simplest is reducing the dose. In terms of protecting hematopoietic tissues, where does this effective, non-toxic minimum dose lie? Material and methods C3H/HEN mice were administered varying doses of amifostine (25–100 mg...

  9. The Effect of Amifostine on Submandibular Gland Histology after Radiation

    OpenAIRE

    Junn, Jacqueline C.; Sciubba, James J.; Justin A Bishop; Eva Zinreich; Mei Tang; Levine, Marshall A.; Robert A. Palermo; Carole Fakhry; Blanco, Ray G.; Saunders, John R.; Califano, Joseph A.; Ha, Patrick K.

    2012-01-01

    Background. The purpose of this study was to assess the effects of amifostine on submandibular gland histology in patients receiving chemoradiation therapy. Methods. We conducted a retrospective submandibular gland histologic slide review of HNSCC patients receiving chemoradiation for head and neck squamous cell carcinoma with three different levels of amifostine exposure. We used six scoring parameters: fatty replacement, lobular architecture degeneration, interstitial fibrosis, ductal degen...

  10. Normal tissue radioprotection by amifostine via Warburg-type effects

    Science.gov (United States)

    Koukourakis, Michael I.; Giatromanolaki, Alexandra; Zois, Christos E.; Kalamida, Dimitra; Pouliliou, Stamatia; Karagounis, Ilias V.; Yeh, Tzu-Lan; Abboud, Martine I.; Claridge, Timothy D. W.; Schofield, Christopher J.; Sivridis, Efthimios; Simopoulos, Costantinos; Tokmakidis, Savvas P.; Harris, Adrian L.

    2016-01-01

    The mechanism of Amifostine (WR-2721) mediated radioprotection is poorly understood. The effects of amifostine on human basal metabolism, mouse liver metabolism and on normal and tumor hepatic cells were studied. Indirect calorimetric canopy tests showed significant reductions in oxygen consumption and of carbon dioxide emission in cancer patients receiving amifostine. Glucose levels significantly decreased and lactate levels increased in patient venous blood. Although amifostine in vitro did not inhibit the activity of the prolyl-hydroxylase PHD2, experiments with mouse liver showed that on a short timescale WR-1065 induced expression of the Hypoxia Inducible Factor HIF1α, lactate dehydrogenase LDH5, glucose transporter GLUT2, phosphorylated pyruvate dehydrogenase pPDH and PDH-kinase. This effect was confirmed on normal mouse NCTC hepatocytes, but not on hepatoma cells. A sharp reduction of acetyl-CoA and ATP levels in NCTC cells indicated reduced mitochondrial usage of pyruvate. Transient changes of mitochondrial membrane potential and reactive oxygen species ROS production were evident. Amifostine selectively protects NCTC cells against radiation, whilst HepG2 neoplastic cells are sensitized. The radiation protection was correlates with HIF levels. These findings shed new light on the mechanism of amifostine cytoprotection and encourage clinical research with this agent for the treatment of primary and metastatic liver cancer. PMID:27507219

  11. Normal tissue radioprotection by amifostine via Warburg-type effects.

    Science.gov (United States)

    Koukourakis, Michael I; Giatromanolaki, Alexandra; Zois, Christos E; Kalamida, Dimitra; Pouliliou, Stamatia; Karagounis, Ilias V; Yeh, Tzu-Lan; Abboud, Martine I; Claridge, Timothy D W; Schofield, Christopher J; Sivridis, Efthimios; Simopoulos, Costantinos; Tokmakidis, Savvas P; Harris, Adrian L

    2016-01-01

    The mechanism of Amifostine (WR-2721) mediated radioprotection is poorly understood. The effects of amifostine on human basal metabolism, mouse liver metabolism and on normal and tumor hepatic cells were studied. Indirect calorimetric canopy tests showed significant reductions in oxygen consumption and of carbon dioxide emission in cancer patients receiving amifostine. Glucose levels significantly decreased and lactate levels increased in patient venous blood. Although amifostine in vitro did not inhibit the activity of the prolyl-hydroxylase PHD2, experiments with mouse liver showed that on a short timescale WR-1065 induced expression of the Hypoxia Inducible Factor HIF1α, lactate dehydrogenase LDH5, glucose transporter GLUT2, phosphorylated pyruvate dehydrogenase pPDH and PDH-kinase. This effect was confirmed on normal mouse NCTC hepatocytes, but not on hepatoma cells. A sharp reduction of acetyl-CoA and ATP levels in NCTC cells indicated reduced mitochondrial usage of pyruvate. Transient changes of mitochondrial membrane potential and reactive oxygen species ROS production were evident. Amifostine selectively protects NCTC cells against radiation, whilst HepG2 neoplastic cells are sensitized. The radiation protection was correlates with HIF levels. These findings shed new light on the mechanism of amifostine cytoprotection and encourage clinical research with this agent for the treatment of primary and metastatic liver cancer. PMID:27507219

  12. Evaluation of protective effect of amifostine on dacarbazine induced genotoxicity.

    Science.gov (United States)

    Etebari, M; Jafarian-Dehkordi, A; Lame, V

    2015-01-01

    Anticancer therapy with alkylating agents has been used for many years. Dacarbazine (DTIC) as an alkylating agent is used alone or in combination with other chemotherapy drugs. In order to inhibit the formation of secondary cancers resulting from chemotherapy with DTIC, preventional strategies is necessary. The present study was undertaken to evaluate the genoprotective effect of amifostine on the genotoxic effects of DTIC in cell culture condition. To determine the optimum genotoxic concentration of DTIC, HepG2 cells were incubated with various DTIC concentrations including 5, 10 and 20 μg/ml for 2 h and the genotoxic effects were evaluated by the comet assay. The result of this part of the study showed that incubation of HepG2 cells with DTIC at 5 μg/ml was sufficient to produce genotoxic effect. In order to determine the protective effects of amifostine on genotoxicity induced by DTIC, HepG2 cells were incubated with different concentrations of amifostine (2, 3 and 5 mg/ml) for 1 h which was followed by incubation with DTIC at 5 μg/ml for 2 h. One hour incubation of cells with different concentrations of amifostine before incubation with DITC indicated that at least 5 mg/ml concentration of amifostine can prevent genotoxic effects induced by DTIC on HepG2 cells under described condition. In conclusion amifostine could prevent DNA damage induced by DTIC on HepG2 cells. PMID:26430459

  13. The Effect of Amifostine on Submandibular Gland Histology after Radiation

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    Jacqueline C. Junn

    2012-01-01

    Full Text Available Background. The purpose of this study was to assess the effects of amifostine on submandibular gland histology in patients receiving chemoradiation therapy. Methods. We conducted a retrospective submandibular gland histologic slide review of HNSCC patients receiving chemoradiation for head and neck squamous cell carcinoma with three different levels of amifostine exposure. We used six scoring parameters: fatty replacement, lobular architecture degeneration, interstitial fibrosis, ductal degeneration, acinar degeneration, and inflammatory component presence. Results. Differences in gender, tumor stage, amifostine dose, age, number of days after neck dissection, and smoking history (pack years exposure were not significant between the three groups, although there was a difference between groups in the primary subsite (P=0.006. The nonparametric Cuzick's test for histologic parameters with varied amifostine treatment showed no significance among the three groups. Conclusions. Although patients did not receive a full dose of amifostine due to side effects, varying doses of amifostine had no apparent evident cytoprotective effects in three groups of cancer patients treated with primary chemoradiation.

  14. The Effect of Amifostine on Submandibular Gland Histology after Radiation

    Science.gov (United States)

    Junn, Jacqueline C.; Sciubba, James J.; Bishop, Justin A.; Zinreich, Eva; Tang, Mei; Levine, Marshall A.; Palermo, Robert A.; Fakhry, Carole; Blanco, Ray G.; Saunders, John R.; Califano, Joseph A.; Ha, Patrick K.

    2012-01-01

    Background. The purpose of this study was to assess the effects of amifostine on submandibular gland histology in patients receiving chemoradiation therapy. Methods. We conducted a retrospective submandibular gland histologic slide review of HNSCC patients receiving chemoradiation for head and neck squamous cell carcinoma with three different levels of amifostine exposure. We used six scoring parameters: fatty replacement, lobular architecture degeneration, interstitial fibrosis, ductal degeneration, acinar degeneration, and inflammatory component presence. Results. Differences in gender, tumor stage, amifostine dose, age, number of days after neck dissection, and smoking history (pack years) exposure were not significant between the three groups, although there was a difference between groups in the primary subsite (P = 0.006). The nonparametric Cuzick's test for histologic parameters with varied amifostine treatment showed no significance among the three groups. Conclusions. Although patients did not receive a full dose of amifostine due to side effects, varying doses of amifostine had no apparent evident cytoprotective effects in three groups of cancer patients treated with primary chemoradiation. PMID:22844290

  15. Pharmacokinetics of cisplatin with and without amifostine in tumour- bearing nude mice

    NARCIS (Netherlands)

    Korst, A.E.C.; Boven, E.; Sterre, M.L.T. van der; Fichtinger-Schepman, A.M.J.; Vijgh, W.J.F. van der

    1998-01-01

    Amifostine (Ethyol, WR-2721) is in use in the clinic as a protector against platinum-induced toxicities. We have previously reported that amifostine induced a potentiation of the antitumour activity of carboplatin in human ovarian cancer xenografts. An influence of amifostine on the pharmacokinetics

  16. Stevens-Johnson syndrome and toxic epidermal necrolysis induced by amifostine during head and neck radiotherapy

    International Nuclear Information System (INIS)

    Amifostine is an organic thiophosphate prodrug used for cytoprotection against toxic effects of radiotherapy and chemotherapy. In a European prospective study of SJS/TEN, six patients were suspected to have SJS/TEN associated with amifostine. Our findings suggest that the risk of life-threatening cutaneous adverse reactions to amifostine could be significantly increased

  17. Alteration of radiation induced hematotoxicity by Amifostine (Ethyol {sup trademark}); Veraenderte bestrahlungsinduzierte Haematotoxizitaet durch Amifostin (Ethyol {sup trademark})

    Energy Technology Data Exchange (ETDEWEB)

    Momm, F.; Bechtold, C.; Fischer, K.; Tsekos, A.; Henke, M. [Freiburg Univ. (Germany). Abt. Roentgen- und Strahlentherapie

    1999-11-01

    Background: Radiotherapy - even of small volumes - can decrease leukocyte counts. We examined whether the radioprotector amifostine can reduce this hematotoxicity. Patients and methods: Twenty-six patients undergoing radiotherapy for squamous cell carcinoma of the head and neck were evaluated. All were given 60 (to 70) Gy 5x2 Gy per week in standard radiation techniques. Thirteen patients are randomized to receive 200 mg/m{sup 2} amifostine i.v., 30 minutes before radiation. Blood counts and differentials were determined before, during and following radiotherapy. Differences of these parameters are calculated and compared by t-test. Results: The blood hemoglobin and the thrombocyte levels did not change during the radiotherapy course, neither for the amifostine treated, nor the control patients. Similarly the leukocyte counts of amifostine treated patients did not change during irradiation. The control patients, however, had a decrease of leukocytes from 8.4 to 6.0x10{sup 3}/{mu}l, p=0.03, and the reduction of the neutrophilic granulocyte count was more impressive for these patients. Conclusion: In this explorative study amifostine diminished radiation induced leukocyte toxicity. (orig.) [German] Hintergrund: Eine Strahlentherapie - selbst kleiner Volumina - kann die Blutbildung beeintraechtigen. Wir untersuchten die Wirkung des Radioprotektors Amifostin auf diese Haematotoxizitaet. Patienten und Methoden: 26 Patienten mit Kopf-Hals-Tumoren wurden evaluiert. Sie wurden mit 60 (bis 70) Gy und einer Fraktionierung von 5mal 2 Gy/Woche in Standardtechnik bestrahlt, 13 von ihnen wurden zusaetzlich - nach Randomisierung - mit Amifostin (200 mg/m{sup 3} intravenoes, 30 Minuten vor jeder Fraktion) behandelt. Vor, waehrend und nach der Radiotherapie wurden Haemoglobinwert, Thrombozytenzahl, Leukozytenzahl und Differentialblutbild bestimmt. Die Veraenderungen dieser Werte waehrend der Bestrahlung wurden als Differenz bestimmt und mit einem t-Test verglichen. Ergebnisse: Die

  18. Supportive use of amifostine in patients with head and neck tumors undergoing radio-chemotherapy. Is it possible to limit the duration of the application of amifostine?

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    Peters, K.; Muecke, R.; Hamann, D.; Ziegler, P.G.; Fietkau, R. [Rostock Univ. (Germany). Klinik und Poliklinik fuer Strahlentherapie

    1999-11-01

    Background: Amifostine is a new cancer-supporting agent to protect normal tissue in patients receiving radio-chemotherapy. The main question of our study is whether the application of amifostine can be limited on the duration of chemotherapy in patients with advanced head and neck tumors undergoing radio-chemotherapy. Patients and methods: In a randomized study 14 patients were treated with amifostine (500 mg, day 1 to 5 and 29 to 33) during concurrent radio-chemotherapy with carboplatin (70 mg/m{sup 2}, day 1 to 5 and 29 to 33), 14 patients were treated without amifostine. The analyzed parameters were dermatitis, mucositis, skin temperature, white blood and platelet count, creatinine and scintigram of salivary glands. Median survival of the amifostine group was 19 months, of the control group 10 months. Results: There were no relevant differences in all analyzed parameters between both arms of the study. Conclusion: Our form of amifostine application is probably not able to obtain a relevant reduction of the toxicity of radio-chemotherapy. (orig.) [German] Hintergrund: Amifostin wird supportiv eingesetzt, um die Toxizitaet einer Chemotherapie und/oder Bestrahlung zu reduzieren. In einer randomisierten Studie untersuchten wir, ob die Amifostin-Gabe zeitlich auf die Tage der Chemotherapie bei simultaner Radiochemotherapie begrenzt werden kann. Patienten und Methode: Bisher wurden 28 Patienten mit fortgeschrittenen Tumoren im Kopf-Hals-Bereich randomisiert. Im Behandlungsarm (14 Patienten) wurde Amifostin (500 mg) an den Tagen 1 bis 5 und 29 bis 33 einer Radiochemotherapie mit Carboplatin (70 mg/m{sup 2}; Tag 1 bis 5 und 29 bis 33) appliziert. Bei 14 Patienten erfolgte die Radiochemotherapie ohne Amifostin. Die untersuchten Parameter waren Haut- und Schleimhautreaktion, Haupttemperatur, Leukozyten, Thrombozyten, Kreatinin und Speicheldruesenszintigraphie. Ergebnisse: Die Auswertung ergab bei allen untersuchten Parametern keinen wesentlichen Unterschied zwischen den

  19. Radioprotective effects of amifostine in vitro and in vivo measured with the comet assay

    International Nuclear Information System (INIS)

    Purpose: The authors investigated whether a potential radioprotective effect of amifostine (WR-2721) after in vitro or in vivo administration can be detected with the comet assay. Moreover, it was determined whether radioprotection by WR-2721 is dependent on the concentration of amifostine or alkaline phosphatase (AP, the enzyme which activates the prodrug). Furthermore, the authors tried to detect possible interindividual differences in radioprotection by amifostine. Material and methods: In vitro administration of amifostine: Freshly isolated lymphocytes from two healthy volunteers were incubated with different concentrations of AP (0-210 U/ml) and amifostine (0-5,000 μg/ml). In vivo administration of amifostine: Blood samples were collected from six postoperative rectal cancer patients before and after intravenous administration of amifostine 500 mg (no pretreatment with radio- or chemotherapy). Leukocytes and lymphocytes were irradiated and repaired in vitro and investigated with the alkaline comet assay. The radioprotective effect was evaluated by calculating dose-modifying factors (DMFs) and the paired t-test. Results: Amifostine alone did not alter the radiation-induced DNA damage in vitro. The addition of at least 0.5-1 U/ml AP was required. A significant radioprotective effect (p<0.05) was seen after administration of amifostine in vitro for all concentrations investigated (250-5,000 μg/ml, initial DNA damage). A comparable radioprotective effect after in vivo administration of 500 mg amifostine was measured with a mean DMF of 0.87. Interindividual differences were present in vivo and in vitro. Conclusion: Amifostine 500 mg intravenously yields an adequate radioprotective concentration. The effect was only marginally improved by extreme concentrations of amifostine in vitro experiments. The comet assay is capable of detecting small changes in radiosensitivity by amifostine. (orig.)

  20. Radioprotective effects of amifostine in vitro and in vivo measured with the comet assay

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, A.-C.; Pigorsch, S.; Dunst, J. [Martin Luther University of Halle-Wittenberg, Halle (Germany). Department of Radiotherapy; Beyer, C. [Martin Luther University of Halle-Wittenberg, Halle (Germany). Institute of Clinical Chemistry and Pathobiochemistry; Lautenschlaeger, C. [Martin Luther University of Halle-Wittenberg, Halle (Germany). Institute of Biomathematics

    2004-08-01

    Purpose: The authors investigated whether a potential radioprotective effect of amifostine (WR-2721) after in vitro or in vivo administration can be detected with the comet assay. Moreover, it was determined whether radioprotection by WR-2721 is dependent on the concentration of amifostine or alkaline phosphatase (AP, the enzyme which activates the prodrug). Furthermore, the authors tried to detect possible interindividual differences in radioprotection by amifostine. Material and methods: In vitro administration of amifostine: Freshly isolated lymphocytes from two healthy volunteers were incubated with different concentrations of AP (0-210 U/ml) and amifostine (0-5,000 {mu}g/ml). In vivo administration of amifostine: Blood samples were collected from six postoperative rectal cancer patients before and after intravenous administration of amifostine 500 mg (no pretreatment with radio- or chemotherapy). Leukocytes and lymphocytes were irradiated and repaired in vitro and investigated with the alkaline comet assay. The radioprotective effect was evaluated by calculating dose-modifying factors (DMFs) and the paired t-test. Results: Amifostine alone did not alter the radiation-induced DNA damage in vitro. The addition of at least 0.5-1 U/ml AP was required. A significant radioprotective effect (p<0.05) was seen after administration of amifostine in vitro for all concentrations investigated (250-5,000 {mu}g/ml, initial DNA damage). A comparable radioprotective effect after in vivo administration of 500 mg amifostine was measured with a mean DMF of 0.87. Interindividual differences were present in vivo and in vitro. Conclusion: Amifostine 500 mg intravenously yields an adequate radioprotective concentration. The effect was only marginally improved by extreme concentrations of amifostine in vitro experiments. The comet assay is capable of detecting small changes in radiosensitivity by amifostine. (orig.)

  1. Reduction of renal uptake of radiolabeled octreotate by amifostine coadministration

    NARCIS (Netherlands)

    M.L. Melis (Marleen); R. Valkema (Roelf); E.P. Krenning (Eric); M. de Jong (Marcel)

    2012-01-01

    textabstractMegalin-mediated renal retention of radiolabeled somatostatin analogs may lead to nephrotoxicity during peptide receptor radionuclide therapy (PRRT). The cytoprotective agent amifostine protected rats from long-term nephrotoxicity after PRRT with 177Lu-DOTA,Tyr3-octreotate. This study de

  2. The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application

    OpenAIRE

    Cem Uzal; Atakan Sezer; Ufuk Usta; Necdet Süt; Alaattin Özen; Mehmet Ali Yağcı

    2012-01-01

    Objective: The aim of the study was to evaluate the radioprotective efficacy of intrarectal administration of amifostine in radiation-induced proctitis compared to intraperitoneal administration.Materials and Methods: Thirty-two Sprague-Dawley rats were randomly divided into four groups: Control (CONT), irradiation alone (RT), intraperitoneal amifostine plus irradiation (IPAMI), and intrarectal amifostine plus irradiation (IRAMI). The rats in the RT, IPAMI and IRAMI groups were irradiated ind...

  3. The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application

    OpenAIRE

    UZAL, Cem; ALAS, Ruşen Coşar; USTA, UFUK; Süt, Necdet; ÖZEN, Alaattin; Yağcı, Mehmet Ali

    2012-01-01

    Objective: The aim of the study was to evaluate the radioprotective efficacy of intrarectal administration of amifostine in radiation-induced proctitis compared to intraperitoneal administration. Materials and Methods: Thirty-two Sprague-Dawley rats were randomly divided into four groups: Control (CONT), irradiation alone (RT), intraperitoneal amifostine plus irradiation (IPAMI), and intrarectal amifostine plus irradiation (IRAMI). The rats in the RT, IPAMI and IRAMI groups were irr...

  4. Amifostine (WR2721) Confers DNA Protection to In Vivo Cisplatin-Treated Murine Peripheral Blood Leukocytes

    OpenAIRE

    Prieto González, E. A.; Fuchs, A. G.; Sánchez, González S.

    2009-01-01

    Amifostine [S-2-3-aminopropil amino ethyl phosphorotioic acid], a modulator agent for antineoplastic drugs involved in free radicals generation has given controversial results in cisplatin treated leukocytes in vitro. We have evaluated the amifostine protection over leukocytes in vivo, using comet assay. Groups of five OF1 male mice were given one of three doses of amifostine (56, 105 and 200 mg/Kg) after a cisplatin single injection (10 mg/Kg). Serum malonyldialdehide levels, catalase and su...

  5. SOD2 Mediates Amifostine-Induced Protection against Glutamate in PC12 Cells

    OpenAIRE

    Ji Jia; Lei Zhang; Xiaolei Shi; Mingchun Wu; Xiang Zhou; Xiaonan Liu; Tingting Huo

    2016-01-01

    Background. Cytoprotectant amifostine attenuates radiation-induced oxidative injury by increasing intracellular manganese superoxide dismutase (SOD2) in peripheral tissue. However, whether amifostine could protect neuronal cells against oxidative injury has not been reported. The purpose of this study is to explore the protection of amifostine in PC12 cells. Methods. PC12 cells exposed to glutamate were used to mimic neuronal oxidative injury. SOD assay kit was taken to evaluate intracellular...

  6. Prevention of radiation-induced liver and kiney toxicity: a role for amifostine

    OpenAIRE

    KALDIR, Mine Uğuzalp; Çaloğlu, Vuslat Yürüt; ALAS, Ruşen Coşar; ÇERMİK, Tevfik Fikret; Altaner, Şemsi; ESKİOCAK, Sevgi; Saynak, Mert; TOKATLI, Füsun; KOÇAK, Zafer; UZAL, Cem

    2007-01-01

    OBJECTIVES To investigate the protective effect of amifostine against radiation induced liver and kidney injury of rats, using scintigraphic and histopathologic parameters. METHODS Female Wistar Albino rats were randomly allocated to 3 groups: control, radiotherapy alone (RT), and amifostine+RT (n=10). Single-dose of 600 cGy X-ray was performed with a single field compromised liver and right kidney. Amifostine was administered intraperitoneally at a dose of 400 mg/kg, 30 minutes before irrad...

  7. Respiratory Effects of Amifostine and DRDE-07: Probable Prophylactic Agents of Sulphur Mustard in Rats

    OpenAIRE

    Seema Singh; Vimal Malviya; Anshoo Gautam; Ram Singh; Uma Pathak; Raza, S K; Vijayaraghavan, R.

    2006-01-01

    Amifostine (S-2[3-aminopropylamino]ethyl phosphorothioate) and one of its analogues,DRDE-07 (S-2[2-aminoethylamino]ethyl phenyl sulphide) are promising prophylactic agents forsulphur mustard (SM; a blistering agent) toxicity. When given orally, DRDE-07 was more effectivethan amifostine as a prophylactic agent against SM administered percutaneously. Variouspharmacological and toxicological studies are required before the introduction of a chemical asa drug. The respiratory effects of amifostin...

  8. Combined use of Amifostine and Misonidazole in experimental radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Tsukiyama, Iwao (National Cancer Center, Tokyo (Japan). Hospital)

    1983-04-01

    Combined effects of radioprotective (Amifostine) and radiosensitizing (Misonidazole) agents on normal and malignant tissues were studied. Two assays were used : ED50, the dose nessesary to induce complete epilation in half the irradiated mice : and TRT50, the time required for half the irradiated tumors to decrease to half th irradiated volume. Irradiation was performed under air-breathing conditions or tourniquet-induced local hypoxia. Four methods of treatment were used, the first group of mice received no drug prior to exposure ; the second received 200mg Misonidazole per Kg body weight intraperitoneally 30 minutes before exposure ; the third received 200mg Amifostine per body weight intraperitoneally 30 minutes before exposure ; and the forth received both of these drugs as described above. Under air-breathing conditions, a greater radioprotective effect was observed in the mice treated with Amifostine alone. An unexpectedly great radiosensitizing effect for normal tissues was observed in the mice treated with Misonidazole alone. In the mice treated with both drugs, the sensitizing effect of Misonidazole against mormal tissue was not evident. Only the protective effect was observed. Under hypoxic conditions there was no effect on normal tissue protection when the mice were treated with Amifostine alone and higher radiosensitizing effect on normal tissue was observed than under air-breathing conditions when the mice were treated with Misonidazole alone. No radioprotective effects were observed with transplantable mouse tumors when the mice were treated with Amifostine alone. A greater radiosensitizing effect was observed with fractionated (400rad x 5) irradiation than with single doses (2000rad x 1) when the mice were treated with Misonidazole alone. Highly radiosensitizing effects were noted under hypoxic conditions than air-breathing conditions. Similar results were obtained in animals treated with both drugs.

  9. Respiratory Effects of Amifostine and DRDE-07: Probable Prophylactic Agents of Sulphur Mustard in Rats

    Directory of Open Access Journals (Sweden)

    Seema Singh

    2006-10-01

    Full Text Available Amifostine (S-2[3-aminopropylamino]ethyl phosphorothioate and one of its analogues,DRDE-07 (S-2[2-aminoethylamino]ethyl phenyl sulphide are promising prophylactic agents forsulphur mustard (SM; a blistering agent toxicity. When given orally, DRDE-07 was more effectivethan amifostine as a prophylactic agent against SM administered percutaneously. Variouspharmacological and toxicological studies are required before the introduction of a chemical asa drug. The respiratory effects of amifostine and DRDE-07 were carried out in rats using a bodyplethysmograph fitted with a volumetric pressure transducer for sensing the respiratory flowsignals. The signals were amplified, digitised, and stored on a personal computer for furtheranalysis. After taking control recordings of respiratory signals, different doses (0.5 LD50, 1.0 LD50and 2.0 LD50 of amifostine and DRDE-07 were administered orally (LD50 amifostine = 2262 mg/kg; DRDE-07 = 1599 mg/kg, and the respiratory changes were monitored for 4 h. Amifostine andDRDE-07 showed a uniform breathing pattern even in 2.0 LD50 dose. However, a significant dosedependentdecrease in respiratory frequency was observed following amifostine administration.DRDE-07 did not show any significant change. The tidal volume was not altered significantlyboth in amifostine and DRDE-07 administered animals. The study shows that DRDE-07, even inlethal doses, may not affect the respiration immediately, whereas, amifostine may decrease therespiratory frequency.

  10. Improvement of the in vitro safety profile and cytoprotective efficacy of amifostine against chemotherapy by PEGylation strategy.

    Science.gov (United States)

    Yang, Xiao; Ding, Yanping; Ji, Tianjiao; Zhao, Xiao; Wang, Hai; Zhao, Xiaozheng; Zhao, Ruifang; Wei, Jingyan; Qi, Sheng; Nie, Guangjun

    2016-05-15

    Amifostine, an organic thiophosphate prodrug, has been clinically utilized for selective protection of normal tissues with high expression of alkaline phosphatase from oxidative damage elicited by chemotherapy or radiotherapy. However, the patients receiving amifostine suffer from severe dose-dependent adverse effects. Strategies for improvement of the protective efficacy and toxicity profile of amifostine are urgently required. Here we constructed a PEGylated amifostine (PEG-amifostine) through conjugation of amifostine to the 4-arm PEG (5000Da) by a mild one-step reaction. The relatively large PEG-amifostine molecules clustered into spherical nanoparticles, resulting in distinct hydrolysis properties, cell uptake profile and antioxidative activity compared with the free small molecules. PEGylation prolonged the hydrolysis time of amifostine, providing sustained transformation to its functional metabolites. PEG-amifostine could be internalized into cells and translocated to acidic organelles in a time-dependent manner. The intrinsic cytotoxicity of amifostine, which is related to the reductive reactivity of its metabolites and their ability to diffuse readily, was attenuated after PEGylation. This modification impeded the interaction between free sulfhydryls and functional biomolecules, providing PEG-amifostine with an improved safety profile in vitro. Moreover, PEG-amifostine showed higher efficiency in the elimination of reactive oxygen species and prevention of cisplatin-induced cytotoxicity compared with free amifostine. Overall, our study for the first time developed a PEGylated form of amifostine which significantly improved the efficacy and decreased the adverse effects of this antioxidant in vitro with great promise for clinical translation. In vivo study is urgently needed to confirm and redeem the cytoprotective effects of the PEG-amifostine in chemotherapy. PMID:26944193

  11. Protective effects of amifostine on ischemia-reperfusion injury of rat kidneys

    Directory of Open Access Journals (Sweden)

    Ayse Arducoglu Merter

    2015-01-01

    Conclusion: Amifostine could decrease the degree and severity of necrosis after reperfusion. Amifostine could not prevent membrane lipid peroxidation caused by superoxide anion radicals in kidney but they could protect tissues from the harmful effects of ischemia/reperfusion injury by increasing the level of reduced GSH which is a well-known oxygen radical eliminator.

  12. Influence of amifostine on the pharmacokinetics of cisplatin in cancer patients

    NARCIS (Netherlands)

    Korst, A.E.C.; Sterre, M.L.T. van der; Gall, H.E.; Fichtinger-Schepman, A.M.J.; Vermorken, J.B.; Vijgh, W.J.F. van der

    1998-01-01

    The pharmacokinetics of cisplatin was investigated in 13 patients receiving 18 courses of cisplatin alone or in combination with amifostine to investigate the influence of amifostine (WR 2721; Ethyol) on the pharmacokinetics of cisplatin. Cisplatin was administered as a 1-h i.v. infusion, whereas am

  13. Amifostine Treatment of a Patient with Refractory Acute Myeloid Leukemia

    OpenAIRE

    Tekgündüz, Emre; ERİKÇİ, ALEV AKYOL; Ahmet ÖZTÜRK

    2009-01-01

    The prognosis for the majority of acute myeloid leukemia (AML) patients without a donor is dismal whether conventional salvage chemotherapy regimens or investigational strategies are used, and most of these patients will eventually die of their disease. There is no standard chemotherapy regimen that provides durable complete remission in patients with refractory AML. Beneficial effects of amifostine, either alone or in combination with conventional chemotherapy, was demonstrated in patients w...

  14. Evaluation of protective effect of amifostine on dacarbazine induced genotoxicity

    OpenAIRE

    Etebari, M.; Jafarian-Dehkordi, A.; Lame, V.

    2015-01-01

    Anticancer therapy with alkylating agents has been used for many years. Dacarbazine (DTIC) as an alkylating agent is used alone or in combination with other chemotherapy drugs. In order to inhibit the formation of secondary cancers resulting from chemotherapy with DTIC, preventional strategies is necessary. The present study was undertaken to evaluate the genoprotective effect of amifostine on the genotoxic effects of DTIC in cell culture condition. To determine the optimum genotoxic concentr...

  15. Amifostine (WR2721) Drug Controls Radiation Induced Damage in Rats

    International Nuclear Information System (INIS)

    Amifostine is a pro-drug in which selectivity is largely determined by the preferential formation and uptake of its cytoprotective metabolite, WR-1065, in normal tissues as a result of differences in membrane-bound alkaline phosphatase activity. Animals were categorized into four groups as follows: control group, WR-2721-intraperitoneally injected group at a dose of 100 mg/ kg, 1.5 Gy gamma-irradiated groups for 5 days (day post day) receiving final dose up to 7.5 Gy and WR-2721 injected group at 30 minutes before exposing to every fractionated dose of gamma-irradiation. Animals were sacrificed after 7 and 16 days after the final exposure to gamma-irradiation. The results obtained showed increased levels of plasma creatinine, plasma urea, plasma total protein, alanine and aspartate aminotransferases (ALT and AST), alkaline phosphatase (ALP), total bilirubin and gamma glutamyle transferase (gamma GT) and decreased levels of Albumin/ Globulin ratio (NG) in irradiated animal group compared with the control one. Administration of Amifostine before radiation exposure has significantly improved the radiation-induced changes in all these tested parameters. It could be concluded that application of Amifostine may minimize radiation damage and attenuate the side effects resulted from radiotherapy exposure

  16. [Amifostine used in the treatment of patients with myelodysplastic syndrome].

    Science.gov (United States)

    Li, Shu-Xia; Zhu, Hong-Li; Lu, Xue-Chun; Fan, Hui; Yao, Shan-Qian; Ma, Jian; Yang, Qing-Ming; Cai, Li-Li; Zhuang, Xiao-Meng; Yang, Yang

    2007-02-01

    The study was aimed to investigate the curative effects and adverse effects of amifostine in the treatment of patients with myelodysplastic syndrome (MDS). Amifostine (AMF) was used alone (4/12) or combined with recombinant human erythropoietin (rh-EPO) (8/12) in 12 MDS patients. The therapeutic regimen was adopted with AMF 0.4 g/day for 5 days, then took a break of 2 days and then went on for 3 weeks consecutively, that was reputed as one treatment cycle. rh-EPO 6 000 U was used for 3 days per week. The results showed that 12 patients all attained hematological improvement in peripheral blood. 11 cases showed major effective response rate (91.7%), while 1 case showed minor response rate (8.3%). The effective response rate of hemoglobin, leukocytes and platelets was 100%, 75% and 58.3% respectively. The intervals of red cell transfusions (RCT) in 2 cases living on red cell transfusion before AMF treatment were prolonged after AMF treatments, and the amount of each RCT was decreased obviously. The side effect was usually discomfort of digestive system, but all patients can endure. In conclusion, Amifostine is a potential drug in the treatment of MDS patients with safety especially to those elder patients who often suffered from other multiple organ disfunctions, and the curative effect will be improved by more treatment cycles. PMID:17490528

  17. Amifostine: An Effective Prophylactic Agent against Sulphur Mustard Toxicity (Short Communication

    Directory of Open Access Journals (Sweden)

    Uma Pathak

    2002-10-01

    Full Text Available Amifostine, S-2-(aminopropylamino ethylphosphorothioate and two of its analogues have been evaluated as prophylactic agent against SM toxicity. The compounds were administered intraperitoncally (i.p. at 0.2 LD/sub59 dose in mice 30 min prior to dermal application of SM. The protective efficacy was determined by observing the mortality for 14 days. The protection offered by amifostine was better than its analogues. Subsequent study on time-dependent protection, carried out with amifostine (0.2 LD/sub50, i.p. provided significant protection when the drug was administered as 30 min pre-treatment and simultaneous treatment against SM at 155 mg.kg/-1 dose (equal to 19-fold LD/sub50. Furthermore, oral administration of amifostine (30 min pre-treatment showed similar results. These findings suggest that amifostine is a promising prophylactic agent against SM toxicity.

  18. Amifostine is a potent radioprotector of salivary glands in radioiodine therapy. Structural and ultrastructural findings

    Energy Technology Data Exchange (ETDEWEB)

    Kutta, H. [Dept. of Anatomy, Christian Albrecht Univ. of Kiel (Germany); Dept. of Oto-Rhino-Laryngology, Head and Neck Surgery, Univ. Hospital Hamburg-Eppendorf, Hamburg (Germany); Kampen, U. [Clinic of Nuclear Medicine, Christian Albrecht Univ. of Kiel (Germany); Sagowski, C. [Dept. of Oto-Rhino-Laryngology, Head and Neck Surgery, Univ. Hospital Hamburg-Eppendorf, Hamburg (Germany); Brenner, W. [Clinic of Nuclear Medicine, Christian Albrecht Univ. of Kiel (Germany); Dept. of Nuclear Medicine, Univ. Hospital Hamburg-Eppendorf, Hamburg (Germany); Bohuslavizki, K.H. [Nuclear Medicine, Hamburg (Germany); Paulsen, F. [Dept. of Anatomy, Christian Albrecht Univ. of Kiel (Germany); Dept. of Anatomy and Cell Biology, Martin-Luther-Univ. of Halle-Wittenberg, Halle/Saale (Germany)

    2005-04-01

    Background and purpose: salivary gland impairment following high-dose radioiodine treatment is well recognized. Since differentiated thyroid cancer has a good prognosis, reduction of long-term side effects is important. This study investigates the radioprotective effects of amifostine in salivary glands of rabbits receiving high-dose radioiodine therapy so as to obtain deeper insight in changes on the cellular and ultrastructural level. Material and methods: a total of 20 rabbits were investigated. High-dose radioiodine therapy applying 1 GBq {sup 131}I was performed in 16 animals. Eight of these 16 animals received 200 mg/m{sup 2} body surface amifostine prior to high-dose radioiodine therapy. Four additional rabbits served as controls, two receiving amifostine, the other two no treatment at all. Subsequently, salivary glands (submandibular and parotid glands, respectively) of all animals were examined by light and transmission electron microscopy. Results: parenchymal damage of both parotid and submandibular glands, specially acinar structures comprising cell organelles and nuclei, of animals pretreated with amifostine was much less pronounced than in animals without amifostine pretreatment. Conclusion: the results indicate that parenchymal damage in salivary glands induced by high-dose radioiodine therapy can significantly be reduced by amifostine. Therefore, amifostine therapy may increase quality of life in patients with differentiated thyroid cancer after radioiodine treatment. (orig.)

  19. Cytoprotective Efficacy of Amifostine Against Radiation- Induced Rectal Toxicity: Objective and Subjective Grading Scales for Radiomucositis

    Directory of Open Access Journals (Sweden)

    John R. Kouvaris

    2008-04-01

    Full Text Available Curative radiation therapy of pelvic malignancies, frequently results in doselimitingtoxicities such as serous, mucoid, or more rarely, bloody diarrhea. Several studieshave evaluated the cytoprotective effects of amifostine in preventing rectal mucositisassociated with radiation treatment. We searched Medline for published comparativestudies that evaluated the use of amifostine to reduce radiation-induced toxicity associatedwith pelvic irradiation. In ten studies there was an evidence-based cytoprotection (P less than 0.05by amifostine. Although results are variable, current evidence suggests that amifostine mayhave a radioprotective effect in the rectal mucosa, particularly when administeredintrarectally. Significant improvements were seen in both symptomatic and objective(rectosigmoidoscopy end points. There is a need to conduct well-designed clinical trialswith sufficient numbers of participants to confirm these findings together with a costbenefitstudy. Objective measurements using rectosigmoidoscopy are superior tosubjective measures such as WHO or RTOG/EORTC toxicity grading scales.

  20. Assessment of the effect of local application of amifostine on acute radiation-induced oral mucositis in guinea pigs

    OpenAIRE

    Li, Chang Jiang; Wang, Sheng Zi; Wang, Shu Yi; Zhang, Yan Ping

    2014-01-01

    The aim of present study was to assess the radioprotective effects of the local application of amifostine to treat acute buccal mucositis in guinea pigs. A total of 32 guinea pigs were randomized into four groups: (Group A) topically administered 50 mg of amifostine plus radiotherapy (RT); (Group B) 100 mg amifostine plus RT; (Group C) normal saline plus RT; and (Group D) normal saline plus sham RT. The opportunity for administration was 15 min before irradiation. When administered, the cotto...

  1. 氨磷汀的合成%Synthesis of Amifostine

    Institute of Scientific and Technical Information of China (English)

    雷华; 张春红; 米成根; 程度; 黄文才

    2012-01-01

    N-(2-溴乙基)-1,3-丙二胺二氢溴酸盐和硫代磷酸钠在PEG 600作用下缩合,反应结束后加入三乙胺-乙醇混合液析出氨磷汀粗品,收率92.0%,纯度94.6%;再经过水-乙醇两次精制后可得到纯度99.0%以上的细胞保护剂氨磷汀精制品,精制率53%.%Amifostine, the cytoprotective agent, was synthesized from iV-(2-bromoethyl)-l,3-propanediamine dihydrobromide by condensation with sodium thiophosphate in the presence of PEG 600 in water and precipitation after addition of triethylamine and ethanol to give crude amifostine with a yield of 92.0% and purity of 94.6%, the crude product was purified twice with H2O-EtOH to afford the product with purity of above 99.0%, with the refining rate of 53%.

  2. Chromosomale Residualschäden nach Radiochemotherapie mit und ohne Gabe von Amifostin

    OpenAIRE

    Claussen, Mareike Franziska

    2007-01-01

    Hintergrund: Amifostin ist eine radioprotektiv wirkende Substanz, die zur Verringerung der akuten Nebenwirkungen bei konventionell fraktionierter Radiotherapie angewandt wird. In der vorliegenden Studie wurde Amifostin bei Patienten eingesetzt, die wegen eines Rektumkarzinoms eine postoperative Radiochemotherapie erhielten. Es wurde bereits beschrieben, dass diese Patienten nach zusätzlicher Amifostingabe eine geringere Akuttoxizität an Haut und Darm zeigten. Nun sollte festgestellt werden, o...

  3. Cytoprotective Efficacy of Amifostine Against Radiation- Induced Rectal Toxicity: Objective and Subjective Grading Scales for Radiomucositis

    OpenAIRE

    John R. Kouvaris; Kouloulias, Vassilis E.

    2008-01-01

    Curative radiation therapy of pelvic malignancies, frequently results in doselimitingtoxicities such as serous, mucoid, or more rarely, bloody diarrhea. Several studieshave evaluated the cytoprotective effects of amifostine in preventing rectal mucositisassociated with radiation treatment. We searched Medline for published comparativestudies that evaluated the use of amifostine to reduce radiation-induced toxicity associatedwith pelvic irradiation. In ten studies there was an evidence-based c...

  4. Amifostine: An Effective Prophylactic Agent against Sulphur Mustard Toxicity (Short Communication)

    OpenAIRE

    Uma Pathak; Raza, S K; Kumar, P.; Vijayaraghavan, R.; D. K. Jaiswal

    2002-01-01

    Amifostine, S-2-(aminopropylamino) ethylphosphorothioate and two of its analogues have been evaluated as prophylactic agent against SM toxicity. The compounds were administered intraperitoncally (i.p.) at 0.2 LD/sub59 dose in mice 30 min prior to dermal application of SM. The protective efficacy was determined by observing the mortality for 14 days. The protection offered by amifostine was better than its analogues. Subsequent study on time-dependent protection, carried out with amifo...

  5. Protective effects of amifostine on ischemia-reperfusion injury of rat kidneys

    OpenAIRE

    Ayse Arducoglu Merter; Burhan Mayir; Okan Erdogan; Taner Colak

    2015-01-01

    Objectives: Amifostine is a drug which can eliminate free oxygen radicals that appear in the body after radiation or chemotherapeutic agent exposure. It is used to decrease the renal toxicity of cisplatin. The aim of this study was to determine the role of amifostine in warm ischemia kidney model for prevention of ischemia/reperfusion injury and also to find out the mechanism for prevention from ischemia/reperfusion injury if such an effect does exist. Materials and Methods: Adult female ...

  6. The protective effect of amifostine on ultraviolet B-exposed xeroderma pigmentosum mice

    OpenAIRE

    Henry, SL; Christiansen, D; Kazmier, FR; Besch-Williford, CL; Concannon, MJ

    2010-01-01

    Background: Amifostine is a pharmaceutical agent that is used clinically to counteract the side-effects of chemotherapy and radiotherapy. It acts as a free radical scavenger that protects against harmful DNA cross-linking. The purpose of this study was to determine the effect of amifostine on the development of skin cancer in xeroderma pigmentosum (XP) mice exposed to ultraviolet B radiation (UVB). Methods: Twenty-five XP mice were equally divided into five groups. Group 1 (control) received ...

  7. Assessment of the Cytoprotective Efficacy of Amifostine with Quantitative Salivary Gland Scintigraphy

    OpenAIRE

    Bilgehan Karadayı; Müge Akmansu; Ahmet Dirier; Özgür Akdemir

    2005-01-01

    The main objective of our study was to assess and confirm the radioprotective effect of amifostine in protecting major salivary glands with dynamic quantitative scintigraphic evaluation.The study design was non-randomized clinical trial. There were 26 patients with head and neck cancer who receive primary or adjuvant radiotherapy in the head and neck region. Amifostine administrations were done before radiotherapy in one group while the control group did not take the drug. The primary end-poi...

  8. Ultrasensitive detection of amifostine and alkaline phosphatase based on the growth of CdS quantum dots.

    Science.gov (United States)

    Na, Weidan; Liu, Siyu; Liu, Xiaotong; Su, Xingguang

    2015-11-01

    In this study, we reported a simple and sensitive fluorescence nanosensor for rapid detection of amifostine and alkaline phosphatase (ALP). The novel nanosensor was based on the fluorescence "turn on-off" of CdS quantum dots (QDs). Firstly, Cd(2+) cation could react with S(2-) anion to generate fluorescent CdS QDs in the presence of amifostine. The fluorescence (FL) intensity of amifostine-capped CdS QDs (Amifostine-CdS QDs) was increased with the increasing amounts of amifostine, and could be used for amifostine detection. However, amifostine could be converted to 2-(3-aminopropylamino) ethanethiol (WR1065) in the presence of ALP based on the dephosphorylation of ALP. Under the optimum conditions, the affinity of WR1065 to CdS QDs was weaker than that of amifostine. Therefore the new generation of WR1065-CdS QDs would reduce the FL intensity with the increase of ALP concentration, and the fluorescence of CdS QDs was turn off. The metabolic process of amifostine in the presence of alkaline phosphatase could be also studied via the change of FL intensity of CdS QDs. The present method was cost-effective, convenient, and does not require any complicated synthetic procedures. PMID:26452927

  9. Influence of single and multiple doses of amifostine on the efficacy and the pharmacokinetics of carboplatin in mice.

    OpenAIRE

    Korst, A. E.; Boven, E.; van der Sterre, M. L.; Fichtinger-Schepman, A M; van der Vijgh, W. J.

    1997-01-01

    We have previously reported that amifostine potentiates the anti-tumour activity of carboplatin in mice. The present study was carried out in well-established human ovarian cancer xenografts OVCAR-3, A2780 and FMa grown subcutaneously in the nude mouse. It was found that a single dose of amifostine resulted in a higher increase in the anti-tumour activity of carboplatin than three doses of amifostine. A single dose of amifostine increased the AUC (area under the curve) values of total platinu...

  10. SOD2 Mediates Amifostine-Induced Protection against Glutamate in PC12 Cells

    Directory of Open Access Journals (Sweden)

    Ji Jia

    2016-01-01

    Full Text Available Background. Cytoprotectant amifostine attenuates radiation-induced oxidative injury by increasing intracellular manganese superoxide dismutase (SOD2 in peripheral tissue. However, whether amifostine could protect neuronal cells against oxidative injury has not been reported. The purpose of this study is to explore the protection of amifostine in PC12 cells. Methods. PC12 cells exposed to glutamate were used to mimic neuronal oxidative injury. SOD assay kit was taken to evaluate intracellular Cu/Zn SOD (SOD1 and SOD2 activities; western blot analysis and immunofluorescence staining were performed to investigate SOD2 protein expression; MTT, lactate dehydrogenase (LDH, release and cell morphology were used to evaluate cell injury degree, and apoptotic rate and cleaved caspase-3 expression were taken to assess apoptosis; mitochondrial superoxide production, intracellular reactive oxygen species (ROS, and glutathione (GSH and catalase (CAT levels were evaluated by reagent kits. Results. Amifostine increased SOD2 activity and expression, decreased cell injury and apoptosis, reduced mitochondrial superoxide production and intracellular ROS generation, and restored intracellular GSH and CAT levels in PC12 cells exposed to glutamate. SOD2-siRNA, however, significantly reversed the amifostine-induced cytoprotective and antioxidative actions. Conclusion. SOD2 mediates amifostine-induced protection in PC12 cells exposed to glutamate.

  11. Effects of amifostine on radiation-induced apoptosis in mouse ovary

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Lee, Kyoung Hee; Yoon Yong Dal [Hanyang Univ., Seoul (Korea, Republic of)

    2002-07-01

    The present study was designed to assess the radioprotective effects of amifostine on ovarian follicles. Three week-old female mice with or without pretreatment of amifostine were irradiated with 6.42 Gy of {gamma} -ray. Ovaries were collected 0 and 6h after irradiation. DNA fragmentation pattern and expression of genes and activity of proteins related with apoptosis were investigated by means of RT-PCR and Western blot. Proliferation of granulosa cells was reduced and incidence rate of follicular atresia was increased in ovarian follicles in {gamma} -ray irradiated mice compared to those in control or amifostine-treated group. DNA fragmentation was increased in time-dependent manner in granulosa cells of all irradiated groups. However, no difference between amifostine pre-treated group and irradiated groups was found and the expression of p53 as tumor suppressor gene and Bax as one of pro-apoptotic Bcl-2 family was increased in irradiated mice ovaries. PARP as DNA damage sensor was cleaved and its upstream regulator, Caspase-3 was activated. Fas (CD95), one of membrane bound receptor which initiated apoptosis pathway was expressed by {gamma} -ray. Pretreatment of amifostine before irradiation, however, inhibited the expression of p53 and Bax, the cleavage of PARP and the activation of Caspase-3. In conclusion, amifostine has an inhibitory effect on gonadal cell apoptosis induced by {gamma} -ray irradiation, through lowering the expression of apoptotic signaling peptide and the activation of DNA repair enzymes.

  12. The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application

    Directory of Open Access Journals (Sweden)

    Cem Uzal

    2012-03-01

    Full Text Available Objective: The aim of the study was to evaluate the radioprotective efficacy of intrarectal administration of amifostine in radiation-induced proctitis compared to intraperitoneal administration.Materials and Methods: Thirty-two Sprague-Dawley rats were randomly divided into four groups: Control (CONT, irradiation alone (RT, intraperitoneal amifostine plus irradiation (IPAMI, and intrarectal amifostine plus irradiation (IRAMI. The rats in the RT, IPAMI and IRAMI groups were irradiated individually with a single dose of 17.5 Gy to the pelvis. Amifostine was administered by the intraperitoneal (200 mg/kg or intrarectal (2000 mg/kg route before irradiation. Histopathologic analysis of the rectum was performed 14 days after irradiation. Results: Significant radiation damage appeared in all histopathologic parameters and was reduced by amifostine. Pretreatment with IPAMI significantly reduced the inflammatory infiltrate in the lamina propria (p=0.021, cryptitis (p=0.002 and crypt abscess (p=0.015. However, the protective effect of IRAMI was significant for all parameters with equal or higher significance than IPAMI, including the eosinophil leucocytes count (p=0.02, and distortion of the crypts (p=0.008, and was also significant for regenerative/reparative atypia (p=0.013. Conclusion: Intrarectal high dose topical administration of amifostine is more effective in the prevention of radiation-induced proctitis compared to its intraperitoneal systemic administration.

  13. The effect of amifostine on differentiation of the human megakaryoblastic Dami cell line.

    Science.gov (United States)

    Wang, Hai-Tao; Yang, Bo; Hu, Bo; Chi, Xiao-Hua; Luo, Long-Long; Yang, Hong-Qi; Lang, Xiao-Ling; Geng, Jing; Qiao, Chun-Xia; Li, Yan; Wu, Xiao-Xiong; Zhu, Hong-Li; Lv, Ming; Lu, Xue-Chun

    2016-08-01

    Amifostine is a cytoprotective drug that was initially used to control and treat nuclear radiation injury and is currently used to provide organ protection in cancer patients receiving chemotherapy. Clinical studies have also found that amifostine has some efficacy in the treatment of cytopenia caused by conditions such as myelodysplastic syndrome and immune thrombocytopenia, both of which involve megakaryocyte maturation defects. We hypothesized that amifostine induced the differentiation of megakaryocytes and investigated this by exposing the human Dami megakaryocyte leukemia cell line to amifostine (1 mmol/L). After 12 days of amifostine exposure, optical microscopy showed that the proportion of Dami cells with diameters >20 μm had increased to 24.63%. Transmission electron microscopy identified the development of a platelet demarcation membrane system, while flow cytometry detected increased CD41a expression and decreased CD33 expression on the Dami cell surface. Ploidy analysis found that the number of polyploid cells with >4N DNA content increased to 27.96%. We did not detect any elevation in the mRNA or protein levels of megakaryocytic differentiation-associated transcription factors GATA-binding factor 1 (GATA-1) and nuclear factor, erythroid 2 (NF-E2), but nuclear import assay revealed an increased nuclear translocation of these proteins. These findings indicate that amifostine induced the differentiation of Dami cells into mature megakaryocytes via a mechanism involving increased nuclear translocation of the transcription factors, NF-E2 and GATA-1. PMID:27228575

  14. Residual chromosomal damage after radiochemotherapy with and without amifostine detected by 24-color FISH

    Energy Technology Data Exchange (ETDEWEB)

    Kuechler, A.; Wendt, T.G. [Dept. of Radiation Oncology, Friedrich Schiller Univ., Jena (Germany); Dreidax, M.; Liehr, T.; Claussen, U. [Inst. of Human Genetics and Anthropology, Friedrich Schiller Univ., Jena (Germany); Pigorsch, S.U.; Dunst, J. [Dept. of Radiation Oncology, Martin Luther Univ., Halle (Germany)

    2003-07-01

    Background: Amifostine is a radioprotective drug applied to reduce acute radiation toxicity during a course of conventionally fractionated radiotherapy. In the present study, amifostine was used in patients undergoing adjuvant radiochemotherapy for rectal cancer. It was described previously that additional application of amifostine led to less acute skin and bowel toxicity. The present study was aimed to determine whether amifostine has an influence on the amount of residual chromosomal damage. Material and Methods: Peripheral lymphocytes of twelve rectal cancer patients who had undergone postoperative radiochemotherapy 2-3 years ago were investigated for residual chromosomal damage using 24-color fluorescence in situ hybridization (24-color FISH). All twelve patients had received a total dose of 55.8 Gy in conventional fractionation of 1.8 Gy and a 120-h continuous infusion of 5-fluorouracil (5-FU) chemotherapy (1,000 mg/m{sup 2} per day) in the 1st and 5th week of irradiation. Seven out of twelve patients had been given additional amifostine on chemotherapy days (500 mg total dose as short i.v. infusion immediately prior to the daily radiation fraction). Cultivation of lymphocytes and 24-color FISH were performed according to standard protocols. 100 metaphases per patient were analyzed for chromosomal aberrations in a blind study. Results: Analysis of the average number of breaks per mitosis (B/M) revealed an increased amount of residual chromosomal damage in the group treated with amifostine (0.65 B/M [0.32-0.97]) as well as in those treated without amifostine (0.76 B/M [0.31-1.25]). Also the average number of cells containing aberrations per 100 analyzed metaphases was similar (with amifostine: 22.1 [13-32] vs. 24.4 [13-35] without amifostine). The aberration types, occurring as simple translocations, reciprocal translocations, breaks, dicentrics, inversions, rings and complex chromosomal rearrangements, did not show any specific accumulation in one or the

  15. A randomized phase II study of paclitaxel with carboplatin +/- amifostine as first line treatment in advanced ovarian carcinoma

    NARCIS (Netherlands)

    De Vos, F Y F L; Bos, A M E; Schaapveld, M; de Swart, C A M; de Graaf, H; van der Zee, A G J; Boezen, H M; de Vries, E G E; Willemse, P H B

    2005-01-01

    OBJECTIVE: Will amifostine (A) protect against chemotherapy-induced neuro- and myelotoxicity. PATIENTS AND METHODS: Ninety ovarian cancer patients were randomized to receive standard paclitaxel + carboplatin without (PC) or preceded by amifostine 740 mg/m(2) (PC + A). RESULTS: The mean baseline valu

  16. Effect of Amifostine on Survival Among Patients Treated With Radiotherapy : A Meta-Analysis of Individual Patient Data

    NARCIS (Netherlands)

    Bourhis, Jean; Blanchard, Pierre; Maillard, Emilie; Brizel, David M.; Movsas, Benjamin; Buentzel, Jens; Langendijk, Johannes A.; Komaki, Ritsuko; Leong, Swan Swan; Levendag, Peter; Pignon, Jean Pierre

    2011-01-01

    Purpose Controversy exists regarding whether or not amifostine might reduce the efficacy of cancer treatment. The aim of this meta-analysis was to evaluate the impact of amifostine on overall survival (OS) and progression-free survival (PFS) in patients treated with radiotherapy or chemoradiotherapy

  17. Outcome of local application of amifostine (WR-1065) on epirubicin-induced oral mucositis. A phase II study

    NARCIS (Netherlands)

    Stokman, MA; Wachters, FM; Koopmans, P; Burgerhof, JGM; Groen, HJM; Spijkervet, FKL; Uges, DRA; Hospers, GAP

    2004-01-01

    Background: Intravenous administration of amifostine reduces chemotherapy-induced toxicity. Preclinical experiments showed a reduction in radiation-induced mucositis after local application of the active metabolite of amifostine (WR-1065). This study evaluated the effect of local application of WR-1

  18. Radiotherapy alone, versus radiotherapy with amifostine 3 times weekly, versus radiotherapy with amifostine 5 times weekly - A prospective randomized study in squamous cell head and neck cancer

    NARCIS (Netherlands)

    Jellema, Anke Petra; Slotman, Ben J.; Muller, Martin J.; Leemans, C. Rene; Smeele, Ludi E.; Hoekman, Klaas; Aaronson, Neil K.; Langendijk, Johannes A.

    2006-01-01

    BACKGROUND. The main objective of this study was to investigate whether non-daily intravenous administration of amifostine was as effective as daily intravenous administration with regard to the reduction of the incidence of Grade 2 or greater xerostomia in patients with head and neck cancer. METHOD

  19. Review on salivary glad protection by amifostine in high-dose radiodine treatment; Uebersicht ueber die Moeglichkeiten des Speicheldruesenschutzes durch Amifostin bei ablativer Radioiodtherapie

    Energy Technology Data Exchange (ETDEWEB)

    Bohuslavizki, K.H.; Klutmann, S.; Mester, J.; Clausen, M. [Universitaetskrankenhaus Eppendorf (Germany). Abt. fuer Nuklearmedizin; Brenner, W.; Henze, E. [Kiel Univ. (Germany). Klinik fuer Nuklearmedizin

    1999-06-01

    This study investigated the radioprotective effects of the thiol compound amifostine in animals and humans receiving high-dose radioiodine therapy. From these data derived in an animal model, in a retrospective study with a limited number of patients, and in a prospective double-blind, placebo-controlled patient study we may conclude that parenchymal damage in salivary glands caused by high-dose radioiodine therapy can significantly be reduced by amifostine which may improve quality of life of patients with differentiated thyroid cancer. (orig.) [Deutsch] Da der SH-Gruppendonator Amifostin stark in Speicheldruesen angereichert wird, sollte seine zytoprotektive Wirkung auf Speicheldruesen bei der Radioiodtherapie im Tiermodell, in einem Heilversuch und in einer doppelblind, plazebokontrollierten Studie ueberprueft werden. Die hier im Rahmen eines Tiermodells, im Rahmen eines Heilversuches und prospektiv durch eine doppelblinde, plazebokontrollierten Studie nachgewiesene zytoprotektive Wirkung von Amifostin auf Speicheldruesen laesst den Schluss zu, dass klinisch fassbare Speicheldruesenschaedigungen nach multiplen Radioiodtherapien im Rahmen der Behandlung des differenzierten Schilddruesenkarzinoms weitgehend vermieden werden koennen. (orig.)

  20. Intermittent use of amifostine during postoperative radiochemotherapy and acute toxicity in rectal cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Dunst, J.; Semlin, S.; Pigorsch, S.; Mueller, A.C.; Reese, T. [Halle-Wittenberg Univ., Halle (Germany). Abt. fuer Radiotherapie

    2000-09-01

    From September 1997 through October 1998, 30 patients with stage II/III rectal cancer underwent postoperative radiochemotherapy at our department. All patients had undergone curative (R0) resection and received 50.4 Gy to the pelvis with a 3-field technique using a belly board followed by a boost of 5.4 Gy to the presacral space in conventional fractionation with 1.8 Gy per fraction. 5-FU chemotherapy was administered as 120-hours continuous infusion in the first and fifth radiation week via a central venous catheter in a daily dosage of 1000 mg/m{sup 2}. All patients were offered to participate in a phase-II study using additional amifostine. Fifteen patients participated and received 500 mg amifostine daily on chemotherapy days (days 1 to 5 and 29 to 33) immediately prior to the daily radiation fraction. Fifteen patients did not participate and served as non-randomized control. The study was approved by the ethical committee of the Martin-Luter-University and informed consent was obtained from all patients. Results: The distribution of patients' characteristics and prognostic parameters was comparable in both groups. Side effects of amifostine were mild and included hypotension (53% grade I, 7% grade II) and nausea (47% grade I, 13% grade II). Antiemetics were not routinely used. All patients completed radiochemotherapy plus amifostine without unplanned breaks or dose reductions. One patients developed a cerebral infraction which was considered to be not related to the use of amifostine. As compared to the non-randomized control group, patients with additional amifostine had less acute skin and bowel toxicity (maximum erythema score 1.47{+-}0.64 without vs 0.87{+-}0.52 with amifostine, p=0.009 and maximum diarrhea score 1.07{+-}1.03 vs 0.40{+-}0.63, p=0.044). Oral 5-FU-related mucositis and hematological toxicity were not significantly different. (orig.) [German] Zwischen September 1997 und Oktober 1998 wurden 15 Patienten mit postoperativer

  1. Assessment of the Cytoprotective Efficacy of Amifostine with Quantitative Salivary Gland Scintigraphy

    Directory of Open Access Journals (Sweden)

    Bilgehan Karadayı

    2005-01-01

    Full Text Available The main objective of our study was to assess and confirm the radioprotective effect of amifostine in protecting major salivary glands with dynamic quantitative scintigraphic evaluation.The study design was non-randomized clinical trial. There were 26 patients with head and neck cancer who receive primary or adjuvant radiotherapy in the head and neck region. Amifostine administrations were done before radiotherapy in one group while the control group did not take the drug. The primary end-point was wash-out rate as the quantitative scintigraphic parameter and changing patterns after radiotherapy were compared. Parotid wash-out rate showed some healing at the 3rd month of radiotherapy in the amifostine group, but not in the control group. Submandibular wash-out rate showed some worsening at the 3rd month of radiotherapy in the control group, but not in the amifostine group. Radioprotective effect of amifostine in major salivary glands can be observed with the testing tool of dynamic quantitative salivary gland scintigraphy.

  2. Pre-treatment with amifostine protects against cyclophosphamide-induced disruption of taste in mice.

    Directory of Open Access Journals (Sweden)

    Nabanita Mukherjee

    Full Text Available Cyclophosphamide (CYP, a commonly prescribed chemotherapy drug, has multiple adverse side effects including alteration of taste. The effects on taste are a cause of concern for patients as changes in taste are often associated with loss of appetite, malnutrition, poor recovery and reduced quality of life. Amifostine is a cytoprotective agent that was previously shown to be effective in preventing chemotherapy-induced mucositis and nephrotoxicity. Here we determined its ability to protect against chemotherapy-induced damage to taste buds using a mouse model of CYP injury. We conducted detection threshold tests to measure changes in sucrose taste sensitivity and found that administration of amifostine 30 mins prior to CYP injection protected against CYP-induced loss in taste sensitivity. Morphological studies showed that pre-treatment with amifostine prevented CYP-induced reduction in the number of fungiform taste papillae and increased the number of taste buds. Immunohistochemical assays for markers of the cell cycle showed that amifostine administration prevented CYP-induced inhibition of cell proliferation and also protected against loss of mature taste cells after CYP exposure. Our results indicate that treatment of cancer patients with amifostine prior to chemotherapy may improve their sensitivity for taste stimuli and protect the taste system from the detrimental effects of chemotherapy.

  3. Clinical study of the radioprotective effects of Amifostine (YM-08310, WR-2721) on chronic radiation injury

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, I.; Nagai, T.; Miyaishi, K.; Maehara, Y.; Niibe, H.

    1986-06-01

    We have previously reported that Amifostine, a radioprotective agent, was effective in treating acute radiation mucositis in the head and neck region. We found that when a considerable amount of Amifostine accumulates in the salivary glands, it may be useful in preventing chronic disturbances of salivary secretion. We have observed an increase in the uptake of Ga-67-citrate to the salivary glands when they were irradiated. In this paper, the radioprotective effects of Amifostine, in treating chronic radiation injury of the salivary glands, were studied, using the cessation of an increase in uptake of Ga-67-citrate after radiotherapy as the criterion. The subjects were 105 patients, (280 salivary glands in Ga-scintigrams) with malignancy of the head and neck region treated by irradiation from 1978 to 1984. Ga-negative glands were recognized in 97%, that is, 36 out of 37 glands, before irradiation, and the figure decreased to 19%, seven out of 37, within 1 to 2 weeks (10Gy less than or equal to) after the start of radiotherapy. In patients who were irradiated with more than 30 Gy and in whom scintigraphy was performed at 6 months or more after radiotherapy, Ga-negative glands were recognized in 18 out of 41 glands, 44%, with Amifostine, compared with 13%, four out of 32 glands, without Amifostine. A difference was recognized between these two groups in the negative change in Ga-67 uptake after radiotherapy (p less than 0.05). These facts suggest that Amifostine may have a radioprotective effect on chronic radiation injury.

  4. Protective effects of amifostine and its analogues on sulfur mustard toxicity in vitro and in vivo.

    Science.gov (United States)

    Bhattacharya, R; Rao, P V; Pant, S C; Kumar, P; Tulsawani, R K; Pathak, U; Kulkarni, A; Vijayaraghavan, R

    2001-10-01

    Sulfur mustard (bis(2-chloroethyl)sulfide, SM) is a highly reactive bifunctional alkylating agent that forms sulfonium ions in the body. SM alkylates DNA, leading to DNA strand breaks and cell death in a variety of cell types and tissues. Although several approaches have been proposed to challenge the toxic action(s) of SM, no satisfactory treatment regimen has evolved. The synthetic aminothiol amifostine, earlier known as WR-2721 (S-2-(3-aminopropylamino)ethyl phosphorothioate), has been extensively used as a chemical radioprotector for the normal tissues in cancer radiotherapy and chemotherapy. SM is known as a radiomimetic agent and this prompted us to evaluate the protective efficacy of amifostine (2.5 mM) and three of its analogues, DRDE-06 (S-2 (3-aminopropylamino) ethyl phenyl sulfide), DRDE-07 (S-2 (2-aminoethylamino) ethyl phenyl sulfide), and DRDE-08 (S-2 (4-aminobutylamino) ethyl phenyl sulfide), against SM toxicity in rat liver slices. Of the four agents tested, a 30-min pretreatment of amifostine and DRDE-07 enhanced the LC50 (a concentration producing 50% leakage of lactate dehydrogenase (LDH) or alanine aminotransferase (ALT)) of SM by 5.9- and 3.3-fold for LDH and 10.2- and 5.5-fold for ALT, respectively. Except DNA fragmentation, both these agents significantly attenuated the loss of intracellular K(+) and mitochondrial integrity (MTT assay), depletion of GSH levels, and histopathology produced by a toxic concentration (80 microM) of SM. However, when amifostine and DRDE-07 were introduced 2 h after SM, no significant protection was observed. SM (77.5 or 155 mg/kg) was also applied dermally on female albino mice and challenged by 0.20 LD50 (po) of amifostine, DRDE-06, DRDE-07, or DRDE-08 at -30 min, 0 min, or +6 h. Protection was observed only when the agents were administered at -30 min or 0 min; posttreatment (+6 h) did not offer any protection. The magnitude of in vivo protection was in the following order: DRDE-07 >or= amifostine > DRDE-08

  5. A Phase I Clinical and Pharmacology Study Using Amifostine as a Radioprotector in Dose-escalated Whole Liver Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Mary, E-mail: maryfeng@umich.edu [Department of Radiation Oncology, School of Medicine, University of Michigan, Ann Arbor, Michigan (United States); Smith, David E. [Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan (United States); Normolle, Daniel P. [Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Knol, James A. [Department of Surgery, School of Medicine, University of Michigan, Ann Arbor, Michigan (United States); Pan, Charlie C.; Ben-Josef, Edgar [Department of Radiation Oncology, School of Medicine, University of Michigan, Ann Arbor, Michigan (United States); Lu Zheng; Feng, Meihua R.; Chen Jun [Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan (United States); Ensminger, William [Department of Internal Medicine, School of Medicine, University of Michigan, Ann Arbor, Michigan (United States); Lawrence, Theodore S. [Department of Radiation Oncology, School of Medicine, University of Michigan, Ann Arbor, Michigan (United States)

    2012-08-01

    Purpose: Diffuse intrahepatic tumors are difficult to control. Whole-liver radiotherapy has been limited by toxicity, most notably radiation-induced liver disease. Amifostine is a prodrug free-radical scavenger that selectively protects normal tissues and, in a preclinical model of intrahepatic cancer, systemic amifostine reduced normal liver radiation damage without compromising tumor effect. We hypothesized that amifostine would permit escalation of whole-liver radiation dose to potentially control microscopic disease. We also aimed to characterize the pharmacokinetics of amifostine and its active metabolite WR-1065 to optimize timing of radiotherapy. Methods and Materials: We conducted a radiation dose-escalation trial for patients with diffuse, intrahepatic cancer treated with whole-liver radiation and intravenous amifostine. Radiation dose was assigned using the time-to-event continual reassessment method. A companion pharmacokinetic study was performed. Results: Twenty-three patients were treated, with a maximum dose of 40 Gy. Using a logistical regression model, compared with our previously treated patients, amifostine increased liver tolerance by 3.3 {+-} 1.1 Gy (p = 0.007) (approximately 10%) with similar response rates. Peak concentrations of WR-1065 were 25 {mu}M with an elimination half-life of 1.5 h; these levels are consistent with radioprotective effects of amifostine in patients. Conclusion: These findings demonstrate for the first time that amifostine is a normal liver radioprotector. They further suggest that it may be useful to combine amifostine with fractionated or stereotactic body radiation therapy for patients with focal intrahepatic cancer.

  6. 氨磷汀的合成%Synthesis of Amifostine

    Institute of Scientific and Technical Information of China (English)

    毛远湖; 汤磊; 王建塔

    2014-01-01

    Amifostine , a cytoprotector , was synthesized by reaction of 2 -Aminoethanol with acrylonitrile and via condensation, bromination, salification, and purified.The structures of the intermediates and final product were characterized by IR and 1 HNMR, and the purity was measured via HPLC by contrast with standard substance.By optimizing each step , the total yield was raised to 37.3%and purity of 99.2%.%以2-羟基乙胺为原料,与丙烯腈反应后经还原、溴代、成盐、精制得细胞保护剂氨磷汀,中间体及终产物结构经红外、氢谱确证,并通过HPLC与终产物标准品对照测得其纯度。新的工艺对各步反应进行了优化,收率达37.3%,纯度达99.2%。

  7. Combined therapy with amifostine plus erythropoietin for the treatment of myelodysplastic syndromes

    DEFF Research Database (Denmark)

    Musto, Pellegrino; Santini, Valeria; Balestri, Francesca;

    2002-01-01

    Twelve patients with myelodysplasia were treated with amifostine plus recombinant human erythropoietin (rHuEpo) for 6 weeks. A complete erythroid response was obtained in 2/12(16.6%) and a partial response in 4/12 (33.3%). Two of 8 patients with a platelet count < 100 x 10(9)/L had a complete...

  8. Radioprotective effect of amifostine on parotid gland functioning is region dependent

    NARCIS (Netherlands)

    Konings, AWT; Faber, H; Vissink, A; Coppes, RP

    2005-01-01

    Purpose: To investigation the protective ability of amifostine during partial irradiation of the rat parotid gland. Methods and Materials: Single-dose X-ray irradiation was performed by use of collimators with conformal radiation portals for either the 100% volume (15 Gy) or the 50% cranial/caudal p

  9. Systematic review of amifostine for the management of oral mucositis in cancer patients

    NARCIS (Netherlands)

    Nicolatou-Galitis, Ourania; Sarri, Triantafyllia; Bowen, Joanne; Di Palma, Mario; Kouloulias, Vassilios E.; Niscola, Pasquale; Riesenbeck, Dorothea; Stokman, Monique; Tissing, Wim; Yeoh, Eric; Elad, Sharon; Lalla, Rajesh V.

    2013-01-01

    The aim of this study was to review the available literature from 1966 until December 31, 2010 and define clinical practice guidelines for the use of amifostine for the prevention and treatment of oral mucositis in cancer patients. A systematic review was conducted by the Mucositis Study Group of th

  10. Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats

    OpenAIRE

    Akbulut, Sami; Elbe, Hulya; Eris, Cengiz; Dogan, Zumrut; Toprak, Gulten; Otan, Emrah; Erdemli, Erman; TURKOZ, Yusuf

    2014-01-01

    AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity.

  11. Effect of Amifostine on Locally Advanced Non-small Cell Lung Cancer Patients Treated with Radiotherapy: A Meta-analysis of Randomized Controlled Trials

    OpenAIRE

    Wang, Shengye; Zhang, Yiping; Zhang, Suzhan; Ma, Shenglin

    2012-01-01

    Background and objective Controversy exists on whether amifostine can reduce the efficacy and decrease the side effects of non-small cell lung cancer (NSCLC) treated by radiotherapy. The aim of this meta-analysis is to evaluate the efficacy and side effects of amifostine in NSCLC patients treated with radiotherapy. Methods Open published randomized controlled trials on the efficacy and side effects of amifostine in NSCLC patients treated with radiotherapy were collected from Medline, Cochrane...

  12. Comparison of the protective roles of L-carnitine and amifostine against radiation-induced acute ovarian damage by histopathological and biochemical methods

    OpenAIRE

    Vuslat Yurut-Caloglu; Murat Caloglu; Sevgi Eskiocak; Ebru Tastekin; Alaattin Ozen; Nukhet Kurkcu; Fulya Oz-Puyan; Zafer Kocak; Cem Uzal

    2015-01-01

    Purpose: The aim of this study was to compare the radioprotective efficacies of L-carnitine (LC) and amifostine against radiation-induced acute ovarian damage. Materials and Methods: Forty-five, 3-month-old Wistar albino rats were randomly assigned to six groups. Control (CONT, n = 7); irradiation alone RT: radiation therapy (RT, n = 8); amifostine plus irradiation (AMI + RT, n = 8); LC plus irradiation (LC + RT, n = 8); LC and sham irradiation (LC, n = 7); and amifostine and sham irradia...

  13. In vitro effect of amifostine on haematopoietic progenitors exposed to carboplatin and non-alkylating antineoplastic drugs: haematoprotection acts as a drug-specific progenitor rescue.

    OpenAIRE

    Pierelli, L.; Scambia, G; Fattorossi, A; Bonanno, G.; Battaglia, A; Perillo, A.; Menichella, G.; Panici, P. B.; Leone, G; Mancuso, S.

    1998-01-01

    We evaluated the protective ability of amifostine on peripheral blood mononuclear cell (PBMC)-derived colony-forming unit (CFU) and PB CD34+ cells which were previously exposed in vitro to etoposide, carboplatin, doxorubicin and taxotere. Amifostine pretreatment protected PBMC-derived CFU from the toxic effect of etoposide, carboplatin and taxotere. A significant detrimental effect was exerted by amifostine on the growth of doxorubicin-treated PBMC-derived CFU. Liquid cultures of PB CD34+ cel...

  14. Protective effect of Ginkgo flavonoids, amifostine, and leuprorelin against platinum-induced ovarian impairment in rats.

    Science.gov (United States)

    Chang, Z; Wang, H L; Du, H

    2014-01-01

    Platinum-induced ovarian impairment is a consequence of treatment for malignant ovarian tumors. We compared the protective effects of Ginkgo flavonoids, amifostine, and leuprorelin on ovarian impairment in rats. Fifty rats were randomly divided into the A, B, C, D, and E groups, which were given saline, cisplatin, cisplatin plus Ginkgo flavonoids, cisplatin plus amifostine, and cisplatin plus leuprorelin, respectively. Ovarian weight was significantly greater in groups C and D compared with group B (83.5 ± 6.7 and 86.8 ± 10 vs 56.8 ± 5.4 mg). The total follicle numbers were higher in groups C, D, and E than in group B (60.5 ± 3.9, 63.8 ± 5.1, and 67.7 ± 3.5 vs 49.6 ± 4.5), and the apoptotic index was reduced in groups C, D, and E compared with group B (35.7 ± 2.0, 37.4 ± 1.6, and 30.5 ± 2.9 vs 65.3 ± 2.9%). The ovaries in groups B, C, and D had higher protein and mRNA expression levels of cytoplasmic Cytochrome c (Cyt-c) and apoptotic protease activating factor-1 (Apf-1) compared to group A; the Cyt-c mRNA expression was five-fold higher. The mRNA expression of Cyt-c and Apf-1 were significantly lower in groups C, D, and E compared with group B. Administration of leuprorelin, flavonoids, or amifostine protected rats against the ovarian impairment induced by prior intraperitoneal injection of cisplatin. The efficacy of leuprorelin was superior to that of Ginkgo flavonoids and amifostine, but there was no difference between the effects of Ginkgo flavonoids and amifostine. PMID:25078583

  15. Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer

    International Nuclear Information System (INIS)

    Purpose: To determine the prophylactic properties of amifostine against acute and late toxicities from radiochemotherapy in patients with head-and-neck cancer. Methods and Materials: Fifty patients were randomized to receive conventional radiotherapy (RT) (2-Gy fractions, 5 days weekly, to a total of 60-74 Gy, depending on the tumor localization and TNM classification) and carboplatin (90 mg/m2 infusion once per week before RT). Amifostine (300 mg/m2) was administered in the study group only 15-30 min before RT for 6-7.5 weeks. The primary study end point was the grading of acute and late nonhematologic toxicities (mucositis, dysphagia, xerostomia) induced by radiochemotherapy. Secondary end points included treatment duration, hematologic toxicity, and clinical outcome. Results: The treatment duration was significantly shorter in the amifostine-treated group (p=0.013), because treatment interruptions were more frequent in the control group. Acute toxicities (mucositis and dysphagia) were less severe in the amifostine-treated group. By Week 3, all in the control group experienced Grade 2 mucositis compared with only 9% in the amifostine-treated group (p<0.0001). By Week 5, 52.2% of the patients in the control group experienced Grade 4 mucositis compared with 4.5% in the amifostine-treated group (p=0.0006). Similar results were obtained for dysphagia. At 3 months of follow-up, only 27% of patients in the study group experienced Grade 2 xerostomia compared with 73.9% in the control group (p=0.0001). Eighteen months after cessation of therapy, the proportion of patients with Grade 2 xerostomia was 4.5% vs. 30.4% for each respective treatment group (p=0.047). Cytoprotection with amifostine did not affect treatment outcome, with 90.9% complete responses in the amifostine-treated group compared with 78.3% in the control group (p=0.414). Conclusion: Amifostine was effective in reducing mucositis and dysphagia resulting from radiochemotherapy in patients with head

  16. Randomized phase II exploratory study of prophylactic amifostine in cancer patients who receive radical radiotherapy to the pelvis

    OpenAIRE

    Karavasilis Vasileios; Panelos Ioannis; Capizzello Antonio; Tolis Christos; Bai Maria; Batistatou Anna; Tsekeris Pericles; Briasoulis Evangelos; Katsanos Konstantinos H; Christodoulou Dimitrios; Tsianos Epameinondas V

    2010-01-01

    Abstract Background This study aimed to investigate the efficacy of prophylactic amifostine in reducing the risk of severe radiation colitis in cancer patients receiving radical radiotherapy to the pelvis. Methods Patients with pelvic tumours referred for radical radiotherapy who consented participation in this trial, were randomly assigned to receive daily amifostine (A) (subcutaneously, 500 mg flat dose) before radiotherapy or radiotherapy alone (R). Sigmoidoscopy and blinded biopsies were ...

  17. The cytoprotective drug amifostine modifies both expression and activity of the pro-angiogenic factor VEGF-A.

    OpenAIRE

    Bouchecareilh M; Rezvani HR; Canron X; Dedieu S; Mazurier F; Sinisi R; Zanda M.; Moenner M; Bikfalvi A; North S

    2010-01-01

    Abstract Background Amifostine (WR-2721, delivered as Ethyol®) is a phosphorylated aminothiol compound clinically used in addition to cis-platinum to reduce the toxic side effects of therapeutic treatment on normal cells without reducing their efficacy on tumour cells. Its mechanism of action is attributed to the free radical scavenging properties of its active dephosphorylated metabolite WR-1065. However, amifostine has also been described as a potent hypoxia-mimetic compound and as a strong...

  18. Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status

    OpenAIRE

    Miraglia Sandra M; Sasso-Cerri Estela; Vendramini Vanessa

    2010-01-01

    Abstract Background Amifostine is an efficient cytoprotector against toxicity caused by some chemotherapeutic drugs. Doxorubicin, a potent anticancer anthracycline, is known to produce spermatogenic damage even in low doses. Although some studies have suggested that amifostine does not confer protection to doxorubicin-induced testicular damage, schedules and age of treatment have different approach depending on the protocol. Thus, we proposed to investigate the potential cytoprotective action...

  19. Amifostine ameliorates recognition memory defect in acute radiation syndrome caused by relatively low-dose of gamma radiation

    OpenAIRE

    Lee, Hae-June; Kim, Joong-Sun; Song, Myoung-Sub; Seo, Heung-Sik; Yang, Miyoung; Kim, Jong Choon; Jo, Sung-Kee; Shin, Taekyun; Moon, Changjong; Kim, Sung-Ho

    2010-01-01

    This study examined whether amifostine (WR-2721) could attenuate memory impairment and suppress hippocampal neurogenesis in adult mice with the relatively low-dose exposure of acute radiation syndrome (ARS). These were assessed using object recognition memory test, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunohistochemical markers of neurogenesis [Ki-67 and doublecortin (DCX)]. Amifostine treatment (214 mg/kg, i.p.) prior to irradiation significan...

  20. Assessment of the effect of local application of amifostine on acute radiation-induced oral mucositis in guinea pigs.

    Science.gov (United States)

    Li, Chang Jiang; Wang, Sheng Zi; Wang, Shu Yi; Zhang, Yan Ping

    2014-09-01

    The aim of present study was to assess the radioprotective effects of the local application of amifostine to treat acute buccal mucositis in guinea pigs. A total of 32 guinea pigs were randomized into four groups: (Group A) topically administered 50 mg of amifostine plus radiotherapy (RT); (Group B) 100 mg amifostine plus RT; (Group C) normal saline plus RT; and (Group D) normal saline plus sham RT. The opportunity for administration was 15 min before irradiation. When administered, the cotton pieces that had been soaked with 0.5 ml amifostine solution or saline were applied gently on the buccal mucosa of each guinea pig for 30 min. The animals in Groups A, B and C were irradiated individually with a single dose of 30 Gy to the bilateral buccal mucosa. Eight days after irradiation, the animals were scored macroscopically; they were then euthanized, and the buccal mucosal tissues were processed for hematoxylin-eosin staining and ICAM-1 immunohistochemical analysis. In Groups A and B, the mean macroscopic scores were 2.9 ± 0.6 and 2.4 ± 1.1, respectively. There was no significant difference between the two groups (P > 0.05). However, when they were separately compared with Group C (4.4 ± 0.7), a noticeable difference was obtained (P amifostine-treated groups were better than in Group C. The results demonstrated that topical administration of amifostine to the oral mucosa is effective treatment of acute radiation-induced mucositis. PMID:24706999

  1. Amelioration of early radiation effects in oral mucosa (mouse) by intravenous or subcutaneous administration of amifostine

    Energy Technology Data Exchange (ETDEWEB)

    Fleischer, G. [Dept. of Radiotherapy and Radiooncology, Medical Faculty Carl Gustav Carus, Technical Univ., Dresden (Germany); Doerr, W. [Dept. of Radiotherapy and Radiooncology, Medical Faculty Carl Gustav Carus, Technical Univ., Dresden (Germany); Experimental Center, Medical Faculty Carl Gustav Carus, Technical Univ., Dresden (Germany)

    2006-10-15

    Purpose: to quantify the reduction of radiation-induced oral mucositis by amifostine as a function of administration route. Material and methods: mucosal ulceration of lower mouse tongue epithelium was analyzed. Amifostine was injected at 1.8 mg/injection subcutaneously (s.c.) or intravenously (i.v.), 45 min or 10 min prior to irradiation. With single-dose irradiation, a single amifostine injection was given. During daily fractionated irradiation (5 x 3 Gy) for 1 week, amifostine was administered s.c. or i.v. twice (days 0, 3), or s.c. on all irradiation days (days 0-4). With ten fractions over 2 weeks, five s.c. injections were given in week 1 (days 0-4) or week 2 (days 7-11), or both. Two i.v. injections were given either in week 1 (days 0, 3) or week 2 (days 7, 10). All fractionation protocols were terminated by graded test doses to generate full dose-effect curves. Results: in a single-dose control experiment, the ED{sub 50} (dose after which ulcer induction is expected in 50% of the mice) was 11.7 {+-} 1.4 Gy. Intravenous application of amifostine increased the ED{sub 50} to 14.0 {+-} 1.4 Gy (p = 0.024), while s.c. administration had no significant effect. The ED{sub 50} for test irradiation after 5 x 3 Gy was 5.8 {+-} 1.4 Gy. Two s.c. or i.v. amifostine injections yielded ED{sub 50} values of 7.2 {+-} 1.1 Gy (p = 0.0984) or 7.6 {+-} 1.2 Gy (p = 0.0334); five s.c. injections increased the ED{sub 50} to 8.2 {+-} 0.9 Gy (p = 0.0039). The ED{sub 50} after 10 x 3 Gy/2 weeks was 6.6 {+-} 1.8 Gy. Subcutaneous or intravenous administration of amifostine in week 1 yielded a significant increase in ED{sub 50} to 9.4 {+-} 2.5 Gy (p = 0.0099) and 10.0 {+-} 2.2 Gy (p = 0.0014). By contrast, amifostine administration in week 2 had no significant effect. Administration in weeks 1 and 2 resulted in an ED{sub 50} of 10.8 {+-} 3.6 Gy (p= 0.0053). Conclusion: amifostine during daily fractionated irradiation is effective only if administered in the initial treatment phase, i

  2. Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status

    Directory of Open Access Journals (Sweden)

    Miraglia Sandra M

    2010-01-01

    Full Text Available Abstract Background Amifostine is an efficient cytoprotector against toxicity caused by some chemotherapeutic drugs. Doxorubicin, a potent anticancer anthracycline, is known to produce spermatogenic damage even in low doses. Although some studies have suggested that amifostine does not confer protection to doxorubicin-induced testicular damage, schedules and age of treatment have different approach depending on the protocol. Thus, we proposed to investigate the potential cytoprotective action of amifostine against the damage provoked by doxorubicin to prepubertal rat testes (30-day-old by assessing some macro and microscopic morphometric parameters 15, 30 and 60 days after the treatment; for fertility evaluation, quantitative analyses of sperm parameters and reproductive competence in the adult phase were also carried out. Methods Thirty-day-old male rats were distributed into four groups: Doxorubicin (5 mg/kg, Amifostine (400 mg/kg, Amifostine/Doxorubicin (amifostine 15 minutes before doxorubicin and Sham Control (0.9% saline solution. "Standard One Way Anova" parametric and "Anova on Ranks" non-parametric tests were applied according to the behavior of the obtained data; significant differences were considered when p Results The rats killed 30 and 60 days after doxorubicin treatment showed diminution of seminiferous epithelium height and reduction on the frequency of tubular sections containing at least one type of differentiated spermatogonia; reduction of sperm concentration and motility and an increase of sperm anomalous forms where observed in doxorubicin-treated animals. All these parameters were improved in the Amifostine/Doxorubicin group only when compared to Doxorubicin group. Such reduction, however, still remained below the values obtained from the Sham Control group. Nevertheless, the reproductive competence of doxorubicin-treated rats was not improved by amifostine pre-administration. Conclusions These results suggest that

  3. Cytoprotection with amifostine in the simultaneous radio-chemotherapy of recurrent head and neck cancer; Zytoprotection mit Amifostin im Rahmen der Radiochemotherapie bei vorbestrahlten Kopf-Hals-Karzinomen

    Energy Technology Data Exchange (ETDEWEB)

    Buentzel, J.; Weinaug, R.; Kuettner, K. [Zentralklinikum gGmbH Suedthueringen, Suhl (Germany). Klinik fuer Hals-Nasen-Ohren-Heilkunde, Plastische Operationen; Glatzel, M.; Froehlich, D. [Zentralklinikum gGmbH Suedthueringen, Suhl (Germany). Klinik fuer Strahlentherapie; Schuth, J. [Essex Pharma, Muenchen (Germany)

    1999-11-01

    Purpose: The radiotherapeutic possibilities are limited for patients with a recurrent or second head and neck cancer if the patient was already irradiated in the first therapy. In the presented study we investigated the changes of this situation due to the usage of amifostine in the case of re-irradiation (simultaneous radio-chemotherapy). Patients and methods: Between 1995 and 1997 we treated 14 patients with a recurrent or second malignancy of the head and neck region by a simultaneous radio-chemotherapy (20x1.5 Gy, Carboplatin 70 mg/m{sup 2} BSA on days 1 to 5 and 16 to 20, 500 mg amifostine prior to every carboplatin infusion). Six out of 14 patients got an additional brachytherapy (10 to 15 Gy) to increase the local dose because of a residual tomor. In 4 cases the treatment was an adjunctive one, following the surgical tumor debulking. Results: We have seen 3 complete remissions (21.4%), and 8 partial remissions (57.1%). The median time of observation in 13 months now. Three out of 14 patients died, 2 because of the tumor. Hematological toxicities: Side effects Grade 2 WHO were seen only in 1 patient. Acute non-hematological toxicities: Mucositis Grade 0/1 in 7 patients, mucositis Grade 2 in 7 patients, dysphagia Grade 0/1 in 9 patients, dysphagia Grade 2 in 5 patients, xerostomia Grade 1 in 9 patients, xerostomia Grade 2 in 3 patients. We registrated only 1 serious late toxicity due to radio-chemotherapy: 4 months after brachytherapy a patient (with laryngectomy) developed a submental fistula. Conclusion: These first results suggest that the usage of amifostine offers new potential ways for re-irradiation of patients with recurrent or second malignancies in the head neck region. (orig.) [German] Ziel: Bei einem Rezidiv- oder Zweitkarzinom im Kopf-Hals-Bereich sind die radiotherapeutischen Moeglichkeiten bei bereits vorbestrahlten Patienten sehr begrenzt. Inwieweit die Integration des selektiven Zytoprotektivums Amifostin in eine nochmalige Radiochemotherapie

  4. The rat acute-phase protein {alpha}{sub 2}-macroglobulin plays a central role in amifostine-mediated radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Mirjana, Mihailovic; Goran, Poznanovic; Nevena, Grdovic; Melita, Vidakovic; Svetlana, Dinic; Ilijana, Grigorov; Desanka, Bogojevic, E-mail: mista@ibiss.bg.ac.r [Department of Molecular Biology, Institute for Biological Research ' Sinisa Stankovic' , University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade (Serbia)

    2010-09-15

    Previously we reported that elevated circulating concentrations of the acute-phase (AP) protein {alpha}{sub 2}-macroglobulin ({alpha}{sub 2}M), either as typically occurring in pregnant female rats or after administration to male rats, provides radioprotection, displayed as 100% survival of experimental animals exposed to total-body irradiation with 6.7 Gy (LD{sub 50/30}) x-rays, that is as effective as that afforded by the synthetic radioprotector amifostine. The finding that amifostine administration induces a 45-fold increase in {alpha}{sub 2}M in the circulation led us to hypothesise that {alpha}{sub 2}M assumes an essential role in both natural and amifostine-mediated radioprotection in the rat. In the present work we examined the activation of cytoprotective mechanisms in rat hepatocytes after the exogenous administration of {alpha}{sub 2}M and amifostine. Our results showed that the IL6/JAK/STAT3 hepatoprotective signal pathway, described in a variety of liver-injury models, upregulated the {alpha}{sub 2}M gene in amifostine-pretreated animals. In both {alpha}{sub 2}M- and amifostine-pretreated rats we observed the activation of the Akt signalling pathways that mediate cellular survival. At the cellular level this was reflected as a significant reduction of irradiation-induced DNA damage that allowed for the rapid and complete restoration of liver mass and ultimately at the level of the whole organism the complete restoration of body weight. We conclude that the selective upregulation of {alpha}{sub 2}M plays a central role in amifostine-provided radioprotection.

  5. A pilot study of topical intrarectal application of amifostine for prevention of late radiation rectal injury

    International Nuclear Information System (INIS)

    Purpose: Clinical symptomatic late injury to the rectal wall occurs in about one-third of patients with prostate cancer treated with external beam irradiation. Reducing the physical dose to the anterior rectal wall without a similar reduction in the posterior peripheral zone is difficult because of the proximity of the prostate to the anterior rectal wall. On the basis of our previous observations in an animal model that intrarectal application of amifostine resulted in very high concentrations of amifostine and its active metabolite WR-1065 in the rectal wall, a Phase I dose-escalation clinical trial was undertaken. Methods and Materials: Twenty-nine patients with localized prostate cancer were accrued. Eligibility criteria included histologically confirmed adenocarcinoma, Karnofsky performance status ≥70, and no pelvic lymphadenopathy or distant metastases. The total dose to the prostate was 70.2 Gy in 20 patients and 73.8 Gy in 9 patients. Therapy was delivered using a 4-field technique with three-dimensional conformal planning. Amifostine was administered intrarectally as an aqueous solution 30 min before irradiation on the first 15 days of therapy. Amifostine was escalated in cohorts from 500 to 2500 mg. Proctoscopy was performed before therapy and at 9 months after completion. Most patients underwent repeat proctoscopy at 18 months. On Days 1 and 10 of radiotherapy, serum samples were collected for pharmacokinetic studies. The clinical symptoms (Radiation Therapy Oncology Group scale) and a proctoscopy score were assessed during follow-up. Results: All patients completed therapy with no amifostine-related toxicity at any dose level. The application was feasible and well tolerated. No substantial systemic absorption occurred. With a median follow-up of 26 months, 9 patients (33%) developed rectal bleeding (8 Grade 1, 1 Grade 2). At 9 months, 16 and 3 patients developed Grade 1 and Grade 2 telangiectasia, respectively. This was mostly confined to the anterior

  6. Amifostine use in radiation-induced kidney damage. Preclinical evaluation with scintigraphic and histopathologic parameters

    Energy Technology Data Exchange (ETDEWEB)

    Kaldir, M. [The Ministry of Health, Numune Hospital, Erzurum (Turkey); Cosar-Alas, R.; Yurut-Caloglu, V.; Saynak, M.; Caloglu, M.; Kocak, Z.; Tokatli, F.; Uzal, C. [Dept. of Radiation Oncology, Faculty of Medicine, Trakya Univ., Edirne (Turkey); Cermik, T.F. [Dept. of Nuclear Medicine, Faculty of Medicine, Trakya Univ., Edirne (Turkey); Altaner, S. [Dept. of Pathology, Faculty of Medicine, Trakya Univ., Edirne (Turkey); Tuere, M. [Dept. of Biostatistics, Faculty of Medicine, Trakya Univ., Edirne (Turkey); Parlar, S. [Dept. of Medical Radiophysics, Faculty of Medicine, Trakya Univ., Edirne (Turkey)

    2008-07-15

    Purpose: to assess the degree of protective effects of amifostine on kidney functions via semiquantitative static renal scintigraphy and histopathologic analysis. Material and methods: 30 female albino rats were divided into three equal groups as control (CL), radiotherapy alone (RT), and radiotherapy + amifostine (RT+AMI). The animals in the CL and RT groups were given phosphate-buffered saline, whereas the animals in the RT+AMI group received amifostine (200 mg/kg) by intraperitoneal injection 30 min before irradiation. RT and RT+AMI groups were irradiated with a single dose of 6 Gy using a {sup 60}Co unit at a source-skin distance of 80 cm to the whole right kidney. They were followed up for 6 months. CL, RT, and RT+AMI groups underwent static kidney scintigraphy at the beginning of the experiment and, again, on the day before sacrificing. Histopathologically, tubular atrophy and fibrosis of the kidney damage were evaluated. Results: after irradiation, the median value of right kidney function was 48% (44-49%) and 50.5% (49%-52%) in RT and RT+AMI groups, respectively (p = 0.0002). Grade 1 kidney fibrosis was observed to be 60% in the RT group, while it was only 30% in the RT+AMI group. Grade 2 kidney fibrosis was 30% and 0% in the RT and RT+AMI group, respectively. Grade 1 tubular atrophy was 70% and 50% in the RT and RT+AMI group, respectively. Grade 2 tubular atrophy effect was the same in both groups (10%). Conclusion: static kidney scintigraphy represents an objective and reproducible method to noninvasively investigate kidney function following irradiation. Amifostine produced a significant reduction in radiation-induced loss of renal function. (orig.)

  7. Pre-Treatment with Amifostine Protects against Cyclophosphamide-Induced Disruption of Taste in Mice

    OpenAIRE

    Nabanita Mukherjee; Carroll, Brittany L.; Spees, Jeffrey L.; Delay, Eugene R.

    2013-01-01

    Cyclophosphamide (CYP), a commonly prescribed chemotherapy drug, has multiple adverse side effects including alteration of taste. The effects on taste are a cause of concern for patients as changes in taste are often associated with loss of appetite, malnutrition, poor recovery and reduced quality of life. Amifostine is a cytoprotective agent that was previously shown to be effective in preventing chemotherapy-induced mucositis and nephrotoxicity. Here we determined its ability to protect aga...

  8. Effect of Dexrazoxane and Amifostine on the Vertebral Bone Quality of Doxorubicin Treated Male Rats

    OpenAIRE

    F Mwale; Marguier, G.; Ouellet, J.A; Petit, A.; Epure, L.M; Antoniou, J; Chalifour, L E

    2008-01-01

    Doxorubicin (DOX) is widely used in combination cocktails for treatment of childhood hematological cancers and solid tumors. A major factor limiting DOX usage is DOX-induced cardiotoxicity. However, it is not known whether protectants like dexrazoxane (DXR) and amifostine (AMF) can prevent DOX-mediated bone damage. The present study investigated whether administration of AMF alone or in combination with DXR would prevent any DOX-mediated bone damage. Male rat pups were treated with DOX, DXR, ...

  9. Amifostine Protection Against Mitomycin-induced Chromosomal Breakage in Fanconi Anaemia Lymphocytes

    OpenAIRE

    Lopes, Miriam T. P.; Salas, Carlos E.; Fernanda S. G. Kehdy; Camelo, Ricardo M.

    2008-01-01

    Fanconi anaemia (FA) is a rare genetic chromosomal instability syndrome caused by impairment of DNA repair and reactive oxygen species (ROS) imbalance. This disease is also related to bone marrow failure and cancer. Treatment of these complications with radiation and alkylating agents may enhance chromosomal breakage. We have evaluated the effect of amifostine (AMF) on basal and mitomycin C (MMC)-induced chromosomal breakage in FA blood cells using the micronucleus assay. The basal micronucle...

  10. Salivary gland protection by amifostine in high-dose radioiodine therapy of differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bohuslavizki, K.H.; Klutmann, S.; Bleckmann, C.; Mester, J.; Clausen, M. [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Dept. of Nuclear Medicine; Brenner, W.; Lassmann, S.; Henze, E. [Kiel Univ. (Germany). Clinic of Nuclear Medicine

    1999-02-01

    Quantitative salivary gland scintigraphy using 100 to 120 MBq Tc-99m-pertechnetate was performed in 17 patients with differentiated thyroid cancer prior to and 3 months after radioiodine treatment with 6 GBq I-131. Eight patients were treated with 500 mg/m{sup 2} amifostine prior to high-dose radioiodine treatment and compared retrospectively with 9 control patients. Xerostomia was graded according to WHO criteria. In 9 control patients high-dose radioiodine treatment significantly (p<0.01) reduced Tc-99m-pertechnetate uptake by 35.4{+-}22.0% and 31.7{+-}21.1% in parotid and submandibular glands, respectively. Of these 9 patients, 3 exhibited xerostomia Grade I (WHO). In contrast, in 8 amifostine-treated patients, there was no significant (p=0.878) decrease in parenchymal function following high-dose radioiodine treatment, and xerostomia did not occur in any of them. (orig.) [Deutsch] Im Rahmen eines Heilversuchs wurde eine limitierte Anzahl von Patienten untersucht. Vor und drei Monate nach Gabe von 6 GBq I-131 wurde eine quantitative Speicheldruesenszintigraphie mit 100 bis 120 MBq Tc-99m-Pertechnetat an 17 Patienten mit differenzierten Schilddruesenkarzinomen durchgefuehrt. Acht Patienten erhielten vor Radiojodtherapie 500 mg/m{sup 2} Amifostin und wurden mit einer historischen Kontrollgruppe aus neun Patienten verglichen. Eine Xerostomie wurde nach WHO-Kriterien beurteilt. Die Patienten der Kontrollgruppe wiesen sowohl fuer die Glandulae parotides als auch fuer die Glandulae submandibulares eine signifikante Verminderung der Tc-99m-Pertechnetat-Aufnahme um 35,4{+-}22,0% bzw. 31,7{+-}21,1% als Zeichen einer Parenchymschaedigung auf. Bei drei dieser neuen Patienten fand sich eine Xerostomie Grad I (WHO). Im Gegensatz dazu konnte bei den mit Amifostin behandelten Patienten keine signifikante Verminderung der Parechymfunktion festgestellt werden (p=0,878). Dementsprechend wies keiner dieser Patienten eine Xerostomie auf. (orig.)

  11. WR-1065, the Active Metabolite of Amifostine, Mitigates Radiation-Induced Delayed Genomic Instability

    OpenAIRE

    Dziegielewski, Jaroslaw; Janet E. Baulch; Goetz, Wilfried; Coleman, Mitchell C.; Douglas R Spitz; Murley, Jeffrey S.; David J Grdina; Morgan, William F.

    2008-01-01

    Compounds that can protect cells from the effects of radiation are important for clinical use, in the event of an accidental or terrorist-generated radiation event, and for astronauts traveling in space. One of the major concerns regarding the use of radio-protective agents is that they may protect cells initially, but predispose surviving cells to increased genomic instability later. In this study we used WR-1065, the active metabolite of amifostine, to determine how protection from direct e...

  12. Use of amifostine in the treatment of recurrent solid tumours in children

    OpenAIRE

    Sidi, V; Arsos, G; Papakonstantinou, E; Hatzipantelis, E; Fragandrea, I; N. Gombakis; Koliouskas, E

    2007-01-01

    Preclinical and clinical evaluation of amifostine (AMI) administration in conjunction with systemic chemotherapy supports its role as a cytoprotective agent of normal tissues without loss of impairing the antitumour effectiveness of chemotherapeutic agents. Since only a limited number of clinical studies has been performed using AMI in paediatric pts with malignancies we investigated the protective effect of AMI against carboplatin-induced myelotoxicity and nephrotoxicity in a paediatric grou...

  13. Prophylactic Administration of Amifostine Protects Vessel Thickness in the Setting of Irradiated Bone

    OpenAIRE

    Page, Erin E.; Deshpande, Sagar S.; Nelson, Noah S.; Felice, Peter A.; Donneys, Alexis; Rodriguez, Jose J.; Deshpande, Samir S.; Buchman, Steven R.

    2014-01-01

    Although often beneficial in the treatment of head and neck cancer (HNC), radiation therapy (XRT) leads to the depletion of vascular supply and eventually decreased perfusion of the tissue. Specifically, previous studies have demonstrated the depletion of vessel volume fraction (VVF) and vessel thickness (VT) associated with XRT. Amifostine (AMF) provides protection from the detrimental effects of radiation damage, allowing for reliable post-irradiation fracture healing in the murine mandible...

  14. Radioiodine-induced kidney damage and protective effect of amifostine: An experimental study

    OpenAIRE

    Aktoz, T; Durmus-Altun, G; Usta, U; Torun, N; Ergulen, A; Atakan, I H

    2012-01-01

    Background: Ablative radioiodine-131 (131I) therapy is used in the standart treatment procedure of thyroid carcinoma and procedures using 131I represent the majority of Nuclear Medicine therapeutic procedures. The principal route of 131I excretion after the administration of 131I is the urine. Amifostine is an organic thiophosphate ester prodrug and the kidney concentrations of the active metabolite WR-1065 are about 100 times higher than tumour concentrations. To our knowledge, there is no p...

  15. Comparison of uroprotective efficacy of mesna and amifostine in Cyclophosphamide- induced hemorrhagic cystitis in rats

    OpenAIRE

    Kanat Ozkan; Kurt E; Yalcinkaya U; Evrensel T; Manavoglu O

    2006-01-01

    Background:Hemorrhagic cystitis (HC) is a dose limiting side effect of cyclophosphamide (CYP). AIM: In this study, we aimed to investigate the role of amifostine in the protection of CYP-induced HC and compare its efficacy with mesna. SETTING AND DESIGN: This animal study was conducted in the Experimental Animals Breeding and Research Center of the Medical Faculty of Uludag University. MATERIALS AND METHODS: Male Wistar rats (150-200 g; 10 rats per group) were randomly assigned to four ...

  16. Amifostin in subkutaner Anwendung bei Patienten mit Kopf-Hals-Tumoren

    OpenAIRE

    Wilder, Daniel

    2006-01-01

    Hintergrund: Amifostin (Ethyol®), ein phosphorylierter Aminothioalkohol mit der chemischen Bezeichnung S-2[3-aminopropylamino]-ethyl-thiophosphorsäure, ist eine Substanz mit einem breiten zytoprotektiven Spektrum für die radio- und chemotherapeutisch induzierten Nebenwirkungen. Die Substanz fungiert dabei im Sinne einer Prodrug. Daraus wird, in Abhängigkeit von der alkalischen Phosphatase, der dephosphorylierte aktive Metaboliten WR-1065 gebildet. Dieser ist für die protektiven Wirkungen ...

  17. Does Amifostine Reduce Metabolic Rate? Effect of the Drug on Gas Exchange and Acute Ventilatory Hypoxic Response in Humans

    Directory of Open Access Journals (Sweden)

    Jaideep J. Pandit

    2015-04-01

    Full Text Available Amifostine is added to chemoradiation regimens in the treatment of many cancers on the basis that, by reducing the metabolic rate, it protects normal cells from toxic effects of therapy. We tested this hypothesis by measuring the metabolic rate (by gas exchange over 255 min in 6 healthy subjects, at two doses (500 mg and 1000 mg of amifostine infused over 15 min at the start of the protocol. We also assessed the ventilatory response to six 1 min exposures to isocapnic hypoxia mid-protocol. There was no change in metabolic rate with amifostine as measured by oxygen uptake (p = 0.113. However in carbon dioxide output and respiratory quotient, we detected a small decline over time in control and drug protocols, consistent with a gradual change from carbohydrate to fat metabolism over the course of the relatively long study protocol. A novel result was that amifostine (1000 mg increased the mean ± SD acute hypoxic ventilatory response from 12.4 ± 5.1 L/min to 20.3 ± 11.9 L/min (p = 0.045. In conclusion, any cellular protective effects of amifostine are unlikely due to metabolic effects. The stimulatory effect on hypoxic ventilatory responses may be due to increased levels of hypoxia inducible factor, either peripherally in the carotid body, or centrally in the brain.

  18. Two New Faces of Amifostine: Protector from DNA Damage in Normal Cells and Inhibitor of DNA Repair in Cancer Cells.

    Science.gov (United States)

    Hofer, Michal; Falk, Martin; Komůrková, Denisa; Falková, Iva; Bačíková, Alena; Klejdus, Bořivoj; Pagáčová, Eva; Štefančíková, Lenka; Weiterová, Lenka; Angelis, Karel J; Kozubek, Stanislav; Dušek, Ladislav; Galbavý, Štefan

    2016-04-14

    Amifostine protects normal cells from DNA damage induction by ionizing radiation or chemotherapeutics, whereas cancer cells typically remain uninfluenced. While confirming this phenomenon, we have revealed by comet assay and currently the most sensitive method of DNA double strand break (DSB) quantification (based on γH2AX/53BP1 high-resolution immunofluorescence microscopy) that amifostine treatment supports DSB repair in γ-irradiated normal NHDF fibroblasts but alters it in MCF7 carcinoma cells. These effects follow from the significantly lower activity of alkaline phosphatase measured in MCF7 cells and their supernatants as compared with NHDF fibroblasts. Liquid chromatography-mass spectrometry confirmed that the amifostine conversion to WR-1065 was significantly more intensive in normal NHDF cells than in tumor MCF cells. In conclusion, due to common differences between normal and cancer cells in their abilities to convert amifostine to its active metabolite WR-1065, amifostine may not only protect in multiple ways normal cells from radiation-induced DNA damage but also make cancer cells suffer from DSB repair alteration. PMID:26978566

  19. Does amifostine reduce metabolic rate? Effect of the drug on gas exchange and acute ventilatory hypoxic response in humans.

    Science.gov (United States)

    Pandit, Jaideep J; Allen, Caroline; Little, Evelyn; Formenti, Federico; Harris, Adrian L; Robbins, Peter A

    2015-01-01

    Amifostine is added to chemoradiation regimens in the treatment of many cancers on the basis that, by reducing the metabolic rate, it protects normal cells from toxic effects of therapy. We tested this hypothesis by measuring the metabolic rate (by gas exchange) over 255 min in 6 healthy subjects, at two doses (500 mg and 1000 mg) of amifostine infused over 15 min at the start of the protocol. We also assessed the ventilatory response to six 1 min exposures to isocapnic hypoxia mid-protocol. There was no change in metabolic rate with amifostine as measured by oxygen uptake (p = 0.113). However in carbon dioxide output and respiratory quotient, we detected a small decline over time in control and drug protocols, consistent with a gradual change from carbohydrate to fat metabolism over the course of the relatively long study protocol. A novel result was that amifostine (1000 mg) increased the mean ± SD acute hypoxic ventilatory response from 12.4 ± 5.1 L/min to 20.3 ± 11.9 L/min (p = 0.045). In conclusion, any cellular protective effects of amifostine are unlikely due to metabolic effects. The stimulatory effect on hypoxic ventilatory responses may be due to increased levels of hypoxia inducible factor, either peripherally in the carotid body, or centrally in the brain. PMID:25894815

  20. Randomized phase II exploratory study of prophylactic amifostine in cancer patients who receive radical radiotherapy to the pelvis

    Directory of Open Access Journals (Sweden)

    Karavasilis Vasileios

    2010-06-01

    Full Text Available Abstract Background This study aimed to investigate the efficacy of prophylactic amifostine in reducing the risk of severe radiation colitis in cancer patients receiving radical radiotherapy to the pelvis. Methods Patients with pelvic tumours referred for radical radiotherapy who consented participation in this trial, were randomly assigned to receive daily amifostine (A (subcutaneously, 500 mg flat dose before radiotherapy or radiotherapy alone (R. Sigmoidoscopy and blinded biopsies were scheduled to conduct prior to initiation and following completion of radiotherapy and again 6 to 9 months later. Radiation colitis was assessed by clinical, endoscopic and histolopathological criteria. Results A total 44 patients were enrolled in this trial, the majority with rectal (20 patients and cervical cancer (12 patients and were assigned 23 in R arm and 21 in the A arm. In total 119 sigmoidoscopies were performed and 18 patients (18/44, 40.9% were diagnosed with radiation colitis (15 grade 1 and 2, and 3 grade 3 and 4. Of them, 6 patients belonged to the A group (6/21, 28.6% and 12 to the R group (12/23, 52.2%. Acute and grade IV radiation colitis was only developed in four patients (17.4% in the R group. Amifostine side effects were mild. Amifostine treated patients were less likely to develop histologically detectable mucosal lesions, which indicate protection from acute mucosal injury. Conclusions Amifostine given subcutaneously can lower the risk of acute severe radiation colitis in patients who receive radical radiotherapy to pelvic tumors.

  1. Postmastectomy Hypofractionated and Accelerated Radiation Therapy With (and Without) Subcutaneous Amifostine Cytoprotection

    Energy Technology Data Exchange (ETDEWEB)

    Koukourakis, Michael I., E-mail: targ@her.forthnet.gr [Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis (Greece); Panteliadou, Marianthi; Abatzoglou, Ioannis M.; Sismanidou, Kyriaki [Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis (Greece); Sivridis, Efthimios; Giatromanolaki, Alexandra [Department of Pathology, Democritus University of Thrace, Alexandroupolis (Greece)

    2013-01-01

    Purpose: Postmastectomy radiation therapy (PMRT) provides major local control and survival benefits. More aggressive radiation therapy schemes may, however, be necessary in specific subgroups, provided they are safely administered. We report the tolerance and efficacy of a highly accelerated and hypofractionated regimen (HypoARC). Methods and Materials: One hundred twelve high-risk patients who had undergone mastectomy received 10 consecutive fractions of 3.5 Gy in 12 days (thoracic wall and axillary/supraclavicular areas). Two consecutive additional fractions of 4 Gy were given to the surgical scar area (electrons 8-10 MeV) and 1 3.5-Gy fraction to the axilla (in cases with extensive nodal involvement). A minimum follow-up of 24 months (median, 44 months) was allowed before analysis. Of 112 patients, 21 (18.7%) refused to receive amifostine, the remaining receiving tolerance-based individualized doses (500-1000 mg/day subcutaneously). Results: By use of a dose individualization algorithm, 68.1%, 11%, and 18.7% of patients received 1000 mg, 750 mg, and 500 mg/day of amifostine. Patchy moist skin desquamation outside and inside the booster fields was noted in 14 of 112 (12.5%) and 26 of 112 (23.2%) patients, respectively. No case of acute pneumonitis was recorded. High amifostine dose offered a significant skin protection. Within a median follow-up time of 44 months, moderate subcutaneous edema outside and within the booster thoracic area was noted in 5 of 112 (4.4%) and 8 of 112 (7.1%) cases, respectively. Intense asymptomatic radiographic findings of in field lung fibrosis were noted in 4 of 112 (3.6%) patients. Amifostine showed a significant protection against lung and soft tissue fibrosis. A 97% projected 5-year local relapse free survival and 84% 5-year disease-specific survival were recorded. Lack of steroid receptor expression, simple human epidermal growth factor 2 positivity, or triple negative phenotype defined higher metastasis rates but had no effect on

  2. Daily amifostine given concomitantly to chemoradiation in head and neck cancer. A pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Trog, D.; Bank, P.; Wendt, T.G. [Friedrich-Schiller Univ., Jena (Germany). Dept. of Radiation Oncology; Koscielny, S.; Beleites, E. [Friedrich-Schiller Univ., Jena (Germany). Dept. of Ear Nose Throat Diseases

    1999-09-01

    Background: In patients with loco-regionally advanced head and neck cancer conventionally fractionated radiotherapy alone results in poor loco-regional control and survival rates. Treatment intensification by simultaneous administration of cytotoxic drugs produces higher acute morbidity. Therefore chemical radioprotection of normal tissues may be of clinical benefit. Patients and Methods: In a pilot study patients with advanced nonresectable head neck cancer treated with conventionally fractionated radical radiotherapy (60 to 66 Gy total doses) and concomitantly given 5-fluorouracil as protracted venous infusion, 250 mg/sqm/24 h over the entire treatment period were given amifostine 300 mg absolutely before each fraction. Acute treatment related mobidity was scored according to CTC classification and loco-regional control and survival rates were estimated. Comparison was made with a historical control group of identical chemoradiation but without amifostine application. Results: Chemoradiation induced oral mucositis was delayed and showed significant lower degrees at all 10 Gy increments (p<0.05) except 60 Gy and over (p>0.05). No significant toxicity was recorded with respect to blood pressure, serum calcium, potassium, hematologic parameters, emesis, nausea or body weight loss. Progression free survival and overall survival probability at 2 years were not statistically different in both cohorts. Conclusion: Amifostine given before each fraction of radiotherapy over 6 weeks has no cumulative toxicity, was well tolerated and may reduce treatment induced oral mucositis. No tumor protective effect was observed. (orig.) [German] Hintergrund: Bei Patienten mit lokoregionaer fortgeschrittenen Karzinomen im Kopf-Hals-Bereich fuehrt die alleinige konventionell fraktionierte Radiotherapie zu unuenstigen lokoregionaeren Tumorkontrollraten und Ueberlebensraten. Die Therapieintensivierung durch simultane Radiochemotherapie fuehrt zu gesteigerter Akutmorbiditaet. Die chemische

  3. Amifostine ameliorates recognition memory defect in acute radiation syndrome caused by relatively low-dose of gamma radiation

    Science.gov (United States)

    Lee, Hae-June; Kim, Joong-Sun; Song, Myoung-Sub; Seo, Heung-Sik; Yang, Miyoung; Kim, Jong Choon; Jo, Sung-Kee; Shin, Taekyun

    2010-01-01

    This study examined whether amifostine (WR-2721) could attenuate memory impairment and suppress hippocampal neurogenesis in adult mice with the relatively low-dose exposure of acute radiation syndrome (ARS). These were assessed using object recognition memory test, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunohistochemical markers of neurogenesis [Ki-67 and doublecortin (DCX)]. Amifostine treatment (214 mg/kg, i.p.) prior to irradiation significantly attenuated the recognition memory defect in ARS, and markedly blocked the apoptotic death and decrease of Ki-67- and DCX-positive cells in ARS. Therefore, amifostine may attenuate recognition memory defect in a relatively low-dose exposure of ARS in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis. PMID:20195069

  4. Results of definitive combined radio-chemotherapy in head and neck tumors with simultaneous salivary gland protection by amifostine administration; Ergebnisse der primaeren kombinierten Radiochemotherapie von Kopf-Hals-Tumoren mit simultaner Speicheldruesenprotektion durch Amifostin

    Energy Technology Data Exchange (ETDEWEB)

    Schultze, J.; Kimmig, B. [Kiel Univ. (Germany). Klinik fuer Strahlentherapie

    1999-11-01

    Aim: Demonstration and critical evaluation of the use of cytoprotective agents in radiation therapy. Patients and methods: In 1996 9 patients with head and neck tumors were irradiated with a mean dose of 66 Gy and simultaneous application of amifostine. Primaries were in the oropharynx (3), tongue (2), tonsilla (2) as well as nasopharynx and soft palate. Parallel carboplatinum was administered 6 times with a dose of 100 mg/week and amifostine twice a week with 500 mg over 6 weeks. The evaluation was performed clinically and by sialoscintigraphy. Results: There were no lasting side effects, but episodes of hypotension in 7 to 9 patients and nausea. Radiogenic acute toxicity was nearly uneffected, complaints from xerostomia, however, were diminished. All patients showed increased dermal pigmentation and dermatitis. Sialoscintigraphies 6 months after therapy proved better salivary gland function with correlated better patient condition. Conclusion: Amifostine might gain a role in the prevention of lasting radiogenic xerostomia. The required dose is not yet clear. A broader use of amifostine would be favored by lower costs of the substance. (orig.) [German] Ziel: Es soll der Einsatz zytoprotektiver Substanzen in der Strahlentherapie vorgestellt und kritisch bewertet werden. Patienten und Methoden: Im Jahre 1996 wurde bei neun Patienten eine Strahlentherapie im Kopf-Hals-Bereich bis median 66 Gy Gesamtdosis mit gleichzeitiger Applikation von Amifostin durchgefuehrt. Zugrundeliegende Erkrankungen waren Oropharynxkarzinome (3), Zungengrund- und -randkarzinome (2), Tonsillenkarzinome (2) sowie ein Nasopharynx- und ein Gaumenbogenkarzinom. Parallel wurde sechsmal eine Carboplat-Applikation mit je 100 mg einmal pro Woche durchgefuehrt. Amifostin wurde in einer Dosis von 2mal 50 mg/Woche ueber sechs Wochen appliziert. Die Evaluation erfolgte klinisch sowie unter Hinzuziehung der quantitativen Speicheldruesenszintigraphie. Ergebnisse: Andauernde Nebenwirkungen durch die

  5. Randomized phase III trial of postoperative radiochemotherapy ± amifostine in head and neck cancer. Is there evidence for radioprotection?

    International Nuclear Information System (INIS)

    Purpose: Experimental and clincial data suggest a reduction of radiation-induced acute toxicity by amifostine (A). We investigated this issue in a randomized trial comparing radiochemotherapy (RT + CT) versus radiochemotherapy plus amifostine (RC + CT + A) in patients with head and neck cancer. Patients and Methods: 56 patients with oro-/hypopharynx or larynx cancer (T1-2 N1-2 G3, T3-4 N0-2 G1-3) were randomized to received RC + CT alone or RC + CT + A. Patients were irradiated up to 60 Gy (R0) or 70 Gy (R1/2) and received chemotherapy (70 mg/m2 carboplatin, day 1-5 week 1 and 5 of radiotherapy). 250 mg amifostine were applied daily before each radiotherapy session. Acute toxicity was evaluated according to the common toxicity criteria (CTC). As for acute xerostomia, patients with laryngeal cancer were excluded from evaluation. Results: 50 patients were evaluable (25 patients in the RC + CT, 25 patients in the RC + CT + A group). Clinical characteristics were well balanced in both treatment groups. Amifostine provided reduction in acute xerostomia and mucositis but had no obvious influence on Karnofsky performance status, body weight, cutaneous side effects, and alopecia. The differences between both groups were statistically significant for acute xerostomia and nonsignificant, but with a trend for mucositis. Conclusions: According to our results, there is a radioprotective effect on salivary glands and a potential effect on oral mucosa by amifostine in postoperative radiotherapy combined with carboplatin. To improve the radio- and chemoprotective effects of amifostine in clinical practice, the application of a higher dose (> 250 mg) seems to be necessary. (orig.)

  6. Raman spectroscopy delineates radiation-induced injury and partial rescue by amifostine in bone: a murine mandibular model.

    Science.gov (United States)

    Felice, Peter A; Gong, Bo; Ahsan, Salman; Deshpande, Sagar S; Nelson, Noah S; Donneys, Alexis; Tchanque-Fossuo, Catherine; Morris, Michael D; Buchman, Steven R

    2015-05-01

    Despite its therapeutic role in head and neck cancer, radiation administration degrades the biomechanical properties of bone and can lead to pathologic fracture and osteoradionecrosis. Our laboratories have previously demonstrated that prophylactic amifostine administration preserves the biomechanical properties of irradiated bone and that Raman spectroscopy accurately evaluates bone composition ex vivo. As such, we hypothesize that Raman spectroscopy can offer insight into the temporal and mechanical effects of both irradiation and amifostine administration on bone to potentially predict and even prevent radiation-induced injury. Male Sprague-Dawley rats (350-400 g) were randomized into control, radiation exposure (XRT), and amifostine pre-treatment/radiation exposure groups (AMF-XRT). Irradiated animals received fractionated 70 Gy radiation to the left hemi-mandible, while AMF-XRT animals received amifostine just prior to radiation. Hemi-mandibles were harvested at 18 weeks after radiation, analyzed via Raman spectroscopy, and compared with specimens previously harvested at 8 weeks after radiation. Mineral (ρ958) and collagen (ρ1665) depolarization ratios were significantly lower in XRT specimens than in AMF-XRT and control specimens at both 8 and 18 weeks. amifostine administration resulted in a full return of mineral and collagen depolarization ratios to normal levels at 18 weeks. Raman spectroscopy demonstrates radiation-induced damage to the chemical composition and ultrastructure of bone while amifostine prophylaxis results in a recovery towards normal, native mineral and collagen composition and orientation. These findings have the potential to impact on clinical evaluations and interventions by preventing or detecting radiation-induced injury in patients requiring radiotherapy as part of a treatment regimen. PMID:25319554

  7. Randomized phase III trial of postoperative radiochemotherapy {+-} amifostine in head and neck cancer. Is there evidence for radioprotection?

    Energy Technology Data Exchange (ETDEWEB)

    Vacha, P.; Fehlauer, F.; Mahlmann, B.; Marx, M.; Richter, E. [Dept. of Radiation Oncology and Nuclear Medicine, Univ. of Luebeck (Germany); Hinke, A. [WiSP Research Inst., Langenfeld (Germany); Sommer, K. [Dept. of Head and Neck Surgery, Univ. of Luebeck (Germany); Feyerabend, T. [Practice for Radiation Therapy Bonn-Rhein-Sieg, Bonn (Germany)

    2003-06-01

    Purpose: Experimental and clincial data suggest a reduction of radiation-induced acute toxicity by amifostine (A). We investigated this issue in a randomized trial comparing radiochemotherapy (RT + CT) versus radiochemotherapy plus amifostine (RC + CT + A) in patients with head and neck cancer. Patients and Methods: 56 patients with oro-/hypopharynx or larynx cancer (T1-2 N1-2 G3, T3-4 N0-2 G1-3) were randomized to received RC + CT alone or RC + CT + A. Patients were irradiated up to 60 Gy (R0) or 70 Gy (R1/2) and received chemotherapy (70 mg/m{sup 2} carboplatin, day 1-5 week 1 and 5 of radiotherapy). 250 mg amifostine were applied daily before each radiotherapy session. Acute toxicity was evaluated according to the common toxicity criteria (CTC). As for acute xerostomia, patients with laryngeal cancer were excluded from evaluation. Results: 50 patients were evaluable (25 patients in the RC + CT, 25 patients in the RC + CT + A group). Clinical characteristics were well balanced in both treatment groups. Amifostine provided reduction in acute xerostomia and mucositis but had no obvious influence on Karnofsky performance status, body weight, cutaneous side effects, and alopecia. The differences between both groups were statistically significant for acute xerostomia and nonsignificant, but with a trend for mucositis. Conclusions: According to our results, there is a radioprotective effect on salivary glands and a potential effect on oral mucosa by amifostine in postoperative radiotherapy combined with carboplatin. To improve the radio- and chemoprotective effects of amifostine in clinical practice, the application of a higher dose (> 250 mg) seems to be necessary. (orig.)

  8. A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplanation

    OpenAIRE

    Hartmann, J T; Vangerow, A von; Fels, L M; Knop, S.; Stolte, H.; Kanz, L; Bokemeyer, C

    2001-01-01

    This pilot study evaluates the degree of side effects during high-dose chemotherapy (HD-VIC) plus autologous bone marrow transplant (HDCT) and its possible prevention by the cytoprotective thiol-derivate amifostine. Additionally, the in-patient medical costs of both treatment arms were compared. 40 patients with solid tumours were randomized to receive HD-VIC chemotherapy with or without amifostine (910 mg/m2 at day 1–3) given as a short infusion prior to carboplatin and ifosfamide. Patients ...

  9. Does Amifostine Reduce Metabolic Rate? Effect of the Drug on Gas Exchange and Acute Ventilatory Hypoxic Response in Humans

    OpenAIRE

    Jaideep J. Pandit; Caroline Allen; Evelyn Little; Federico Formenti; Harris, Adrian L.; Robbins, Peter A.

    2015-01-01

    Amifostine is added to chemoradiation regimens in the treatment of many cancers on the basis that, by reducing the metabolic rate, it protects normal cells from toxic effects of therapy. We tested this hypothesis by measuring the metabolic rate (by gas exchange) over 255 min in 6 healthy subjects, at two doses (500 mg and 1000 mg) of amifostine infused over 15 min at the start of the protocol. We also assessed the ventilatory response to six 1 min exposures to isocapnic hypoxia mid-protocol. ...

  10. The histopathological comparison of L-carnitine with amifostine for protective efficacy on radiation-induced acute small intestinal toxicity

    OpenAIRE

    Murat Caloglu; Vuslat Yurut Caloglu; Tulin Yalta; Omer Yalcin; Cem Uzal

    2012-01-01

    Background: The aim of the study was to compare the protective efficacy of l-carnitine (LC) to amifostine on radiation-induced acute small intestine damage. Materials and Methods: Thirty, 4-week-old Wistar albino rats were randomly assigned to four groups - Group 1: control (CONT, n = 6), Group 2: irradiation alone (RT, n = 8), Group 3: amifostine plus irradiation (AMI+RT, n = 8), and Group 4: l-Carnitine plus irradiation (LC+RT, n = 8). The rats in all groups were irradiated individually...

  11. L-Carnitine Protection Against Cisplatin Nephrotoxicity In Rats: Comparison with Amifostin Using Quantitative Renal Tc 99m DMSA Uptake

    OpenAIRE

    Yakup Yürekli; Perihan Ünak; Çiğdem Yenisey; Türkan Ertay; Fazilet Zumrut Biber Müftüler; Emin İlker Medine

    2011-01-01

    Objective: In this study, we aimed to investigate the cytoprotective effect of L-carnitine against cisplatin-induced nephrotoxicity and to compare its efficacy with that of amifostin by quantitative renal Tc 99m DMSA uptake. Material and Methods: Male Wistar rats were randomly divided into six groups of six animals each. 1) Control (saline; 5 ml/kg intraperitoneally); 2) L-carnitine (CAR; 300 mg/kg intraperitoneally); 3) Amifostine (AMI; 200 mg /kg intraperitoneally); 4) Cisplatin (CIS;7 mg/k...

  12. Analgesic and anti-inflammatory activity of amifostine, DRDE-07, and their analogs, in mice

    OpenAIRE

    Bhutia Yangchen; Vijayaraghavan Rajagopalan; Pathak Uma

    2010-01-01

    Objectives : To find out the analgesic and anti-inflammatory activity, if any, of Amifostine [S-2(3 amino propyl amino) ethyl phosphorothioate], DRDE-07 [S-2(3 amino ethyl amino) ethyl phenyl sulphide] and their analogs DRDE-30 and DRDE-35, the probable prophylactic agent for sulphur mustard (SM). Materials and Methods : In order to find out the analgesic activities of the compounds two methods were employed, namely, acetic acid-induced writhing test and formalin-induced paw licking. The pe...

  13. Effects of insulin-like growth factor-1 (IGF-1) and amifostine in spinal cord reirradiation

    Energy Technology Data Exchange (ETDEWEB)

    Nieder, C.; Andratschke, N. [TU Muenchen (Germany). Dept. of Radiation Oncology; Price, R.E.; Rivera, B. [University of Texas M.D. Anderson Cancer Center, Houston, TX (United States). Dept. of Veterinary Medicine and Surgery; Ang, K. Kian [University of Texas M.D. Anderson Cancer Center, Houston, TX (United States). Dept. of Radiation Oncology

    2005-11-01

    Purpose: To test whether insulin-like growth factor-1 (IGF-1) and amifostine modulate the reirradiation tolerance of rat cervical spinal cord. Initial experiments by the authors' group suggested that administration of each agent alone significantly increased the median latent time to radiation myelopathy (RM) in previously unirradiated animals but did not change the dose-response relationship. Because of different modes of action, a follow-up study was undertaken to test the combined treatment. Material and Methods: The cervical spinal cord of 51 adult Fisher F-344 rats received a single fraction of 16 Gy, which corresponds to approximately 75% of the median paresis dose (ED{sub 50}), followed 5 months later by a second radiation dose, which ranged from 17 to 21 Gy. The study animals received a single intrathecal injection of 0.3 mg amifostine into the cisterna magna 30-60 min before reirradiation plus three subcutaneous doses of IGF-1 (700 {mu}g) starting from 24 h before to 24 h after reirradiation. Control animals received saline injections via the same routes. Animals were followed until RM developed or until 12 months from reirradiation. Histopathologic examinations were performed post mortem. Results: No animals showed any neurologic abnormalities before reirradiation. RM occurred in controls versus treated rats after a mean latency of 218 versus 314 days (19 Gy; p=0.11) and 104 versus 186 days (21 Gy; p=0.002) from second dose (Figure 1). ED{sub 50} was 18.2 versus 19.4 Gy (p=0.15; Figure 2). Treatment with IGF-1 and amifostine did not significantly influence the rates of tumor induction or intercurrent death. Conclusion: IGF-1 and amifostine significantly reduced RM rates after 21 Gy. The shift of the dose-response curve suggests an increase of the ED{sub 50} for single-dose treatment by approximately 7%. Thus, brief therapeutic intervention might slightly decrease radiation-induced neurotoxicity in a retreatment situation. (orig.)

  14. Radioprotective effects of ginsan and amifostine (WR-2721) against {gamma}-ray induction of micronuclei in mice bone marrow erythroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Ivanova, Tatiana; Song, Jie Young; Han, Young Soo; Jung, In Sung; Yun, Yeon Sook [KIRAMS, Seoul (Korea, Republic of)

    2004-07-01

    It is common knowledge that the use of combinations of agents is a promising approach for maximizing radioprotection with minimal adverse effects. So it has been known that amifostine has powerful protective action against irradiation. However, its toxicity has limited its application in medicine or in hazardous radiation environments.

  15. Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: An FTIR microspectroscopic imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Cakmak G.; Miller L.; Zorlu, F.; Severcan, F.

    2012-03-03

    Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH{sub 2} groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH{sub 3} groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems.

  16. Does amifostine have radioprotective effects on salivary glands in high-dose radioactive iodine-treated differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Chao; Wang, Guoming; Zuo, Shuyao [Qingdao University, Department of Nuclear Medicine, Affiliated Hospital, Medical College, Qingdao, Shandong Province (China); Xie, Jiawei [Qingdao University, Medical College, Qingdao (China); Jiang, Zhongxin [Qingdao University, Affiliated Hospital, Medical College, Qingdao (China)

    2010-09-15

    To assess the effects of amifostine on salivary glands in radioactive iodine-treated differentiated thyroid cancer. We searched the MEDLINE, EMBASE and the Cochrane Library for randomized controlled clinical trials which compared the effects of amifostine with those of placebo or acid-stimulating agents. Two randomized controlled clinical trials with a total of 130 patients were included. Both studies had a low risk of bias. There were no statistically significant differences between the effects of amifostine and acid-stimulating agents on the incidence of xerostomia (RR 0.24, 95% CI 0.01 to 9.52), the decrease of scintigraphically measured uptake of {sup 99m}Tc by the parotid (RR 0.30, 95% CI -2.28 to 2.88) or submandibular glands (RR 1.90, 95% CI -1.46 to 5.26) at 12 months, or the reduction in blood pressure (RR 5.00, 95% CI 0.25 to 99.16). Neither of the included trials investigated death from any cause, morbidity, health-related quality of life or costs. The results of two randomized controlled clinical trials suggest that amifostine has no significant radioprotective effects on salivary glands in radioactive iodine treatment of differentiated thyroid cancer. The use of acid-stimulating agents to increase salivation should remain the first choice during radioactive iodine treatment of differentiated thyroid cancer. Patients should also be well informed of the importance of hydration and acid stimulation. (orig.)

  17. The histopathological comparison of L-carnitine with amifostine for protective efficacy on radiation-induced acute small intestinal toxicity

    Directory of Open Access Journals (Sweden)

    Murat Caloglu

    2012-01-01

    Full Text Available Background: The aim of the study was to compare the protective efficacy of l-carnitine (LC to amifostine on radiation-induced acute small intestine damage. Materials and Methods: Thirty, 4-week-old Wistar albino rats were randomly assigned to four groups - Group 1: control (CONT, n = 6, Group 2: irradiation alone (RT, n = 8, Group 3: amifostine plus irradiation (AMI+RT, n = 8, and Group 4: l-Carnitine plus irradiation (LC+RT, n = 8. The rats in all groups were irradiated individually with a single dose of 20 Gy to the total abdomen, except those in CONT. LC (300 mg/kg or amifostine (200 mg/kg was used 30 min before irradiation. Histopathological analysis of small intestine was carried out after euthanasia. Results: Pretreatment with amifostine reduced the radiation-induced acute degenerative damage (P = 0.009 compared to the RT group. Pretreatment with LC did not obtain any significant difference compared to the RT group. The vascular damage significantly reduced in both of the AMI+RT (P = 0.003 and LC+RT group (P = 0.029 compared to the RT group. The overall damage score was significantly lower in the AMI+RT group than the RT group (P = 0.009. There was not any significant difference between the LC+RT and RT group. Conclusions: Amifostine has a marked radioprotective effect against all histopathological changes on small intestinal tissue while LC has limited effects which are mainly on vascular structure.

  18. Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate

    International Nuclear Information System (INIS)

    In peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues, the kidneys are the major dose-limiting organs, because of tubular reabsorption and retention of radioactivity. Preventing renal uptake or toxicity will allow for higher tumour radiation doses. We tested the cytoprotective drug amifostine, which selectively protects healthy tissue during chemo- and radiotherapy, for its renoprotective capacities after PRRT with high-dose [177Lu-DOTA0,Tyr3]octreotate. Male Lewis rats were injected with 278 or 555 MBq [177Lu-DOTA0,Tyr3]octreotate to create renal damage and were followed up for 130 days. For renoprotection, rats received either amifostine or co-injection with lysine. Kidneys, blood and urine were collected for toxicity measurements. At 130 days after PRRT, a single-photon emission computed tomography (SPECT) scan was performed to quantify tubular uptake of 99mTc-dimercaptosuccinic acid (DMSA), a measure of tubular function. Treatment with 555 MBq [177Lu-DOTA0,Tyr3]octreotate resulted in body weight loss, elevated creatinine and proteinuria. Amifostine and lysine treatment significantly prevented this rise in creatinine and the level of proteinuria, but did not improve the histological damage. In contrast, after 278 MBq [177Lu-DOTA0,Tyr3]octreotate, creatinine values were slightly, but not significantly, elevated compared with the control rats. Proteinuria and histological damage were different from controls and were significantly improved by amifostine treatment. Quantification of 99mTc-DMSA SPECT scintigrams at 130 days after [177Lu-DOTA0,Tyr3]octreotate therapy correlated well with 1/creatinine (r 2 = 0.772, p 177Lu-DOTA0,Tyr3]octreotate. Besides lysine, amifostine might be used in clinical PRRT as well as to maximise anti-tumour efficacy. (orig.)

  19. Analgesic and anti-inflammatory activity of amifostine, DRDE-07, and their analogs, in mice

    Directory of Open Access Journals (Sweden)

    Bhutia Yangchen

    2010-01-01

    Full Text Available Objectives : To find out the analgesic and anti-inflammatory activity, if any, of Amifostine [S-2(3 amino propyl amino ethyl phosphorothioate], DRDE-07 [S-2(3 amino ethyl amino ethyl phenyl sulphide] and their analogs DRDE-30 and DRDE-35, the probable prophylactic agent for sulphur mustard (SM. Materials and Methods : In order to find out the analgesic activities of the compounds two methods were employed, namely, acetic acid-induced writhing test and formalin-induced paw licking. The persistent pain model of formalin-induced hind paw licking was carried out to test the effect of the compounds on neurogenic pain or early phase (0 to 5 minutes and on the peripheral pain or the late phase (15 to 30 minutes. To test the effect of the compound in acute inflammation, carrageenan-induced hind paw edema was carried out. This model of inflammation involves a variety of mediators of inflammation. Results : DRDE-07 (81.7% and DRDE-30 (79.4% showed significant reduction in the acetic acid-induced writhing test. DRDE-07 (93.1%, DRDE-30 (82%, and DRDE-35 (61.3% showed significant reduction in the second or late phase of formalin-induced paw licking. All the analogs (more than 60% including amifostine (43.9% showed significant reduction of paw edema in the carrageenan-induced paw edema in mice. Conclusion : The analgesic and anti-inflammatory activity of the antidotes were comparable with aspirin.

  20. Amifostine Treatment Mitigates the Damaging Effects of Radiation on Distraction Osteogenesis in the Murine Mandible.

    Science.gov (United States)

    Monson, Laura A; Nelson, Noah S; Donneys, Alexis; Farberg, Aaron S; Tchanque-Fossuo, Catherine N; Deshpande, Sagar S; Buchman, Steven R

    2016-08-01

    According to the American Society of Clinical Oncology, in 2012, more than 53,000 new cases of head and neck cancers (HNCs) were reported in the United States alone and nearly 12,000 deaths occurred relating to HNC. Although radiotherapy (XRT) has increased survival, the adverse effects can be unrelenting and their management is rarely remedial. Current treatment dictates surgical mandibular reconstruction using free tissue transfer. These complex operations entail extended hospitalizations and attendant complications often lead to delays in initiation of adjuvant therapy, jeopardizing prognosis as well as quality of life. The creation of new bone by distraction osteogenesis (DO) generates a replacement of deficient tissue from local substrate and could have immense potential therapeutic ramifications. Radiotherapy drastically impairs bone healing, precluding its use as a reconstructive method for HNC. We posit that the deleterious effects of XRT on bone formation could be pharmacologically mitigated. To test this hypothesis, we used a rodent model of DO and treated with amifostine, a radioprotectant, to assuage the XRT-induced injury on new bone formation. Amifostine had a profound salutary effect on bone regeneration, allowing the successful implementation of DO as a reconstructive technique. The optimization of bone regeneration in the irradiated mandible has immense potential for translation from the bench to the bedside, providing improved therapeutic options for patients subjected to XRT. PMID:27070667

  1. Clinical study of radioprotective effects of amifostine (YM-08310, WR-2721) on long-term outcome for patients with cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mitsuhashi, Norio; Takahashi, Iku; Takahashi, Mitsuhiro; Hayakawa, Kazushige; Niibe, Hideo (Gumma Univ. School of Medicine (Japan))

    1993-06-15

    A retrospective analysis was performed to investigate the radioprotective effects of amifostine on the long-term outcome of radiation therapy for patients with carcinoma of the uterine cervix. Eighty-three patients with histologically proven epidermoid carcinoma (Stage II-IVA disease) of the uterine cervix were treated with definite radiation therapy between January 1978 and December 1984. Forty-six patients were treated with radiation alone, whereas 37 patients were treated with radiation plus amifostine daily from the initiation of the course of radiation therapy. The median total dose of amifostine given was 1300 mg/m[sub 2], with a range of 280 mg/m[sup 2] to 3700 mg/m[sup 2]. The 5-year overall actuarial survival for the patients treated with radiation along and with radiation plus amifostine were: 72% and 88% in Stage II disease (p = 0.45); 52% and 50% in Stage III disease (p = 0.68); and 40% and 43% in Stage IVA disease (p = 0.51), respectively. The 5-year intra-pelvic recurrence rates in the patients treated with amifostine were almost the same as those observed in the patients treated without amifostine (0% vs. 6% in Stage II disease; 15% vs. 10% in Stage III disease; 25% vs. 40% in Stage IVA disease). There was also no statistically significant difference of the chronic rectal or bladder complication rate between the groups treated by each regimen. The authors concluded that any radioprotective effects of amifostine on tumor tissue and any beneficial effects of amifostine against chronic radiation injury were not observed in the patients with cervical cancer followed up for more than 5 years after radiation therapy. 17 refs., 3 figs., 3 tabs.

  2. Effect of Amifostine in Head and Neck Cancer Patients Treated with Radiotherapy: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials

    OpenAIRE

    Jundong Gu; Siwei Zhu; Xuebing Li; Hua Wu; Yang Li; Feng Hua

    2014-01-01

    BACKGROUND: Amifostine is the most clinical used chemical radioprotector, but its effect in patients treated with radiation is not consistent. METHODS: By searching Medline, CENTRAL, EMBASE, ASCO, ESMO, and CNKI databases, the published randomized controlled trials (RCTs) about the efficacy of amifostine in HNSCC patients treated with radiotherapy were collected. The pooled efficacy and side effects of this drug were calculated by RevMan software. RESULTS: Seventeen trials including a total o...

  3. Prevention of radiochemotherapy-induced toxicity with amifostine in patients with malignant orbital tumors involving the lacrimal gland: a pilot study

    OpenAIRE

    Greiner Richard; Curschmann Juergen; Ghadjar Pirus; Goldblum David; Aebersold Daniel

    2008-01-01

    Abstract Background To use amifostine concurrently with radiochemotherapy (CT-RT) or radiotherapy (RT) alone in order to prevent dry eye syndrome in patients with malignancies located in the fronto-orbital region. Methods Five patients (2 males, 3 females) with diagnosed malignancies (Non-Hodgkin B-cell Lymphoma, neuroendocrine carcinoma) involving the lacrimal gland, in which either combined CT-RT or local RT were indicated, were prophylactically treated with amifostine (500 mg sc). Single R...

  4. L-Carnitine Protection Against Cisplatin Nephrotoxicity In Rats: Comparison with Amifostin Using Quantitative Renal Tc 99m DMSA Uptake

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    Yakup Yürekli

    2011-04-01

    Full Text Available Objective: In this study, we aimed to investigate the cytoprotective effect of L-carnitine against cisplatin-induced nephrotoxicity and to compare its efficacy with that of amifostin by quantitative renal Tc 99m DMSA uptake. Material and Methods: Male Wistar rats were randomly divided into six groups of six animals each. 1 Control (saline; 5 ml/kg intraperitoneally; 2 L-carnitine (CAR; 300 mg/kg intraperitoneally; 3 Amifostine (AMI; 200 mg /kg intraperitoneally; 4 Cisplatin (CIS;7 mg/kg intraperitoneally; 5 Cisplatin plus L-carnitine (CIS + CAR; 6 Cisplatin plus amifostine (CIS + AMI. L-carnitine and amifostine were injected 30 minutes before cisplatin in Group 5 and 6. Tc 99m DMSA, 7.4 MBq/0.2 ml, was injected through the tail vein 72 hours after the drug administration. Rats were killed and kidneys removed by dissection 2 hours after the injection of the radiopharmaceutical. The percentage of the injected dose per gram of kidney tissue (%ID/g was calculated. Renal function was monitored by measuring BUN and plasma levels of creatinine. Lipid peroxidation and glutathione content were determined by measuring malondialdehyde (MDA and reduced glutathione (GSH in kidney tissue homogenates. Results: Tc 99m DMSA uptake per gram tissue of the kidney as %ID/g was 29.54±4.72, 29.86 ± 7.47 and 26.37 ± 4.54 in the control, CAR and AMI groups respectively. %ID/g was the lowest of all the groups, 11.60±3.59 (p<0.01, in the cisplatin group. Carnitine or amifostine administration 30 minutes before cisplatin injection resulted a significant increase in %ID/g, 21.28±7.73 and 18.97±3.24 respectively, compared to those of cisplatin-treated rats (p<0.002. A marked increase in plasma BUN and creatinine indicating nephrotoxicity and acute renal failure was observed in the cisplatin-treated group. MDA and GSH levels were concordant with cisplatin-induced oxidative stress in the kidney tissue. Conclusion: The results showed that L-carnitine significantly

  5. Beneficial effect of the oxygen free radical scavenger amifostine (WR-2721 on spinal cord ischemia/reperfusion injury in rabbits

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    Karanikolas Menelaos

    2009-09-01

    Full Text Available Abstract Background Paraplegia is the most devastating complication of thoracic or thoraco-abdominal aortic surgery. During these operations, an ischemia-reperfusion process is inevitable and the produced radical oxygen species cause severe oxidative stress for the spinal cord. In this study we examined the influence of Amifostine, a triphosphate free oxygen scavenger, on oxidative stress of spinal cord ischemia-reperfusion in rabbits. Methods Eighteen male, New Zealand white rabbits were anesthetized and spinal cord ischemia was induced by temporary occlusion of the descending thoracic aorta by a coronary artery balloon catheter, advanced through the femoral artery. The animals were randomly divided in 3 groups. Group I functioned as control. In group II the descending aorta was occluded for 30 minutes and then reperfused for 75 min. In group III, 500 mg Amifostine was infused into the distal aorta during the second half-time of ischemia period. At the end of reperfusion all animals were sacrificed and spinal cord specimens were examined for superoxide radicals by an ultra sensitive fluorescent assay. Results Superoxide radical levels ranged, in group I between 1.52 and 1.76 (1.64 ± 0.10, in group II between 1.96 and 2.50 (2.10 ± 0.23, and in group III (amifostine between 1.21 and 1.60 (1.40 ± 0.19 (p = 0.00, showing a decrease of 43% in the Group of Amifostine. A lipid peroxidation marker measurement ranged, in group I between 0.278 and 0.305 (0.296 ± 0.013, in group II between 0.427 and 0.497 (0.463 ± 0.025, and in group III (amifostine between 0.343 and 0.357 (0.350 ± 0.007 (p Conclusion By direct and indirect methods of measuring the oxidative stress of spinal cord after ischemia/reperfusion, it is suggested that intra-aortic Amifostine infusion during spinal cord ischemia phase, significantly attenuated the spinal cord oxidative injury in rabbits.

  6. Cytoprotection with amifostine in radiotherapy or combined radio-chemotherapy of head and neck cancer; Zytoprotektion mit Amifostin in der Strahlentherapie bzw. Strahlen-/Chemotherapie von Kopf-Hals-Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Altmann, S.; Hoffmanns, H. [Krankenhaus Maria-Hilf, Moenchengladbach (Germany). Strahlentherapie und Radiologische Onkologie

    1999-11-01

    Background: A considerable amount of experimental and clinical data prove the cytoprotective effect of amifostine on normal tissue exposed to different types of antineoplastic treatments. The present study examines its influence on the short-term toxicity of either radiotherapy alone or combined radio-chemotherapy in patients with advanced head and neck cancer. Patients and methods: Twenty-three patients with advanced head and neck cancer, mainly Stage III and IV, were treated with preoperative radiation (n=1), pre- as well as postoperative radiotherapy (n=5), postoperative radiation (n=9) or combined postoperative radio-chemotherapy (n=6). Before each radiation application a total dose of 500 mg amifostine was administered intravenously over 15 minutes. The documentation of this unselected patient group was compared retrospectively to a historical control group comprising 17 patients. Results: In 15 patients (65%) of the amifostine group, therapy induced side effects such as mucositis and dermatitis of WHO Grade {<=}2 were detected, requiring interruptions of the radiotherapy (mean: 6.5, maximum 17 days). No mucosa or dermatologic toxicity of WHO Grade 3 or 4 was observed in this group. Significantly more acute toxicity was detected in the historical control group. Stomatitis or epitheliolysis of WHO Grade 3 occurred in 7 patients (41%). The side effects induced by the antineoplastic therapy caused an interruption of treatment in 15 patients (88%) (mean: 16, maximum 40 days; p=0.0016). Conclusion: The application of amifostine before each radiation treatment seems to result in a distinct reduction of short-term toxicity of radiotherapy or combined radio-chemotherapy in patients with head and neck cancer, allowing for a better adherence to the planned radiation time schedule. (orig.) [German] Hintergrund: Zahlreiche experimentelle und klinische Daten belegen die zytoprotektive Wirkung von Amifostin auf gesundes Gewebe bei Anwendung verschiedener antineoplastischer

  7. Amifostine (WR-2721, a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study

    Directory of Open Access Journals (Sweden)

    C.A. De Souza

    2000-07-01

    Full Text Available Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY (7 g/m2, used to mobilize peripheral blood progenitor cells (PBPC and to reduce tumor burden. We enrolled 29 patients, 22 (75.9% affected by aggressive and 7 (24.1% by indolent non-Hodgkin's lymphoma (NHL, who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0.04. None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively. Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.

  8. Prophylactic Efficacy of Amifostine, DRDE-07, and their Analogues against Percutaneously Administered Nitrogen Mustards and Sulphur Mustard

    Directory of Open Access Journals (Sweden)

    Manoj Sharma

    2009-09-01

    Full Text Available Nitrogen mustards (HN-1, HN-2 and HN-3 and sulphur mustard are alkylating and blister-inducing chemical warfare agents. This study was aimed at investigating the prophylactic efficacy of amifostine, DRDE-07, and their analogues and some recommended antidotes against dermally-applied nitrogen mustards and sulphur mustard in preventing their systemic toxicity in mice. The antidotes were administered as single oral dose, 30 min prior to the mustard agent application. For DRDE-07, 0.2 LD50 (249 mg/kg was used and for other analogues, equimolar dose of DRDE-07 was used. For amifostine, N-acetyl cysteine, melatonin and sodium thiosulphate, oral dose was 185 mg/kg, 250 mg/kg, 250 mg/kg, and 1000 mg/kg respectively. The animals were observed for mortality for 14 days. The protection index (PI was calculated as a ratio of LD50 with treatment to LD50 without treatment. The protection of the antidotes was also determined by intraperitoneal route and half of the oral dose of the antidotes was given. The estimated percutaneous LD50 of HN-1, HN-2, HN-3 and sulphur mustard was 11.9 mg/kg, 20.0 mg/kg, 7.1 mg/kg and 7.1 mg/kg, respectively. Compounds that showed marginal protection against HN-1 were DRDE-10 and melatonin with a PI of 1.4. Compounds that showed marginal protection against HN-2 were amifostine, DRDE-07, DRDE-09, DRDE-30, DRDE-35 and melatonin with a PI of 1.4. Compounds that showed marginal protection against HN-3 were amifostine, DRDE-30, DRDE-35, sodium thiosulphate and melatonin with a PI of 1.7. In the case of sulphur mustard, DRDE-07, DRDE-10, DRDE-21, DRDE-30, and DRDE-35 gave a good protection with a PI of more than 5.0. Amifostine and sodium thiosulphate gave a PI of 4.5 and 4.0, respectively, while DRDE-09, N-acetyl cysteine and melatonin gave less protection against sulphur mustard. Intraperitoneally administered amifostine, DRDE-30, sodium thiosulphate and melatonin gave marginal protection against HN-2 with a PI of 1.2, while

  9. Potentiation of the Anti-Tumor Effect of Merocyanine 540-Mediated Photodynamic Therapy by Amifostine and Amphotericin B

    OpenAIRE

    Tsujino, Ichiro; Miyagi, Kiyoko; Sampson, Reynée W.; Sieber, Fritz

    2006-01-01

    Leukemia and lymphoma cells are much more sensitive to Merocyanine 540 (MC540)-mediated photodynamic therapy (PDT) than normal pluripotent hematopoietic stem cells and normal granulocyte/macrophage progenitors (CFU-GM). By contrast, most solid tumor cells are only moderately sensitive to MC540-PDT. The limited activity against solid tumor cells has detracted from MC540's appeal as a broad-spectrum purging agent. We report here that non-cytotoxic concentrations of amifostine (Ethyol, Ethiofos,...

  10. A randomized trial of amifostine as a cytoprotective agent in patients receiving chemotherapy for small cell lung cancer

    OpenAIRE

    Johnson, P. W. M.; Muers, M. F.; Peake, M D; Poulter, K M; Gurney, E M; Napp, V; Hepburn, P M; Brown, J. M.

    2001-01-01

    A randomized trial was conducted to determine whether administration of Amifostine with chemotherapy for small cell lung cancer could decrease the toxicity. 84 patients with small cell lung cancer of favourable prognosis (limited disease, performance status 0–1; limited disease with performance status 2 but normal sodium and alkaline phosphatase, or extensive diseas with performance status 0–1, normal sodium and alkaline phosphatase) received treatment with Ifosfamide 3 g/m2intravenously, Car...

  11. Raman spectroscopy delineates radiation-induced injury and partial rescue by amifostine in bone: a murine mandibular model

    OpenAIRE

    Felice, Peter A.; Gong, Bo; Ahsan, Salman; Deshpande, Sagar S.; Nelson, Noah S.; Donneys, Alexis; Tchanque-Fossuo, Catherine; Morris, Michael D.; Buchman, Steven R.

    2014-01-01

    Despite its therapeutic role in head and neck cancer, radiation administration degrades the biomechanical properties of bone and can lead to pathologic fracture and osteoradionecrosis. Our laboratories have previously demonstrated that prophylactic amifostine administration preserves the biomechanical properties of irradiated bone and that Raman spectroscopy accurately evaluates bone composition ex vivo. As such, we hypothesize that Raman spectroscopy can offer insight into the temporal and m...

  12. Beneficial effect of the oxygen free radical scavenger amifostine (WR-2721) on spinal cord ischemia/reperfusion injury in rabbits

    OpenAIRE

    Karanikolas Menelaos; Koletsis Efstratios N; Georgiou Christos D; Grintzalis Konstantinos; Papapostolou Ioannis; Apostolakis Efstratios; Chronidou Fany; Papathanasopoulos Panagiotis; Dougenis Dimitrios

    2009-01-01

    Abstract Background Paraplegia is the most devastating complication of thoracic or thoraco-abdominal aortic surgery. During these operations, an ischemia-reperfusion process is inevitable and the produced radical oxygen species cause severe oxidative stress for the spinal cord. In this study we examined the influence of Amifostine, a triphosphate free oxygen scavenger, on oxidative stress of spinal cord ischemia-reperfusion in rabbits. Methods Eighteen male, New Zealand white rabbits were ane...

  13. Prophylactic Efficacy of Amifostine, DRDE-07, and their Analogues against Percutaneously Administered Nitrogen Mustards and Sulphur Mustard

    OpenAIRE

    Manoj Sharma; Vijayaraghavan, R.; Uma Pathak; K. Ganesan

    2009-01-01

    Nitrogen mustards (HN-1, HN-2 and HN-3) and sulphur mustard are alkylating and blister-inducing chemical warfare agents. This study was aimed at investigating the prophylactic efficacy of amifostine, DRDE-07, and their analogues and some recommended antidotes against dermally-applied nitrogen mustards and sulphur mustard in preventing their systemic toxicity in mice. The antidotes were administered as single oral dose, 30 min prior to the mustard agent application. For DRDE-07, 0.2 LD50 (249 ...

  14. Comparison of the protective roles of L-carnitine and amifostine against radiation-induced acute ovarian damage by histopathological and biochemical methods

    Directory of Open Access Journals (Sweden)

    Vuslat Yurut-Caloglu

    2015-01-01

    Full Text Available Purpose: The aim of this study was to compare the radioprotective efficacies of L-carnitine (LC and amifostine against radiation-induced acute ovarian damage. Materials and Methods: Forty-five, 3-month-old Wistar albino rats were randomly assigned to six groups. Control (CONT, n = 7; irradiation alone RT: radiation therapy (RT, n = 8; amifostine plus irradiation (AMI + RT, n = 8; LC plus irradiation (LC + RT, n = 8; LC and sham irradiation (LC, n = 7; and amifostine and sham irradiation (AMI, n = 7. The rats in the AMI + RT, LC + RT and RT groups were irradiated with a single dose of 20 Gy to the whole abdomen. LC (300 mg/kg and amifostine (200 mg/kg was given intraperitoneally 30 min before irradiation. Five days after irradiation, both antral follicles and corpus luteum in the right ovaries were counted, and tissue levels of malondialdehyde (MDA and advanced oxidation protein product (AOPP were measured. Results: Irradiation significantly decreased antral follicles and corpus luteum (P: 0.005 and P 0.05. The level of MDA and AOPP significantly increased after irradiation (P = 0.001 and P 0.005. The levels of both MDA and AOPP were also similar when LC + RT is compared with AMI + RT group (P > 0.005. Conclusions: L-carnitine and amifostine have a noteworthy and similar radioprotective effect against radiation-induced acute ovarian toxicity.

  15. The cytoprotective drug amifostine modifies both expression and activity of the pro-angiogenic factor VEGF-A

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    Bouchecareilh M

    2010-03-01

    Full Text Available Abstract Background Amifostine (WR-2721, delivered as Ethyol® is a phosphorylated aminothiol compound clinically used in addition to cis-platinum to reduce the toxic side effects of therapeutic treatment on normal cells without reducing their efficacy on tumour cells. Its mechanism of action is attributed to the free radical scavenging properties of its active dephosphorylated metabolite WR-1065. However, amifostine has also been described as a potent hypoxia-mimetic compound and as a strong p53 inducer; both effects are known to potently modulate vascular endothelial growth factor (VEGF-A expression. The angiogenic properties of this drug have not been clearly defined. Methods Cancer cell lines and endothelial cells were used in culture and treated with Amifostine in order to study (i the expression of angiogenesis related genes and proteins and (ii the effects of the drug on VEGF-A induced in vitro angiogenesis. Results We demonstrated that the treatment of several human cancer cell lines with therapeutical doses of WR-1065 led to a strong induction of different VEGF-A mRNA isoforms independently of HIF-1α. VEGF-A induction by WR-1065 depends on the activation of the eIF2alpha/ATF4 pathway. This up-regulation of VEGF-A mRNA was accompanied by an increased secretion of VEGF-A proteins fully active in stimulating vascular endothelial cells (EC. Nevertheless, direct treatment of EC with amifostine impaired their ability to respond to exogenous VEGF-A, an effect that correlated to the down-regulation of VEGFR-2 expression, to the reduction in cell surface binding of VEGF-A and to the decreased phosphorylation of the downstream p42/44 kinases. Conclusions Taken together, our results indicate that amifostine treatment modulates tumour angiogenesis by two apparently opposite mechanisms - the increased VEGF-A expression by tumour cells and the inhibition of EC capacity to respond to VEGF-A stimulation.

  16. Acupoint Sticking at Shenque (CV 8) with Ginger-preparedBan Xia (Rhizoma Pinelliae) for Nausea and Vomiting Induced by Amifostine

    Institute of Scientific and Technical Information of China (English)

    Wang Li-na; Hu Hong-yan; Qiu Yi-ling; Zhou Yu-hong

    2014-01-01

    Objective: To observe the treatment effect of acupoint sticking at Shenque (CV 8) with ginger-preparedBan Xia (Rhizoma Pinelliae) on nausea and vomiting induced by Amifostine for myelodysplastic syndromes (MDS). Methods: Totally 124 eligible subjects intervened by Amifostine were randomized into 2 groups by the visiting order,an observation group and a control group,62 in each group. The control group was intervened by conventional treatment, while the observation group was by acupoint sticking at Shenque (CV 8) with ginger-preparedBan Xia (Rhizoma Pinelliae) in addition to the same conventional treatment. The occurrence rate of nausea and vomiting in the two groups were observed. Results: After intervention, the occurrence rate of nausea and vomiting in the observation group was significantly lower than that in the control group (P Conclusion: Acupoint sticking at Shenque (CV 8) with ginger-prepared Ban Xia (Rhizoma Pinelliae)can produce a content effect on nausea and vomiting induced by Amifostine for MDS.

  17. Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine

    Energy Technology Data Exchange (ETDEWEB)

    Zois, Christos E. [Department of Radiotherapy - Oncology, Democritus University of Thrace, Alexandroupolis 68100 (Greece); Giatromanolaki, Alexandra [Department of Pathology, Democritus University of Thrace, Alexandroupolis (Greece); Kainulainen, Heikki [Department of Biology of Physical Activity, University of Jyvaeskylae (Finland); Botaitis, Sotirios [Department of Experimental Surgery, Democritus University of Thrace, Alexandroupolis (Greece); Torvinen, Sira [Department of Biology of Physical Activity, University of Jyvaeskylae (Finland); Simopoulos, Constantinos [Department of Experimental Surgery, Democritus University of Thrace, Alexandroupolis (Greece); Kortsaris, Alexandros [Department of Biochemistry, Democritus University of Thrace, Alexandroupolis (Greece); Sivridis, Efthimios [Department of Pathology, Democritus University of Thrace, Alexandroupolis (Greece); Koukourakis, Michael I., E-mail: targ@her.forthnet.gr [Department of Radiotherapy - Oncology, Democritus University of Thrace, Alexandroupolis 68100 (Greece)

    2011-01-07

    Research highlights: {yields} We investigated the effect 6 Gy of WBI on the autophagic machinery of normal mouse lung. {yields} Irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. {yields} The membrane bound LC3A-II protein levels increased in the cytosolic fraction (not in the pellet), contrasting the patterns noted after starvation-induced autophagy. {yields} Administration of amifostine, reversed all the LC3A and p62 findings, suggesting protection of the normal autophagic function. -- Abstract: Purpose: The effect of ionizing irradiation on the autophagic response of normal tissues is largely unexplored. Abnormal autophagic function may interfere the protein quality control leading to cell degeneration and dysfunction. This study investigates its effect on the autophagic machinery of normal mouse lung. Methods and materials: Mice were exposed to 6 Gy of whole body {gamma}-radiation and sacrificed at various time points. The expression of MAP1LC3A/LC3A/Atg8, beclin-1, p62/sequestosome-1 and of the Bnip3 proteins was analyzed. Results: Following irradiation, the LC3A-I and LC3A-II protein levels increased significantly at 72 h and 7 days. Strikingly, LC3A-II protein was increased (5.6-fold at 7 days; p < 0.001) only in the cytosolic fraction, but remained unchanged in the membrane fraction. The p62 protein, was significantly increased in both supernatant and pellet fraction (p < 0.001), suggesting an autophagosome turnover deregulation. These findings contrast the patterns of starvation-induced autophagy up-regulation. Beclin-1 levels remained unchanged. The Bnip3 protein was significantly increased at 8 h, but it sharply decreased at 72 h (p < 0.05). Administration of amifostine (200 mg/kg), 30 min before irradiation, reversed all the LC3A and p62 findings on blots, suggesting restoration of the normal autophagic function

  18. Prophylactic administration of Amifostine protects vessel thickness in the setting of irradiated bone.

    Science.gov (United States)

    Page, Erin E; Deshpande, Sagar S; Nelson, Noah S; Felice, Peter A; Donneys, Alexis; Rodriguez, Jose J; Deshpande, Samir S; Buchman, Steven R

    2015-01-01

    Although often beneficial in the treatment of head and neck cancer (HNC), radiation therapy (XRT) leads to the depletion of vascular supply and eventually decreased perfusion of the tissue. Specifically, previous studies have demonstrated the depletion of vessel volume fraction (VVF) and vessel thickness (VT) associated with XRT. Amifostine (AMF) provides protection from the detrimental effects of radiation damage, allowing for reliable post-irradiation fracture healing in the murine mandible. The purpose of this study is to investigate the prophylactic ability of AMF to protect the vascular network in an irradiated field. Sprague-Dawley rats (n = 17) were divided into 3 groups: control (C, n = 5), radiated (XRT, n = 7), and radiated mandibles treated with Amifostine (AMF XRT, n = 5). Both groups receiving radiation underwent a previously established, human equivalent dose of XRT totaling 35 Gy, equally fractionated over 5 days. The AMF XRT group received a weight dependent (0.5 mg AMF/5 g body weight) subcutaneous injection of AMF 45 min prior to XRT. Following a 56-day recovery period, mandibles were perfused, dissected, and imaged with μCT. ANOVA was used for comparisons between groups and p < 0.05 was considered statistically significant. Stereologic analysis demonstrated a significant and quantifiable restoration of VT in AMF treated mandibles as compared to those treated with radiation alone (0.061 ± 0.011 mm versus 0.042 ± 0.004 mm, p = 0.027). Interestingly, further analysis demonstrated no significant difference in VT between control mandibles and those treated with AMF (0.067 ± 0.016 mm versus 0.061 ± 0.011 mm, p = 0.633). AMF treatment also showed an increase in VVF, however those results were not statistically significant from VVF values demonstrated by the XRT group. Our data support the contention that AMF therapy acts prophylactically to protect vessel thickness. Based on these findings, we support the continued

  19. Carboplatin combined with amifostine, a bone marrow protectant, in the treatment of non-small-cell lung cancer: a randomised phase II study.

    OpenAIRE

    Betticher, D. C.; Anderson, H.; Ranson, M.; Meely, K.; Oster, W; Thatcher, N

    1995-01-01

    Amifostine (WR-2721), a thiol compound, has been shown to protect normal tissue from alkylating agents and cisplatin-induced toxicity without loss of anti-tumour effects. To confirm this result, we conducted a phase II randomised trial to determine if the addition of amifostine reduces the toxicity of carboplatin without loss of anti-tumour activity in patients with inoperable non-small-cell lung cancer (NSCLC). After the first course of carboplatin (600 mg m-2 i.v. infusion), 21 patients wer...

  20. Amifostine in Cancer Radiotherapy Injury Research%氨磷汀在肿瘤放射治疗损伤中的研究进展

    Institute of Scientific and Technical Information of China (English)

    孙先阁; 何奋军

    2013-01-01

    Amifostine is the only cytoprotective agent used in a broad range of clinical radiotherapy. In this paper,amifostine’s cytoprotective mechanisms in radiotherapy and its clinical application was reviewed.%氨磷汀(Amifostine)是临床唯一应用的广谱放射治疗细胞保护剂。文章就氨磷汀在肿瘤放射治疗中的保护机制及临床应用的相关文献进行综述。

  1. Safety Study of Amifostine for Injection%注射用氨磷汀安全性研究

    Institute of Scientific and Technical Information of China (English)

    张广伟; 徐晓月

    2011-01-01

    目的 研究注射用氨磷汀的安全性,为临床应用提供依据.方法 进行豚鼠全身主动过敏试验(ASA),首先隔日每只豚鼠每次腹腔注射供试品,共3次,再于首次注射后第14日和第21日由耳缘静脉注射供试品,观察动物过敏反应;进行大鼠被动皮肤过敏试验(PCA),大鼠皮内注射抗体血清,静脉注射伊文思蓝,观察蓝色反应斑;进行体外溶血试验,观察供试品在3h内有无溶血和凝聚现象;进行血管刺激试验,家兔连续5 d耳缘静脉注射供试品,观察其对注射局部血管的刺激.结果 注射用氨磷汀豚鼠全身主动过敏性试验及大鼠被动皮肤过敏性试验均未见过敏反应;体外溶血试验在3h内未见溶血和凝聚现象;血管刺激性试验病理组织学检查未见血管刺激性反应.结论 注射用氨磷汀安全、可靠.%Objective To evaluate the safety of Anifostine for Injection to provide the evidence for its clinical application. Methods The active systemic anaphylaxis(ASA) was investigated by guinea pigs, in which each guinea pig was allergized by intraperitoneal injecting Amifostine for Injection every other day, total 3 times. Amifostine for Injection was injected via ear vein for observing the anaphylactic reaction on 14 d and 21 d after the first injection. The rat passive cutaneous anaphylactic reaction was assayed by intravenous injection of Evans blue after intracutaneous injection of serum antibodies for observing blue reaction spots. In the in vitro hemolytic test, hemolysis and coagulation were observed in 3 h. In the vessel stimulation test, the local blood vessel stimulation was observed after injecting Amifostine For Injection for successive 5 d. Results There was no allergic reaction to the guinea pigs and rats, no hemolytic and coagulation reaction and no stimulation to ear vein. Conclusion Amifostine for Injection is safe and reliable.

  2. CCM-AMI, a Polyethylene Glycol Micelle with Amifostine, as an Acute Radiation Syndrome Protectant in C57BL/6 Mice.

    Science.gov (United States)

    Chen, Chia-Hung; Kuo, Min-Liang; Wang, Jen-Ling; Liao, Wei-Chuan; Chang, Li-Ching; Chan, Leong-Perng; Lin, Johnson

    2015-09-01

    Acute radiation syndrome results from radiation exposure, such as in accidental nuclear disasters. Safe and effective radioprotectants, mitigators, and treatment drugs must be developed as medical countermeasures against radiation exposure. Here, the authors evaluated CCM-Ami, a novel polyethylene glycol micelle encapsulated with amifostine, for its radioprotective properties after total-body irradiation from a 60Co source. Male C57BL/6 mice (6-8 wk old) were intravenously injected with 45 mg kg(-1) of CCM-Ami 90 min before exposure to 7.2 and 8.5 Gy irradiation at a dose rate of 0.04 Gy min(-1). Both survival benefit and hematopoietic protection were observed after prophylactic CCM-Ami administration when compared with the effects measured in excipient control and amifostine groups. Pharmacokinetic results showed that after the intravenous injection, the plasma concentration of WR-1065, the active form of amifostine, was higher in CCM-Ami-treated mice than in amifostine-treated mice. These findings suggest that CCM-Ami-mediated hematopoietic protection plays a key role in enhancing survival of mice exposed to radiation toxicity and thus indicate that CCM-Ami is a radioprotectant that can be used safely and effectively in nuclear disasters. PMID:26222219

  3. A phase II randomized study of topical intrarectal administration of amifostine for the prevention of acute radiation-induced rectal toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Kouloulias, V.E. [Dept. of Radiation Oncology, Aretaieion Univ. Hospital, Univ. of Athens Medical School, Athens (Greece); Dept. of Electrical and Computer Engineering, National Technical Univ. of Athens, Athens (Greece); Center of Radiation Oncology, YGEIA Diagnostic and Therapeutic Center of Athens, Athens (Greece); Kouvaris, J.R.; Kokakis, J.D.; Antypas, C.; Mallas, E.; Vosdoganis, S.P.; Vlahos, L.J. [Dept. of Radiation Oncology, Aretaieion Univ. Hospital, Univ. of Athens Medical School, Athens (Greece); Pissakas, G. [Radiotherapy Dept., Agios Savvas Anticancer Hospital, Athens (Greece); Matsopoulos, G. [Dept. of Electrical and Computer Engineering, National Technical Univ. of Athens, Athens (Greece); Michopoulos, S. [Gastroenterology Unit, Alexandra General Hospital, Athens (Greece); Kostakopoulos, A. [Urology Dept., Sismanoglio Hospital, Univ. of Athens Medical School, Athens (Greece)

    2004-09-01

    Purpose: to investigate the cytoprotective effect of intrarectal amifostine administration on acute radiation-induced rectal toxicity. Patients and methods: 67 patients with T1b-2 NO MO prostate cancer were randomized to receive amifostine intrarectally (group A, n - 33) or not (group B, n = 34) before irradiation. Therapy was delivered using a four-field technique with three-dimensional conformal planning. In group A, 1,500 mg amifostine was administered intrarectally as an aqueous solution in a 40-ml enema. Two different toxicity scales were used: EORTC/RTOG rectal and urologic toxicity criteria along with a Subjective-RectoSigmoid (S-RS) scale based on the endoscopic terminology of the World Organization for Digestive Endoscopy. Objective measurements with rectosigmoidoscopy were performed at baseline and 1-2 days after the completion of radiotherapy. The area under curve for the time course of mucositis (RTOG criteria) during irradiation represented the mucositis index (MI). Results: intrarectal amifostine was feasible and well tolerated without any systemic or local side effects. According to the RTOG toxicity scale, five out of 33 patients showed grade 1 mucositis in group A versus 15 out of 34 patients with grade 1/2 in group B (p = 0.026). Mean rectal MI was 0.3 {+-} 0.1 in group A versus 2.2 {+-} 0.4 in group B (p < 0.001), while S-RS score was 3.9 {+-} 0.5 in group A versus 6.3 {+-} 0.7 in group B (p < 0.001). The incidence of urinary toxicity was the same in both groups. Conclusion: intrarectal administration of amifostine seems to have a cytoprotective efficacy in acute radiation-induced rectal mucositis. Further randomized studies are needed for definitive therapeutic decisions. (orig.)

  4. Effect of Amifostine on Locally Advanced Non-small Cell Lung Cancer Patients Treated with Radiotherapy: A Meta-analysis of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Shengye WANG

    2012-09-01

    Full Text Available Background and objective Controversy exists on whether amifostine can reduce the efficacy and decrease the side effects of non-small cell lung cancer (NSCLC treated by radiotherapy. The aim of this meta-analysis is to evaluate the efficacy and side effects of amifostine in NSCLC patients treated with radiotherapy. Methods Open published randomized controlled trials on the efficacy and side effects of amifostine in NSCLC patients treated with radiotherapy were collected from Medline, Cochrane Central Register of Controlled Trials, EMBSE, CBM, CNKI, WANFANG, American Society of Clinical Oncology, and European Society of Medical Oncology databases. The pooled efficacy and side effects of amifostine in these patients were calculated using the statistics software Stata 11.0. Results Nine trials that included 769 (381 and 388 in each arm patients were analyzed. The pooled relative risk of complete, partial, and objective responses were 1.16 (95%CI: 0.90-1.50, Z=1.07, P=0.29, 1.02 (95%CI: 0.87-1.19, Z=0.21, P=0.83 and 1.06 (95%CI: 0.97-1.17, Z=1.31, P=0.20, respectively. The side effects in seven trials including 738 (367 and 371 in each arm patients were analyzed. The pooled relative risk of developing grades 3 to 4 esophagitis and pneumonitis were 0.51 (95%CI: 0.37-0.72, Z=3.88, P<0.001 and 0.51 (95%CI: 0.26-0.99, Z=1.98, P=0.04, respectively. Conclusion Amifostine can significantly decrease the risk of developing serious esophagitis and pneumonitis without reducing the response rate in NSCLC patients treated by radiotherapy.

  5. Analysis of the cytoprotective effect of amifostine on the irradiated inner ear of guinea pigs: an experimental study Análise do efeito citoprotetor da amifostina na orelha interna irradiada de cobaias: estudo experimental

    OpenAIRE

    Ricardo Miranda Lessa; José Antônio Aparecido de Oliveira; Maria Rossato; Thomaz Ghilardi Netto

    2009-01-01

    Radiation can cause damage to the inner ear, from a simple hearing loss all the way to profound deafness. Amifostine is a cytoprotective substance extensively used during radio-chemotherapy for malignant tumors. AIM: the objective of the present investigation was to establish the antioxidant and radioprotective effects of amifostine on the organ of Corti of albino guinea pigs irradiated in the head and neck region. MATERIALS AND METHODS: An experimental study conducted on four groups of guine...

  6. The protection of the myocardium by amifostine against mitoxantrone-induced acute cardiotoxicity in rats

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    Vefki Gürhan Kadıköylü

    2010-06-01

    Full Text Available Objective: Amifostine (AMI has been used for the prevention of doxorubicin-induced cardiotoxicity in several experimental and a few clinical studies. The aim of this study was to investigate the effects of AMI on lipid peroxidation, protective enzymes, and mitoxantrone (MITO-induced acute cardiotoxicity in the rat heart using biochemical tests and histopathological examinations.Materials and Methods: Thirty-six rats were divided into six groups (n=6 in each. Control rats were given intraperitoneal (i.p. serum saline and AMI group rats were given 200 mg/kg AMI i.p. Rats received MITO-2.5 and 5 mg/kg i.p. in the MITO-2.5 and MITO-5 groups. AMI 200 mg/kg i.p. was administered 30 min. before the same doses of MITO in the MITO-2.5+AMI and MITO-5+AMI groups. Results: The levels of cardiac enzymes such as creatinine phosphokinase-myocardial band and cardiac troponin T did not change. Malondialdehyde (MDA levels increased in MITO groups compared to controls. Catalase and glutathione (GSH levels in the MITO and MITO+AMI groups were higher than in controls. Superoxide dismutase and glutathione peroxidase levels were not different between MITO groups and controls. There was no difference in MDA levels between MITO+AMI groups and controls. Calcium deposition was not detected. The scores of fibrosis, apoptosis, inflammation, and degeneration in MITO groups were higher than in controls. The scores of fibrosis, degeneration and inflammation in MITO+AMI groups were lower. Conclusion: MITO caused lipid peroxidation and myocardial damage, and the myocardium increased catalase and GSH levels to prevent this damage. AMI can protect against MITO-induced acute cardiotoxicity, decreasing myocardial damage and lipid peroxidation.

  7. Amifostine Protection Against Mitomycin-induced Chromosomal Breakage in Fanconi Anaemia Lymphocytes

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    Miriam T. P. Lopes

    2008-08-01

    Full Text Available Fanconi anaemia (FA is a rare genetic chromosomal instability syndrome caused by impairment of DNA repair and reactive oxygen species (ROS imbalance. This disease is also related to bone marrow failure and cancer. Treatment of these complications with radiation and alkylating agents may enhance chromosomal breakage. We have evaluated the effect of amifostine (AMF on basal and mitomycin C (MMC-induced chromosomal breakage in FA blood cells using the micronucleus assay. The basal micronuclei count was higher among FA patients than healthy subjects. Pre-treatment with AMF significantly inhibited micronucleation induced by MMC in healthy subjects (23.4 ± 4.0 – MMC vs 12.3 ± 2.9 – AMF →MMC MN/1000CB, p < 0.01, one way ANOVA as well as in FA patients (80.0 ± 5.8 – MMC vs 40.1 ± 5.8 – AMF →MMC MN/1000CB, p < 0.01, ANOVA. Release of ROS by peripheral blood mononuclear cells treated with AMF →MMC and measured by chemoluminometry showed that AMF-protection was statistically higher among FA patients than in healthy individuals. Based on these results we suggest that AMF prevents chromosomal breakage induced by MMC, probably by its antioxidant effect.

  8. Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and- neck cancer: 2-year follow-up of a prospective, randomized, phase III trial

    International Nuclear Information System (INIS)

    Purpose: To evaluate chronic xerostomia and tumor control 18 and 24 months after initial treatment with amifostine in a randomized controlled trial of patients with head-and-neck cancer; at 12 months after radiotherapy (RT), amifostine had been shown to reduce xerostomia without changing tumor control. Methods and Materials: Adults with head-and-neck cancer who underwent once-daily RT for 5-7 weeks (total dose, 50-70 Gy) received either open-label amifostine (200 mg/m2 i.v.) 15-30 min before each fraction of radiation (n = 150) or RT alone (control; n = 153). Results: Amifostine administration was associated with a reduced incidence of Grade ≥2 xerostomia over 2 years of follow-up (p = 0.002), an increase in the proportion of patients with meaningful (>0.1 g) unstimulated saliva production at 24 months (p = 0.011), and reduced mouth dryness scores on a patient benefit questionnaire at 24 months (p < 0.001). Locoregional control rate, progression-free survival, and overall survival were not significantly different between the amifostine group and the control group. Conclusions: Amifostine administration during head-and-neck RT reduces the severity and duration of xerostomia 2 years after treatment and does not seem to compromise locoregional control rates, progression-free survival, or overall survival

  9. Acute toxicity of postoperative radiochemotherapy with amifostine vs radiochemotherapy alone in head and neck cancer patients. Preliminary results of a randomized trial; Nebenwirkungen einer postoperativen Radiochemotherapie mit Amifostin versus alleiniger Radiochemotherapie bei Kopf-Hals-Tumoren. Vorlaeufige Ergebnisse einer prospektiv randomisierten Untersuchung

    Energy Technology Data Exchange (ETDEWEB)

    Vacha, P.; Marx, M.; Engel, A.; Richter, E.; Feyerabend, T. [Medizinische Univ. Luebeck (Germany). Klinik fuer Strahlentherapie und Nuklearmedizin

    1999-11-01

    Purpose: Experimental and clinical data suggest a reduction of radiation-induced acute toxicity by amifostine. We investigated this issue in a randomized trial comparing radiochemotherapy (RCT) versus radiochemotherapy and amifostine (RCT+A) in patients with head and neck cancer. Patients and methods: Forty-seven patients with pharyngeal or laryngeal cancer (T{sub 1-2}N{sub 1-2}G{sub 3},T{sub 3-4}N{sub 0-2}G{sub 1-3}) were randomized to receive RCT alone (21 patients) or RCT+A (21 patients). Patients were irradiated up to 60 Gy (R{sub 0}) or 70 Gy (R{sub 1/2}). Chemotherapy consisted of 70 mg/m{sup 2} carboplatin and was administered over 5 days in the 1st and 5th week of the radiotherapy course. 250 mg amifostine were applied daily just before each radiotherapy session. Acute toxicity was evaluated according to the Common Toxicity Criteria (CTC). As for xerostomia no patients with laryngeal cancer were assessed because in these cases only small volumes of the salivary glands were within the treatment volume. To evaluate the overall toxicity a summarized CTC score of all observed side effects was calculated. Results: Forty-two patients were evaluable. Clinical characteristics (age, sex, Karnofsky index, tumor-staging) were well balanced in both treatment groups. Amifostine provided reduction in xerostomia and mucositis. Conclusions: According to our preliminary results amifostine has a radioprotective effect on salivary glands. Mucositis can be reduced during radiochemotherapy. At this point of patient accrual the difference between both groups are statistically not significant. To improve the radioprotective effects of amifostine in clinical practice the application of a higher dose (>250 mg) seems to be necessary. (orig.) [German] Ziel: Diese Untersuchung soll die Frage beantworten, ob bei der postoperativen Radiochemotherapie von Patienten mit HNO-Tumoren eine zusaetzliche Amifostin-Medikation Ausmass und Haeufigkeit akuter Strahlenreaktionen vermindert

  10. Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Rolleman, Edgar J.; Forrer, Flavio; Bernard, Bert; Bijster, Magda; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Vermeij, Marcel [Erasmus MC, Department of Pathology, Rotterdam (Netherlands)

    2007-05-15

    In peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues, the kidneys are the major dose-limiting organs, because of tubular reabsorption and retention of radioactivity. Preventing renal uptake or toxicity will allow for higher tumour radiation doses. We tested the cytoprotective drug amifostine, which selectively protects healthy tissue during chemo- and radiotherapy, for its renoprotective capacities after PRRT with high-dose [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. Male Lewis rats were injected with 278 or 555 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate to create renal damage and were followed up for 130 days. For renoprotection, rats received either amifostine or co-injection with lysine. Kidneys, blood and urine were collected for toxicity measurements. At 130 days after PRRT, a single-photon emission computed tomography (SPECT) scan was performed to quantify tubular uptake of {sup 99m}Tc-dimercaptosuccinic acid (DMSA), a measure of tubular function. Treatment with 555 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate resulted in body weight loss, elevated creatinine and proteinuria. Amifostine and lysine treatment significantly prevented this rise in creatinine and the level of proteinuria, but did not improve the histological damage. In contrast, after 278 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate, creatinine values were slightly, but not significantly, elevated compared with the control rats. Proteinuria and histological damage were different from controls and were significantly improved by amifostine treatment. Quantification of {sup 99m}Tc-DMSA SPECT scintigrams at 130 days after [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate therapy correlated well with 1/creatinine (r {sup 2} = 0.772, p < 0.001). Amifostine and lysine effectively decreased functional renal damage caused by high-dose [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. Besides lysine, amifostine might be used in clinical PRRT as well

  11. Efficacy of amifostine in protection against doxorubicin-induced acute cardiotoxic effects in rats

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    Dragojević-Simić Viktorija

    2013-01-01

    Full Text Available Background/Aim. Amifostine (AMI is a broad-spectrum cytoprotector which protects against variety of radio- and chemotherapy-related toxicities without decreasing their antitumor action. The aim of the study was to investigate the potential protective effects of AMI against acute cardiotoxic effects of doxorubicin (DOX in male Wistar rats. Methods. AMI (300 mg/kg ip was given 30 min before DOX (6 mg/kg and 10mg/kg b.w., iv. The evaluation of DOXinduced cardiotoxic effects, as well as cardioprotective efficacy of AMI was performed 48 h after their administration by determining serum activities of enzymes known to be markers of cardiac damage (creatine kinase - CK, aspartate aminotransferase - AST, lactate dehydrogenase - LDH, and its isoenzyme α-hydroxybutirate dehydrogenase - α- HBDH, as well as the histopathological and ultrastructural analysis of the heart tissue. Results. AMI successfully prevented a significant increase in serum activity of CK, AST, LDH and α-HBDH in animals treated with DOX in the dose of 6 mg/kg (121.14 ± 18.37 vs 167.70 ± 44.24; 771.42 ± 161.99 vs 1057.00 ± 300.00; 3230.00 ± 1031.73 vs 4243.10 ± 904.06; 202.57 ± 42.46 vs 294.90 ± 80.20 UI/l, respectively, and ameliorated DOX-induced structural damage of the rat myocardium. Pretreatment with AMI in rats given 10 mg/kg DOX reduced the cardiac damage score (CDS from 2.62 ± 0.51 to 1.62 ± 0.51, i.e. to the CDS value obtained with the lower dose of DOX (6 mg/kg. The ultrastructural analysis of the rat myocardium showed that AMI successfully protected the sarcolemma of cardiomyocytes and reduced mitochondria damage induced by DOX given in the dose of 6 mg/kg. Besides, capillaries were less morphologically changed and apoptosis of endothelial cells was extremely rare in AMI-protected animals. AMI itself did not cause any prominent changes in the examined parameters in comparison with the control rats. Conclusion. AMI provided a significant protection against DOX

  12. 氨磷汀引起低血压1例%Hypotension induced by amifostine in one patient

    Institute of Scientific and Technical Information of China (English)

    王轶娜; 杨宇; 罗荧荃

    2003-01-01

    @@ 氨磷汀(amifostine)是美国FDA批准上市的第1个化疗前应用的正常细胞保护剂,又称WR-2721.临床前研究[1]和Ⅱ,Ⅲ期临床试验[2]已阐明氨磷汀能明显减少抗癌药物引起的骨髓、肾脏、神经和心脏等毒性.其主要的不良反应是低血压和胃肠道反应,作者未见国内有氨磷汀引起低血压的临床报道,我科收治的1名老年肺癌病人在使用氨磷汀时出现了严重低血压,现报道如下.

  13. Use of the cytoprotector amifostine in patients under chemotherapy and/or radiotherapy; Utilizacao do citoprotetor amifostina em pacientes durante tratamento oncologico com quimioterapia e/ou radioterapia

    Energy Technology Data Exchange (ETDEWEB)

    Zanchi, Clarissa; Suyenaga, Edna Sayuri; Perassolo, Magda Susana [Centro Universitario Feevale, Novo Hamburgo, RS (Brazil). Curso de Ciencias Farmaceuticas]. E-mails: clarissazanchi@gmail.com; suyenaga@feevale.br; magdaperassolo@feevale.br

    2008-07-01

    In recent years, several cytoprotective agents have been developed o protect normal cells form the toxic effects of chemotherapy and radiotherapy. The ideal cytoprotectant agent would be that one able to allow the intensification of chemotherapy's dose.; to protect largest number of normal tissues and organs when used with a variety of chemotherapy agents; to confer specific protection for normal tissues; to preserve anti tumor effect and to have little and/or manageable toxicity and side effects. Amifostine fits in on these questions also presenting a broad spectrum of action. This paper aims the discussion of the use of cryoprotective amifostine, their main characteristics/functions, adverse effects, action mechanism, administration and recommended dosage. (author)

  14. Effect of amifostine in head and neck cancer patients treated with radiotherapy: a systematic review and meta-analysis based on randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Jundong Gu

    Full Text Available BACKGROUND: Amifostine is the most clinical used chemical radioprotector, but its effect in patients treated with radiation is not consistent. METHODS: By searching Medline, CENTRAL, EMBASE, ASCO, ESMO, and CNKI databases, the published randomized controlled trials (RCTs about the efficacy of amifostine in HNSCC patients treated with radiotherapy were collected. The pooled efficacy and side effects of this drug were calculated by RevMan software. RESULTS: Seventeen trials including a total of 1167 patients (604 and 563 each arm were analyzed in the meta-analysis. The pooled data showed that the use of amifostine significantly reduce the risk of developing Grade 3-4 mucositis (relative risk [RR],0.72; 95% confidence interval [CI],0.54-0.95; p<0.00001, Grade 2-4 acute xerostomia (RR,0.70; 95%CI,0.52-0.96; p = 0.02, or late xerostomia (RR,0.60; 95%CI,0.49-0.74; p<0.00001 and Grade 3-4 dysphagia (RR,0.39; 95%CI,0.17-0.92; p = 0.03. However, subgroup analysis demonstrated that no statistically significant reduction of Grade 3-4 mucositis (RR,0.97; 95% CI,0.74-1.26; p = 0.80, Grade 2-4 acute xerostomia (RR,0.35; 95%CI,0.02-5.44; p = 0.45, or late xerostomia (RR,0.40; 95%CI,0.13-1.24; p = 0.11 and Grade 3-4 dysphagia (RR,0.23; 95%CI,0.01-4.78; p = 0.35 was observed in patients treated with concomitant chemoradiotherapy. Compared with placebo or observation, amifostine does not show tumor protective effect in complete response (RR,1.02; 95%CI,0.89-1.17; p = 0.76 and partial response (RR,0.90; 95%CI, 0.56-1.44; p = 0.66. For the hematologic side effect, no statistical difference of Grade 3-4 leucopenia (RR,0.60; 95%CI,0.35-1.05; p = 0.07, anemia (RR,0.80; 95%CI, 0.42-1.53; p = 0.50 and thrombocytopenia (RR,0.43; 95%CI,0.16-1.15; p = 0.09 were found between amifostine and control groups. The most common amifostine related side effects were nausea, emesis, hypotension and allergic with an average incidence rate (Grade 3-4 of 5%, 6%, 4% and 4% respectively

  15. Radioprotection of salivary glands by amifostine in high-dose radioiodine treatment. Results of a double-blinded, placebo-controlled study in patients with differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bohuslavizki, K.H.; Klutmann, S.; Kroeger, S.; Buchert, R.; Bleckmann, C.; Mester, J.; Clausen, M. [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Abt. Nuklearmedizin; Brenner, W.; Henze, E. [Kiel Univ. (Germany). Klinik fuer Nuklearmedizin

    1999-11-01

    Background and purpose: Parenchymal impairment of salivary glands following high-dose radioiodine treatment is a well-known side effect in general caused by free radicals. Therefore, the radioprotective effect of the radical scavenger amifostine was evaluated prospectively in patients receiving high-dose radioiodine treatment. Patients and methods: Parenchymal function was assessed by quantitative salivary gland scintigraphy performed in 50 patients with differentiated thyroid cancer prior to and 3 months after high-dose radioiodine treatment with either 3 GBq {sup 131}I (n=21) or 6 BGq {sup 131}I (n=29) in a double-blinded, placebo-controlled study. Twenty-five patients treated with 500 mg/m{sup 2} amifostine intravenously prior to high-dose radioiodine treatment were compared to 25 control patients receiving physiological saline solution. Xerostomia was graded according to WHO-criteria. Results: In 25 control patients high-dose radioiodine treatment significantly (p<0.001) reduced parenchymal function of parotid and submandibular glands by 40.2{+-}14.1% and 39.9{+-}15.3%, respectively. Nine out of these 25 patients developed Grade I and 2 Grade II xerostomia. In contrast, in 25 amifostine-treated patients there was no significant (p=0.691) decrease in parenchymal function following high-dose radioiodine treatment, and xerostomia did not occur in any of them. Conclusion: Parenchymal damage of salivary glands induced by high-dose radioiodine treatment can be significantly reduced by amifostine which may improve quality of life of patients with differentiated thyroid cancer. (orig.) [German] Hintergrund und Ziel: Eine Schaedigung der Speicheldruesen mit konsekutiver Xerostomie ist eine bekannte, durch freie Radikale verursachte Nebenwirkung der ablativen Radioiodtherapie bei Patienten mit differenziertem Schilddruesenkarzinom. Daher wurde der Effekt des Radikalfaengers Amifostin bei ablativer Radioiodtherapie geprueft. Patienten und Methoden: Es wurden insgesamt 50

  16. Application of amifostine in the chemotherapy of cancer patients%氨磷汀在肿瘤患者化疗中的应用

    Institute of Scientific and Technical Information of China (English)

    邢龙; 布仁巴图

    2015-01-01

    目的:本文阐述了氨磷汀在肿瘤患者化疗中的作用机制和临床应用。氨磷汀可有效预防肿瘤化疗致肾、骨髓、外周神经及口腔黏膜毒性,疗效显著且耐受性好,有极好的应用前景。%In this paper,the author elaborates the action mechanism and clinical application of amifostine in the chemotherapy of cancer patients.Amifostine could effectively prevent the kidney,bone marrow,peripheral nerve and the oral mucosa toxicity caused by cancer chemotherapy.Its curative effect was remarkable and the tolerance was good.It had an excellent application prospect.

  17. Amifostine (WR-2721), a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study

    OpenAIRE

    De Souza C.A.; Santini G; Marino G.; Nati S.; Congiu A. M.; Vigorito A.C.; Damasio E.

    2000-01-01

    Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We...

  18. Amifostine as radioprotective agent for the rectal mucosa during irradiation of pelvic tumors. A phase II randomized study using various toxicity scales and rectosigmoidoscopy

    Energy Technology Data Exchange (ETDEWEB)

    Kouvaris, J.; Antypas, C.; Kokakis, J.; Vlahos, L. [Radiology-Radiotherapy Dept., National Technical Univ. of Athens (Greece); Kouloulias, V. [Radiology-Radiotherapy Dept., National Technical Univ. of Athens (Greece); Dept. of Electrical and Computer Engineering, Inst. of Communication and Computer Systems, National Technical Univ. of Athens (Greece); Malas, E. [Endoscopy-Gastroenterology Unit, Dept. of Surgical Oncology, Aretaieion Univ. Hospital, Athens (Greece); Michopoulos, S. [Dept. of Gastroenterology, Alexandra General Hospital of Athens (Greece); Matsopoulos, G. [Dept. of Electrical and Computer Engineering, Inst. of Communication and Computer Systems, National Technical Univ. of Athens (Greece)

    2003-03-01

    Aim: To evaluate the cytoprotective effect of amifostine against radiation-induced acute toxicity to the rectal mucosa. Patients and Methods: 36 patients irradiated for prostate or gynecologic cancer were randomized to receive amifostine (n = 18, group A) or not (n = 18, group B). The radiation-induced acute rectal toxicity was evaluated by using three different toxicity scales: WHO scale, EORTC/RTOG toxicity criteria, and a modified toxicity scale based on the LENT-SOMA grading scale and the endoscopic terminology of the World Organization for Digestive Endoscopy. The objective measurements were coming from flexible rectosigmoidoscopy performed at baseline and 1-2 days after completion of the radiotherapy schedule. Anterior-posterior fields were used in the gynecologic patients while 3-D conformal 4-field technique was applied in the prostate cancer patients. The area under the curve (AUC) for dose-volume histograms (DVHs) of the rectum was also assessed during a 3-D treatment planning schedule, and no significant differences were assessed between the two groups, indicating a homogeneous dose-volume effect. Results: Amifostine was well tolerated. No grade 2 or higher WHO and EORTC/RTOG acute toxicity was noted in group A, while acute rectal toxicity ({>=} grade 1) was observed in 16/18 patients of group B versus 2/18 of group A (p < 0.001). The onset as well as the duration of acute rectal toxicity were significantly improved in group A (p = 0.002). Rectosigmoidoscopy revealed more severe rectal mucositis in noncytoprotected patients (group B), and modified LENT-SOMA overall mucositis grading score was significantly lower in group A (p = 0.003). Conclusion: Amifostine seems to have a significant cytoprotective efficacy in acute radiation-induced rectal mucositis in terms of symptomatic and objective endpoints. (orig.)

  19. Prevention of radiochemotherapy-induced toxicity with amifostine in patients with malignant orbital tumors involving the lacrimal gland: a pilot study

    Directory of Open Access Journals (Sweden)

    Greiner Richard

    2008-09-01

    Full Text Available Abstract Background To use amifostine concurrently with radiochemotherapy (CT-RT or radiotherapy (RT alone in order to prevent dry eye syndrome in patients with malignancies located in the fronto-orbital region. Methods Five patients (2 males, 3 females with diagnosed malignancies (Non-Hodgkin B-cell Lymphoma, neuroendocrine carcinoma involving the lacrimal gland, in which either combined CT-RT or local RT were indicated, were prophylactically treated with amifostine (500 mg sc. Single RT fraction dose, total dose and treatment duration were individually adjusted to the patient's need. Acute and late adverse effects were recorded using the RTOG score. Subjective and objective dry eye assessment was performed for the post-treatment control of lacrimal gland function. Results All patients have completed CT-RT or RT as indicated. The median total duration of RT was 29 days (range, 23 – 39 days and the median total RT dose was 40 Gy (range, 36 – 60 Gy. Median lacrimal gland exposure was 35.9 Gy (range, 16.8 – 42.6 Gy. Very good partial or complete tumor remission was achieved in all patients. The treatment was well tolerated without major toxic reactions. Post-treatment control did not reveal in any patient either subjective or objective signs of a dry eye syndrome. Conclusion The addition of amifostine to RT/CT-RT of patients with tumors localized in orbital region was found to be associated with absence of dry eye syndrome.

  20. Development and Validation of an HPLC Method for Determination of Amifostine and/or Its Metabolite (WR-1065) In Human Plasma Using OPA Derivatization and UV Detection

    OpenAIRE

    Samiei, Nasim; FOROUTAN, SEYED MOHSEN; Shafaati, Alireza; Zarghi, Afshin

    2015-01-01

    A rapid, sensitive and reproducible HPLC method was developed and validated for the analysis of amifostine (AMF) and/or its metabolite, WR-1065 in human plasma. The method involves the alkylation of free sulfydryl group with iodoacetic acid followed by derivatization of the drug and its metabolite with o-phthaldialdehyde (OPA) and UVdetection at 340 nm. The derivatized AMF and WR-1065 were eluted in less than 11 min, and in the case of the metabolite with no interferences from the endogenous ...

  1. Concurrent administration of Docetaxel and Stealth® liposomal doxorubicin with radiotherapy in non-small cell lung cancer : excellent tolerance using subcutaneous amifostine for cytoprotection

    OpenAIRE

    Koukourakis, M I; Romanidis, K.; Froudarakis, M; Kyrgias, G; Koukourakis, G V; Retalis, G; Bahlitzanakis, N

    2002-01-01

    The substantial augmentation of the radiation sequelae during chemo–radiotherapy with novel drugs masks the real potential of such regimens. In this study we examined whether subcutaneous administration of amifostine can reduce the toxicity of a highly aggressive chemo–radiotherapy scheme with Stealth® liposomal doxorubicin (Caelyx®) and Docetaxel (Taxotere®) in non-small cell lung cancer. Twenty-five patients with stage IIIb non-small cell lung cancer were recruited in a phase I/II dose esca...

  2. 氨磷汀用于化疗患者的临床观察%Observation on the Clinical Effects of Amifostine for Patients Received Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    陈黎; 范开席

    2003-01-01

    为观察氨磷汀(Amifostine)疗效及副作用,对 25 例恶性肿瘤患者化疗前应用氨磷汀后的多项临床指标进行自身对照分析.结果显示,氨磷汀能减轻化疗对骨髓、肝功能及神经系统的毒性,副作用有恶心、呕吐、一过性血压下降等.观察结果认为氨磷汀是一种很有前途的正常细胞保护药物.

  3. 化学保护剂阿米福汀在晚期胃癌病人中的应用%Chemoprotection of amifostine in advanced gastric cancer patients

    Institute of Scientific and Technical Information of China (English)

    龚丽萍; 尹鸣

    2004-01-01

    目的研究化疗保护剂阿米福汀(amifostine)对晚期胃癌化疗病人的应用价值.方法采用自身对照,对比单纯化疗组与阿米福汀+静脉化疗组的毒副反应.结果阿米福汀+静脉化疗组消化道反应有所增加,总体毒副反应较单纯化疗组明显减少,但无统计学差异(P=0.225).结论阿米福汀作为高效、安全的化疗保护剂,值得在大剂量化疗以及既往化疗出现明显毒副反应的患者中应用.

  4. 氨磷汀在化疗中细胞保护作用的观察%Cell-protection effects of Amifostine for chemotherapy

    Institute of Scientific and Technical Information of China (English)

    孙玉蓓; 江丰收; 胡冰

    2004-01-01

    目的探讨Amifostine在肿瘤患者化疗中的细胞保护作用.方法对20例既往化疗前有Ⅰ°~Ⅳ°度血液学、肾脏、肝脏毒性的患者化疗前应用Amifostine.结果入组病人化疗前用amifostine与未用amifostine的血液学毒性、肾脏毒性的差异有显著性(P<0.05).结论Amifostine在化疗前应用是一种有效的细胞保护剂.

  5. 氨磷汀防治奥沙利铂神经毒性的临床研究%Clinical Study of Amifostine for Preventing Oxaliplatin-Induced Neurotoxicity

    Institute of Scientific and Technical Information of China (English)

    陈旭烽; 王永辉; 楼建

    2011-01-01

    Objective To assess the clinical efficacy of amifostine in preventing neurotoxicity induced by oxaliplatin. Methods A total of 80 patients with colorectal cancer or gastric cancer were enrolled and randomly assigned to the experimental group (amifostine, 40 cases) and the control group(40 cases). All cases received the chemotherapy with FOLFOX4 regimen. The experimental group was given amifostine 8 mg, dexamethasone 5 mg amifostine 500 mg/m2 just before chemotherapy, while the control group was given only amifostine 8 mg and dexamethasone 5 mg. The neurological toxicity was assessed in each therapeutical cycle. Results Twenty- two point five percent cases in amifostine group occurred degree Ⅰ- Ⅱ peripheral neurotoxicity after 6 therapeutical cycles of chemotherapy, which was significantly lower than 47. 50% in the control group( P<0. 01). Seven point five percent cases in amifostine group occurred degree Ⅲ peripheral neurotoxicity,which was significantly lower than 17.50% in the control group(P <0. 05). The occurrence rate of other adverse reactions had no obvious difference between the two groups. Conclusion Amifostine could prevent the occurrence of oxaliplatin- induced neurotoxicity and reduce its severity in the patients with digestive tract tumors.%目的 研究氨磷汀防治奥沙利铂神经毒性的临床效果.方法 将80例奥沙利铂胃肠道肿瘤患者随机均分为试验组和对照组,所有患者均采用含奥沙利铂的FOLFOX4方案进行化学治疗,化学治疗前试验组使用昂丹司琼8 mg、地塞米松5 mg和氨磷汀500 mg/m2,对照组仅予昂丹司琼8 mg和地塞米松5 mg.每个治疗周期评估患者外周神经毒性.结果 6个周期的化学治疗后,氨磷汀组有22.50%的患者发生Ⅰ~Ⅱ度外周神经毒性,明显低于对照组的47.50%(P<0.01),有7.50%的患者发生Ⅲ度外周神经毒性,显著低于对照组的17.50%(P<0.05).其他化学治疗相关毒副反应发生率两

  6. Analysis of the cytoprotective effect of amifostine on the irradiated inner ear of guinea pigs: an experimental study Análise do efeito citoprotetor da amifostina na orelha interna irradiada de cobaias: estudo experimental

    Directory of Open Access Journals (Sweden)

    Ricardo Miranda Lessa

    2009-10-01

    Full Text Available Radiation can cause damage to the inner ear, from a simple hearing loss all the way to profound deafness. Amifostine is a cytoprotective substance extensively used during radio-chemotherapy for malignant tumors. AIM: the objective of the present investigation was to establish the antioxidant and radioprotective effects of amifostine on the organ of Corti of albino guinea pigs irradiated in the head and neck region. MATERIALS AND METHODS: An experimental study conducted on four groups of guinea pigs were used; One group received only amifostine, one group was submitted to a single dose of 350 cGy and the other two were similarly irradiated but received amifostine doses of 100 or 200 mg/kg. All animals were slaughtered 30 days after the experiment, their bullae were removed and the damaged outer hair cells were counted. RESULT: The extent of injury was lower in the outer hair cells of the two groups treated with amifostine compared to the group that was only irradiated. There was no difference between the group treated with 100 and 200 mg/kg of amifostine. The group that received only amifostine had no cochlear damage. CONCLUSION: Amifostine is an effective cytoprotective substance in the Organ of Corti of irradiated guinea pigs.A radiação pode causar lesão na orelha interna podendo provocar surdez sensório-neural e inclusive levar à anacusia. A amifostina é uma substância citoprotetora seletiva de tecidos sadios, amplamente utilizada durante a radio e quimioterapia de tumores malignos. OBJETIVO: O objetivo deste estudo experimental foi verificar se existe efeito antioxidante e radioprotetor da amifostina no órgão de Corti de cobaias albinas irradiadas em região de cabeça e pescoço. MATERIAL E MÉTODO: O estudo realizado envolveu quatro grupos de animais: um grupo foi submetido à irradiação em dose única de 350cGy. Dois grupos receberam a mesma dose de radiação, porém receberam doses de 100 e 200mg/kg de amifostina, 30 minutos

  7. The Role of Amifostine in Treating Idiopathic Thrombocytopenic Purpura%氨磷汀在治疗特发性血小板减少性紫癜中的作用

    Institute of Scientific and Technical Information of China (English)

    靳英; 李明阳; 刘波; 张伟; 朱宏丽

    2012-01-01

    特发性血小板减少性紫癜(ITP)并不少见,该病诊断不难,治疗方法多.但本例患者高龄、既往治疗出现副作用,用药受限,常规药物效果不佳,经氨磷汀治疗而使患者得以痊愈,目前已随访观察5个月无复发.结合文献,氨磷汀对高龄、难治性病例安全有效,提示氨磷汀可能是ITP治疗中一种较有潜力的药物.%This is to discuss Amifostine mechanism by analyzing one case with Idiopathic Thromhocytopenic Purpura (ITP). ITP is not difficult to diagnozed. Many drugs are used to treat it. One 92 —year—old male patient with 1TP was not ameliorated by routine treatment. Finally he was cured by Amifostine . Then he was followed —up for 5 months without recurrence. We can say that Amifostine is safe and effective, further more it is possible a potentional medicine to cure elderly serious ITP.

  8. 观察氨磷汀对肺癌化疗患者血液学的保护作用%Hematological protective effects of amifostine for lung cancer chemotherapy patients

    Institute of Scientific and Technical Information of China (English)

    吕振选; 王丽萍; 樊青霞; 王留兴; 王瑞林

    2011-01-01

    Objective To study the hematological protective effects of amifostine on lung cancer patients receiving chemotherapy. Methods Fifty-seven patients were treated by two kinds of treatments: one was chemotherapy (control group), the other was chemotherapy plus amifostine (treatment group).Hematological toxicity was observed before and after chemotherapy.Results Hematological toxicity of treatment group reduced obviously,compared with control group. Conclusions Amifostine can apparently reduce the hematological toxicity of patients receiving chemotherapy.%目的 观察氨磷汀对肺癌化疗患者的减轻血液学毒性作用.方法 将57例肺癌患者分为对照组(化疗第1周期,未用氨磷汀)和治疗组(化疗第2周期,联用氨磷汀)进行自身对照观察,化疗前后监测血液学毒性.结果 化疗后血液学毒性治疗组较对照组明显降低.结论 氨磷汀可明显减少肺癌患者化疗相关性血液学毒性.

  9. Clinical study on amifostine for preventing bortezomib - induced peripheral neuropathy%阿米福汀在预防硼替佐米所致周围神经病变中的疗效观察

    Institute of Scientific and Technical Information of China (English)

    王建芳; 王洪涛; 李迎春; 苗苗; 刘卓刚

    2012-01-01

    Objective To evaluate the efficacy of amifostine for preventing bortezomib - induced peripheral neuropathy. Methods A total of 54 cases of multiple myeloma in our hospital from June 2008 to June 2011 were retrospectively analyzed, 30 patients in control group received bortezomib and dexamethasone therapy and 24 patients in prevention group undergoing the additional amifostine. Results The rates of peripheral neuropathy in control group and prevention group were 46. 7% and 33.3% (P > 0. 05 ). Conclusion Amifostine has no significant preventive effect on bortezomib - induced peripheral neuropathy%目的 评价阿米福汀在预防硼替佐米所致周围神经病变中的疗效.方法 回顾性分析本院多发性骨髓瘤患者(MM)54例,对照组接受硼替佐米+地塞米松治疗(30例),预防组接受硼替佐米+地塞米松+阿米福汀治疗(24例).结果 对照组周围神经病变发病率为46.7%,预防组为33.3%,两组无显著性差异(P>0.05).结论 阿米福汀在预防硼替佐米所致周围神经病变中无明显作用.

  10. 磷酸钙骨水泥/氨磷汀/顺铂复合体体外药物缓释及体内修复骨缺损和抑瘤实验%Drug Delivery of CPC/Amifostine/Cisplatin Complex in vitro and Its Ability in Repairing Bone Defect and Eliminating Tumor in vivo

    Institute of Scientific and Technical Information of China (English)

    刘彦宁; 刘淼; 任鹏宇

    2010-01-01

    目的 探讨磷酸钙骨水泥/氨磷汀/顺铂(CPC/amifostine/cisplatin)复合体在填充和重建肿瘤性骨缺损中的可行性.方法 在体外测定CPC/amifostine/cisplatin复合体缓释药物的情况,建立兔股骨骨缺损和裸鼠骨肉瘤模型,植入CPC/amifostine/cisplatin复合体后测定缺损修复情况和对肿瘤的抑制能力.结果 CPC/amifostine/cisplatin复合体和CPC具有相似的骨修复情况,同时具有CPC所没有的持续缓释药物的能力和抑制骨肉瘤生长的能力.结论 CPC/amifostine/cisplatin复合体用作肿瘤性骨缺损的填充材料是可行的.

  11. The effect of amifostine on Survivin expression in HL-60 cells in vitro%亚砷酸联合阿米福汀对HL-60细胞中Survivin表达的影响

    Institute of Scientific and Technical Information of China (English)

    武婕萍; 马梁明; 周永安; 朱镭

    2008-01-01

    目的 探讨亚砷酸(As2O3)联合阿米福汀(AMI)诱导人髓系白血病细胞HL-60凋亡的可能机制.方法 不同浓度As2O3,单用和联合AMI对HL-60细胞进行不同时间干预,用MTT比色法检测细胞的生长抑制作用,用半定量RT-PCR法检测抑凋亡基因Survivin mRNA的表达水平.结果 As2O3组和联合组均可显著抑制HL-60细胞的增生,呈浓度依赖性,联合组对其抑制作用明显大于As2O3组.联合组降低Survivin的表达作用比As2O3组更明显.结论 As2O3通过下调抑凋亡基因Survivin的表达诱导HL-60凋亡;AMI可增强As2O3对Survivin的下调作用,增强HL-60细胞对As2O3的敏感性,发挥促凋亡效应.%Objective To explore the mechanisms of apoptosis induced by arsenic trioxide and amifostine in human acute promyelocytic leukemia cell lines HL-60 in vitro.Methods HL-60 cells were treated with different concentrations of arsenic trioxide alone and combined with amifostine.The inhibitory ratio of the ceils were measured by MTT assay.and the expression of Survivin Was detected by semiquantitate RT-PCR.Results Proliferation of HL-60 cells exposed to arsenic trioxide dwpped down with increasing dose of the dmg and this effect Was significantly hisher when arsenic trioxide Was used in combination with amifostine.Furthermore.there was a more significant decrease in Survivin expression in HL-60 cells treated with arsenic trioxide in combination with amifostine as compared to the cells treated only with arsenic trioxide.Conclusion Arsenic trioxide induced HL-60 cells to undergo apoptosis by downregulating the expression of Survivin. Amifostine enhanced the sensitivity of HL-60 cells to arsenic trioxide by downregulating the expression of Survivin,thus promoting apoptosis effect.

  12. Prediction and Bioinformatics Analysis of Human Gene Expression Profiling Regulated by Amifostine%依硫磷酸调控人类基因表达谱的预测及生物信息学分析

    Institute of Scientific and Technical Information of China (English)

    杨波; 脱朝伟; 蔡力力; 迟小华; 卢学春; 张峰; 脱帅; 朱宏丽; 刘丽宏; 严江伟

    2011-01-01

    Objective of this study was to perform bioinformatics analysis of the characteristics of gene expression profiling regulated by amifostine and predict its novel potential biological function to provide a direction for further exploring pharmacological actions of amifostine and study methods. Amifostine was used as a key word to search intemet-based free gene expression database including GEO, affymetrix gene chip database, GenBank, SAGE,GeneCard, InterPro, ProtoNet, UniProt and BLOCKS and the sifted amifostine-regulated gene expression profiling data was subjected to validity testing, gene expression difference analysis and functional clustering and gene annotation. The results showed that only one data of gene expression profiling regulated by amifostine was sifted from GEO database (accession: GSE3212). Through validity testing and gene expression difference analysis, significant difference (p <0.01 ) was only found in 2.14% of the whole genome (460/192000). Gene annotation analysis showed that 139 out of 460 genes were known genes, in which 77 genes were up-regulated and 62 genes were down-regulated. 13 out of 139 genes were newly expressed following amifostine treatment of K562 cells, however expression of 5 genes was completely inhibited. Functional clustering displayed that 139 genes were divided into 1 l categories and their biological function was involved in hematopoietic and immunologic regulation, apoptosis and cell cycle. It is concluded that bioinformatics method can be applied to analysis of gene expression profiling regulated by amifostine. Amifostine has a regulatory effect on human gene expression profiling and this action is mainly presented in biological processes including hematopoiesis,immunologic regulation, apoptosis and cell cycle and so on. The effect of amifostine on human gene expression need to be further testified in experimental condition.%本研究对依硫磷酸调控人类基因表达谱进行生物信息学分析,预测其可

  13. Amifostine alleviates radiation-induced lethal small bowel damage via promotion of 14-3-3σ-mediated nuclear p53 accumulation.

    Science.gov (United States)

    Huang, Eng-Yen; Wang, Feng-Sheng; Chen, Yu-Min; Chen, Yi-Fan; Wang, Chung-Chi; Lin, I-Hui; Huang, Yu-Jie; Yang, Kuender D

    2014-10-30

    Amifostine (AM) is a radioprotector that scavenges free radicals and is used in patients undergoing radiotherapy. p53 has long been implicated in cell cycle arrest for cellular repair after radiation exposure. We therefore investigated the protective p53-dependent mechanism of AM on small bowel damage after lethal whole-abdominal irradiation (WAI). AM increased both the survival rate of rats and crypt survival following lethal 18 Gy WAI. The p53 inhibitor PFT-α compromised AM-mediated effects when administered prior to AM administration. AM significantly increased clonogenic survival in IEC-6 cells expressing wild type p53 but not in p53 knockdown cells. AM significantly increased p53 nuclear accumulation and p53 tetramer expression before irradiation through the inhibition of p53 degradation. AM inhibited p53 interactions with MDM2 but enhanced p53 interactions with 14-3-3σ. Knockdown of 14-3-3σ also compromised the effect of AM on clonogenic survival and p53 nuclear accumulation in IEC-6 cells. For the first time, our data reveal that AM alleviates lethal small bowel damage through the induction of 14-3-3σ and subsequent accumulation of p53. Enhancement of the p53/14-3-3σ interaction results in p53 tetramerization in the nucleus that rescues lethal small bowel damage. PMID:25230151

  14. 阿米福汀保护肾脏的疗效观察%Amifostin in protection of kidney from cisplatinum injury

    Institute of Scientific and Technical Information of China (English)

    崔慧娟; 张树军; 李佩文; 管忠震; 孙晓菲; 沈铿; 吴明; 胡小电; 刘淑俊; 邸立军; 张树才

    2002-01-01

    目的观察阿米福汀(amifostin)保护肾脏免受顺铂(DDP)损害的疗效及药物不良反应和安全性.方法 193例恶性肿瘤患者随机分为化疗加阿米福汀组(观察组)和单纯化疗组(对照组),观察组102例,对照组91例.观察组和对照组患者于疗前和疗后不同时期分别测定其血象、血钙、肝功能、血尿素氮(BUN)、肌酐(Cr)、尿N-乙酰-β-D-氨基葡萄糖苷酶与肌酐比值(NAG/C)和尿微量白蛋白与肌酐的比值(MAB/C).结果观察组2个疗程的第2天,其MAB/C与疗前的差值低于对照组第2天的MAB/C与疗前的差值,经统计学检验,P0.05).阿米福汀的副作用为轻度的血压降低和恶心呕吐及部分患者低血钙.

  15. 氨磷汀治疗苯致骨髓增生异常综合征五例%Amifostine in treatment of five patients with myelodysplastic syndrome

    Institute of Scientific and Technical Information of China (English)

    钱红兰; 沈志坚; 胡旭东; 胡永仙; 俞康

    2006-01-01

    长期接触苯可引起慢性苯中毒,以造血系统损害为主要表现,早期可出现白细胞下降、血小板减少,甚至全血细胞减少,严重者可引起再生障碍性贫血、骨髓增生异常综合征(MDS)或白血病.国内时有报道慢性苯中毒致MDS,但对于氨磷汀(amifostine,WR-2721)治疗苯致MDS的疗效尚无人报道.氨磷汀是一种特异性的全细胞保护剂,在国外已有人将其用于对抗MDS的无效造血.我们应用氨磷汀治疗苯致MDS患者并观察了其疗效,现将2003年10月至2005年8月我科收治5例患者的疗效报告如下.

  16. Development and Validation of an HPLC Method for Determination of Amifostine and/or Its Metabolite (WR-1065) In Human Plasma Using OPA Derivatization and UV Detection.

    Science.gov (United States)

    Samiei, Nasim; Foroutan, Seyed Mohsen; Shafaati, Alireza; Zarghi, Afshin

    2015-01-01

    A rapid, sensitive and reproducible HPLC method was developed and validated for the analysis of amifostine (AMF) and/or its metabolite, WR-1065 in human plasma. The method involves the alkylation of free sulfydryl group with iodoacetic acid followed by derivatization of the drug and its metabolite with o-phthaldialdehyde (OPA) and UVdetection at 340 nm. The derivatized AMF and WR-1065 were eluted in less than 11 min, and in the case of the metabolite with no interferences from the endogenous plasma peaks. Cystein was used as the internal standard. Analysis was carried out on a Eurosphere Performance (RP-18e, 100 × 4.6 mm) analytical column. The mobile phase was a mixture of methanol and phosphate buffer 0.03 M pH = 2.7 at a ratio of 40: 60v/v, respectively, with a flow rate of 1.5 mLmin(-1). Limit of detection was 0.5 µgmL(-1). The method involved a simple extraction procedure for AMF and/or its metabolite and analytical recovery was 90 ± 0.9%.The calibration curve was linear over the concentration range of 1-200 µgmL(-1). The coefficients of variation for intra-day and inter-day assays were less than 10%. PMID:26664371

  17. 氨磷汀对化疗药物抗卵巢癌细胞的影响%Effect of amifostine on chemistry anticese avarian cancer cell

    Institute of Scientific and Technical Information of China (English)

    王根菊; 韩国荣; 叶银英; 余敏敏

    2006-01-01

    目的评价细胞保护剂氨磷汀(amifostine)对不同化疗药物抗卵巢癌细胞的影响.方法用MTT法分别测定顺铂、长春新碱、依托泊甙和丝裂霉素对体外培养的Ho-8910肿瘤细胞系的抑制作用,实验组加化疗药前30 min经600mg·L-1氨磷汀处理,对照组不用氨磷汀处理,余同实验组,培养后比较两组细胞增殖的抑瘤率.结果实验组与对照组比较,两组肿瘤细胞抑制率无显著性差异(P>0.05).结论氨磷汀不影响顺铂、依托泊甙、丝裂霉素和长春新碱对Ho-8910肿瘤细胞的抑制作用.

  18. Phase I North Central Cancer Treatment Group Trial-N9923 of escalating doses of twice-daily thoracic radiation therapy with amifostine and with alternating chemotherapy in limited stage small-cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: The primary goal was to identify the maximum tolerable dose (MTD) of thoracic radiation therapy (TRT) that can be given with chemotherapy and amifostine for patients with limited-stage small-cell lung cancer (LSCLC). Methods and Materials: Treatment began with two cycles of topotecan (1 mg/m2) Days 1 to 5 and paclitaxel (175 mg/m2) Day 5 (every 3 weeks) given before and after TRT. The TRT began at 6 weeks. The TRT was given in 120 cGy fractions b.i.d. and the dose escalation (from 4,800 cGy, dose level 1, to 6,600 cGy, dose level 4) followed the standard 'cohorts of 3' design. The etoposide (E) (50 mg/day) and cisplatin (C) (3 mg/m2) were given i.v. before the morning TRT and amifostine (500 mg/day) was given before the afternoon RT. This was followed by prophylactic cranial irradiation (PCI). The dose-limiting toxicities (DLTs) were defined as Grade ≥4 hematologic, febrile neutropenia, esophagitis, or other nonhematologic toxicity, Grade ≥3 dyspnea, or Grade ≥2 pneumonitis. Results: Fifteen patients were evaluable for the Phase I portion of the trial. No DLTs were seen at dose levels 1 and 2. Two patients on dose level 4 experienced DLTs: 1 patient had a Grade 4 pneumonitis, dyspnea, fatigue, hypokalemia, and anorexia, and 1 patient had a Grade 5 hypoxia attributable to TRT. One of 6 patients on dose level 3 had a DLT, Grade 3 esophagitis. The Grade ≥3 toxicities seen in at least 10% of patients during TRT were esophagitis (53%), leukopenia (33%), dehydration (20%), neutropenia (13%), and fatigue (13%). The median survival was 14.5 months. Conclusion: The MTD of b.i.d. TRT was 6000 cGy (120 cGy b.i.d.) with EP and amifostine

  19. Results of a planned interim toxicity analysis with trimodality therapy, including carboplatin AUC = 4, paclitaxel, 5-fluorouracil, amifostine, and radiation for locally advanced esophageal cancer: preliminary analyses and treatment recommendations from the North Central Cancer Treatment Group

    OpenAIRE

    Jatoi, Aminah; Martenson, James; Mahoney, Michelle R; Lair, Bradley S; Brindle, Jeffrey S; Nichols, Frank; Caron, Normand; Rowland, Kendrith; Tschetter, Loren; Alberts, Steven

    2004-01-01

    Purpose An aggressive trimodality approach from the Minnie Pearl Cancer Research Network [carboplatin AUC = 6, days 1 and 22; 5-fluorouracil 225 mg/m2 continuous infusion, days 1–42, paclitaxel 200 mg/m2, days 1 and 22; 45 Gy] has resulted in remarkable pathologic response rates but notable toxicity. This trial was designed to mitigate this toxicity by starting with a lower carboplatin dose, AUC = 4, and by adding subcutaneous amifostine. Methods This phase II trial included patients with loc...

  20. The intervention of amifostine in idiopathic thrombocytopenic purpura mouse%氨磷汀对免疫性血小板减少性紫癜动物模型小鼠的干预作用

    Institute of Scientific and Technical Information of China (English)

    周国坚; 王桂明; 蔡小连

    2013-01-01

      目的探讨氨磷汀对免疫性血小板减少性紫癜(ITP)动物模型小鼠血小板、脾脏系数、骨髓巨噬细胞的影响。方法通过获取BALB/C 小鼠血小板抗体,接种到豚鼠身上,获取豚鼠抗小鼠血小板抗体(APS)。将APS腹腔注射BALB/C 小鼠建立免疫性血小板减少性紫癜动物模型,使用氨磷汀腹腔注射进行治疗,观察氨磷汀对模型小鼠的血小板、脾脏系数、骨髓巨噬细胞的影响。结果氨磷汀给药后均使ITP模型小鼠血小板计数上升、脾脏系数减少、骨髓成熟巨核细胞增多,与模型组比较差异有统计学意义(P<0.01)。结论氨磷汀对免疫性血小板减少性紫癜有较为明显的治疗效果。%Objective To study the effect of amifostine on mice models of idiopathic thrombocytopenic purpura(ITP). Methods Guinea pig anti mice platelet serum(GP-APS) was diluted with saline(1:4),and intravitreal injected into mice once in 2 days for 10 days.Two dosage of amifostine was intravitreal injected into mice in 10 days since mice models of ITP were established. Results Amifostine can enhance the amount of platelets,promote the mature of megakaryocyte of mice significantly and improve the histological pathology of spleen. Conclusion Amifostine is an effective and safety medicine in treating ITP, and can be used widely in clinic.

  1. Analysis of amifostine content of amifostine PLGA microsphere by HPLC with pre-column derivatization%高效液相色谱-荧光胺柱前衍生法测定氨磷汀微球中氨磷汀的含量

    Institute of Scientific and Technical Information of China (English)

    孙伟光; 卢婷利; 陈涛; 于洋

    2009-01-01

    OBJECTIVE To establish an HPLC method with pre-column derivatization to determine amifostine in amifostine PLGA microsphere. METHODS After pre-column derivatization with fluorescamine at alkaline condition, the derivatives were injected and separated on a Agilent HC-C18eolumn (250 minx 4. 6 mm,5 μm), with acetonitrile-water-10% phosphoric acid (25 :75:1 )as mobile phase. The fluorescence detector was operated at excitation and emission wavelengths of 395 and 480 nm, re-spectively. The flow rate was 1.0 mL min-1. RESULTS Arnifostine derivatives showed good linearity (r=0. 999 9) in the range of 0. 4-4. 0 mg. L-1. The average recoveries (r=3) of low, middle and high concentration were 95. 83%, 94. 66%,96. 15% with RSD of 1.6%, 1.8%, 1.5% respectively. CONCLUSION The method is simple, rapid, reliable and accurate.%目的:建立一种测定氨磷汀聚乳酸乙醇酸共聚物(PLGA)微球中氨磷汀含量的方法.方法:样品与荧光胺试剂碱性条件下衍生化后,以Agilent HC-C18柱(250 mm×4.6 mm,5 μm)分离,以乙晴-水-10%磷酸溶液(25:75:1)为流动相.流速为1mL·min-1,以荧光检测器检测,激发波长为395 nm,发射波长为480 nm.结果:氨磷汀样品在0.4~4.0 mg·L-1范围内与其峰面积有良好的线性关系(r=0.999 9).低、中、高3个浓度的回收率(n=9)分别为95.83%,94.66%,96.15%;RSD分别为1.6%,1.8%,1.5Z.结论:该方法灵敏度高,准确迅速,重复性好,能够满足氨磷汀微球中氨磷汀含量的分析测定.

  2. Clinically Meaningful Differences in Patient-Reported Outcomes With Amifostine in Combination With Chemoradiation for Locally Advanced Non-Small-Cell Lung Cancer: An Analysis of RTOG 9801

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study is to analyze changes in quality of life (QOL) and symptoms from pretreatment to 6 weeks posttreatment in a Phase III randomized study (Radiation Therapy Oncology Group 9801) of amifostine (AM) vs. no AM in patients with Stages II-III non-small-cell lung cancer receiving paclitaxel and carboplatin as induction and then concurrently with hyperfractionated radiation therapy (RT). Methods and Materials: One hundred thirty-eight patients with baseline and 6-week posttreatment QOL data were analyzed. There were no significant differences in baseline demographics between those who did and did not have QOL data. The QOL and symptoms were assessed by using the European Organization for Research and Treatment of Cancer (EORTC) Global QOL and Pain subscales and the EORTC-Lung Cancer-13 symptom tool. Clinically relevant changes in QOL were characterized by 10-point differences in individual scores pre/post treatment. A daily diary of patient-rated difficulty swallowing and a weekly physician-rated dysphagia log (using National Cancer Institute Common Toxicity Criteria) were completed during treatment. Weight loss was monitored. Differences in outcomes were examined according to smoking status, alcohol use, and sex. Results: Patients receiving AM reported significantly greater pain reduction after chemoradiation (34% vs. no AM, 21%), less difficulty swallowing during chemoradiation, and less weight loss than patients not receiving AM. However, physician-rated assessments of dysphagia were not significantly different by treatment arm. There were no other significant changes in QOL or symptoms according to treatment arm, smoking status, alcohol use, or sex. Conclusions: Patient evaluations of difficulty swallowing and pain suggest benefits from AM use that are distinct from clinician-rated assessments

  3. 阿米福汀对直肠癌同步放化疗患者的保护作用%Protective effect of amifostine in the concurrent radiochemotherapy for patients with rectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    牛楠; 杨明丽; 陈威; 曾越灿; 吴荣

    2016-01-01

    目的:探讨阿米福汀(AMI)对直肠癌同步放化疗患者的保护作用。方法选取经病理组织学证实的直肠癌患者80例,随机分为治疗组和对照组,每组各40例。所有患者均予盆腔适形调强放射治疗及口服卡培他滨同步化疗。治疗组在同步放化疗基础上加用AMI治疗,观察两组患者的不良反应,并进行对比分析。结果治疗组Ⅱ~Ⅳ级急性直肠炎的发生率为12.5%,明显低于对照组的32.5%,差异具有统计学意义(P﹤0.05);两组患者均无Ⅲ~Ⅳ级泌尿系统不良反应发生;治疗组中性粒细胞减少发生率为22.5%,明显低于对照组的45%,差异具有统计学意义(P﹤0.05)。AMI相关不良反应有:低血压2例,Ⅲ级呕吐2例,面部温热感1例;无因AMI相关不良反应而中断治疗者。结论 AMI可预防或减轻放化疗带来的不良反应,值得临床推广应用。%Objective To observe the protective effects of amifostine in the concurrent radiochemotherapy for pa-tients with rectal carcinoma. Method 80 patients with pathologically confirmed rectal carcinoma were randomized into study group or control group, with 40 cases in each. All patients were treated by general treatment of intensity modulated radiation therapy (IMRT) and oral capecitabine concurrent chemotherapy. While the patients in the study group were giv-en intravenous amifostine additionally on the basis of general treatment, the adverse reactions in both two groups were ob-served and comparatively analyzed. Result The incidence of acute proctitis of grade Ⅱ~Ⅳ was 12.5%, significantly lower in the study group compared with the control group at 32.5%(P<0.05);no acute cystitis of gradeⅢ~Ⅳwas found in neither groups;the incidence of neutropenia was 22.5%in study group, which was significantly lower than that of con-trol group at 45%(P<0.05). Amifostine-related adverse reactions included:2 cases of hypotension, 2 cases of grade

  4. Effects of amifostine on microglial injury induced by glutamate%氨磷汀对谷氨酸所致N9小胶质细胞损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    张霞婧; 何二涛; 贾济; 朱萧玲; 王强; 朱正华; 胡胜; 陈绍洋

    2012-01-01

    目的 观察氨磷汀对谷氨酸( glutamate,Glu)所致N9小胶质细胞损伤的保护作用.方法 建立Glu损伤模型,探索最适氨磷汀浓度,实验分4组:空白对照组(Con组),正常培养小胶质细胞24 h;Glu损伤组(Glu组),含10 mmol/L Glu的培养基处理N9细胞24 h;氨磷汀组(Ami+Glu组),含1 mmol/L氨磷汀和10 mmol/L Glu的培养基处理N9细胞24 h;TBOA组(Ami+TBOA+Glu组),含100 μmol/L TBOA、1 mmol/L氨磷汀和10 mmol/L Glu的培养液培养N9小胶质细胞24h.采用四甲基偶氮唑盐(MTT)法检测细胞代谢率,检测培养液乳酸脱氢酶(lactate dehydrogenase,LDH)、超氧化物歧化酶(superoxide dismutase,SOD)、一氧化氮(nitrogen monoxide,NO)的含量,收集贴壁细胞超声破碎,检测谷胱甘肽(glutathione,GSH)含量.结果 与损伤组比较,1 mmol/L氨磷汀保护组细胞代谢率(88.9±1.7)%升高(P<0.05),LDH释放量(141±40)%减少(P<0.05),SOD含量(128±13)%增加(P<0.01),GSH含量(88±8)%增加(P<0.01),NO释放量(147±34)%下降(P<0.01);该作用可被兴奋性氨基酸转运体(excitatory amino acid transporter,EAAT)拮抗剂TBOA逆转.结论氨磷汀通过抗氧化机制减轻Glu对N9小胶质细胞的损伤.%Objective To investigate the effects of Amifostine on glutamate (Glu) induced microglia injury. Methods There are 4 groups:Con group,N9 microgial was cultured normally for 24 h,Glu group,N9 microgial was treated with 10 mmol/L Glu,Ami+Glu group,N9 microgial was treated with 1 mmol/L Amífostine and 10 mmol/L Glu,Ami+TBOA+Glu group,N9 microgial was treated with 100 μmol/L TBOA, 1 mmol/L Amifostine and 10 mmol/L Glu for 24 h.Metabolism of microglial,lactate dehydrogenase (LDH) release,superoxide dismutase (SOD) activity,nitrogen monoxide (NO) release and glutathione (GSH) level were evaluated. Results As compared to control group,microglial metabolism (88.9±1.7)% increased (P<0.05),SOD activity (128±13)% increased (P<0.01) and GSH level(88±8)% increased

  5. Assessment research of the protective effect of Amifostine on radiation-induced lung injury of rats%阿米福汀对大鼠肺放射性肺损伤保护作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    梅欣; 章倩; 刘迎玫; 陈佳艺; 章真; 郭小毛

    2013-01-01

    Background and purpose:Radiation-induced lung injury is a common complication in thoracic tumor after radiation therapy. How to protect the lung tissues from radiation injury is very important during radiotherapy. As a kind of radiation-protective agents, this study aimed to assess the protective effects of amifostine on acute lung tissues’ radiation-induced injury in the rats by radiated with chest wall tangent technology. Methods:Thirty-five female Fish-344 rats were randomized into 2 arms of 2 different fraction schedule:Conventional fraction, 20 rats were irradiated in 50 Gy per 25 fractions in 25 days. They were further randomized into 2 subgroups:10 with amifostine and 10 rats radiation alone without drug. Single fraction, 15 rats irradiated with 20 Gy in one fraction to the right lung. Three subgroups were randomized as:5 rats in irradiation plus amifostine;5 rats irradiation alone and 5 in control subgroup. Amifostine (140 mg/kg) was given intraperitoneally 30 minutes before irradiation. Breathing rate, weight variation and plasmas of transforming growth factor-β(TGF-β) 1 levels were recorded after irradiation. The lung tissue of irradiated side and the same side of control group were processed for hematoxylin and eosin staining, Masson’s and Weigen’s staining and TGF-β1 immunohistochemistry staining. Results:In both arms, breathing rate increased in rats got irradiated, however, the coming time of fastest breathing rate delayed in rats with amifostine. There is no difference among all subgroups of TGF-β1 level in the plasma. Hematoxylin and eosin staining and Masson’s and Weigen’s staining revealed alveolar wall became thicker and the pulmonary tissue fibrosis in irradiation alone group. However, in the radiation with amifostine group, no matter what schedule of fractionation, much more of the lung architecture was preserved and fibrosis was lessened. Immunohistochemistry staining was expressed positive to strongly positive in irradiation

  6. 依硫磷酸对人慢性髓细胞白血病K562细胞系增殖的抑制作用%Inhibitory effect of amifostine on proliferation of human chronic myeloblastic leukemia K562 cell line

    Institute of Scientific and Technical Information of China (English)

    黄玉; 迟小华; 杨波; 张峰; 井绪臣; 卢学春; 朱宏丽; 宋东晓; 刘丽宏

    2011-01-01

    Objective To observe the effect of amifostine on proliferation of K562 cells. Methods Amifostine was proportionally diluted to 0.2mg/ml, 0.5mg/ml, 0.75mg/ml, l.Omg/ml, 1.6mg/ml, and 3.2mg/ml groups. K562 cells were incubated with different concentrations of amifostine and cell growth status was chronologically observed under a microscope. Cell proliferation was detected by CCK-8 assay and cell growth curve was plotted for calculating inhibition ratio. Results Amifostine could remarkably inhibit the proliferation of K562 cells with a cell doubling time of 48h. Amifostine inhibited the proliferation of K.562 cells in a time-and dose- dependent manner. The proliferation of K562 cells was significantly inhibited 48h after treatment with amifostine at the concentration of 0.75mg/ml or higher(P<0.05). The greatest inhibitory rate was 91% in 3.2mg/ml amifostine group with numerous cells died. Conclusion Amifostine can inhibit the proliferation of K562 cells, which provides an experimental basis for the treatment of hematological toxicity which is correlated with chemotherapy for chronic myeloid leukemia with amifostine.%目的 观察依硫磷酸对人慢性髓细胞白血病K562细胞系增殖的抑制作用.方法 依硫磷酸(粉末)以1640培养液稀释成0.2mg/ml、0.5mg/ml、0.75mg/ml、1.0mg/ml、1.6mg/ml、3.2mg/ml共6个浓度组,分别处理增殖期人慢性髓细胞白血病K562细胞,镜下观察不同时间点各浓度组细胞生长情况,应用CCK-8法检测细胞增殖能力,绘制生长曲线,计算抑制率和半数抑制浓度(IC50).结果 依硫磷酸对K562细胞增殖具有抑制作用,细胞倍增时间为48h,并且具有时间和剂量依赖性.在给药48h>0.75mg/ml浓度的依硫磷酸对K562细胞增殖具有抑制作用(P<0.05),而3.2mg/ml浓度的依硫磷酸与K562细胞培养72h后对其增殖抑制作用最强,抑制率为91%.结论 依硫磷酸对K562细胞增殖具有抑制作用,为临床应用依硫磷酸治疗慢性髓细胞白血病提供了实验基础.

  7. Clinical treatment of amifostine reduces radiation injury on head and neck cancer%氨磷汀减轻头颈部恶性肿瘤放疗损伤的临床观察

    Institute of Scientific and Technical Information of China (English)

    高玉伟; 尹立杰; 丁田贵; 王杰; 陈巍

    2012-01-01

    Objective To observe the Influence of amifostine combined with three dimensional-conformal radiotherapy (3 D-CRT) of head and neck cancer radiation injury effects. Methods 216 cases of patients with head and neck cancer were randomly divided into treatment group and control group. 108 patients in the control group were given 3D-CRT,the others in the treatment group were applied amifostine before the application of radiation. Results The elevated rate of Karnofsky score in the two groups was significantly different (P < 0. 05 ). The effective rates were 75. 0% vs 58. 3% (P > 0. 05) . The major toxicity (mucositis、 xerostomia、dysphagia、blood system toxicity、nervous system toxicity) in the treatment group was lower than that in the control group (P < 0. 05) . Conclusions Amifostine can reduce the head and neck cancer radiation injury, and improving patients quality of life without adverse effect on clinical curative effect.%目的 探讨氨磷汀联合三维适形放疗对头颈部恶性肿瘤放疗损伤的影响.方法 216例头颈部恶性肿瘤患者随机分为治疗组和对照组.每组108例,行三维适形放疗治疗,总剂量50~72Gy分28 ~40次5.6 ~8周完成.治疗组放射治疗前静脉点滴氨磷汀注射剂.结果 治疗组有效率为75.0%,对照组有效率为58.3%,两组差异无统计学意义(P>0.05).治疗组患者的生活质量评分提高率明显高于对照组,两组差异有统计学意义(P<0.05).治疗组黏膜炎、口干、吞咽困难、血液系统毒性、神经系统毒性发生率均明显低于对照组,两组差异有统计学意义(P<0.05).结论 氨磷汀可减轻头颈部恶性肿瘤放疗损伤,提高患者生存质量,并不影响临床疗效.

  8. Amifostine Effect on Protecting Normal Tissue From Radiation Therapy Due to Nasopharyngeal Carcinoma%阿米福汀在鼻咽癌放疗中对正常组织的保护作用分析

    Institute of Scientific and Technical Information of China (English)

    陈琳; 于瑞莲; 梁良

    2014-01-01

    目的:分析阿米福汀在鼻咽癌放疗中对正常组织的保护作用。方法选取2010年1月至2012年12月我科收治入院的鼻咽癌患者42例,分为阿米福汀组和对照组。阿米福汀组于放疗前30 min静脉滴注阿米福汀,对照组则进行常规放疗治疗,观察和比较两组患者放疗后产生的皮肤损伤、口腔黏膜损伤、口干等急性放射性损伤以及恶心呕吐等毒副反应。结果经阿米福汀联合治疗的患者放射性皮肤损伤、口腔黏膜损伤、口干等反应较对照组患者轻,具有统计学意义。结论阿米福汀在鼻咽癌放疗中能够保护正常组织细胞,有效降低了患者放射性损伤。%Objective To evaluate Amifostine effect on protecting normal tissue from radiation therapy due to NPC . Methods Forty two patients of NPC were divided into two groups .Radiation therapy(70 Gy)was given to all the patients.Ami-fostin was injected into the patients before 30 min in the treatment group .The control group without Amifostine .The radiation-in-duced skin damage、catarrh of oral cavity、xerostomia and side-effect were evaluated respectively .Results The radiation-induced skin damage、catarrh of oral cavity and xerostomia in the treatment group were remarkly slighter than in the control group .Conclu-sion Amifostine is able to protect normal tissue from radiation therapy due to NPC .

  9. 生物信息学方法优化依硫磷酸联合方案治疗骨髓增生异常综合征的应用研究%Application of bioinformatics analysis to optimize amifostine combination therapeutic regimen of myelodysplastic syndrome

    Institute of Scientific and Technical Information of China (English)

    卢学春; 杨波; 朱宏丽; 范辉; 李素霞; 刘洋; 姚善谦

    2009-01-01

    Objective To apply bioinformatics analysis to study the potential mechanism of amifostine for the treatment of myelodysplastie syndrome (MDS) and optimize amifostine combination regimen to further improve the efficacy and prognosis of MDS. Methods Bioinformatics analysis: internetbased human gene expression open database was used to predict the genomic profiling by regulation of amifostine and gene expression of MDS. And then possible target genes of amifostine were screened to predict the feasibility of amifostine combination regimen. Finally, similar analysis of gene expression profiling was conducted to forecast the potential therapeutic drugs for MDS. Clinical investigation: eighteen patients with MDS, non-responding to traditional drugs, were enrolled. According to the latest WHO classification, the patients were divided into 7 patients of refractory anemia (RA), 2 patients of refractory anemia with ring siderublust (RAILS) and 9 patients of refractory cytopenia with multilineage dysplasia (RCMD).Distributions of age was 19-91 years old (mean: 79). There were 17 males and 1 female. The regimen of amifostine plus recombinant human erythropoietin (rhEPO) was used to treat the MDS patients.Administration formula was as follows : the intravenous drip of amifostine at a dosage of 0.4 gram per day was given 5 days weekly for 4 consecutive weeks ; the subcutaneous injection of rhEPO at a dosage of 6 000 IU was given 3 times weekly. Therapeutic effect was evaluated 2 weeks post-therapy. Results Approximately 2.6 percent of human gene involved in apoptosis, cell cycle and differentiation was regulated by amifostine.Especially, upregnlation of ELK1 expression, which belongs to downstream functional gene of EPO pathway,and downregulation of Cyclin D1 expression were successfully predicted. Based on the potential therapeutic mechanism amifostine for MDS, amifostine plus EPO had dual effects on MDS, i. e. promotion of hematopoiesis and inhibition of tumor cell

  10. Assessment of the protective effect of amifostine on radiation induced pulmonary injury%阿米福汀对放射性肺损伤保护作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    冯勤付; Vujaskovic; Z; 等

    2001-01-01

    目的用荷瘤和无瘤大鼠的放射性肺损伤模式评价阿米福汀(Amifostine,WR-2721)的放射性肺损伤保护作用. 方法选150~160?g的Fisher-344雌性大鼠,在右后胸壁种植R3230 AC 人乳腺癌细胞株,肿瘤长至直径为1.0~1.5?cm时和无肿瘤大鼠随机进入实验组.用4?MV X射线、剂量DT35?Gy?5分次5?d照射右全肺,每次照射前30?min腹腔内注射Amifostine(150?mg/kg).照射后观测呼吸频率、肿瘤大小和转化生长因子(TGF-β1)水平.当出现呼吸困难伴体重下降时,终止观察,否则在6个月后终止观察.肺组织进行羟脯胺酸和TGF-β1表达等生物学检测.结果治疗后第3?d体重下降明显,照射加Amifostine(15%)和单用Amifostine(11%)与单纯放射(7%)间有明显的差别.肿瘤生长延迟和肿瘤生长情况及因肿瘤肺转移死亡贡献生存率,用药与未用药者相似.无瘤大鼠单纯照射组的平均呼吸频率增加早(第9周开始)、幅度高(125~127次/min),照射加药组在第12周开始,115~118次/min(P<0.001).单纯照射组羟脯胺酸含量明显高于照射加amifostine组(P=0.042)、单用药组和对照组(P<0.01).血浆TGF-β1 含量在照射后1~3个月增加、2个月达高峰,单放组的TGF-β1含量[(5.32±1.21)?ng/mL]明显高于用药组[(2.80±0.23)?ng/mL](P=0.038).结论 Amifostine在分次照射时,能增加肺组织对放射性损伤的耐受,对肿瘤无保护作用,毒性反应轻.TGF-β1在肺损伤中起重要的作用,其含量变化与放射性肺损伤的程度相关.

  11. Determination of Amifostine in Human Saliva by HPLC-MS/MS%高效液相色谱串联质谱法测定唾液中氨磷汀浓度

    Institute of Scientific and Technical Information of China (English)

    黎长江; 欧美贤; 王胜资; 黄滔敏; 陈念祖

    2013-01-01

    OBJECTIVE To establish an HPLC-MS/MS method ( high performance liquid chromatography-tandem mass spec-trometry) for the direct determination of amifostine in human saliva. METHODS Saliva samples were collected from six adult healthy volunteers. After protein precipitation and addition of the internal standard (IS) huperzine-A ( HupA) , HPLC- MS/MS was used to analyze amifostine. The analysis was conducted using a ZIC-HILIC analytical column (2. 1 mm × 100 mm,3.5 μn). Electrospray i-onization was used with multiple reaction monitoring ( MRM) mode. RESULTS The lower limit of quantification (LLOQ) of the method was 0. 938 mg · L -1 ( S/N > 10). The standard curve was linear in the range of 0. 938 - 30 mg · L-1 ( r = 0. 999 1, n = 6 ). The inter-day and intra-day RSDs were all less than 15% for the low, medium and high concentration quality control samples (1. 0, 5. 0 and 25 mg · L ). The values of recovery were all more than 85%. CONCLUSION The method is direct, rapid, simple and sensitive, and suitable for the determination of amifostine in saliva samples.%目的 建立高效液相色谱串联质谱(HPLC-MS/MS)直接检测唾液中氨磷汀(amifostine,AMI)的方法.方法 收集6位健康成年志愿者唾液为基质,石杉碱甲(huperzine-A,HupA)为内标,采用蛋白沉淀法,用高效液相色谱串联质谱测定唾液中的氨磷汀.色谱柱为ZIC-HILIC亲水色谱分析柱(2.1 mm×100 mm,3.5μm),质谱分析采用多反应监测扫描模式(MRM),离子源为电喷雾离子源(ESI).结果 氨磷汀在唾液中检测到的线性范围为0.938~30 mg· L-1,线性关系良好,典型代表方程为:y=0.072x-0.00526 (r=0.999 1)(n=6),定量下限为0.938 mg· L-1(S/N> 10).唾液样品的低、中、高3个质控浓度(1.0、5.0和25 mg·L-1)批内、批间精密度(RSD)均小于15%,其方法回收率均大于85%.结论 本实验所建立的氨磷汀检测方法直接、快捷、简便、灵敏度高及定性好,适用于唾液中氨磷汀的测定及科学研究.

  12. 阿米福汀联合ESHAP方案治疗复发或难治性中高度恶性非霍奇金淋巴瘤的临床疗效%Clinical study on amifostine combined with ESHAP regimen in the treatment of patients with relapsed or refractory intermediate or high-grade non-Hodgkin's lymphoma

    Institute of Scientific and Technical Information of China (English)

    刘隽; 朱琦; 胡钧培

    2006-01-01

    目的评价阿米福汀联合ESHAP(Amifostine-ESHAP)方案治疗复发或难治性中高度恶性非霍奇金淋巴瘤(NHL)的临床疗效和不良反应.方法采用Amifostine-ESHAP/ESHAP方案分组治疗38例复发或难治性中高度恶性NHL.结果Amifostine-ESHAP组21例患者共接受84个疗程化疗,10例完全缓解,4例部分缓解;ESHAP组17例患者共接受62个疗程化疗,7例完全缓解,3例部分缓解,总有效率分别为66.7%和58.8%,差异无统计学意义(P>0.05);2组中老年和年轻患者总有效率差异均无统计学意义(P>0.05).2组主要治疗相关的不良反应为骨髓抑制,Amifostine-ESHAP组重度白细胞减少和血小板减少发生率分别为14.3%和23.8%,明显低于ESHAP组(35.3%和41.2%,以老年患者为主),其中老年和年轻患者的不良反应发生率无显著差异.结论Amifostine-ESHAP方案是复发或难治性中高度恶性NHL,尤其是老年患者的有效挽救治疗方案,其中阿米福汀能有效预防化疗相关的骨髓抑制而不影响其疗效.

  13. 氨磷汀在血液肿瘤治疗中的应用与展望%Clinical application and expectation of amifostine applied during treatment of hematological malignancies

    Institute of Scientific and Technical Information of China (English)

    任婧; 陈虎

    2009-01-01

    Although hemopoietic stem cell transplant have been used in treating malignant diseases of hematological system using high-dose chemotherapy and radiotherapy before transplant or non-transplant is very important. When the dose of chemotherapy and radiotherapy exceeds the ability the tissues can bear, normal tissue can be badly damaged, which limits the therapeutic efficacy of chemotherapy and radiotherapy. Treatments of hematological malignancies are expected to achieve the best therapeutic efficacy and the least damage of normal cells and tissues. Amifostine is an inorganic thiophosphate eytoprotective agent,its chemname is S-2(3-aminopropyl) amino dihydrogen phosphate.h is a prodrug whose active constitutent is free thiol,it can clears free radicals produced from cytotoxic drugs and radiotherapy in tissues exposed to them. It is a broad-spectrum cytoprotective agent which can protect multifarious normal tissues against damage of chemotherapy and radiotherapy. Using amifostine in proconditioning of hemopoietic stem cell transplant can lessen hematological and renal toxicity, it can also lessen renal toxicity produced by chemotherapeutics as platinum,cyclophosphamide and vincristine. The main purpose of this review is to discuss the cytoprotection of amifostine in hematological malignancies.%虽然干细胞移植治疗血液肿瘤取得了良好疗效,但大剂量放疗及化疗治疗血液肿瘤仍很重要,放疗或化疗对正常组织造成的严重损伤限制了其要达到的治疗效果.达到最大的治疗效果并对正常细胞和组织产生最小的破坏作用是临床工作者追求的目标.氨磷汀(商品名:阿米福汀)是无机硫代磷酸盐细胞保护剂,它的化学名是S-2-[(3-氨基丙基)氨基]-硫代乙醇磷酸酯.它是一种前体药物,活性成分为游离的硫羟基,可以清除细胞毒性药物在组织中产生的自由基.它是一种广谱选择性细胞保护剂,能保护多种正常组织免受化疗及放疗的损伤.

  14. Efficacy of amifostine combined with chemotherapy for patients with Ewing sarcoma or PNET%氨磷汀联合化疗治疗Ewing肉瘤/PNET的临床观察

    Institute of Scientific and Technical Information of China (English)

    王翌庆; 刘云霞

    2012-01-01

    目的 探讨氨磷汀联合化疗治疗Ewing肉瘤/PNET的疗效、不良反应和安全性.方法 32例Ewing肉瘤/PNET患者分为化疗加氨磷汀组(观察组)及单纯化疗组(对照组),观察组12例,对照组20例.行IFO-IFO-DDP-ADM化疗2周期后评价疗效、不良反应.结果 观察组完全缓解(CR)及非常好的部分缓解率(VGPR)为91.6%,对照组为90.0%,两组比较差异无统计学意义(P>0.05).比较两组各种Ⅰ度~Ⅳ度不良反应发生率,差异无统计学意义(P>0.05).比较两组发生的Ⅳ度不良反应,观察组Ⅳ度白细胞减少为25.0%,对照组为70.0%;观察组Ⅳ度粒细胞减少25.0%,对照组为75.0%,差异均有统计学意义(P<0.05).结论 氨磷汀联合化疗治疗Ewing肉瘤/PNET不改变化疗疗效,不增加各种常见不良反应发生率;可以明显减少化疗后Ⅳ度白细胞及粒细胞减少的发生率,安全性好.%Objective To investigate the efficacy and adverse reactions of chemotherapy combined with amifostine for patients with Ewing sarcoma or primary neuroectodermal tumor ( PNET). Methods Thirty-two patients with Ewing sarcoma/PNET were divided into Group A ( amifostine group, n = 12) and Group B ( control group, n =20). After two cycles of IFO-IFO-DDP-ADM chemotherapy, the efficacy and adverse reaction of chemotherapy were observed. Results The rate of complete remission (CR) and very good partial response ( VGPR) was 91. 6% in Group A, and 90. 0% in Group B (P > 0. 05 ) . There was no significant difference in rate of adverse reaction I ~ IV between two groups (P > 0. 05 ) . The rate of IV leukopenia in Group A was 25. 0% and 70. 0% in Group B (P < 0. 05 ). The rate of W neutropenia in Group A was 25. 0% and 75. 0% in Group B ( P < 0. 05 ). Conclusion Amifostine combined with chemotherapy for patients with Ewing sarcoma/PNET may not change the efficacy or adverse reaction, while the rate of IV leukopenia and neutropenia would be reduced.

  15. Clinical efficacy and safety of amifostine on elderly patients with acute leukemia receiving chemotherapy%氨磷汀对老年急性白血病化疗患者的疗效与安全性评价

    Institute of Scientific and Technical Information of China (English)

    曲志刚; 方炳木; 马光丽; 江锦红; 章俏雷; 汪笑秋; 王晓丽; 刘永华

    2015-01-01

    Objective To evaluate the clinical efficacy and safety of amifostine on elderly acute leukemia patients receiving chemotherapy.Methods Fifty-eight patients with acute leukemia treated with chemo-therapy and amifostine were recruited in this study and then divided into two groups, 28 cases in elderly group (≥60 years) and 30 cases in control group (0.05).After chemotherapy, there were 82 (80.4%) and 102 (80.3%) cases showing decreasing systolic blood pressure in elderly group and control group, respectively, and 71 ( 69.6%) and 83 ( 62.9%) cases showing decreasing diastolic blood pressure ( P >0.05).Conclusion The application of amifostine on elderly acute leukemia patients who has received chemotherapy is safe and could relieve chemotherapy-induced adverse reactions.%目的:评价氨磷汀在老年急性白血病化疗患者中的临床疗效及安全性。方法58例多次接受化疗和氨磷汀细胞保护治疗的急性白血病患者分为2组,老年组28例(年龄≥60岁)和对照组30例(年龄<60岁)。2组于化疗前15~30 min静脉推注氨磷汀600 mg· m-2,持续15 min,连续用4个周期,比较氨磷汀对2组患者恶心呕吐等化疗不良反应发生率及血压的影响。结果老年组与对照组患者恶心呕吐、皮疹、口干等不良反应发生率差异无统计学意义(P>0.05);老年组患者收缩压下降82例次(80.4%),舒张压下降71例次(69.6%);对照组收缩压下降106例次(80.3%),舒张压下降83例次(62.9%),2组患者收缩压与舒张压下降比例差异无统计学意义(P>0.05)。结论在接受化疗的老年急性白血病患者中用氨磷汀是安全的,可减少老年患者化疗相关不良反应。

  16. 氨磷汀对化疗中外周血造血干/祖细胞的保护作用%The protective effects of amifostine on hematopoietic stem/progenitor cells against the chemotheraputic damage

    Institute of Scientific and Technical Information of China (English)

    周敏; 陈宝安; 李翠萍; 高冲; 丁家华; 孙耘玉; 高峰; 邵泽叶

    2004-01-01

    目的评估氨磷汀(amifostine,AMF)在保护造血干/祖细胞免受化疗药物依托泊甙(etoposide,VP-16)损伤方面的作用.方法提取新鲜和冻存的外周血造血干细胞(PBSC)和HL-60细胞,分为AMF+VP-16组、VP-16组和空白对照组,用台盼蓝拒染法检测细胞活性,CFU-GM集落培养计数,流式细胞仪测定细胞的凋亡率.结果新鲜和冻存的PBSC样本中,AMF+VP-16组的细胞存活率和集落形成能力较VP-16组显著提高(均P<0.05);HL-60细胞样本中,AMF+VP-16组与VP-16组凋亡率的差异无统计学意义(P>0.05).结论AMF能保护造血干/祖细胞免受化疗药物VP-16的损伤,并且不影响VP-16对HL-60细胞的杀伤效果.

  17. 阿米福汀对HL-60细胞中survivin表达的影响%Effect of amifostine on survivin expression in HL-60 cells in vitro

    Institute of Scientific and Technical Information of China (English)

    武婕萍; 马梁明; 周永安

    2007-01-01

    目的 探讨阿米福汀(WR-2721,amifostine,AMI)对人髓系白血病细胞HL-60中survivin表达的影响.方法 不同浓度AMI(1,10,1 000 μmol/L)干预HL-60细胞24,48,72 h,用MTT比色法检测细胞的生长抑制作用;用半定量RT-PCR方法检测抑凋亡基因survivin mRNA的表达水平.结果 阿米福汀可显著抑制HL-60细胞的增殖和下调抑凋亡基因survivin 的表达水平,且均有明显浓度和时间依赖性.结论 AMI可能通过下调抑凋亡基因survivin的表达,解除其抑制凋亡效应,从而抑制HL-60细胞的增殖.

  18. An Analysis of Chemoprotection with Amifostine in 25 Cases with Ovarian Carcinoma%氨磷汀对卵巢癌化疗患者的保护作用25例分析

    Institute of Scientific and Technical Information of China (English)

    蒋一玲; 张菡

    2007-01-01

    [目的] 探讨化疗保护剂氨磷汀(Amifostine)对卵巢癌化疗患者的应用价值.[方法] 25例卵巢癌患者接受单纯化疗组(紫杉醇+顺铂)与氨磷汀+静脉化疗组(紫杉醇+顺铂),化疗前后检测血常规、血生化、血清CA-125及影像学CT增强扫描,对比观察化疗药物的毒副反应和临床疗效.[结果] 与自身对照相比较,氨磷汀+静脉化疗组消化道反应有所增加(评分分别为35分及46分,P0.05).[结论] 氨磷汀作为高效、安全的化疗保护剂,值得在大剂量化疗以及既往化疗出现明显毒副反应的卵巢癌患者中应用.

  19. Effect of amifostine on chemistry anticese HeLa cell%氨磷汀对化疗药物抗宫颈癌HeLa细胞的影响

    Institute of Scientific and Technical Information of China (English)

    王根菊; 韩国荣; 叶银英; 余敏敏

    2007-01-01

    目的:评价氨磷汀(amifostine)对不同化疗药物抗宫颈癌HeLa细胞的影响.方法:用MTT法分别测定顺铂、长春新碱、依托泊甙和丝裂霉素对体外培养的HeLa肿瘤细胞系的抑制作用,实验组加化疗药前30 min经600 mg·L-1氨磷汀处理,对照组则只用化疗药物处理,余同实验组,培养后比较两组细胞增殖的抑制率.结果:用氨磷汀在体外加药前30 min加入HeLa肿瘤细胞的实验组,与对照组比较,两组肿瘤细胞抑制率无显著性差异(P>0.05).结论:氨磷汀不影响顺铂、依托泊甙、丝裂霉素和长春新碱对HeLa肿瘤细胞的抑制作用.

  20. 氨磷汀静脉注射配合放射治疗的观察与护理%Observation and nursing care of patients accepting intravenous amifostine combining with radiotherapy

    Institute of Scientific and Technical Information of China (English)

    李惠艳

    2010-01-01

    @@ 氨磷汀(amifostine,AMI)是抗肿瘤放射治疗时一种正常组织保护剂,又称WR-2721,静脉注射的AMI能迅速而精确地被正常组织摄取,其中的活性代谢产物WR-1065一旦进人组织细胞就开始发挥保护正常组织的作用,减轻放疗引起的细胞DNA损伤.正常组织摄取WR-1065的能力不一,应用过程中也会出现一些不良反应,氨磷汀的副反应主要是呕吐、血压下降、嗜睡,还出现四肢酸软、乏力、周身不适的感觉,从轻度皮疹到寒战的过敏症状罕有发生.

  1. Amifostine-conjugated pH-sensitive calcium phosphate-covered magnetic-amphiphilic gelatin nanoparticles for controlled intracellular dual drug release for dual-targeting in HER-2-overexpressing breast cancer.

    Science.gov (United States)

    Li, Wei-Ming; Chiang, Chih-Sheng; Huang, Wei-Chen; Su, Chia-Wei; Chiang, Min-Yu; Chen, Jian-Yi; Chen, San-Yuan

    2015-12-28

    We developed a surfactant-free method utilizing amifostine to stably link a targeting ligand (Herceptin) to amphiphilic gelatin (AG)-iron oxide@calcium phosphate (CaP) nanoparticles with hydrophobic curcumin (CUR) and hydrophilic doxorubicin (DOX) encapsulated in the AG core and CaP shell (AGIO@CaP-CD), respectively. This multi-functional nanoparticle system has a pH-sensitive CaP shell and degradable amphiphilic gelatin (AG) core, which enables controllable sequential release of the two drugs. The dual-targeting system of AGIO@CaP-CD (HER-AGIO@CaP-CD) with a bioligand and magnetic targeting resulted in significantly elevated cellular uptake in HER2-overexpressing SKBr3 cells and more efficacious therapy than delivery of targeting ligand alone due to the synergistic cell multi-drug resistance/apoptosis-inducing effect of the CUR and DOX combination. This nanoparticle combined with Herceptin and iron oxide nanoparticles not only provided a dual-targeting functionality, but also encapsulated CUR and DOX as a dual-drug delivery system for the combination therapy. This study further demonstrated that the therapeutic efficacy of this dual-targeting co-delivery system can be improved by modifying the application duration of magnetic targeting, which makes this combination therapy system a powerful new tool for in vitro/in vivo cancer therapy, especially for HER2-positive cancers. PMID:26478017

  2. 磷酸钙骨水泥/氨磷汀/顺铂复合体理化特性及其修复骨缺损的实验研究%Physicochemical and sustained drug release properities of calcium phosphate cement/amifostine/cisplatin complex and its effect in repairing bone defect due to tumor resection in rabbits

    Institute of Scientific and Technical Information of China (English)

    刘彦宁; 刘淼; 任鹏宇

    2010-01-01

    目的 对磷酸钙骨水泥/氨磷汀/顺铂(CPC/amifostine/cisplatin)复合体用作肿瘤性骨缺损的填充材料进行可行性研究.方法 按照质量比为1000:2:5的比例将磷酸钙骨水泥、顺铂、氨磷汀复合制备成人工骨复合体,对其进行固化时间、力学强度、孔隙率测定和扫描电镜、体外药物缓释、对骨肉瘤细胞的杀伤作用实验观察以及体内修复兔股骨骨缺损的实验研究.结果 CPC/amifostine/cisplatin复合体在固化时间、力学强度、孔隙率方面同单纯磷酸钙复合体相比没有差别,具有可持续缓释药物的作用,且氨磷汀的加入不影响顺铂对骨肉瘤细胞的毒性作用,在兔体内可观察到材料本身的降解和新骨长人材料内部的病理学证据.结论 CPC/amifostine/cisplatin复合体用作骨缺损的填充材料对于局部残存肿瘤细胞的消灭和缺损本身的修复是可行的.

  3. HPLC method using pre-column derivatization for determinating the content of amifostine%柱前衍生化HPLC法测定注射用氨磷汀的含量

    Institute of Scientific and Technical Information of China (English)

    黄滔敏; 陈念祖; 王东蕾; 赖永华; 王胜资

    2013-01-01

    Objective To establish a HPLC method for the determination of amifostine. Methods 9-fluorenylmethyl chloroformate (FMOC-C1) was used for derivatization. An agilent C18 column (4. 6 mm×150 mm, 5 μm) was adopted as stationary phase. Elution was carried out with acetonitrile (solvent A) and water (solvent B) at a flow-rate of 1 mL/min. Gradient HPLC was used with the solvent ratio changed from 30 : 70 (for 4 min) to 98 : 2 (from 4. 1 min to 10 min) for solvent A: B, respectively,and the rebalancing time was 7 min. The detection wavelength was 265 ran and the temperature of column was 25℃. Results Amifostine had a good linearity (r>0. 999,n = 6) in the range of 5 - 100 μg/mL. The recovery values were between 97% and 103% ,RSD<2. 0% (n = 3). The detection limit value was 100 ng/mL. The samples were stable in 6 hour and qualified between 90% and 110%. Conclusions The method was proved to be accurate,sensitive and reliable.%目的 建立一种测定注射用氨磷汀含量的HPLC法.方法 氨磷汀经氯甲酸芴甲酯(9-fluorenylmethylchloroformate,FMOC-C1)衍生化后用HPLC法分析.采用Agilent C18柱(150 mm×4.6 mm,5μm)色谱柱,流动相A:乙腈,B:水.0~4 min,A:B=30:70;4.1~10 rnin,A:B=98:2,每次进样前再平衡7min;柱温25℃,流速1 mL/min,检测波长265 nm.外标法计算含量.结果 在该色谱条件下,氨磷汀在5~100μg/mL浓度范围内有良好的线性关系(r>0.999,n=6),回收率为97%~103%(n=5),RSD< 2.0%(n=5).最低检测质量浓度为100 ng/mL.样品在6h内稳定.测得样品含量合格,在90%~110%之间.结论 经方法学实验验证,该方法简便、快速、结果准确、可靠、重现性好.

  4. 氨磷汀在骨肉瘤大剂量联合化疗中的骨髓保护作用%Marrow Protection Effect of Amifostine in Chemotherapy Patients with Osteosareoma

    Institute of Scientific and Technical Information of China (English)

    王翌庆; 刘云霞

    2012-01-01

    目的 探讨氨磷汀在骨肉瘤大剂量多药联合化疗中使用对血液学毒性的影响.方法 42例骨肉瘤患者随机分为化疗加氨磷汀组(观察组)及单纯化疗组(对照组),各21例.行MTX-MTX-DDP-ADM化疗,比较化疗后血液学毒性的发生情况.结果 第3周期化疗后观察组Ⅳ.粒细胞减少为28.6%,对照组为66.7%,两组比较有显著性差异(P0.05).第4周期化疗后观察组Ⅳ.白细胞减少为33.3%,对照组为81.0%;观察组Ⅳ.粒细胞减少为33.3%,对照组为81.0%,两组比较均有显著性差异(P<0.01).比较两组患者输红细胞的均次数,观察组明显低于对照组(P<0.0l).结论 氨磷汀在骨肉瘤大剂量联合化疗中使用后可以明显减少化疗后发生Ⅳ.白细胞及粒细胞减少的发生率,降低输红细胞的均次数.对生存率无明显影响,安全性好.%OBJECTIVE To explore the effect of amifostine on bematological toxicity in chemotherapy patients with osteosareoma. METHODS Forty two patients were divided into treatment group and control group, 21 patients in each group. After MTX-MTX-DDP-ADM chemotherapy, the hematological toxicity of chemotherapy was observed. RESULTS After three cycles of chemotherapy, the rate of Ⅳ° neutropenia in treatment group was 28.6% , and 66.7% in control group(P<0.05). After four cycles of chemotherapy, the rate of Ⅳ° leukopenia in treatment group was 33.3%, and 81.0% in control group(P<0.01). The rate of Ⅳ° neutropenia in treatment group was 33.3%, and 81.0% in control group(P<0.01). Compared the average number of red blood cell transfusion with the two group, the number of treatment group was significantly lower than that of control group(P<0.0l). CONCLUSION After amifostine used in chemotherapy patients with osteosareoma, the rate of Ⅳ° leukopenia and neutropenia, as well as the average number of red blood cell transfusion was reduced. It has no influence on survival rate and it is safe.

  5. Effect of amifostine on lung uptake of paraquat and prevention from lung injury in rats%氨磷汀对百草枯染毒大鼠肺摄取及肺损伤的影响

    Institute of Scientific and Technical Information of China (English)

    阳彩云; 张锡刚; 张天宏

    2012-01-01

    Objective To study the effect of amifostine on lung uptake of PQ, and its preventive effect against lung injury. Methods 75 rats were randomly divided into the normal control group (n=S), the model group (n=10, further divided into 8h-model group and 24h- model group according to the samplingtime of 8h and 24h after poisioning, with 5 in each group), and the drug intervention group (n=60). Based on the dosage of amifostine [30mg/kg, 60mg/kg and lOOmg/kg (labelled as L, M and H)], interval time [0.7Sh and l.Sh (labelled with 1 and 2)] and sampling time (8h and 24h). The intervention group was divided into 12 groups: 8h-Ll, 8h-Ml, 8h-Hl, 8h-L2, 8h-M2, 8h-H2, 24h-Ll, 24h-Ml, 24h-Hl, 24h-L2, 24h-M2 and 24h-H2, with 5 rats in each group. Except the normal control group, these rats were poisoned by injecting 3Smg/kg of PQ; After lh, amifostine was injected three times into the rats of the drug intervention groups at different doses and interval time. All the 75 rats were sacrificed at 8h or 24h after poisioning, and lung tissue was harvested, and PQconcentration in the plasma and the lung tissue was determined. The contents of SOD and MDA were assayed. Results The PQ concentration of L drug intervention groups in the lung tissue was significantly lower than that of M and H drug intervention groups and model groups. The PQ_ concentration in the plasma in the drug intervention groups was not different from that in the model groups. Except for the H drug intervention groups, there was no significant change in SOD. Both SOD and MDA contents in the lung tissue were significantly different in the other drug intervention groups (SOD increased obviously while MDA was reduced obviously). SOD in the groups of 0.75h interval time was higher than that in the l.Sh interval time groups. Conclusion Repeated administration of low-dose of amifostine after poisioning can inhibit lung uptake of PQ in rats, and significantly reduce the oxidative damage induced by the PQ_poisoning.%目的

  6. Protective effect and mechanism of amifostine on intestinal acute radiation sickness%氨磷汀对小鼠肠型急性放射病的防护作用及其机制

    Institute of Scientific and Technical Information of China (English)

    赵致维; 崔宇; 王丽梅; 善亚君; 柳晓兰; 唐红卫; 从玉文

    2015-01-01

    目的 研究氨磷汀(amifostine,WR2721)对小鼠肠型急性放射病的防护作用及其机制.方法 建立小鼠肠型急性放射病模型.C57BL/6J小鼠随机分为对照组和WR2721给药组,接受15 Gy 60Co-γ全身照射,照后移植健康小鼠骨髓细胞,观察小鼠受照后30 d的存活率和平均生存时间,以及用隐窝细胞微克隆实验,研究照后3.5d隐窝细胞数量及小肠黏膜情况.结果 对照组小鼠均在10 d内死亡,WR2721给药组存活率提高到80%;对照组和WR2721给药组平均隐窝数分别为(6.1±0.7)个、(28.0±1.1)个,差异有统计学意义(P <0.0001);对照组和WR2721给药组绒毛高度分别为(51.48±2.04)μm、(73.29±3.24) μm,差异有统计学意义(P <0.0001).结论 WR2721对肠型急性放射病小鼠有保护作用,通过提高隐窝干细胞增殖活性,促进黏膜的恢复,提高小鼠的存活率.

  7. 阿米福汀在局部晚期非小细胞肺癌放疗中的作用研究%Short-term Effect of Amifostine on Locally Advanced NSCLC Patients Treated with Radiotherapy

    Institute of Scientific and Technical Information of China (English)

    林展; 严浩林; 朱海生; 梁雷锋

    2013-01-01

    目的 探讨阿米福汀在局部晚期非小细胞肺癌(NSCLC)放疗中对近期疗效的影响及降低放射性食管炎和放射性肺炎的作用.方法 2008年1月-2010年2月我院放疗科收治62例局部晚期NSCLC患者,采用随机数字表法分为单纯三维适形放疗组(对照组)和阿米福汀+三维适形放疗组(试验组).试验组每次放疗前15~30 min给予阿米福汀300 mg/m2,静脉滴注.每周放疗5次,持续6周.放疗结束后6周评价两组患者的近期疗效.放疗期间每周记录1次放射性食管炎、放射性肺炎的发生率.结果 两组共44例患者完成了预定试验,对照组23例,试验组21例.对照组完全缓解(CR)1例,部分缓解(PR)11例,客观有效率为52%;试验组CR 2例,PR 12例,客观有效率为67%,两组客观有效率比较差异无统计学意义(χ2=0.95,P>0.05).对照组累计发生放射性食管炎15例(65%),放射性肺炎16例(70%);试验组累计发生放射性食管炎和放射性肺炎各5例(24%),两组放射性食管炎和放射性肺炎累计发生率比较,差异均有统计学意义(P值分别为0.017和0.003).结论 阿米福汀可以降低 NSCLC放疗中放射性食管炎和放射性肺炎的发生率,但不降低放疗的近期疗效.%Objective To evaluate the short - term effect of locally advanced NSCLC patients treated with radiotherapy and to understand its effect on alleviating radiation esophagitis and radiation pneumonitis. Methods 62 patients with locally advanced NSCLC admitted to radiotherapy department of our hospital from January 2008 to February 2010 were randomly divided into pure 3D conformal radiotherapy group ( control group ) and amifostine combined with 3D conformal radiotherapy group ( experiment group ). The experiment group was given 15 to 30 min intravenous drip of 300 mg/m amifostine. Six weeks after radiotherapy , the short - term effect of the two groups was assessed. During radiotherapy, the incidences of radiation esophagitis and radiation

  8. Efficacy analysis of amifostine combined with arsenic trioxide and vitamin C in the treatment of patients with high-risk myelodysplastic syndromes%氨磷汀联合三氧化二砷与维生素C治疗高危骨髓增生异常综合征的疗效分析

    Institute of Scientific and Technical Information of China (English)

    万鼎铭; 张媛; 张素平; 曹伟杰; 边志磊

    2013-01-01

    目的 观察氨磷汀联合三氧化二砷(As2O3)与维生素C治疗高危骨髓增生异常综合征的疗效.方法 15例患者应用氨磷汀500 mg/d,静脉滴注,As2O3 10 mg/d,静脉滴注,结束4h后应用维生素C2.0 g/d,静脉滴注,每周连续用药5d,间隔2d,4周为1个疗程.结果 完全缓解2例(13.3%),部分缓解3例(20.0%),血液学改善5例(33.3%),5例(33.3%)无效,总有效率为66.7%.结论 氨磷汀联合As2O3与维生素C治疗高危骨髓增生异常综合征疗效确切,且未见明显不良反应.%Objective To observe the efficacy of amifostine combined with arsenic trioxide and vitamin C on patients with high-risk myelodysplastic syndromes.Methods Fifteen patients received amifostine 500 mg/d,arsenic trioxide 10 mg/d by intravenous infusion and then recieved vitamin C 2.0 g/d by intravenous infusion after 4 hours,continuous medication for 5 days a week,interval 2 days,4 weeks repeated for a course.Results Complete remission in 2 cases (13.3%),partial remission in 3 cases (20.0%),hematologic improved in 5 cases(33.3%),invalid in 5 cases(33.3%),and the total effective rate was 66.7%.Conclusions Amifostine combined with arsenic trioxide and vitamin C is effective and has no significant adverse reactions in treating high-risk myelodysplastic syndromes.

  9. Protection of Amifostine on Oxygen-glucose Deprivation-induced Ischemia Reperfusion Injury in PC 12 Cells%氨磷汀对氧糖剥夺引起的PC12细胞缺血再灌注损伤的保护作用研究

    Institute of Scientific and Technical Information of China (English)

    张蕾; 李新; 贾济; 王世全; 刘靓; 王强; 王百忍; 熊利泽

    2011-01-01

    目的:研究氨磷汀对体外培养的神经元样细胞的缺血再灌注损伤的保护作用,为其最终用于临床脑缺血的治疗打下基础.方法:体外培养的PC12细胞氧糖剥夺4h后复氧复糖,给予不同浓度的氨磷汀处理,20h后镜下观察细胞形态学变化,用TT和LDH检测细胞活力和损伤情况,免疫荧光染色观察凋亡细胞,流式细胞仪计数凋亡细胞的比例.结果:高浓度氨磷汀对正常PC12细胞活力有抑制作用(P<0.05),而低浓度则无.氨磷汀可以提高缺血再灌注损伤PC12细胞活力(P<0.05),减少LDH释放(P<0.05),保护细胞正常形态,抑制细胞凋亡(P<0.05).结论:氨磷汀对氧糖剥夺引起的神经元样细胞的缺血再灌注损伤具有保护作用.%Objective: To investigate the effect of amifostine on the ischemia-reperfusion injury in neuron-like PC12 cells. Methods:PC12 cells were exposed to oxygen-glucose deprivation (OGD) for 4h followed by 20h reoxygenation. Various doses ofamfostine were added into the medium. Cell morphological changes were observed under microscopy and cell viability and integrity were detected by MTT and LDH techniques. Cell apoptosis was detected by Tunel staining and flow cytometry. Results: High concentration of amfostine could inhibite PC12 cell viability (P<0.05). Amifostine attenuated the cell viability loss (P<0.05) and LDH leakage (P<0.05) induced by OGD, protected PC12 cell morphology and decreased cell apoptosis (P<0.05). Conclusion: The amifostine had a protective effect on the OGD-induced ischemia reperfusion in neuronal cells.

  10. 阿米福汀对骨髓造血细胞保护作用的临床观察%Amifostin in protection of hematopoietic cell from cytotoxic drugs injury

    Institute of Scientific and Technical Information of China (English)

    班丽英; 高亚杰; 高平; 周涛; 张椿霞

    2004-01-01

    目的观察阿米福汀(Amifostin)保护骨髓造血细胞免受化疗药物损害的作用.方法采用临床随机自身对照方法,将38例接受联合化疗的患者随机分为AB、BA两组,均接受2周期相同方案的化疗.AB组第1周期化疗合并应用阿米福汀,第2周期单用化疗;BA组第1周期单用化疗,第2周期化疗合并应用阿米福汀.结果并用阿米福汀组,白细胞下降Ⅰ度15例(39.5%)高于单用化疗组7例(18.4%),差异有显著性(P<0.05),Ⅲ-Ⅵ度5例(13.2%)明显低于单用化疗组14例(36.8%),差异有显著性(P<0.05),并用阿米福汀组,中性粒细胞下降Ⅰ度15例(39.5%)高于单用化疗组9例(23.7%),差异有显著性(P<0.05),Ⅲ-Ⅵ度5例(13.2%)明显低于单用化疗组17例(44.7%),差异有显著性(P<0.05);并用阿米福汀组,血小板下降Ⅲ-Ⅵ度仅1例,单用化疗组出现6例.结论阿米福汀可以明显降低化疗药物对骨髓抑制的程度,表明阿米福汀对骨髓造血功能有保护作用,其不良反应轻微.

  11. Otoproteção da amifostina aos efeitos ototóxicos da cisplatina: estudo em cobaias albinas por emissões otoacústicas produtos de distorção e microscopia eletrônica de varredura Amifostine otoprotection to cisplatin ototoxicity: a guinea pig study using otoacoustic emission distortion products (DPOEA and scanning electron microscopy

    Directory of Open Access Journals (Sweden)

    Miguel Angelo Hyppolito

    2005-06-01

    side effects of cisplatin ototoxicity are significant: irreversible bilateral hearing damage to high frequencies (4 kHz - 8 kHz. Reports recognize some drugs that are associated with cisplatin to obtain an otoprotector effect. The ototoxicity mechanisms of cisplatin are related to injury of hair cell oxidation mechanism, especially of outer hair cells. AIM: Using otoacoustic emissions distortion products (DPOEA and scanning electron microscopy we intended to verify the action of amifostine, a radioprotective drug that has well known antioxidant characteristics and otoprotector effects to cisplatin injury. STUDY DESIGN: Experimental. MATERIAL AND METHODS: We used an experimental guinea pig model. The study was performed as follows: group 1: 6 animals, 12 ears, cisplatin 8.0 mg/Kg/day (IP, 3 days. Group 2: 6 animals, 12 ears, amifostine 100 mg/Kg/day (IP and after 90 minutes, cisplatin 8.0 mg/Kg/day (IP, 3 days and group 3: 3 animals, 6 ears, amifostine 100 mg/Kg/day (IP, 3 days. RESULTS: DPOEA were present before and after treatment in groups 2 and 3. The normal cilium architecture of outer hair cells was supported in all cochlear turns in groups 2 and 3. We concluded that amifostine has a potential otoprotector effect against cisplatin ototoxicity and could be used in clinical trials.

  12. Amifostine Reduces Radiation-induced Pneumonitis in Patients with Non-small Cell Lung Cancer:A Meta-analysis%阿米福汀减少非小细胞肺癌放射性肺炎发生的 Meta 分析

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    朱恒博; 许斌; 宋启斌

    2015-01-01

    Objective To evaluate the efficacy of amifostine in diminishing the incidence of radiation‐induced pneumonitis in patients with non‐small cell lung cancer (NSCLC)by using the meta‐analysis.Methods Medline ,Embase ,Cenfang ,CNKI , CBM ,Wanfang ,ASCO ,and ESMO databases were searched for randomized controlled trials(RCTs)on use of amifostine during radiotherapy for NSCLC and the papers were published before February 2015.Meta‐analysis was used to evaluate the efficacy of amifostine in decreasing the incidence of radiation‐induced pneumonitis.Results A total of 8 RCTs were identified with 394 ca‐ses in amfostine group and 402 in control group.The pooled relative risk(RR)of developing radiation‐induced pneumonitis(grade≥3)was 0.50(95% CI:0.37 -0.69 ,Z=4.33 ,P<0.01)in amfostine group when compared with control group.Conclusion Amifostine can significantly decrease the risk of developing radiation‐induced pneumonitis in NSCLC patients treated by radio‐therapy.%目的:应用M eta分析的方法探讨阿米福汀减少非小细胞肺癌放射性肺炎发生的临床价值。方法计算机检索Medline、Embase(Excerpt Medica Database)、CENTRAL(Cochrane Central Register of Controlled Trails)、中国期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、万方数据库、美国临床肿瘤学会(ASCO)、欧洲肿瘤协会(ESMO)官方网等,检索公开发表的有关非小细胞肺癌放疗期间应用阿米福汀的随机临床对照研究(randomized controlled trail , RCT)。检索时限均为从建库至2015年1月。对阿米福汀降低放射性肺炎发生率的有效性进行Meta分析。结果共纳入8个随机临床对照实验,阿米福汀组394例,对照组402例。结果显示放疗期间接受阿米福汀治疗的患者与对照组相比,Ⅲ度及以上的放射性肺炎发生的相对危险度(relative risk ,RR)为0.50(95% CI:0.37~0.69,Z=4.33,P<0.01)。结

  13. Effect of Amifostine on Locally Advanced Non-small Cell Lung Cancer Patients Treated with Radiotherapy: A Meta-analysis of Randomized Controlled Trials%阿米福汀在局部晚期非小细胞肺癌放疗中作用的meta分析

    Institute of Scientific and Technical Information of China (English)

    王升晔; 张沂平; 张苏展; 马胜林

    2012-01-01

    背景与目的 阿米福汀( Amifostine)是否影响非小细胞肺癌(non-small cell lung cancer NSCLC)放疗疗效并降低放疗相关副反应一直存在较大争议,本研究旨在探讨阿米福汀在局部晚期NSCLC放疗近期疗效及预防放疗副反应中的作用.方法 检索Medline、CENTRAL( the Cochrane central register of controlled trials)、EMBASE、中国生物医学文献数据库系统(CRM)、中国期刊全文数据库(CNKI)、万方数据库、美国临床肿瘤学会( ASCO)、欧洲肿瘤协会(EMSO)官方网等,检索公开发表的有关局部晚期NSCLC放疗期间应用阿米福汀的随机临床对照研究.应用Stata 11.0统计软件分析阿米福汀对放疗近期疗效及副反应发生率的影响.结果最终纳入9项研究,阿米福汀组患者381例,对照组388例.涉及近期疗效的研究8项,阿米福汀组患者328例,对照组333例.结果 显示放疗期间接受阿米福汀治疗的患者完全缓解( complete response,CR)、部分缓解(partial response,PR)和客观缓解( objective response,OR)的相对危险度(relative risk,RR)分别为1.16(95%CI:0 90-1.50,Z=1.07,P=0.29)、1.02(95%CI:0.87-1.19,Z-0.21,P=0.83)和1.06( 95%CI:0.97-1.17,Z=1.31,P=0.20).涉及放疗副反应研究7项,阿米福汀组患者367例,对照组371例,放疗期间接受阿米福汀治疗的患者3级-4级放射性食管炎和放射性肺炎发生的RR分别为0.51(95%CI:0.37-0.72,Z=3.88,P<0.001)和0.51( 95%CI:0.26-0.99,Z=1.98,P=0.04).结论 阿米福汀可以降低NSCLC放疗中放射性食管炎和放射性肺炎的发生率,但不降低放疗的近期疗效.%Background and objective Controversy exists on whether amifostine can reduce the efficacy and decrease the side effects of non-small cell lung cancer (NSCLC) treated by radiotherapy. The aim of this meta-analysis is to evaluate the efficacy and side effects of amifostine in NSCLC patients treated with radiotherapy. Methods Open published randomized controlled trials on

  14. 超氧化物歧化酶与阿米福汀对小鼠急性放射损伤预防作用的比较%Investigating preventive effects of superoxide dismutase and amifostine on acute radiation injury of mice

    Institute of Scientific and Technical Information of China (English)

    潘剑茹; 郑光进; 何火聪; 吴君心; 苏颖; 刘树滔; 饶平凡

    2012-01-01

    本研究建立了小鼠全身放疗的损伤模型,以比较预给药超氧化物歧化酶(SOD)和阿米福汀对小鼠放射治疗损伤的防护效果.C57BL/6小鼠用6GyX射线进行全身一次性照射,在放射后24 h处死,测定小鼠外周血红、白细胞数量,胸腺指数和脾脏指数,以及肝脏抗氧化活力.结果表明:与放疗对照组相比,放疗前给药SOD组对放疗鼠的外周血白细胞数量和胸腺指数有显著的保护作用,使之分别增加66.7%和19.1%.测得放疗前给药阿米福汀对放射鼠的外周血白细胞数量和脾脏指数有显著的保护作用,使之分别增加106.9%和22.6%.此外,与放疗对照组相比,放疗前给药SOD对放疗鼠的肝脏抗氧化能力也有显著提高,可使肝脏的MDA水平下降12.7%,SOD活力增加10.8%,T-AOC活力增加45.0%,放疗前给药阿米福汀可使放疗鼠肝脏的MDA水平下降22.3%.%The radiation injury models of mice were established and the preventive effects of superoxide dismutase (SOD) compared with amifostine from radiation damage were investigated. C57BL/6 mice were whole-body irradiated with 6Gy X-rays and sacrificed by cervical dislocation at 24 h after irradiation. The red blood cells and white blood cells counts in peripheral blood;thymus index;spleen index;and hepatic antioxidant activity were determined;respectively. The results show that compared with the group received irradiation only;SOD pretreatment has significant effect on white blood cells counts meanwhile thymus index is significantly elevated by 19.1%. Amifostine pretreatment has also significant effect on white blood cells counts and spleen index is significantly elevated by 22.6%. In addition;SOD pretreatment can significant protect hepatic antioxidant activity and decrease nalondialdehyde (MDA) level by 12.7% in irradiated while the total anti-oxidizing capability (T-AOC) is up by 45.0%. However;amifostine treatment could only remarkably decreased MDA level by 22.3%.

  15. Clinical observation of amifostine's protective effect to the intestinal function in conventional radiotherapy of cervical cancer%氨磷汀在宫颈癌常规放疗中对肠道功能保护作用的临床观察

    Institute of Scientific and Technical Information of China (English)

    李婷婷; 师国珍; 李国文; 师秀琴

    2009-01-01

    目的 观察广谱细胞保护剂氨磷汀在宫颈癌全盆腔放疗中对肠道功能的保护作用.方法 选择20例病理诊断明确的宫颈癌患者(Ⅱb~Ⅳ),随机分为两组,观察组10例,放疗前应用氨磷汀(放疗总剂量DT:35~40 Gy,3~4周,放疗后视情况可手术).对照组10例,单纯放射治疗(总剂量DT:35~40 Gy,3~4周,放疗后视情况可手术).比较两组间放疗后肠道功能的变化情况.结果 观察组10例中2例出现2~3级肠道不良反应,发生率为20%.对照组10例中7例出现2~3级肠道不良反应,发生率为70%.两组比较,观察组放疗后肠道不良反应比对照组明显减轻,差异有统计学意义(P<0.05).结论 氨磷汀在宫颈癌全盆腔放疗中对肠道功能具有保护作用.%Objective To observe the protective effect of cell broad-spectrum protection agent amifostine for intestinal function in the whole pelvic radiation therapy of cervical cancer.Methods Choosed 20 patients with pathological diagnosis of cervical cancer in patients with clear-cut(Ⅱb-Ⅳ)and the patients were randomly divided into two groups.The 10 cases of observation group applied amifostine before the application of radiation(of the total radiation dose DT:35-40 GY,3-4 weeks,surgery after radiotherapy,as the case may be).Control group of 10 cases,were treated with radiation alone(total dose of DT:35-40 Gy,3-4 weeks,surgery after radiation,as the case may be).Comparison between two groups of intestinal function changes after radiotherapy.Resluts In the group observed,2 cases occurred in 10 cases of grade 2-3 intestinal side effects,the incidence rate was 20%.In control group,7 cases occurred in 10 cases of grade 2-3 intestinal side effects,the incidence rate was 70%.Comparing the two groups,intestinal side effects of the group observed significantly reduced after radiation therapy,there was statistically significant difference(P<0.05).Conclusions Amifostine can protect intestinal function in the whole

  16. Expression of Survivin in Patients with acute myeloid Leukemia and effect of amifostine on survivin expression%骨髓细胞中 survivin 表达与急性髓系白血病的关系及阿米福汀对其的影响

    Institute of Scientific and Technical Information of China (English)

    杨颖莹; 刘郝静; 王丹

    2015-01-01

    目的:分析骨髓细胞中 survivi 表达与进行髓系白血病的关系及阿米福汀对其的影响。方法选取我院在2013年2月-2015年4月初诊为急性髓系白血病患者60例为观察组,另外选取我院同期健康体检人员50例为对照组,分析骨髓细胞 survivin 表达,并分析阿米福汀对 survivin 表达的影响。结果观察组患者 survivin 表达阳性率(83.3%)明显高于对照组(32.0%),P <0.05,不同浓度阿米福汀均能够抑制 HL-60细胞,不同干预时间组与丁组之间差异明显,P <0.05。疗效评估,37例患者白血病细胞 survivin 表达阳性,9例患者表达阴性,存在明显差异。不同阿米福汀浓度作用下,survivin 表达灰度值均与丁组存在明显差异,P >0.05,不同干预时间作用下 survivin 表达存在明显差异,P <0.05。结论骨髓细胞中 survivin 表达与白血病发展存在密切关系,阿米福汀能够下调凋亡基因 sur-vivin 的表达。%Objective To expression of Survivin in Patients with acute myeloid Leukemia and explore the effect of amifostine on survivin.Methods 60 patients with Leukemia in hospital as observer Group were divided from february 2013 to april 2015,healthy patients in our hospital over the same period were selected as the control group,survivin ex-pression in bone marrow cells were analyzed,the impact of amifostine on survivin expression was analyzed.Results The positive rate of survivin expression in observation group (83.3%)was significantly higher (32.0%),P 0.05,the next time the role of different inter-ventions survivin expression significantly different,P <0.05.Conclusion Closely relationship between survivin expres-sion in myeloid leukemia cells,amifostine can decrease the expression of apoptotic gene survivin.

  17. 氨磷汀对奥沙利铂所致周围神经毒性的改善作用的病例对照研究%The randomized controlled trial of amifostine in improving neurotoxicity induced by oxaliplatin on gastroenteric tumor patients

    Institute of Scientific and Technical Information of China (English)

    王芬; 王树滨; 申东兰; 彭安; 李柱; 农巧红

    2014-01-01

    目的:评价氨磷汀对胃肠道肿瘤化疗药物奥沙利铂所致神经毒性的改善作用。方法将行FOLF-OX6方案化疗的86例胃肠道肿瘤患者随机分为氨磷汀组(给予奥沙利铂前静脉注射氨磷汀,n=43)和对照组(不予氨磷汀,n=43)。每2个周期评估神经毒性。结果经过8个周期化疗后,氨磷汀组患者3~4级神经毒性发生率(4.9%)较对照组(16.3%)有明显降低,组间差异具有统计学意义(P<0.001)。氨磷汀组患者化疗后正中神经和腓神经的感觉神经传导速度分别为(53.75±2.96)m/s和(54.94±2.98)m/s,均明显优于对照组的(45.16±3.13)m/s和(5.05±3.02)m/s,组间差异具有统计学意义(P<0.001)。化疗近期有效率两组间无显著差异(P=0.451)。结论氨磷汀对奥沙利铂化疗所致神经毒性具有明显改善作用,且不影响化疗的近期疗效。%Objective To explore the effect of amifostine in improving neurotoxicity induced by oxaliplatin on gastroenteric tumor patients. Method A total of 86 patients with gastroenteric tumor were enrolled and randomized into treatment group (combined with intravenous amifostine 500 mg/m2 before oxaliplatin, 43 cases) and control group (43 cases). All patients received FOLFOX6 regimen. Neurological toxicities were assessed every 2 cycles. Re-sult The occurrence rates of grade 3-4 peripheral neurotoxicity after 8 cycles of chemotherapy were significantly lower in treatment group than in control group (4.9% vs 16.3%, P<0.001). The sensory nerve conduction velocity (SCV) was significantly improved in treatment group [SCVmedian nerve = (53.75 ± 2.96) m/s, SCVperoneal nerve = (54.94 ± 2.98) m/s] than in control group [SCVmedian nerve = (45.16 ± 3.13 m/s, SCVperoneal nerve = (5.05 ± 3.02 m/s] (P<0.001). The short-time efficacy of chemotherapy were similar in two groups (P=0.451). Conclusion Amifostine can im-prove the neurotoxicity induced by

  18. 氨磷斯丁%Amifostine

    Institute of Scientific and Technical Information of China (English)

    潘启超

    2000-01-01

    众所周知,化疗与放疗在杀伤癌细胞的同时,对正常细胞亦有损伤作用,即所谓选择性不高.要用细胞保护剂保护正常细胞而不保护恶性细胞,保护宿主而不降低抗癌效果.最近安磷斯丁的出现,基本上满足了上述要求.

  19. The effects of evidence - based nursing on prevention of the side - effect of chemotherapy assisted by amifostine%循证护理在预防氨磷汀配合化疗治疗副作用中的应用

    Institute of Scientific and Technical Information of China (English)

    韩卫丽

    2012-01-01

    目的 探讨循证护理干预能否减轻氨磷汀配合化疗治疗的副作用.方法 运用循证护理和常规护理对66例次恶性肿瘤患者使用氨磷汀配合化疗副作用进行干预,未干预组(33例次)采用常规护理措施,干预组(33例次)实施循证护理,比较未干预组和干预组化疗副作用.结果 干预组低血压、恶心、呕吐、头晕、乏力、低血钙副作用较未干预组减少(P <0.000),两组发热无明显差异(P>0.05).结论 通过应用循证护理,利用循证支持,制订并实施行之有效的预防措施,可减少氨磷汀配合化学治疗副作用的发生.%Objective To study if the evidence - based nursing could relieve the side - effect of chemotherapy assisted by amifosfine.Methods Evidence - based nursing and usual care were used to interfere the side - effects of chemotherapy assisted by amifostine in 66patients with cancer.The patients were divided into non - intervention group with accepted usual care ( 33 cases) and intervention group (33 cases) with evidence -based nursing.And side- effects of the chemotherapy of the two groups were compared.Results The incidence of hypotension,nausea,vomiting,dizziness,anergy,hypocalcemia in the intervention group were lower than those in non - intervention group (P =0.00) besides the fever index (t =1.0,P =0.32).Conclusions Evidence - based nursing and related prognostic treatments could decrease the side - effects of chemotherapy assisted by amifostine.

  20. 阿米福汀对鼻咽癌放射性口腔黏膜及涎腺损伤的保护作用%Protective effect of amifostine in irradiation mucositis of the oral cavity and dry mouth after nasapharyngcal carcinoma

    Institute of Scientific and Technical Information of China (English)

    范志刚; 林焕新; 柳仲秋; 贺启华; 张淑莲; 李伟

    2011-01-01

    目的 观察阿米福汀对鼻咽癌放射治疗后放射性口腔黏膜及涎腺损伤的保护作用.方法 鼻咽癌患者在放疗期间,对照组予多贝氏漱口液,每天漱口4次;观察组在此基础上再予以注射阿米福汀;观察两组对放射性口腔黏膜及涎腺损伤的防治效果.结果 阿米福汀可明显延缓或减轻放射性口腔黏膜反应及口干的发生,对照组0~2级口腔黏膜反应、口干发生率分别为30.8%(8/26)和34.6%(9/26),而阿米福汀观察组则为86.7%(26/30)和83.3%(25/30);同时对照组的3级以上口腔黏膜反应与口干发生率为69.2%和65.4%,观察组则为13.3%和16.7%,两组口腔黏膜反应与口干程度比较差异均具有显著意义(均P<0.05).结论 阿米福汀是一种安全有效的放疗反应保护剂,它可减缓和减轻放射性口腔黏膜反应与口干的程度.%Objective To assess the radioprotective effects of amifestine on mucositis of the oral cavity and salivary gland after nasapharygeal carcinoma. Methods During radiotherapy of nasopharyngeal carcinoma, patients in the control group were subjected to Bayesian gargle mouthwash 4 times a day and treated more than a day. The patients of test group were on the basis of Amifostine injection. The patients were observed on the oral mucesa and salivary glands of radioactive injury prevention effect. Results Amifosfine can significantly delay or reduce radiation-induced oral mucositis and dry mouth occurs. The control group had 0 to 2 oral mucositis, dry month rates were 30. 8% (8/26) and 34.6% (9/26). In amifestine test group mucositis, dry mouth rates were 86.7% (26/30) and 70.0% (25/30). In the control group, three or more oral mucositis and dry mouth rate were 69.2% and 65.4%. In test group, three or more oral mucositis and dry mouth rate were 13.3% and 16.7%. There were significant differences both oral mucositis and dry mouth between two groups ( P < 0.05 ). Conclusion Amifostine is safe and

  1. Short-Term Curative Effect of Amifostine Combined with rhEPO on Aged Patients wilh Myelodysplastic Syndrome%氨磷汀联合重组人红细胞生成素治疗高龄骨髓增生异常综合征近期疗效观察

    Institute of Scientific and Technical Information of China (English)

    卢学春; 朱宏丽; 姚善谦; 范辉; 庄晓萌; 杨洋

    2005-01-01

    本研究的目的是观察氨磷汀(amifostine,AMF)联合红细胞生成素(EPO)治疗高龄骨髓增生异常综合征(MDS)患者的近期疗效.治疗的2例高龄MDS患者中1例为MDS-RA患者(91岁),另1例为MDS-RCMD患者(86岁).治疗方案为rh-EPO 6 000 U皮下注射,1周3次;AMF0.4 g静脉滴注,每周连续5天,休息2天,连用4周.结果表明:4周后2例患者均显示出很好的近期疗效,其中MDS-RA患者输血时间间隔均较治疗前有的延长.1例MDS-RA患者的网织红细胞在治疗开始后第1周即恢复正常,并一直保持在正常水平;另1例MDS-RCMD患者治疗后血像三系细胞量均明显上升,异常增高的网织红细胞数量呈下降趋势.结论:AMF联合rh-EPO在治疗高龄MDS患者可能有良好的应用前景,但其临床远期疗效还有待于进一步研究.

  2. Clinical effect of amifostine combined with erythropoietin in the treatment of patients with MDS%氨磷汀联合红细胞生成素治疗骨髓增生异常综合征患者的效果观察

    Institute of Scientific and Technical Information of China (English)

    朱琳燕; 汪玉芳; 陈世明; 柯金勇

    2014-01-01

    目的:探讨氨磷汀联合红细胞生成素治疗骨髓增生异常综合征( MDS)的临床疗效。方法对血液内科收治的MDS患者28例采用随机数字表法分为联合组和对照组各14例,对照组采用氨磷汀0ú.5 g静脉滴注,联合组在对照组基础上加用红细胞生成素6000 U皮下注射,3次/周,疗程3个月,比较2组患者的临床疗效。结果治疗前2组的白细胞、血小板、血红蛋白比较差异不显著( P >0.05),治疗后2组均升高,但差异亦无统计学意义( P >0.05),治疗3个月后,脱离输血+输血量减少50%以上的患者比例联合组为78.57%,高于对照组的35.72%,差异有统计学意义(χ2=5.250, P =0.022)。联合组近期总有效率为78.57%,高于对照组的64.29%,但差异无统计学意义(χ2=0.700, P =0.403)。2组患者的1年生存率均为100%,2年生存率与3年生存率比较,联合组均高于对照组(78.57%vs 57.14%,57.14%vs.35.71%),但差异无统计学意义( P >0.05)。联合组中位生存时间为32个月,显著长于对照组的25个月(χ2=3.532, P =0.038)。结论氨磷汀联合红细胞生成素治疗MDS对改善患者的血象及生存时间有一定作用。%Objective To investigate the effect of amifostine combined with erythropoietin in the treatment of myelo -dysplastic syndrome ( MDS) .Methods Twenty-eight MDS patients from the Department of internal medicine were randomly divided into combined group and control group with 14 cases in each group , the control group used amifostine intravenous infu-sion of 0.5 g, the combined group besides the treatment as the control group , also use of erythropoietin 6 000 U subcutaneous injections, 3 times/week, the course of treatment was 3 months, the clinical curative effect of 2 groups were compared .Re-sults Before treatment, white blood cells, platelets

  3. 氨磷汀调控人类造血及免疫相关基因的筛选及生物信息学预测%Screening for human hematopoietic and immune-related genes regulated by amifostine and their bioinformatics predicting

    Institute of Scientific and Technical Information of China (English)

    迟小华; 井绪臣; 刘丽宏; 杨波; 卢学春; 脱帅; 脱朝伟

    2011-01-01

    目的 利用开放性基因芯片数据库筛选氨磷汀调控人类造血及免疫相关基因并对其进行生物信息学分析.方法 以氨磷汀(Amifostine)为关键词,在互联网开放性数据库包括GEO、SAGE、GeneCard、InterPro、ProtoNet、UniProt和BLOCKS中搜索基因表达数据,对筛选出的数据库进行生物信息学分析,计算差异表达基因,再利用The Database for Annotation,Visualization andIntegrated Discovery(DAVID)数据库进行造血及免疫相关基因的功能聚类分析.结果 仅在GEO数据库中筛选出1个氨磷汀调控人类基因组表达数据库.分析表明,氨磷汀处理K562细胞后,人类全基因组仅2.14%(460/192 000)的基因在转录水平表达有显著差异(P<0.01).460个差异基因中有139条为已知功能基因,聚类分析共筛出17个与造血及免疫相关的基因,分属于8大类生物学通路,其中上调基因15个,下调基因2个.结论 充分利用开放性基因芯片数据库,可经济、方便和快捷地分析药物调控人类基因表达谱特点,为预测和验证药物新的药理作用提供指导.

  4. 阿米福汀在非小细胞肺癌放疗中对正常组织的保护研究%Amifostine protective effect for normal tissue in the radiotherapy of non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    赵衍

    2014-01-01

    目的:分析阿米福汀在非小细胞肺癌放疗中对正常组织的作用。方法随机选取我院治疗的137例非小细胞肺癌患者作为研究对象,根据治疗方案分为观察组69例(放疗加阿米福汀)和对照组68例(单纯放疗),对比分析两组患者的疗效以及不良反应。结果观察组总有效率56.52%,对照组总有效率54.41%,经统计学比较,P>0.05,无显著性差异;观察组放射性肺损伤发生率15.94%,且未发生V级损伤,对照组放射性肺损伤发生率30.88%,V级损伤发生率为2.94%,经统计学分析,P0. 05). The incidence of radiation-induced lung injury was 15. 94% and V level injury did not occur in the observation group. The incidence of radiation-induced lung injury was 30. 88%, and the incidence of V level injury was 2. 94% in the control group (P<0. 05). In the observation group after treatment, hemoglobin was 118. 26 ± 32. 49 g/L, white blood cells was ( 5. 11 ± 1. 28 ) × 109/L, platelets was ( 213. 97 ± 40. 38) ×109/L, CD3+ (57. 19 ± 10. 21)%, CD4+ (45. 63 ± 10. 58)%, and NK cell (21. 15 ± 7. 69)% (P <0. 05). Conclusion In non-small cell lung cancer radiotherapy, amifostine can effectively protect normal tissue or-ganization and reduce the side effects.

  5. Chemoprotective Effects of Amifostine and Fengling Polysaccharide on Human Peripheral Blood Granulocyte-Macrophage Progenitor Cells%氨磷汀与峰龄多糖对人外周血粒-巨噬祖细胞的化疗保护作用

    Institute of Scientific and Technical Information of China (English)

    黄成垠; 陈宝安; 李翠萍; 周敏; 傅强

    2004-01-01

    目的观察氨磷汀(amifostine,化学代号:WR-2721)和峰龄多糖(fengling polysacchride,FLPS)对人外周血粒-巨噬祖细胞(CFU-GM)及HL60白血病细胞的化疗保护作用.方法应用Ficoll分离单个核细胞(MNC);甲基纤维素半固体培养法测定CFU-GM集落;XTT法测定HL60细胞存活率;WR-2721及FLPS处理的MNC,与VP-16作用后,测定CFU-GM集落产率,研究WR-2721和FLPS对CFU-GM的保护作用.结果经WR-2721和FLPS处理的MNC与VP-1637℃作用14 h后,CFUGM集落产率均明显高于VP-16对照组,CFU-GM集落数在VP-16对照组、空白对照组、WR-2721+VP-16组、FLPS+VP-16组和WR-2721+FLPS+VP-16组分别为每1×105个MNC 30.9±22.5、83.2±43.8、64.6±41.2、55.3±33.5和78.3±48.2,与VP-16对照组相比,P值均<0.01;WR-2721处理后的HL60细胞对VP-16的敏感性增强,IC50由52.5μg/ml下降为40.5μg/ml;VP-16对FLPS处理前后的HL60细胞的作用无明显改变.结论WR-2721和FLPS对人外周血CFU-GM具有明显化疗保护作用.WR-2721能增强HL60细胞对VP-16的敏感性.FLPS对HL60细胞的化疗损伤无保护作用.

  6. 氨磷汀对胃肠道肿瘤L-OHP联合CF/5-FU方案化疗患者重要脏器保护作用的临床观察%Protection effect of amifostine on patients with gastrointestinal tumor under L-OHP and CF/5-FU chemotherapy

    Institute of Scientific and Technical Information of China (English)

    高亮; 王永向; 卢丽琴; 赵同伟

    2008-01-01

    目的 探讨氨磷汀(Amifostine,阿米福汀)对胃肠道肿瘤L-OHP联合CF/5-FU方案化疗患者重要脏器的保护作用及药物不良反应.方法 96例胃肠道肿瘤患者随机分为两组,对照组48例接受L-OHP联合CF/5-FU方案化疗及常规对症支持治疗,治疗组48例接受同一方案化疗及常规对症支持治疗,同时加用氨磷汀,观察两组肝功能、肾功能、血常规、末梢神经系统变化及药物不良反应.结果 化疗相关肝功能损害:对照组出现8例,治疗组出现2例(P0.05);白细胞下降:对照组出现28例,治疗组出现13例(P<0.05);血小板下降:对照组出现12例,治疗组出现4例(P<0.05);血红蛋白下降:对照组出现13例,治疗组出现5例(P<0.05);末梢神经系统毒性:对照组出现31例,治疗组出现17例(P<0.05).氨磷汀主要不良反应为恶心、呕吐;个别患者出现口中金属异味、短暂的低血钙、流泪、流涕症状.结论 氨磷汀能明显减少化疗后肝功能损害,白细胞、血小板及血红蛋白下降,以及末梢神经毒性的发生.氨磷汀药物不良反应较少,主要为恶心、呕吐,个别患者出现口中金属异味、短暂的低血钙、流泪、流涕等症状.

  7. Amifostine reduces lung vascular permeability via suppression of inflammatory signaling

    OpenAIRE

    Fu, Panfeng; Birukova, Anna A.; Sammani, Saad; Burdette, Dylan; Murley, Jeffrey S.; Garcia, Joe G. N.; David J Grdina; Birukov, Konstantin G.

    2008-01-01

    Multiple events are involved in the development of acute inflammation and injury in the lungs. A progressive rise of oxidative stress due to altered reduction-oxidation (redox) homeostasis appears to be one of the hallmarks of lung pathologies such as injury, inflammation and ischemia/reperfusion. However, despite the growing evidence that alteration of the redox balance in the lungs, antioxidant therapy may attenuate acute lung injury and inflammation. We studied the effect of thiol antioxid...

  8. Combination Chemotherapy Plus Amifostine in Treating Patients With Advanced Cancer

    Science.gov (United States)

    2013-12-18

    Chronic Myeloproliferative Disorders; Drug/Agent Toxicity by Tissue/Organ; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

  9. Amifostine Metabolite WR-1065 Disrupts Homologous Recombination in Mammalian Cells

    OpenAIRE

    Dziegielewski, Jaroslaw; Goetz, Wilfried; Murley, Jeffrey S.; David J Grdina; Morgan, William F.; Janet E. Baulch

    2010-01-01

    Repair of DNA damage through homologous recombination (HR) pathways plays a crucial role in maintaining genome stability. However, overstimulation of HR pathways in response to genotoxic stress may abnormally elevate recombination frequencies, leading to increased mutation rates and delayed genomic instability. Radiation-induced genomic instability has been detected after exposure to both low- and high-linear energy transfer (LET) radiations, but the mechanisms responsible for initiating or p...

  10. Radiation Therapy, Amifostine, and Chemotherapy in Treating Young Patients With Newly Diagnosed Nasopharyngeal Cancer

    Science.gov (United States)

    2015-03-03

    Stage I Lymphoepithelioma of the Nasopharynx; Stage I Squamous Cell Carcinoma of the Nasopharynx; Stage II Lymphoepithelioma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx

  11. Combination Chemotherapy Plus Amifostine in Treating Patients With Metastatic or Unresectable Cancer

    Science.gov (United States)

    2009-02-06

    Bladder Cancer; Brain and Central Nervous System Tumors; Carcinoma of Unknown Primary; Extragonadal Germ Cell Tumor; Head and Neck Cancer; Kidney Cancer; Lung Cancer; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific

  12. Amifostine:一种广谱细胞保护剂与恶性血液病

    Institute of Scientific and Technical Information of China (English)

    傅敢; 刘巍; 陈方平

    2001-01-01

    Amifostine作为一种化疗正常细胞广谱保护剂具有内在促干细胞增殖作用,可提高白血病大剂量化疗效果,增强自体干细胞移植体外净化作用,改善骨髓异常增生综合征无效造血,在恶性血液病患者的应用具有广阔前景.

  13. Amifostine在恶性肿瘤放疗中的应用%Advanced research of Amifostine in the radiotherapy to malignant tumors

    Institute of Scientific and Technical Information of China (English)

    夏红强; 金冶宁

    2009-01-01

    放疗是治疗恶性肿瘤的主要治疗方法之一,但往往不可避免地出现骨髓抑制等不良反应.细胞保护剂阿米福汀可以对骨髓、肝、肾等起保护作用而不影响抗肿瘤疗效.皮下注射或直肠内给药可能更适合某些病人.其细胞保护作用有一定剂量依赖性和局限性.尚不能影响肿瘤患者的生存率.

  14. Nursing care of senile patients accepted amifostine treatment%高龄病人使用氨磷汀治疗的护理

    Institute of Scientific and Technical Information of China (English)

    成晓玲; 王晓媛

    2006-01-01

    @@ 氨磷汀(即阿米福汀)是在美国批准上市的第一个泛细胞保护剂,又称WR-2721.它是一种前体药,在组织中被细胞膜结合的碱性磷酸酶水解脱磷酸后半合成活性代谢产物,进而保护正常组织免受放疗引起的细胞损害[1].

  15. Amifostine Pre-treatment Attenuates Lung Injury, But Not Inflammation, in Rats Intracheally Instilled with Particulate Matter Rich in Transition Metals

    Science.gov (United States)

    Exposure to particulate matter (PM) is associated with increased cardiovascular disease morbidity and mortality. These correlations are strengthened in individuals with pre-existing cardiovascular disease, including hypertension. Extensive evidence supports a significant role for...

  16. Efficacy of amifostine in the treatment of myelodysplastic syndrome: a meta-analysis of 220 patients from 18 studies%依硫磷酸治疗骨髓增生异常综合征疗效的Meta分析

    Institute of Scientific and Technical Information of China (English)

    卢学春; 迟小华; 朱宏丽; 杨波

    2009-01-01

    目的:分析依硫磷酸治疗骨髓增生异常综合征(MDS)的临床疗效和不良反应,以指导MDS的治疗.方法:以amifostine、myelodysplastic syndrome和therapuetics以及依硫磷酸和MDS为主题词在中英文数据库中检索所有依硫磷酸治疗MDS的临床研究.结果:共检索到24篇依硫磷酸治疗MDS的论文,一共有220例患者纳入研究,其中符合总疗效分析条件的患者一共有195例.在60例输血依赖患者当中,24例(14.7%)治疗后脱离输血,36例(60.0%)输血间隔延长一倍以上;140例粒细胞缺乏患者治疗后69例(49.3%)粒细胞上升超过一倍以上;在57例RAEB和RAEB-t患者当中,无一例幼稚细胞减少.不良反应主要有食欲下降61例(41.2%),恶心53例(35.8%),皮疹13例(8.8%),呕吐12例(8.1%),低血压11例(7.4%),疲劳感9例(6.1%),打喷嚏3例(2.0%),无症状低钙血症2例(1.3%),深静脉血栓2例(占1.3%).结论:依硫磷酸可用于治疗细胞减少的难治性/复发性MDS.但对于血栓性疾病患者慎用.

  17. 氨磷汀皮下注射联合放射治疗的护理%Nursing care of patients undergoing subcutaneous iniection of amifostine combined with radiotherapy

    Institute of Scientific and Technical Information of China (English)

    翁美芳; 谢淑萍; 戚红萍

    2008-01-01

    @@ 放射治疗的目标是通过电离辐射根治肿瘤,杀灭亚临床肿瘤灶或是使肿瘤体积减小而更有利于外科切除;在保护正常组织的前提下提高放射治疗的疗效是放射肿瘤学的目标之一[1].

  18. Radioprotective Effect of Epigallocatechin-3-Gallate on Salivary Gland Dysfunction After Radioiodine Ablation in a Murine Model

    Science.gov (United States)

    Choi, Jeong-Seok; An, Hye-Young; Park, In Suh; Kim, Seok-Ki; Kim, Young-Mo; Lim, Jae-Yol

    2016-01-01

    Objectives. Radioiodine (RI) therapy is known to subject cellular components of salivary glands (SG) to oxidative stress leading to SG dysfunction. However, the protective effects of antioxidants on RI-induced SG damage have not been well investigated. The authors investigated the morphometric and functional effects of epigallocatechin-3-gallate (EGCG) administered prior to RI therapy and compared this with the effects of amifostine (a well-known antioxidant) in a murine model of RI sialadenitis. Methods. Four-week-old female C57BL/6 mice (n=48) were divided into four groups; a normal control group, a RI-treated group (0.01 mCi/g mouse, orally), an EGCG and RI-treated group, and an amifostine and RI-treated group. Animals in these groups were divided into 3 subgroups and euthanized at 15, 30, and 90 days post-RI treatment. Salivary flow rates and lag times were measured, and morphologic and histologic examinations and TUNEL (terminal deoxynucleotidyl transferase biotin-dUDP nick end labeling) assays were performed. Changes in salivary 99mTc pertechnetate uptake and excretion were followed by single-photon emission computed tomography. Results. Salivary flow rates and lag times to salivation in the EGCG or amifostine groups were better than in the RI-treated group. Histologic examinations of SGs in the EGCG or amifostine group showed more mucin-rich parenchyma and less periductal fibrosis than in the RI-treated group. Fewer apoptotic cells were observed in acini, ducts, and among endothelial cells in the EGCG or amifostine group than in the RI group. In addition, patterns of 99mTc pertechnetate excretion were quite different in the EGCG or amifostine group than in the RI group. Conclusion. EGCG supplementation before RI therapy could protect from RI-induced SG damage in a manner comparable to amifostine, and thus, offers a possible means of preventing SG damage by RI. PMID:27136365

  19. Otoproteção da amifostina aos efeitos ototóxicos da cisplatina: estudo em cobaias albinas por emissões otoacústicas produtos de distorção e microscopia eletrônica de varredura Amifostine otoprotection to cisplatin ototoxicity: a guinea pig study using otoacoustic emission distortion products (DPOEA) and scanning electron microscopy

    OpenAIRE

    Miguel Angelo Hyppolito; Antonio A. de Oliveira; Ricardo Miranda Lessa; Maria Rossato

    2005-01-01

    A Cisplatina é uma potente droga antineoplásica, largamente utilizada para o tratamento do câncer, tanto em adultos quanto em crianças. Dentre seus efeitos colaterais, a ototoxicidade se apresenta como um dos mais importantes e leva à perda auditiva irreversível, bilateral, para as altas freqüências (4KHz -8KHz). Estudos têm tentado identificar drogas que, associadas à cisplatina, possam atuar como otoprotetores. Sabe-se que o mecanismo da ototoxicidade pela cisplatina está relacionado a alte...

  20. Metformin Exhibits Radiation Countermeasures Efficacy When Used Alone or in Combination with Sulfhydryl Containing Drugs

    OpenAIRE

    Miller, Richard C.; Murley, Jeffrey S.; David J Grdina

    2014-01-01

    Metformin, a biguanide drug used in the treatment of type II diabetes, was evaluated alone and in combination with amifostine, captopril, MESNA or N-acetyl-cysteine (NAC) for its ability to protect when administered 24 h after irradiation. Mouse embryo fibroblasts (MEF), human microvascular endothelial cells (HMEC) and SA-NH mouse sarcoma cells were exposed to 4 Gy in vitro. C3H mice were exposed to 7 Gy and evaluated utilizing an endogenous spleen colony assay system. Amifostine and WR1065, ...

  1. Mutagenicity and antimutagenicity studies of DRDE-07 and its analogs against sulfur mustard in the in vitro Ames Salmonella/microsome assay.

    Science.gov (United States)

    Vijayan, Vinod; Pathak, Uma; Meshram, Ghansham Pundilikji

    2014-10-01

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM), a chemical warfare agent, is classified as a class I human carcinogen by IARC. No effective antidote against this agent is available. The synthetic aminothiol, amifostine, earlier known as WR-2721, has been extensively used as a chemical radioprotector for normal tissues in cancer radiotherapy and chemotherapy. SM is a radiomimetic agent; this prompted us to evaluate the protective efficacy of amifostine and three of its analogs, DRDE-07 [S-2(2-aminoethylamino) ethyl phenyl sulphide], DRDE-30 [S-2(2-aminoethyl amino) ethyl propyl sulphide] and DRDE-35 [S-2(2-aminoethyl amino) ethyl butyl sulphide], against sulfur mustard-induced mutagenicity in the Ames Salmonella/microsome assay. The antidotes were also evaluated for possible mutagenic activity. DRDE-07 was mutagenic in strain TA104 in the absence of S9; DRDE-30 was mutagenic in strain TA100; amifostine and DRDE-35 did not show mutagenic activity in any of the five tester strains used. SM is mutagenic in strains TA97a and TA102, with or without S9 activation. In the antimutagenicity studies, DRDE-07 and DRDE-35 showed promising antimutagenic activity against SM in the absence of S9, in comparison to amifostine. DRDE-07 and DRDE-35 are promising protective agents against SM-induced mutagenicity.

  2. Pulmonary toxicity in a rabbit model of stereotactic lung radiation therapy: efficacy of a radioprotector.

    Science.gov (United States)

    Mata, Jaime; Sheng, Ke; Hagspiel, Klaus; Ruppert, Kai; Sylvester, Peter; Mugler, John; Fernandes, Carolina; Guan, Steven; Larner, James; Read, Paul

    2014-08-01

    This study aimed to assess the efficacy of the radioprotector amifostine in limiting radiation toxicity in a rabbit model of lung stereotactic body radiation therapy (SBRT) by correlating contrast-enhanced magnetic resonance angiography (ce-MRA), computed tomography (CT), and helium-3 (He-3) magnetic resonance imaging (MRI) with histopathology. Multiple MRI techniques were tested to obtain complementing physiologic information. Thirteen rabbits received SBRT to the right lower lobe of the lung. Specifically, 4 received 3 × 11 Gray (Gy), 6 received 3 × 11 Gy and 50 mg/kg of amifostine pre-SRBT, and 3 received 3 × 7, 3 × 9, or 3 × 13 Gy. Imaging was performed at baseline and 4, 8, 12, and 16 weeks post-SBRT. Ce-MRA perfusion difference between lungs in the irradiated group at 16 weeks post-treatment was statistically significant (P = .04) whereas the difference in the irradiated + amifostine group was not (P = .30). Histologically observed low red blood cell (RBC) count and CT hypodensity suggests changes were primarily related to perfusion; however, structural changes, such as increased alveolar size, were also present. No changes in He-3 MRI lung ventilation were observed in either group. Although radiation-induced injury detected in rabbits as CT hypodensity contrasted with increased density observed in humans/rodents, the changes in ce-MRA and CT were still significantly reduced after the addition of amifostine to SBRT. Use of CT and selected MRI techniques helped to pinpoint primary physiologic changes. PMID:24926529

  3. The sulfhydryl containing compounds WR-2721 and glutathione as radio- and chemoprotective agents. A review, indications for use and prospects

    NARCIS (Netherlands)

    Hospers, GAP; Eisenhauer, EA; de Vries, EGE

    1999-01-01

    Radio- and chemotherapy for the treatment of malignancies are often associated with significant toxicity. One approach to reduce the toxicity is the concomitant treatment with chemoprotective agents. This article reviews two sulfhydryl compounds, namely the agent WR-2721 (amifostine), a compound rec

  4. A New Orally Active, Aminothiol Radioprotector-Free of Nausea and Hypotension Side Effects at Its Highest Radioprotective Doses

    Energy Technology Data Exchange (ETDEWEB)

    Soref, Cheryl M. [ProCertus BioPharm, Inc., Madison, WI (United States); Hacker, Timothy A. [Department of Medicine, Cardiovascular Physiology Core, University of Wisconsin-Madison, Madison, WI (United States); Fahl, William E., E-mail: fahl@oncology.wisc.edu [ProCertus BioPharm, Inc., Madison, WI (United States); McArdle Laboratory for Cancer Research, University of Wisconsin Carbone Cancer Center, Madison, WI (United States)

    2012-04-01

    Purpose: A new aminothiol, PrC-210, was tested for orally conferred radioprotection (rats, mice; 9.0 Gy whole-body, which was otherwise lethal to 100% of the animals) and presence of the debilitating side effects (nausea/vomiting, hypotension/fainting) that restrict use of the current aminothiol, amifostine (Ethyol, WR-2721). Methods and Materials: PrC-210 in water was administered to rats and mice at times before irradiation, and percent-survival was recorded for 60 days. Subcutaneous (SC) amifostine (positive control) or SC PrC-210 was administered to ferrets (Mustela putorius furo) and retching/emesis responses were recorded. Intraperitoneal amifostine (positive control) or PrC-210 was administered to arterial cannulated rats to score drug-induced hypotension. Results: Oral PrC-210 conferred 100% survival in rat and mouse models against an otherwise 100% lethal whole-body radiation dose (9.0 Gy). Oral PrC-210, administered by gavage 30-90 min before irradiation, conferred a broad window of radioprotection. The comparison of PrC-210 and amifostine side effects was striking because there was no retching or emesis in 10 ferrets treated with PrC-210 and no induced hypotension in arterial cannulated rats treated with PrC-210. The tested PrC-210 doses were the ferret and rat equivalent doses of the 0.5 maximum tolerated dose (MTD) PrC-210 dose in mice. The human equivalent of this mouse 0.5 MTD PrC-210 dose would likely be the highest PrC-210 dose used in humans. By comparison, the mouse 0.5 MTD amifostine dose, 400 {mu}g/g body weight (equivalent to the human amifostine dose of 910 mg/m{sup 2}), when tested at equivalent ferret and rat doses in the above models produced 100% retching/vomiting in ferrets and 100% incidence of significant, progressive hypotension in rats. Conclusions: The PrC-210 aminothiol, with no detectable nausea/vomiting or hypotension side effects in these preclinical models, is a logical candidate for human drug development to use in healthy

  5. A New Orally Active, Aminothiol Radioprotector-Free of Nausea and Hypotension Side Effects at Its Highest Radioprotective Doses

    International Nuclear Information System (INIS)

    Purpose: A new aminothiol, PrC-210, was tested for orally conferred radioprotection (rats, mice; 9.0 Gy whole-body, which was otherwise lethal to 100% of the animals) and presence of the debilitating side effects (nausea/vomiting, hypotension/fainting) that restrict use of the current aminothiol, amifostine (Ethyol, WR-2721). Methods and Materials: PrC-210 in water was administered to rats and mice at times before irradiation, and percent-survival was recorded for 60 days. Subcutaneous (SC) amifostine (positive control) or SC PrC-210 was administered to ferrets (Mustela putorius furo) and retching/emesis responses were recorded. Intraperitoneal amifostine (positive control) or PrC-210 was administered to arterial cannulated rats to score drug-induced hypotension. Results: Oral PrC-210 conferred 100% survival in rat and mouse models against an otherwise 100% lethal whole-body radiation dose (9.0 Gy). Oral PrC-210, administered by gavage 30–90 min before irradiation, conferred a broad window of radioprotection. The comparison of PrC-210 and amifostine side effects was striking because there was no retching or emesis in 10 ferrets treated with PrC-210 and no induced hypotension in arterial cannulated rats treated with PrC-210. The tested PrC-210 doses were the ferret and rat equivalent doses of the 0.5 maximum tolerated dose (MTD) PrC-210 dose in mice. The human equivalent of this mouse 0.5 MTD PrC-210 dose would likely be the highest PrC-210 dose used in humans. By comparison, the mouse 0.5 MTD amifostine dose, 400 μg/g body weight (equivalent to the human amifostine dose of 910 mg/m2), when tested at equivalent ferret and rat doses in the above models produced 100% retching/vomiting in ferrets and 100% incidence of significant, progressive hypotension in rats. Conclusions: The PrC-210 aminothiol, with no detectable nausea/vomiting or hypotension side effects in these preclinical models, is a logical candidate for human drug development to use in healthy humans in

  6. Therapeutic effects of cytoprotective agent on breast reconstruction after breast cancer surgery

    OpenAIRE

    He, Xinjia; Wang, Lihua; Li, Wei; Yu, Zhuang; Wang, Xingang

    2015-01-01

    Most patients will choose breast reconstruction after breast cancer surgery, while radiotherapy will damage skin and soft tissue so that will have adverse effect on reconstruction. In this study, we assume that the usage of Amifostine can reduce the incidence of complications after breast reconstruction so that provides more choices of reconstruction operation. Dividing SD rats into surgical placement expansion material group (include 15 ml normal saline) and simple operation group. Then furt...

  7. GST-TAT-SOD: Cell Permeable Bifunctional Antioxidant Enzyme—A Potential Selective Radioprotector

    OpenAIRE

    Jianru Pan; Huocong He; Ying Su; Guangjin Zheng; Junxin Wu; Shutao Liu; Pingfan Rao

    2016-01-01

    Superoxide dismutase (SOD) fusion of TAT was proved to be radioprotective in our previous work. On that basis, a bifunctional recombinant protein which was the fusion of glutathione S-transferase (GST), SOD, and TAT was constructed and named GST-TAT-SOD. Herein we report the investigation of the cytotoxicity, cell-penetrating activity, and in vitro radioprotective effect of GST-TAT-SOD compared with wild SOD, single-function recombinant protein SOD-TAT, and amifostine. We demonstrated that wi...

  8. Effect of radioprotective agents on X-ray cataracts

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, V.N.; Ikebe, H.; Giblin, F.J.; Clark, J.I.; Livesey, J.C. (Oakland Univ., Rochester, MI (USA))

    1989-01-01

    The effect of some protective agents on cataract development is briefly reviewed and new evidence is presented on the efficacy of a phosphorothioate compound (Amifostine) in inhibiting the development of X-ray-induced cataract. Morphological studies showed that at the end of 4 months, lenses from X-irradiated rats which had not received any drugs showed liquefaction in the equatorial region and at the posterior pole, as well as a marked swelling of the fibers in the anterior cortex. Animals which received 1.16g/kg of WR77913 showed considerable protection against the development of radiation induced cataracts with morphological changes in the lens being less severe than in animals receiving no drugs. When animals were treated with 0.5g/kg of Amifostine (WR2721) the lenses showed much greater protection against cataract development than with WR77913. Amifostine appears to be more effective than WR77913 in inhibiting X-ray-induced cataract development. 20 refs.

  9. GST-TAT-SOD: Cell Permeable Bifunctional Antioxidant Enzyme-A Potential Selective Radioprotector.

    Science.gov (United States)

    Pan, Jianru; He, Huocong; Su, Ying; Zheng, Guangjin; Wu, Junxin; Liu, Shutao; Rao, Pingfan

    2016-01-01

    Superoxide dismutase (SOD) fusion of TAT was proved to be radioprotective in our previous work. On that basis, a bifunctional recombinant protein which was the fusion of glutathione S-transferase (GST), SOD, and TAT was constructed and named GST-TAT-SOD. Herein we report the investigation of the cytotoxicity, cell-penetrating activity, and in vitro radioprotective effect of GST-TAT-SOD compared with wild SOD, single-function recombinant protein SOD-TAT, and amifostine. We demonstrated that wild SOD had little radioprotective effect on irradiated L-02 and Hep G2 cells while amifostine was protective to both cell lines. SOD-TAT or GST-TAT-SOD pretreatment 3 h prior to radiation protects irradiated normal liver cells against radiation damage by eliminating intracellular excrescent superoxide, reducing cellular MDA level, enhancing cellular antioxidant ability and colony formation ability, and reducing apoptosis rate. Compared with SOD-TAT, GST-TAT-SOD was proved to have better protective effect on irradiated normal liver cells and minimal effect on irradiated hepatoma cells. Besides, GST-TAT-SOD was safe for normal cells and effectively transduced into different organs in mice, including the brain. The characteristics of this protein suggest that it may be a potential radioprotective agent in cancer therapy better than amifostine. Fusion of two antioxidant enzymes and cell-penetrating peptides is potentially valuable in the development of radioprotective agent. PMID:27313832

  10. GST-TAT-SOD: Cell Permeable Bifunctional Antioxidant Enzyme—A Potential Selective Radioprotector

    Science.gov (United States)

    Pan, Jianru; He, Huocong; Su, Ying; Zheng, Guangjin; Wu, Junxin; Liu, Shutao; Rao, Pingfan

    2016-01-01

    Superoxide dismutase (SOD) fusion of TAT was proved to be radioprotective in our previous work. On that basis, a bifunctional recombinant protein which was the fusion of glutathione S-transferase (GST), SOD, and TAT was constructed and named GST-TAT-SOD. Herein we report the investigation of the cytotoxicity, cell-penetrating activity, and in vitro radioprotective effect of GST-TAT-SOD compared with wild SOD, single-function recombinant protein SOD-TAT, and amifostine. We demonstrated that wild SOD had little radioprotective effect on irradiated L-02 and Hep G2 cells while amifostine was protective to both cell lines. SOD-TAT or GST-TAT-SOD pretreatment 3 h prior to radiation protects irradiated normal liver cells against radiation damage by eliminating intracellular excrescent superoxide, reducing cellular MDA level, enhancing cellular antioxidant ability and colony formation ability, and reducing apoptosis rate. Compared with SOD-TAT, GST-TAT-SOD was proved to have better protective effect on irradiated normal liver cells and minimal effect on irradiated hepatoma cells. Besides, GST-TAT-SOD was safe for normal cells and effectively transduced into different organs in mice, including the brain. The characteristics of this protein suggest that it may be a potential radioprotective agent in cancer therapy better than amifostine. Fusion of two antioxidant enzymes and cell-penetrating peptides is potentially valuable in the development of radioprotective agent. PMID:27313832

  11. GST-TAT-SOD: Cell Permeable Bifunctional Antioxidant Enzyme—A Potential Selective Radioprotector

    Directory of Open Access Journals (Sweden)

    Jianru Pan

    2016-01-01

    Full Text Available Superoxide dismutase (SOD fusion of TAT was proved to be radioprotective in our previous work. On that basis, a bifunctional recombinant protein which was the fusion of glutathione S-transferase (GST, SOD, and TAT was constructed and named GST-TAT-SOD. Herein we report the investigation of the cytotoxicity, cell-penetrating activity, and in vitro radioprotective effect of GST-TAT-SOD compared with wild SOD, single-function recombinant protein SOD-TAT, and amifostine. We demonstrated that wild SOD had little radioprotective effect on irradiated L-02 and Hep G2 cells while amifostine was protective to both cell lines. SOD-TAT or GST-TAT-SOD pretreatment 3 h prior to radiation protects irradiated normal liver cells against radiation damage by eliminating intracellular excrescent superoxide, reducing cellular MDA level, enhancing cellular antioxidant ability and colony formation ability, and reducing apoptosis rate. Compared with SOD-TAT, GST-TAT-SOD was proved to have better protective effect on irradiated normal liver cells and minimal effect on irradiated hepatoma cells. Besides, GST-TAT-SOD was safe for normal cells and effectively transduced into different organs in mice, including the brain. The characteristics of this protein suggest that it may be a potential radioprotective agent in cancer therapy better than amifostine. Fusion of two antioxidant enzymes and cell-penetrating peptides is potentially valuable in the development of radioprotective agent.

  12. Radioprotective effects of kojic acid against mortality induced by gamma irradiation in mice

    International Nuclear Information System (INIS)

    To evaluate the protective effects of kojic acid on mortality induced by gamma irradiation in mice. The efficacy was compared with amifostine as a reference radioprotector. This experimental study was conducted in the Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari and Babolsar Radiotherapy Hospital, Babolsar, Iran, between October 2006 and January 2008. Kojic acid was administrated subcutaneously as single doses of 142, 175, 232, and 350 mg/kg, one hour prior to a lethal dose of gamma irradiation (8 Gy). Amifostine was injected subcutaneously at a dose of 200 mg/kg at a similar irradiation dose. The mortality was recorded 30 days after irradiation. The antioxidant activity of the kojic acid was assessed using the 1, 1-diphenyl-2-picrylhydrazyl free stable radical (DPPH) method. One hundred and twenty NMRI mice were divided into 6 groups with 20 mice in each group. At 30 days after treatment, the percentage of survival in each group was: control, 5%; 142 mg/kg, 5%; 175 mg/kg, 0%; 232 mg/kg, 30%; 350 mg/kg, 40%; and amifostine, 40% one hour treatment prior gamma irradiation. The survival rate was statistically increased in animals treated with kojic acid (350 mg/kg), one hour prior irradiation, as compared with the irradiated control group. Kojic acid exhibited concentration-dependent scavenging activity on DPPH possessing strong antioxidant activity. Kojic acid with antioxidant activity reduced the mortality induced by gamma irradiation. (author)

  13. 细胞防护剂WR-2721研究进展%Advances in research of the cytoprotector WR-2721

    Institute of Scientific and Technical Information of China (English)

    顾宏涛

    2003-01-01

    WR-2721(amifostine)是一种广谱的细胞保护剂,在体内通过其活性形式WR-1065保护正常细胞,减轻放、化疗毒副作用,促进造血细胞恢复,使患者可以耐受大剂量放、化疗.WR-2721可能成为高恶性和耐药性肿瘤治疗新策略之一.

  14. Radioprotektivni učinci amifostina i melatonina na ljudske limfocite izložene gama-zračenju u uvjetima in vitro

    OpenAIRE

    Kopjar, Nevenka; Miočić, Slavica; Ramić, Snježana; Milić, Mirta; Viculin, Tomislav

    2006-01-01

    Primjena zračenja u liječenju zloćudnih bolesti (radioterapija) značajno pridonosi preživljenju bolesnika, ali izaziva i niz neželjenih učinaka na zdrave stanice i tkiva. Nuspojave ionizirajućeg zračenja mogu se značajno smanjiti s pomoću kemijskih spojeva s antioksidativnim učinkom koji djeluju kao ‘hvatači’ slobodnih radikala i štite vrlo osjetljivu molekulu DNA. Među spojeve s pretpostavljenim ili dokazanim radioprotektivnim učincima ubrajaju se amifostin i melatonin, koji su predmet istra...

  15. Small Molecule GS-Nitroxide Ameliorates Ionizing Irradiation-Induced Delay in Bone Wound Healing in a Novel Murine Model

    OpenAIRE

    Gokhale, Abhay; Rwigema, Jean-Claude; Epperly, Michael; Glowacki, Julie; Wang, Hong; Wipf, Peter; Goff, Julie P.; Dixon, Tracy; Patrene, Ken; Greenberger, Joel S.

    2010-01-01

    We studied radioprotection and mitigation by mitochondrial-targeted Tempol (GS-nitroxide, JP4-039), in a mouse injury/irradiation model of combined injury (fracture/irradiation). Right hind legs of control C57BL/6NHsd female mice, mice pretreated with MnSOD-PL, JP4-039, or with amifostine were irradiated with single and fractionated doses of 0 to 20 Gy. Twenty-four hours later, unicortical holes were drilled into the tibiae of both hind legs; at intervals, tibias were excised, radiographed, a...

  16. 氨磷汀与细胞凋亡的研究进展

    Institute of Scientific and Technical Information of China (English)

    黄成垠; 陈宝安; 李翠萍

    2003-01-01

    氨磷汀(Amifostine)是一种广谱的细胞保护剂,除了通过稳定细胞DNA分子、消除氧自由基而发挥保护作用外,抑制细胞凋亡是其保护细胞作用的重要机制.本文着重讨论氨磷汀的抗凋亡作用以及可能的分子机制.

  17. 氨磷汀对肺癌患者顺铂化疗的肾保护观察

    Institute of Scientific and Technical Information of China (English)

    徐红

    2002-01-01

    @@ 顺铂是治疗肺癌的主要化疗药物之一,而其主要副作用为肾脏毒性,甚至诱发肾功能衰竭.氨磷汀(amifostine)是广谱选择性细胞保护剂[1],它能选择性保护正常器官免受化、放疗的毒性而不保护肿瘤组织,本文旨在观察该药对顺铂引起肺癌患者肾毒性的保护作用.#

  18. 氨磷汀对骨髓造血细胞的保护作用

    Institute of Scientific and Technical Information of China (English)

    周敏; 孙载阳; 陈宝安

    2001-01-01

    氨磷汀(amifostine)是一种广谱的选择性的细胞保护剂,它能保护多种正常组织免受化疗和放疗的损伤,并且不影响化疗药物对肿瘤细胞的杀伤效果.本文就氨磷汀的药理特性及其降低化疗药物对正常骨髓造血的抑制作用作一综述.

  19. 氨磷汀对草酸铂和氟脲嘧啶脱氧核苷肾毒性的保护作用

    Institute of Scientific and Technical Information of China (English)

    李丽; 许晓娟; 臧秦川; 钱晓萍; 刘宝瑞

    2003-01-01

    @@ 氨磷汀(Amifostine)是美国FDA批准上市的第一个泛细胞保护剂.它是一种有机硫代磷酸化合物,正常组织对其摄取迅速而代谢缓慢,肿瘤组织则有缓慢摄取,结果正常组织因有高浓度氨磷汀而起到清除因化放疗产生的氧自由基作用,但不影响放化疗的抗肿瘤作用.

  20. DEGRO`98. 4th German congress on radiation oncology, biology, physics. Book of abstracts; DEGRO`98. 4. Deutscher Kongress fuer Radioonkologie, Strahlenbiologie und Medizinische Physik. Abstractband

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1998-11-01

    The special issue contains all abstracts of the congress papers and compact information on the subjects of poster sessions and refresher courses. The themes of the technical and poster sessions are: Radiation physics of brachytherapy, CT-simulation and dosimetry, positioning and verification, 3D planning, quality assurance, irradiation planning and imaging, portal imaging; radiobiology in the context of interactions in combined chemotherapy and radiotherapy, cytokine and fibrosis, radiosensitivity and repair, apoptosis, oxygen and radiation effects; CNS; Amifostine as a protective agent in radiotherapy and chemotherapy: breast cancer; upper gastro-intestinal tract; anti-inflammation and proliferation irradiation; stereotaxy; palliative treatments; head and neck cancer, irradiation techniques; hyperthermia; rectal carcinoma; urogenital tract; malignant lymphoma; eyes and orbita; cervical and corpus carcinoma; non-cat-cell bronchial carcinoma. (MG/CB) [Deutsch] Der vorliegende Sonderband legt alle Abstracts der Tagung sowie die Inhaltsangaben der Poster-Sessions und der Refresher-Kurse vor. Die Themen der Vortraege und Poster waren wie folgt: Strahlenphysik der Brachytherapie, der CT-Simulation und Dosimetrie, der Lagerung und Verifikation, der 3D-Planung, der Qualitaetssicherung, der Bestrahlungsplanung und Bildgebung und des Portal Imagings; Strahlenbiologie in Bezug auf Interaktion von Chemo- und Radiotherapie, Zytokine und Fibrose, Strahlenempfindlichkeit und Reparatur, Apoptose, Sauerstoff und Strahlenwirkung; ZNS; Amifostin als Protektor in Radio- und Chemotherapie: Mammakarzinom; oberer Gastrointestinaltrakt; entzuendungs- und antiproliferative Bestrahlung; Stereotaxie; Palliativmedizin; Kopf-Hals-Bereich; Bestrahlungstechniken; Hyperthermie; Rektum- und Analkarzinom; Urogenitaltrakt; maligne Lymphome; Auge und Orbita; Zervix- und Korpuskarzinom; nichtkleinzelliges Bronchialkarzinom. (MG)

  1. Prevention of radiation-induced bone pathology through combined pharmacologic cytoprotection and angiogenic stimulation.

    Science.gov (United States)

    Donneys, Alexis; Nelson, Noah S; Perosky, Joseph E; Polyatskaya, Yekaterina; Rodriguez, Jose J; Figueredo, Christian; Vasseli, Cheyenne A; Ratliff, Hannah C; Deshpande, Sagar S; Kozloff, Kenneth M; Buchman, Steven R

    2016-03-01

    Pathologic fractures and associated non-unions arising in previously irradiated bone are severely debilitating diseases. Although radiation is known to have deleterious effects on healthy tissue cellularity and vascularity, no clinically accepted pharmacologic interventions currently exist to target these destructive mechanisms within osseous tissues. We utilized amifostine-a cellular radioprotectant-and deferoxamine-an angiogenic stimulant-to simultaneously target the cellular and vascular niches within irradiated bone in a rat model of mandibular fracture repair following irradiation. Rats treated with combined therapy were compared to those undergoing treatment with singular amifostine or deferoxamine therapy, nontreated/irradiated animals (XFx) and non-treated/non-irradiated animals (Fx). 3D angiographic modeling, histology, Bone Mineral Density Distribution and mechanical metrics were utilized to assess therapeutic efficacy. We observed diminished metrics for all outcomes when comparing XFx to Fx alone, indicating the damaging effects of radiation. Across all outcomes, only the combined treatment group improved upon XFx levels, normalized all metrics to Fx levels, and was consistently as good as, or superior to the other treatment options (p<0.05). Collectively, our data demonstrate that pharmacologically targeting the cellular and vascular environments within irradiated bone prevents bone injury and enhances fracture healing. PMID:26723578

  2. Contribution of radiotherapy to the treatment of malignant tumors, 3. Combined drugs and radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Niibe, Hideo; Takahashi, Iku; Tamaki, Yoshio (Gunma Univ., Maebashi (Japan). School of Medicine)

    1984-09-01

    Effects of cytotoxic agent, hormone, hypoxic cell sensitizer, and radiation protector combined with radiation therapy in cancer management were analysed. The results were as follows: 1) An increase in response was seen in 25% or more of tumor nodules given radiotherapy combined with misonidazole, anoxic cell sensitizer, compared with radiotherpy alone. But the drug was also found to be neurotoxic and peripheral neuropathy. 2) Evidence has been given that Amifostine may protect the mucosal damage from radiation when Amifostine prior to irradiation was administrated to patients with tumor in the head and neck or in the pelvis. 3) There were no difference between five year survival of radiotherapy alone and with chemotherapy for patients with stage I Non-Hodgkin lymphoma. Chemotherapy following radiotherapy for patients with stage II was more effective treatment method than radiotherapy alone. 4) Radiotherapy for patients with prostate cancer was performed to control only primary site. The success rates of local control were over 80%. The near future holds extensive promise for a combination of radiation therapy, cytotoxic chemotherapy, hormone therapy, hypoxic cell sensitizer, and radiation protectors. All of these when used in the appropriate circumstances may yield significant improvements in the therapeutic ratio and in the long-tern control of tumors.

  3. Clastogenic effect of atranorin, evernic acid, and usnic acid on human lymphocytes.

    Science.gov (United States)

    Stojanović, Gordana S; Stanković, Miroslava; Stojanović, Igor Z; Palić, Ivan; Milovanović, Vesna; Rancić, Sofija

    2014-04-01

    Three lichen secondary metabolites atranorin (1), evernic acid (2), and usnic acid (3), were evaluated for their in vitro clastogenic and antiproliferative effects on human lymphocytes using the cytochalasin-B blocked micronucleus (CBMN) assay at concentrations of 2 microg/mL, 4 microg/mL and 6 microg/mL of final culture solution. The frequency of micronucleus (MN) was scored in binucleated cells, and cytokinesis-block proliferation index (CBPI) was calculated. Among the tested compounds, 3 exhibited the most prominent effect decreasing the frequency of MN in the range of 42.5% - 48.9%, that is about double of the positive control amifostin WR-2721 that reduces MN frequency for 22.0%. The effect of evernic acid was approximately equal to action of amifostin (23.2% -32.9%). Atranorin at concentrations of 2 microg/mL and 4 microg/mL decreasing the frequency of MN only for 11.1% and 1.8%, while in concentration of 6 microg/mL increases the frequency of MN for 9.6 %. The comparable CBPI values of the investigated compounds and control suggested that they did not show a statistically significant inhibitory effect on lymphocyte cell proliferation at applied concentrations. PMID:24868868

  4. Pharmacological management of acute radiation morbidity

    Energy Technology Data Exchange (ETDEWEB)

    Zimmermann, J.S.; Kimmig, B. [Klinik fuer Strahlentherapie (Radioonkologie), Christian-Albrecht-Universitaet Kiel (Germany)

    1998-11-01

    Background: The acute radiation morbidity may be a serious problem for the patient and may be decreased by pharmacological approaches. Material and methods: A database research (Medline, Cancerlit, DIMDI, etc.) was performed in order to obtain pharmacological approaches to decrease the acute radiation morbidity. The evaluation was focused on therapeutic principles but not on special drugs. Results: Different approaches may be chosen to protect healthy tissues from the effects of ionizing radiation: 1. Administration of cyto- or radioprotective agents prior to irradiation, 2. administration of agents to avoid additional secondary toxicity by inflammation or superinfection during the treatment cycle (supportive care) and 3. administration of rescue agents, such as bone marrow CSFs or hyperbaric oxygen (HBO), after therapy. For radioprotection, there are reports on cellular protection by vitamine E, vitamine C, beta carotene, ribose-cysteine, glutamine, Mgcl2/adenosine triphosphate and WR-2721 (amifostine). In general, preclinical studies show that the combination of pretreatment with amifostine, irradiation, and G-CSF after radiation enhances hematologic recovery. Assessment of these combined effects, including local supportive therapies, merits further clinical investigation. There are data from prospective studies as well as from empirical clinical experience, that radioprotection and clinical supportive care may reduce the treatment related morbidity by 10 to 30% either. Conclusions: A further improvement of the therapeutic ratio is to be expected by systemically combined application of radioprotectors, supportive care and rescue agents. (orig.) [Deutsch] Hintergrund: Die strahlentherapeutische Fruehmorbiditaet kann auf das Ergebnis einer Strahlenbehandlung Einfluss nehmen und kann durch medikamentoese Verfahren gelindert werden. Material und Methoden: Eine Datenbankrecherche (Medline, Cancerlit, DIMDI u.a.) wurde durchgefuehrt, um einen Ueberblick ueber

  5. Antiretroviral activity of the aminothiol WR1065 against Human Immunodeficiency virus (HIV-1 in vitro and Simian Immunodeficiency virus (SIV ex vivo

    Directory of Open Access Journals (Sweden)

    Borojerdi Jennifer P

    2009-11-01

    Full Text Available Abstract Background WR1065 is the free-thiol metabolite of the cytoprotective aminothiol amifostine, which is used clinically at very high doses to protect patients against toxicity induced by radiation and chemotherapy. In an earlier study we briefly reported that the aminothiol WR1065 also inhibits HIV-1 replication in phytohemagglutinin (PHA-stimulated human T-cell blasts (TCBs infected in culture for 2 hr before WR1065 exposure. In this study we expanded the original observations to define the dose-response curve for that inhibition, and address the question of additive effects for the combination of WR1065 plus Zidovudine (AZT. Here we also explored the effect of WR1065 on SIV by examining TCBs taken from macaques with well-established infections several months with SIV. Results TCBs from healthy human donors were infected for 2 hr with HIV-1, and viral replication (p24 was measured after 72 hr of incubation with or without WR1065, AZT, or both drugs. HIV-1 replication, in HIV-1-infected human TCBs, was inhibited by 50% at 13 μM WR1065, a dose at which 80% of the cells were viable. Cell cycle parameters were the same or equivalent at 0, 9.5 and 18.7 μM WR1065, showing no drug-related toxicity. Combination of AZT with WR1065 showed that AZT retained antiretroviral potency in the presence of WR1065. Cultured CD8+ T cell-depleted PHA-stimulated TCBs from Macaca mulatta monkeys chronically infected with SIV were incubated 17 days with WR1065, and viral replication (p27 and cell viability were determined. Complete inhibition (100% of SIV replication (p27 was observed when TCBs from 3 monkeys were incubated for 17 days with 18.7 μM WR1065. A lower dose, 9.5 μM WR1065, completely inhibited SIV replication in 2 of the 3 monkeys, but cells from the third macaque, with the highest viral titer, only responded at the high WR1065 dose. Conclusion The study demonstrates that WR1065 and the parent drug amifostine, the FDA-approved drug Ethyol, have

  6. Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug conversion in a dual-tissue microfluidic chip

    International Nuclear Information System (INIS)

    The objective of this paper is to introduce a novel cell printing and microfluidic system to serve as a portable ground model for the study of drug conversion and radiation protection of living liver tissue analogs. The system is applied to study behavior in ground models of space stress, particularly radiation. A microfluidic environment is engineered by two cell types to prepare an improved higher fidelity in vitro micro-liver tissue analog. Cell-laden Matrigel printing and microfluidic chips were used to test radiation shielding to liver cells by the pro-drug amifostine. In this work, the sealed microfluidic chip regulates three variables of interest: radiation exposure, anti-radiation drug treatment and single- or dual-tissue culture environments. This application is intended to obtain a scientific understanding of the response of the multi-cellular biological system for long-term manned space exploration, disease models and biosensors.

  7. Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug conversion in a dual-tissue microfluidic chip

    Energy Technology Data Exchange (ETDEWEB)

    Snyder, J E; Hamid, Q; Wang, C; Chang, R; Sun, W [Department of Mechanical Engineering, Drexel University, Philadelphia, PA 19104 (United States); Emami, K; Wu, H, E-mail: sunwei@drexel.edu, E-mail: weisun@tsinghua.edu.cn [Radiation Biophysics Lab, NASA Johnson Space Center, Houston, TX 77586 (United States)

    2011-09-15

    The objective of this paper is to introduce a novel cell printing and microfluidic system to serve as a portable ground model for the study of drug conversion and radiation protection of living liver tissue analogs. The system is applied to study behavior in ground models of space stress, particularly radiation. A microfluidic environment is engineered by two cell types to prepare an improved higher fidelity in vitro micro-liver tissue analog. Cell-laden Matrigel printing and microfluidic chips were used to test radiation shielding to liver cells by the pro-drug amifostine. In this work, the sealed microfluidic chip regulates three variables of interest: radiation exposure, anti-radiation drug treatment and single- or dual-tissue culture environments. This application is intended to obtain a scientific understanding of the response of the multi-cellular biological system for long-term manned space exploration, disease models and biosensors.

  8. 肺癌患者应用氨磷汀配合放射治疗的观察与护理

    Institute of Scientific and Technical Information of China (English)

    章海珠; 谢淑萍; 陈建华

    2009-01-01

    @@ 氨磷汀(amifostin,又称阿米福汀)是泛细胞保护剂,最初是作为放射保护剂.放射治疗在杀伤肿瘤细胞的同时,对人体正常细胞也有一定的影响.为减轻放射治疗对患者正常组织的放射性损伤,2008年1月至2008年8月,本院放疗科对35例肺癌患者使用氨磷汀配合放疗,取得良好效果,现将观察与护理报告如下.

  9. 放射防护剂氨磷汀的临床应用

    Institute of Scientific and Technical Information of China (English)

    陈暑波; 田野; 陆雪官

    2004-01-01

    氨磷汀(Amifostine,AMI)是放射防护剂的代表性药物.此种药物能够减少由顺铂引起的相关毒性作用,同时保护正常组织,减轻放疗引起的急、慢性损伤而不保护肿瘤细胞.现从放疗引起的细胞毒性作用、放射防护剂AMI的作用机制及其临床应用研究的结果等方面,来说明AMI作为一种放射防护剂应用于临床的价值

  10. Normal Tissue Protectors Against Radiation Injury (Review Paper

    Directory of Open Access Journals (Sweden)

    P. Uma Devi

    2011-02-01

    Full Text Available Radiation damages normal tissues that can adversely affect the success of cancer radiotherapy, safety of nuclear installation workers and military personnel, and public exposed to nuclear accidents. Certain chemicals are able to protect against the harmful effects of radiation. But more than 50 years of research has produced only one approved radioprotective drug, WR-2721 or amifostine. The general utility of WR-2721 is limited by its inherent toxicity and high cost. Efforts to find non-toxic radioprotectors have revealed the promising properties of some medicinal plants. This is an attempt to review the recent publications on radioprotectors and to identify the research needs relevant to developing countries.Defence Science Journal, 2011, 61(2, pp.105-112, DOI:http://dx.doi.org/10.14429/dsj.61.829

  11. Survival After Accidental Extrahepatic Distribution of Y90 Microspheres to the Mesentery During a Radioembolization Procedure

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Ahmadzadehfar, Hojjat [University Hospital, Department of Nuclear Medicine (Germany); Schaefer, Nico [University Hospital, Department of Surgery (Germany); Wilhelm, Kai; Schueller, Heinrich [University Hospital, Department of Radiology, Division of Radiation Oncology (Germany); Ezziddin, Samer, E-mail: samer.ezziddin@ukb.uni-bonn.de [University Hospital, Department of Nuclear Medicine (Germany)

    2012-08-15

    We present the acute management and outcome of a patient after an accidental mesenteric distribution of Y90 microspheres during radioembolization (RE). This report describes and highlights: (1) the incidence of a significant reflux during a RE session while injecting into a replaced right hepatic artery from the superior mesenteric artery, (2) the appearance of diffuse mesenteric Y90 distribution in bremsstrahlung-imaging, (3) the management protocol with the radiation protection agent amifostine, (4) the development of typical adverse effects in the expected time window, and (5) survival of the patient without long-term sequelae. This report should sensitize physicians to this particular problem and may help to avoid as well as manage similar radioembolization incidences.

  12. A review of radioprotective plants

    Directory of Open Access Journals (Sweden)

    Prasan R Bhandari

    2013-01-01

    Full Text Available Radioprotective compounds have been used to diminish morbidity or mortality produced by ionizing irradiation. Initial developments of such agents concentrated on thiol synthetic compounds, like amifostine. This agent decreased mortality; however, there were difficulties in administering aminothiols that led to adverse effects. Unfortunately, no ideal, safe synthetic radioprotectors are available to date; hence, the exploration for other sources, including plants, has been ongoing for several decades. A methodical screening strategy can offer leads to isolating prospective novel candidate drugs from plant sources, for alleviation of radiation injury. This article reviews some of the most promising plants, and their bioactive principles, that are extensively used in traditional systems of medicine, and which have rendered noteworthy radioprotection in both in vitro and in vivo model systems.

  13. 最新藥物資料%New medicine information

    Institute of Scientific and Technical Information of China (English)

    澳門衛生局藥物事務廰

    2003-01-01

    @@ 1.Amifostine(Ethynol(R))引起致命的皮膚反應-Fatal Cutaneous Reaction 本年二月葡國國家藥昌監督管理局對Amifostina(Ethynol(R))發出了一項安全性評論,Amfiostine是一種輔助化療的藥物,能降低末期卵巢癌病人因使用Cisplatin及Cyclophosphamide後受感染及由嗜中性白血球減少所引起之發燒的危險性,此藥亦能使末期固體腫瘤的病人能抵抗由Cisplatin所引起的腎毒性;此外,Amifostine亦能舒緩因放射線治療引起的口腔乾燥.

  14. Protective effects of domestic Anlingding(WR-2721) on nephrotoxicity induced by cis-platin%国产氨磷汀(WR-2721)对顺铂致肾毒性的保护作用

    Institute of Scientific and Technical Information of China (English)

    张康宣; 蔡鸣; 胡芝华

    2001-01-01

    腹腔注射国产放化疗保护剂氨磷汀能明显减低由顺铂(cis-Pt)引起的正常小鼠或大鼠的肾脏毒性,氨磷汀各剂量组血清尿素氮与cis-Pt组相比显著降低(P<0.01),同时可见肾脏组织学损害明显逆转,与进口对照品amifostine(AFT)相比无显著差异.对接受放化疗的腹水型肝癌和肉瘤-180荷瘤小鼠以及体外培养人肺腺癌肿瘤细胞加用氨磷汀均不影响放化疗的疗效,国产品与进口品无明显差异.

  15. 细胞保护剂氨磷汀及其临床应用与展望

    Institute of Scientific and Technical Information of China (English)

    马培奇

    2001-01-01

    1.序言细胞保护剂是用来预防或减少肿瘤化(放)疗所致毒、副作用、进而通过提高肿瘤患者在肿瘤治疗中的顺应性和耐受性而达到提高他们肿瘤治疗效果及其生存质量的一类药物。细胞保护剂的开发虽仅短短20多年的历史,但其间已有右丙亚胺(dexrazoxane)、美司那(mesna)和氨磷汀(amifostine)分别成功地用于预防或降低阿霉素(doxorubicin)的心毒

  16. 细胞保护剂临床应用32例观察

    Institute of Scientific and Technical Information of China (English)

    巩湘浩; 兰东强

    2011-01-01

    @@ 阿米福汀(氨磷汀amifostine WR2721)原是冷战时期美国研制的放射保护剂中的一种,也是FDA(美国食品与药品监督管理局)批准上市的第一个泛细胞保护荆,它能选择性地保护正常的器官免受化(放)疗的毒性攻击.而不保护肿瘤组织.因此,能明显改善病人对化、放疗的耐受性,提高生活质量,自其临床应用以来,有关的报道层出不穷[1].

  17. 氨磷汀对顺铂化疗的影响

    Institute of Scientific and Technical Information of China (English)

    林华; 卞美璐

    2002-01-01

    @@ 顺铂是卵巢癌化疗的首选药物,属细胞毒治疗,在杀伤肿瘤细胞的同时也常杀伤正常细胞.使正常细胞免受化疗药物损害是当今化疗中的新课题.氨磷汀(amifostine 又称WR-2721,Ethyol)是美国FDA批准的第一个泛细胞保护剂,即广谱选择性细胞保护剂[1].我们在用顺铂对卵巢癌化疗的同时使用氨磷汀,使顺铂对肾的毒性及骨髓的抑制作用得到缓解,现报道如下.

  18. Melatonin; an Established Radioprotective Agent Against JapanAND#8217;s Nuclear Disaster

    Directory of Open Access Journals (Sweden)

    Ahmet Korkmaz

    2011-04-01

    Full Text Available In spite of its widespread use and the well known potential hazards associated with exposure to ionizing radiation, countries are poorly ill-equipped to protect their citizens in case of a fallout as seen in northeastern region of Japan. In case of nuclear fallout, there is no practical way to save people from the hazardous effects of ionizing radiation. Health authorities may provide potassium iodide for people to prevent thyroid cancer. Another preventive attempt would be using amifostine, a well known agent with radioprotective features. Melatonin (N-acetyl-5-methoxytryptamine is a pineal product which is also known to have robust radioprotective features. Both human and experimental animal studies have clearly shown that it is a unique antioxidant and a DNA and chromosome protector against a variety of harmful agents including ionizing radiation. [TAF Prev Med Bull 2011; 10(2.000: 127-129

  19. Molecular study of DNA radioprotection by thiols

    Energy Technology Data Exchange (ETDEWEB)

    Savoye, C.; Charlier, M.; Spotheim-Maurizot, M. [Centre National de la Recherche Scientifique (CNRS), 45 - Orleans-la-Source (France); Swenberg, C. [ACRD, Armed Forces Radiobiology Research Institute, Bethesda (United States); Sabattier, R. [Centre Hospitalier Regional d`Orleans, 45 (France)

    1997-03-01

    Polyamines (PA) are natural components of mammalian cells, essential for growth processes. Since a decrease of the cellular level of PA increases the effect of radiotherapy on tumour cells, we have supposed that PA may act as DNA radioprotectors. The search of non-toxic agents that protect specifically normal cells led to the discovery of the agent WR-2721 used now in cancer cancer therapy under the name Ethyol (Amifostine) and of the agent WR-151327. Both have a chemical structure close to that of natural PA. The main radioprotective metabolites of these agents are the thiols WR>61065 and WR-151326. We have compared here here the protective effects of these thiols to those of another simpler thiol, the cysteamine, and of a related PA, the putrescine, on the number and location of fast neutrons-induced DNA strand breaks. (authors)

  20. Esophageal toxicity of radiation therapy: Clinical risk factors and management

    International Nuclear Information System (INIS)

    Acute radiation-induced esophagitis includes all clinical symptoms (odynophagia, dysphagia) occurring within 90 days after thoracic irradiation start. Its severity can be graded using RTOG and CTCAE scales. The clinical risk factors are: age, female gender, initial performance status, pre-therapeutic body mass index, pre-therapeutic dysphagia, tumoral and nodal stage, delivered dose, accelerated hyperfractionated radiotherapy, concomitant association of chemotherapy to radiotherapy and response to the treatment. The dosimetric parameters predictive of esophagitis are: mean dose, V20 Gy, V30 Gy, V40 Gy, V45 Gy and V50 Gy. Amifostine is the only drug to have a proven radioprotective efficacy (evidence level C, ESMO recommendation grade III). The medical management of esophagitis associates a diet excluding irritant food, medication against gastroesophageal reflux, analgesic treatment according to the WHO scale and management of dehydration and de-nutrition by enteral feeding. (authors)

  1. Radiation induced oral mucositis

    Directory of Open Access Journals (Sweden)

    P S Satheesh Kumar

    2009-01-01

    Full Text Available Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii who also received concomitant chemotherapy; (iii who received a total dose over 5,000 cGy; and (iv who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene

  2. Utility of DF-1 for Radioprotection in Lymphocytes

    Science.gov (United States)

    Reynolds, Julia; Casey, Rachael; Wu, Honglu; Huff, Janice; Emami, Kamal; Moore, Valerie; Jeevarajan, Antony

    2007-01-01

    The development of degenerative changes in the vasculature, such as atherosclerosis, is a known consequence of exposure to ionizing radiation, and is thus a concern for astronaut health following long duration space flight. Cellular damage caused by radiation is due to free radical generation and DNA damage. The goal of this project was to assess the ability of a C60-derivative, DF-1, to mitigate cellular damage resulting from radiation exposure in primary human lymphocytes. DF-1 is a water-soluble C60 fullerene encapsulated in dendrimeric functional groups that is proposed to exhibit antioxidant properties. Human lymphocytes are radiosensitive and travel throughout the body potentially causing bystander effects in any tissues they contact. These cells were subjected to varying doses of gamma radiation in the presence or absence of DF-1. Cells were collected at 48 hours post-irradiation for chromosomal aberration studies and at 72 hours post-irradiation for micronuclei studies. These studies showed that the irradiated cells contained more chromosomal aberrations and micronuclei than the control cells. Addition of the DF-1 reduced the amount of observed DNA damage in the irradiated cells. Growth curves were measured for the lymphocytes exposed to 0 and 4 Gray gamma irradiations, and we observed less growth in the cells irradiated at 4 Gy. 2,7-dichlorofluorescein diacetate was used to detect reactive oxygen species production, and increased production of ROS was observed in the irradiated lymphocytes. Human lymphocytes were subjected to varying doses of gamma or photon radiation in the presence and absence of DF-1 and a known radioprotectant, amifostine. After irradiation, the production of reactive oxygen species, growth curves and cell viability were measured. These cells were also collected to quantify chromosomal aberrations and micronuclei formation. We predict that irradiated cells will show the most damage and that DF-1 will provide protective effects similar

  3. A Phase II Study of Submandibular Gland Transfer Prior to Radiation for Prevention of Radiation-induced Xerostomia in Head-and-Neck Cancer (RTOG 0244)

    Energy Technology Data Exchange (ETDEWEB)

    Jha, Naresh, E-mail: naresh.jha@albertahealthservices.ca [University of Alberta, Cross Cancer Institute, Edmonton, Alberta (Canada); Harris, Jonathan [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Seikaly, Hadi [University of Alberta, Edmonton, Alberta (Canada); Jacobs, John R. [Wayne State University School of Medicine, Detroit, Michigan (United States); McEwan, A.J.B. [University of Alberta, Cross Cancer Institute, Edmonton, Alberta (Canada); Robbins, K. Thomas [St. John' s Hospital Cancer Institute, Springfield, Illinois (United States); Grecula, John [Ohio State University Medical Center, Columbus, Ohio (United States); Sharma, Anand K. [Medical University of South Carolina, Charleston, South Carolina (United States); Ang, K. Kian [University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2012-10-01

    Purpose: We report the results of a phase II study to determine the reproducibility of a submandibular salivary gland transfer (SGT) surgical technique for prevention of radiation (XRT)-induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. Methods and Materials: Eligible patients had surgery for primary, neck dissection, and SGT, followed by XRT, during which the transferred salivary gland was shielded. Intensity modulated radiation therapy, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by 2 reviewers and radiation by 1 reviewer. If 13 or more (of 43) were 'not per protocol,' then the technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, grade 2 or higher, and a rate of {<=}51% was acceptable. Results: Forty-four of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was 'per protocol' or within acceptable variation in 34 patients (77.3%) and XRT in 79.5%. Nine patients (20.9%) developed grade 2 acute xerostomia; 2 had grade 0-1 xerostomia (4.7%) but started on amifostine/pilocarpine. Treatment for these 11 patients (25.6%) was considered a failure for the xerostomia endpoint. Thirteen patients died; median follow-up for 31 surviving patients was 2.9 years. Two-year overall and disease-free survival rates were 76.4% and 71.7%, respectively. Conclusions: The technique of submandibular SGT is reproducible in a multicenter setting. Seventy-four percent of patients were prevented from XRT-induced acute xerostomia.

  4. Radioprotection of normal tissue cells

    Energy Technology Data Exchange (ETDEWEB)

    Maier, Patrick; Wenz, Frederik; Herskind, Carsten [Heidelberg University, Department of Radiation Oncology Universitaetsmedizin Mannheim, Medical Faculty Mannheim, Mannheim (Germany)

    2014-08-15

    Improvements of radiotherapy in combination with surgery and systemic therapy have resulted in increased survival rates of tumor patients. However, radiation-induced normal tissue toxicity is still dose limiting. Several strategies have been pursued with the goal to develop substances which may prevent or reduce damage to normal tissue. Drugs applied before radiotherapy are called radioprotectors; those given after radiotherapy to reduce long-term effects are radiomitigators. Despite more than 50 years of research, until now only two substances, amifostine and palifermin, have overcome all obstacles of clinical approval and are applied during radiotherapy of head and neck cancer or total body irradiation, respectively. However, better understanding of the cellular pathways involved in radiation response has allowed the development of several highly promising drugs functioning as scavengers of reactive oxygen species or targeting specific molecules involved in regulation of cell death pathways or cell cycle arrest. The present review describes the major targets for radioprotectors or radiomitigators currently tested in clinical trials. (orig.) [German] Verbesserungen in der Radiotherapie in Kombination mit Chirurgie und Chemotherapie fuehrten zu erhoehten Ueberlebensraten von Tumorpatienten. Trotzdem sind Strahlenfolgen am Normalgewebe weiterhin dosislimitierend. Verschiedene Ansaetze wurden verfolgt, um Substanzen zu entwickeln, die Normalgewebstoxizitaeten verhindern oder verringern. Medikamente, die vor der Radiotherapie verabreicht werden, heissen Radioprotektoren, solche die danach gegeben werden, um langfristige Effekte zu reduzieren, Radiomitigatoren. Trotz mehr als 50 Jahre Forschung ueberwanden nur zwei Substanzen, Amifostin und Palifermin, alle Huerden der klinischen Pruefung und sind fuer die Anwendung waehrend der Radiotherapie von Kopf-Hals-Tumoren bzw. bei Ganzkoerperbestrahlung zugelassen. Jedoch erlaubte das bessere Verstaendnis der Signalwege

  5. A randomized study of melphalan 200 mg/m(2) vs 280 mg/m(2) as a preparative regimen for patients with multiple myeloma undergoing auto-SCT.

    Science.gov (United States)

    Bensinger, W I; Becker, P S; Gooley, T A; Chauncey, T R; Maloney, D G; Gopal, A K; Green, D J; Press, O W; Lill, M; Ifthikharuddin, J J; Vescio, R; Holmberg, L A; Phillips, G L

    2016-01-01

    We aimed to examine whether doses of melphalan higher than 200 mg/m(2) improve response rates when used as conditioning before autologous transplant (ASCT) in multiple myeloma (MM) patients. Patients with MM, n=131, were randomized to 200 mg/m(2) (mel200) vs 280 mg/m(2) (mel280) using amifostine pretreatment. The primary end point was the proportion of patients achieving near complete response (⩾nCR). No treatment-related deaths occurred in this study. Responses following ASCT were for mel200 vs mel280, respectively, ⩾nCR 22 vs 39%, P=0.03, ⩾PR 57 vs 74%, P=0.04. The hazard of mortality was not statistically significantly different between groups (mel200 vs mel280; hazard ratio (HR)=1.15 (95% confidence interval (CI), 0.62-2.13, P=0.66)) nor was the rate of progression/mortality (HR=0.81 (0.52-1.27, P=0.36)). The estimated PFS at 1 and 3 years were 83 and 46%, respectively, for mel200 and 78 and 54%, respectively, for mel280. Amifostine and mel280 were well tolerated, with no grade 4 regimen-related toxicities and only one grade 3 mucositis (none with mel200) and three grade 3 gastrointestinal (GI) toxicities (two in mel200). Hospitalization rates were more frequent in the mel280 group (59 vs 43%, P=0.08). Mel280 resulted in a higher major response rate (CR+nCR) and should be evaluated in larger studies. PMID:26367217

  6. Neonatal irradiation: neurotoxicity and modulation of pharmacological response

    International Nuclear Information System (INIS)

    Neuronal loss may be responsible of many acute and chronic diseases. For this reason, is very important to understand the mechanisms that contribute to neuronal cell death in order to develop pharmacological strategies for the treatment of these disorders. Developing CNS is very sensitive to ionizing radiations. In particular, irradiation of immature cerebellum induce motor (impaired gait), morphological (disarrangement of cytoarchitecture) and biochemical (increase in noradrenaline levels) alterations, mainly related to cerebellar granule cell death induced by reactive oxygen species (ROS) generated after radiation exposure. Cellular changes triggered by ROS include increased intracellular Ca2+ levels, activation of NMDA glutamatergic receptors and apoptosis. With an excitatory neurotransmitter as glutamate and a multifacetic ion as calcium, their regulation in synapses and cytoplasm, respectively, is very vulnerable. Moreover, the highly aerobic condition of neuronal metabolism determines that an oxidative injury lead to ROS accumulation. The neuro protection therapy attempts to interfere with these few processes by using antioxidants, metal chelators, calcium antagonists or glutamatergic antagonists. In the protocol used in our laboratory, neonatal rats were irradiated with 5 Gy gamma radiations in their cephalic ends, and pre or post-treated with selected putative neuro protective agents. After 30-90 days, motor, morphological and biochemical parameters were measured and compared with irradiated and sham-irradiated (control) animals. Drugs as GM1 ganglioside or amifostine were able to restore abnormal parameters. Cerebellar granule cell irradiated 'in vitro' were treated with neuro protective agents prior or after irradiation. Cell viability and several biochemical parameters were analysed after 48 hours. GM1 ganglioside and amifostine were effective in preventing cell death and increase in ROS induced by ionizing radiation exposure. (author)

  7. A Phase II Study of Submandibular Gland Transfer Prior to Radiation for Prevention of Radiation-induced Xerostomia in Head-and-Neck Cancer (RTOG 0244)

    International Nuclear Information System (INIS)

    Purpose: We report the results of a phase II study to determine the reproducibility of a submandibular salivary gland transfer (SGT) surgical technique for prevention of radiation (XRT)-induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. Methods and Materials: Eligible patients had surgery for primary, neck dissection, and SGT, followed by XRT, during which the transferred salivary gland was shielded. Intensity modulated radiation therapy, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by 2 reviewers and radiation by 1 reviewer. If 13 or more (of 43) were “not per protocol,” then the technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, grade 2 or higher, and a rate of ≤51% was acceptable. Results: Forty-four of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was “per protocol” or within acceptable variation in 34 patients (77.3%) and XRT in 79.5%. Nine patients (20.9%) developed grade 2 acute xerostomia; 2 had grade 0-1 xerostomia (4.7%) but started on amifostine/pilocarpine. Treatment for these 11 patients (25.6%) was considered a failure for the xerostomia endpoint. Thirteen patients died; median follow-up for 31 surviving patients was 2.9 years. Two-year overall and disease-free survival rates were 76.4% and 71.7%, respectively. Conclusions: The technique of submandibular SGT is reproducible in a multicenter setting. Seventy-four percent of patients were prevented from XRT-induced acute xerostomia.

  8. Increased deposition of von Willebrand factor in the rat heart after local ionizing irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Boerma, M.; Loenen, M.M. van; Klein, H.R.; Bart, C.I.; Wondergem, J. [Dept. of Clinical Oncology (K1-P), Leiden Univ. Medical Center (Netherlands); Kruse, J.J.C.M. [Dept. of Clinical Oncology (K1-P), Leiden Univ. Medical Center (Netherlands); Dept. of Experimental Therapy (H6), Netherlands Cancer Inst., Amsterdam (Netherlands); Zurcher, C. [Dept. of Clinical Oncology (K1-P), Leiden Univ. Medical Center (Netherlands); Dept. of Pathology, Faculty of Veterinary Medicine, Univ. of Utrecht (Netherlands)

    2004-02-01

    Background and purpose: von willebrand factor (vWf), a glycoprotein involved in blood coagulation, is synthesized by endothelial cells. Increased amounts of vWf in blood plasma or tissue samples are indicative of damaged endothelium. In the present study, mRNA expression and localization of vWf were determined in irradiated rat heart tissue. Material and methods: sprague-dawley rats received local heart irradiation with a single dose of 0, 15, or 20 Gy. Hearts were dissected at different time points (up to 16 months) after irradiation. In a second experiment, rats were injected with the radioprotector amifostine (160 mg/kg, i.p.) 15-20 min before irradiation and sacrificed after 6 months. Immunohistochemistry was performed using a polyclonal anti-vWf antibody. Serial sections were subjected to a general rat endothelial cell immunostaining (RECA-1) or a collagen staining (picrosirius red). mRNA expression was determined by using PCR. Results: in control tissue, all endothelial cells lining the lumen of the endocardium and coronary arteries, but not capillary endothelial cells, were stained for vWf. 1 month after irradiation with both 15 and 20 Gy, myocardial capillaries became immunoreactive. From 3 months onward, staining was observed also within the extracellular matrix (ECM) of fibrotic areas. At mRNA level, no changes in vWf could be observed at all time points after irradiation, suggesting that vWf deposition was not due to increased biosynthesis of the protein. In sections of amifostine-treated rat hearts, vWf staining was increased to a lesser extent. Conclusion: these dose- and time-dependent increases in deposition of vWf indicate the presence of damaged endothelium in the irradiated rat heart. These increases in vWf accumulation precede development of fibrosis in the subendocardial layer and myocardium of the left ventricles, right ventricles, and atria. (orig.)

  9. 大鼠急性放射性肝损伤及其保护的实验研究%Study on Mechanisms of Radiation-induced Hepatic Injury and Its Protection

    Institute of Scientific and Technical Information of China (English)

    夏红强; 邓琳; 金冶宁

    2011-01-01

    目的:探讨活性氧自由基(ROS)、一氧化氮(NO)和TGF-β1在大鼠急性放射性肝损伤中的机制及细胞保护剂安福定对大鼠急性放射性肝损伤的保护作用.方法:健康雄性SD大鼠48只,随机分成正常对照组(C组)、安福定组(A组)、单纯照射组(X组)3组各16例.正常对照组不予照射.其余两组给予一次性全肝照射,照射剂量20Gy.安福定组于照射前30 min腹腔内注射安福定200mg/kg;单纯照射组则照射前腹腔注射等容量的生理盐水.结果:照射后第4、8、14天的血ALT、AST、肝组织光镜未出现明显变化.电镜下明显的超微结构改变.单纯放射组大鼠血浆ROS活性明显高于正常对照组(P<0.05).安福定组血浆MDA含量显著低于正常对照组,而SOD活性则高于正常对照组.单纯放射组大鼠血浆NO含量明显高于正常对照组和安福定组(P<0.05).照射后第14天单纯放射组大鼠血浆TGF-131含量明显高于正常对照组和安福定组(P<0.05).结论:ROS、NO和TGF-β1都参与了急性放射性肝损伤.NO和TGF-β1则分别作为炎症介质和炎性细胞因子在损伤的进程中起关键作用.安福定对放射性肝损伤有保护作用.测定血MDA含量及SOD活性、NO和TGF-β1比血ALT、AST更早提示放射性肝损伤.%Objective : To observe the effects of oxygen free radical( ROS )、nitric oxide( NO )and TGF-β1 on the acute radiation-induced hepatic injury of rats. The protective effect of amifostine against radiation was also discussed. Methods: Forty-eight SDrats were divided into normal group, radiated group, and amifostine-pretreated group. The models were made hy a single radiation of 20Gy on whole liver except the normal group. Amifostine was given intraperitoneally ( 200mg/kg ) 30 minutes before irradiation to amifostine group. The levels of plasma ROS、NO、 TGF-β1 in rats were measured on the 4th,8th and 14th day after radiation. Animals were euthanized 14 days after irradiation, and

  10. Tratamento da mucosite em pacientes submetidos a transplante de medula óssea: uma revisão sistemática Tratamiento de la mucositis en pacientes sometidos a transplante de médula ósea: una revisión sistemática Treatment of mucositis in patients undergoing bone marrow transplantation: a systematic review

    Directory of Open Access Journals (Sweden)

    Patrícia Ferreira

    2011-01-01

    Full Text Available OBJETIVO: Identificar as medidas terapêuticas para redução da gravidade da mucosite oral em pacientes adultos submetidos ao Transplante de Medula Óssea (TMO. MÉTODOS: Revisão sistemática nas bases de dados: LILACS, MEDLINE, CINAHL, EMBASE; CENTRAL (Cochrane Central e DARE (Database of abstracts of reviews of effects, no período de 1972 a julho de 2010, utilizando os descritores mucositis, stomatitis e bone-marrow-transplantation. RESULTADOS: Identificaram-se 3.839 resumos, dos quais 22 foram incluídos na revisão sistemática que descreveram 14 intervenções tópicas e sistêmicas, dentre as quais oito com significância estatística para a redução dessa complicação. As terapias tópicas foram a crioterapia, clorexidine, glutamina, laser e Traumeel® e as sistêmicas, amifostine, Granulokine® e palifermin. CONCLUSÃO: A heterogeneidade dos resultados dessas intervenções e a falta de melhor elucidação para a prática assistencial indicam a necessidade de pesquisas mais precisas para identificar a efetividade de terapias tópicas para a reparação celular das mucosas.OBJETIVO: Identificar las medidas terapéuticas para la reducción de la gravedad de la mucositis oral en pacientes adultos sometidos a Transplante de Médula Ósea (TMO. MÉTODOS: Se trata de una revisión sistemática en las bases de datos: LILACS, MEDLINE, CINAHL, EMBASE; CENTRAL (Cochrane Central y DARE (Database of abstracts of reviews of effects, en el período de 1972 a julio del 2010, utilizando los descriptores mucositis, stomatitis y bone-marrow-transplantation. RESULTADOS: Se identificaron 3.839 resúmenes, y de éstos 22 fueron incluídos en la revisión sistemática que describieron 14 intervenciones tópicas y sistémicas, de las cuales ocho con significancia estadística para la reducción de esa complicación. Las terapias tópicas fueron la crioterapia, clorexidine, glutamina, laser y Traumeel® y las sistémicas, amifostine, Granulokine® y

  11. Radioprotective effects of hawthorn fruit extract against gamma irradiation in mouse bone marrow cells

    International Nuclear Information System (INIS)

    The radioprotective effect of hawthorn (Crataegus microphylla) fruit extract against genotoxicity induced by gamma irradiation has been investigated in mouse bone marrow cells. A single intraperitoneal (ip) administration of hawthorn extract at doses of 25, 50, 100 and 200 mg/kg 1 h prior to gamma irradiation (2 Gy) reduced the frequencies of micronucleated polychromatic erythrocytes (MnPCEs). All four doses of hawthorn extract significantly reduced the frequencies of MnPCEs and increased the PCE/PCE+NCE ratio (polychromatic erythrocyte/polychromatic erythrocyte+normochromatic erythrocyte) in mice bone marrow compared with the non drug-treated irradiated control (p<0.02-0.00001). The maximum reduction in MnPCEs was observed in mice treated with extract at a dose of 200 mg/kg. Administration of amifostine at dose 100 mg/kg and hawthorn at dose 200 mg/kg reduced the frequency of MnPCE almost 4.8 and 5.7 fold; respectively, after being exposed to 2 Gy of gamma rays, compare with the irradiated control group. Crataegus extract exhibited concentration-dependent activity on 1, 1-diphenyl 2-picrylhydrazyl free radical showing that Crataegus contained high amounts of phenolic compounds and the high performance liquid chromatography (HPLC) analysis determined that it contained chlorogenic acid, epicatechin and hyperoside. It appeared that hawthorn extract with antioxidant activity reduced the genotoxicity induced by gamma irradiation in bone marrow cells. (author)

  12. Radio-induced neuropathology: from early effects to late sequelae. Rat behavioural and metabolic studies after sublethal total body irradiation

    International Nuclear Information System (INIS)

    The radioresistance dogma of Central Nervous System (CNS) is now obsolete. Recent progress in neuroscience allow us to reconsider the radiation-induced cognitive dysfunctions observed after radiation therapy or after a nuclear accident, and to devise appropriate diagnostic and therapeutic means. We have developed a Rat model to study the effects of total body irradiation at a sublethal dose (4.5 Gy). This leads to impaired learning and memory of a task being acquired during the first month - which is prevented by administration of a radioprotector (amifostine) - while it does not appear to affect retrograde memory. Early, an apoptotic wave occurs in the sub-ventricular zone, 5 to 9 hours after exposure, while neuro-genesis is suppressed. Two days after irradiation, the metabolic study conducted by NMR HRMAS (High Resolution Magic Angle Spinning) suggests the presence of cerebral oedema and the study of brain lipids in liquid NMR confirms the membrane damages (elevated cholesterol and phospholipids). The lipid profile is then normalized while a gliosis appears. Finally, 1 month post-irradiation, the elevation of GABA, an inhibitory neurotransmitter, in 2 separate brain structures, occurs simultaneously with a taurine decrease in the hippocampus that lasts 6 months. Our integrated model allows validating bio-markers measurable in vivo NMR spectroscopy - the next experimental stage - and testing new radiation-protective agents. (author)

  13. 黄连生地方防治放射性唾液腺损伤的实验研究%Experimental study of Huanglianshengdi decoction on radioprotection of salivary glands

    Institute of Scientific and Technical Information of China (English)

    傅辰春; 王晓萍; 华海清; 赵云艳; 张新良; 丁巍

    2011-01-01

    group and irradiation + amifostine group, with 7 rabits in each group. The X-ray radiation was performed with a dose rate of 3Gy/min, and a whole exposure of 15Gy was attained. The decoction( 10ml/kg) was administrated 3 days before irradiation to 3 days afterward. Amifostine (100mg/kg) was administrated 30 min before irradiation via a marginal ear vein. Control group was treated by normal saline. Four days after radiation, all the rabbits were executed. The parotid gland was observed by light microscopy with HE-staining. The uptake rate, uptake index and ejection fraction of salivary glands were detected by active nucleus 99 TcmO4-. Results Microscopy showed that there was no injury of parotid acinar cells in control group. The injury in radiation group was worse than radiation + decoction group and radiation + amifostine group. And the injury in the latter two groups was similar. The function of salivary glands showed that the uptake rate before and after radiation was (88. 37 ±21. 15)% vs. (33. 44 ± 19.45) % , the uptake index was 1. 615 ±0. 169 vs. 1. 347 ± 0. 226 and the ejection fraction was (56.17 ± 16. 26) % vs. (38. 15 ± 23. 82) %. There was a significant difference between them. The uptake rate, uptake index and ejection in radiation + decoction group were (66.58±23.89)%,1.606±0.166 and (44.56±17.35)%, while in radiation + amifostine group were (72.87 ±27.61)% , 1.495±0. 106 and (45.69 ±19.90)%. There was no difference between before and after radiation in each group and between the two groups after radiation, but had difference compared with radiation group(P<0.05). Control group showed no change before and after radiation. Conclusion The compound Huanglianshengdi decoction can decrease the radiation injury of salivary glands. This may provide a prophylactic approach in the field of radioprotection of salivary glands.

  14. Influence of clinical radiotherapy on fracture healing%临床放疗对骨折愈合的影响

    Institute of Scientific and Technical Information of China (English)

    鲍琨; 苟三怀

    2010-01-01

    临床上运用放射治疗的部分病例并发有骨质破坏,甚至骨折, 放疗对骨折愈合的影响值得关注.该文总结近年相关研究文献,就骨折愈合修复机制、放疗影响骨折修复机制和减小放疗对骨折愈合影响等方面介绍减小放疗不良反应的科研发现及进展.研究证明分次放疗、改变放疗介入时间对减小放疗对骨折愈合影响无显著效果,放疗对骨折愈合有阻碍和削弱作用,容易造成骨折延迟愈合或不愈合.近来研究发现低剂量放疗具有促进组织血液循环和骨折愈合的作用,分次放疗联合氨磷汀(amifostine)能够保护成骨细胞免受电离辐射损害并维持其生理功能.

  15. Radioprotective Agents: Strategies and Translational Advances.

    Science.gov (United States)

    Kamran, Mohammad Zahid; Ranjan, Atul; Kaur, Navrinder; Sur, Souvik; Tandon, Vibha

    2016-04-01

    Radioprotectors are agents required to protect biological system exposed to radiation, either naturally or through radiation leakage, and they protect normal cells from radiation injury in cancer patients undergoing radiotherapy. It is imperative to study radioprotectors and their mechanism of action comprehensively, looking at their potential therapeutic applications. This review intimately chronicles the rich intellectual, pharmacological story of natural and synthetic radioprotectors. A continuous effort is going on by researchers to develop clinically promising radioprotective agents. In this article, for the first time we have discussed the impact of radioprotectors on different signaling pathways in cells, which will create a basis for scientific community working in this area to develop novel molecules with better therapeutic efficacy. The bright future of exceptionally noncytotoxic derivatives of bisbenzimidazoles is also described as radiomodulators. Amifostine, an effective radioprotectant, has been approved by the FDA for limited clinical use. However, due to its adverse side effects, it is not routinely used clinically. Recently, CBLB502 and several analog of a peptide are under clinical trial and showed high success against radiotherapy in cancer. This article reviews the different types of radioprotective agents with emphasis on the strategies for the development of novel radioprotectors for drug development. In addition, direction for future strategies relevant to the development of radioprotectors is also addressed. PMID:26807693

  16. Contemporary Radiation Countermeasure (Review Paper

    Directory of Open Access Journals (Sweden)

    Vivek N. Patel

    2011-02-01

    Full Text Available Radiation countermeasures have been investigated for decades, but the search for ideal protective agents for use prior to or after irradiation still continues. This review focuses on agents that have demonstrated as potential as in vivo countermeasure agents and may subsequently be effectively used in human beings. Such agents are categorised as radioprotectors, radiation mitigators, or therapeutic agents dependening upon their time of administration. These protective or mitigating agents are designed to reduce inadvertent damage to normal tissue caused by radiation. These interventions function via various mechanisms of action ranging from modulating signalling pathways to inhibiting cell death, cytokines, and growth factor. Many agents demonstrated promising results in murine models and are being tested in human beings. Amifostine, and curcumin have shown radioprotection, while genistein, palifermin, and halofuginone have been shown to alleviate the side effects in patients undergoing radiotherapy. Though these compounds show some promise as radiation countermeasure agents, there are several associated limitations and the search for perfect agents still continues.Defence Science Journal, 2011, 61(2, pp.138-145, DOI:http://dx.doi.org/10.14429/dsj.61.834

  17. Vitamin E Analogs as Radiation Response Modifiers

    Directory of Open Access Journals (Sweden)

    Pankaj K. Singh

    2015-01-01

    Full Text Available The potentially life-threatening effects of total body ionizing radiation exposure have been known for more than a century. Despite considerable advances in our understanding of the effects of radiation over the past six decades, efforts to identify effective radiation countermeasures for use in case of a radiological/nuclear emergency have been largely unsuccessful. Vitamin E is known to have antioxidant properties capable of scavenging free radicals, which have critical roles in radiation injuries. Tocopherols and tocotrienols, vitamin E analogs together known as tocols, have shown promise as radioprotectors. Although the pivotal mechanisms of action of tocols have long been thought to be their antioxidant properties and free radical scavenging activities, other alternative mechanisms have been proposed to drive their activity as radioprotectors. Here we provide a brief overview of the effects of ionizing radiation, the mechanistic mediators of radiation-induced damage, and the need for radiation countermeasures. We further outline the role for, efficacy of, and mechanisms of action of tocols as radioprotectors, and we compare and contrast their efficacy and mode of action with that of another well-studied chemical radioprotector, amifostine.

  18. Basic mechanisms of the cellular alterations in T-2 toxin poisoning: Influence on the choice and result of the therapy

    Directory of Open Access Journals (Sweden)

    Jaćević Vesna M.

    2007-01-01

    Full Text Available T-2 mycotoxin, secondary metabolite of Fusarium fungi, is one of the most potent cytotoxic representatives of trichothecene mycotoxin type A. After ingestion, T-2 toxin affects actively dividing cells and irreversible post-mitotic cells. In our experiments, the best protective effects were produced by dexametasone (PI = 3.37 and different methylprednisolone formulations (PI = 2.43-2.64. Significant protective efficacy was shown by nimesulide (PI = 1.44 and N-acethyilcistein (PI = 1.29, but their values were higher in a combination with methylprednisolone (PI = 2.16-2.34. Radioprotector amifostine (WR-2721 expressed good protective effects (PI = 1.26 or/and different absorbent formulations, such as: activated charcoal (PI = 1.13 and various Min-a-zel® powder compounds, which are a well known zeolite clinoptilolite absorbents. Among the five zeolite regimens investigated, only Min-a-zel Plus® showed a significant protective effect (PI = 1.77. In summary, the steroidal anti-inflammatory drugs could be recommended as a regimen of choice for treatment of acute T-2 toxicosis while nonsteroidal anti-inflammatory compounds, different absorbent formulations and their combinations with antioxidants or radioprotectors could be important for the treatment of subacute and chronic T-2 toxin poisonings.

  19. Inhibition of Radiation-Induced Oxidative Damage in the Lung Tissue: May Acetylsalicylic Acid Have a Positive Role?

    Science.gov (United States)

    Demirel, Can; Kilciksiz, Sevil Cagiran; Gurgul, Serkan; Erdal, Nurten; Yigit, Seyran; Tamer, Lulufer; Ayaz, Lokman

    2016-02-01

    The lung is relatively sensitive to irradiation. It is shown that acetylsalicylic acid (ASA) might reduce oxidative injury and that it has a place in protection from cancer. The aim of this study is to evaluate the potential radioprotective effects of ASA. Whole-body irradiation (6 Gy, single dose) was applied to the rats. Glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) levels in the lung tissue were measured. Control (C), Radiation (R), Radiation + ASA (R + ASA; received irradiation and 25 mg/kg of ASA intraperitoneally (i.p.)), and Radiation + Amifostine (R + WR-2721; received irradiation and 200 mg/kg of WR-2721 i.p.) groups were used. The MPO levels decreased statistically significantly in the group administered ASA. Histopathologically, a radioprotective effect of ASA was more evident in the R + ASA group. ASA is an agent which has not been used as a radioprotector in the clinic yet, and it is worth supporting with more advanced studies. PMID:26276129

  20. Preclinical investigation of the pharmacokinetics, metabolism, and protein and red blood cell binding of DRDE-07: a prophylactic agent against sulphur mustard

    Directory of Open Access Journals (Sweden)

    Pankaj Verma

    2014-10-01

    Full Text Available DRDE-07, a newly synthesized amifostine analog currently under clinical investigation in a phase I trial, is a potent antidote against sulfur mustard toxicity. The purpose of this research was to evaluate the pharmacokinetic profile of DRDE-07 in female Swiss Albino mice after a single oral dose of 400 or 600 mg/kg. The physicochemical properties of DRDE-07, including solubility, pKa, Log P, plasma protein binding and plasma/blood partitioning, were determined to support the pharmacokinetic characterization. DRDE-07 concentration was determined by an HPLC-UV method. The profile of plasma concentration versus time was analyzed using a non-compartmental model. Plasma protein binding was assessed using ultrafiltration. DRDE-07 appeared rapidly in plasma after oral administration with peak plasma levels (Cmax observed in less than 15 min. There was a rapid decline in the plasma levels followed by a smaller second peak about 90 min after dosing. The plasma protein binding of DRDE-07 was found to be less than 25% at all concentrations studied. Plasma clearance of DRDE-07 is expected to be ~1.5 fold higher than the blood clearance of DRDE-07. The probable metabolite of DRDE-07 was identified as phenyl-S-ethyl amine.

  1. The radioprotective activities of turpentine-induced inflammation and {alpha}{sub 2}-macroglobulin. The effect of dexamethasone on the radioprotective efficacy of the inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Sevaljevic, L.; Koricanac, G.; Vulovic, M.; Kanazir, D.; Ribarac-Stepic, N. [Vinca Inst. of Nuclear Sciences, Belgrade (Yugoslavia); Dobric, S. [Military Medical Academy, Belgrade (Yugoslavia); Bogojevic, D.; Petrovic, M. [Inst. of Biological Research, Belgrade (Yugoslavia)

    2003-03-01

    This work was aimed at the radioprotective efficacy of turpentine oil (TO), {alpha}{sub 2}-macroglobulin ({alpha}{sub 2}-M), amifostine (Ami) and/or dexamethasone (Dex). These agents were administrated, alone or in combination, prior to irradiation of rats with 6.7 Gy (LD{sub 50/30}). The survival was recorded daily for 4 weeks after irradiation and body weight, peripheral leukocytes and thrombocytes were measured. The plasma concentration of {alpha}{sub 2}-M and other acute phase proteins were determined by crossed immunoelectrophoresis. All rats receiving {alpha}{sub 2}-M and Ami alone or in combination survived the radiation injury, whereas the rate of survival of TO-treated rats was 90%. Radiation and therapy-induced changes in the expression of acute phase protein genes were atypical for the acute phase reaction. Dex alone was lethal for 45% and 55% of control and irradiated rats, respectively. Pretreatment with 1 mg Dex reduced radioprotective efficacy of TO and Ami to 30% and 40%, respectively. Given together TO and Ami provided 70% protection to rats receiving Dex. The TO and {alpha}{sub 2}-M enhanced the rate of survival from 50% to 90% and 100%, respectively. In the presence of 1 mg Dex the TO-induced radioprotectors and Ami exhibited radiosensitizing rather than radioprotecting activities. (author)

  2. 硫醇酊对白血病细胞端粒酶逆转录酶表达和端粒酶活性选择性抑制的作用

    Institute of Scientific and Technical Information of China (English)

    徐立; 杨浩

    2004-01-01

    为了观察硫醇类低分子化合物硫醇酊(Amifostine,AM F)对正常和恶性造血细胞中端粒酶,逆转录酶(hTERT),端粒酶活性的影响,多聚酶链反应( PCR)及酶联免疫吸附方法用于检测白血病细胞及正常人单个核细胞hTERT mPNA表达及端粒酶活性.结果显示AMF可抑制白血病HL60细胞株以及急性白血病病人白血病细胞的hTERT转录表达,并进而导致端粒酶活性减低.正常活化淋巴细胞hTERT和端粒酶活性水平不受AMF影响.表明AM F能够选择性抑制肿瘤细胞端粒酶活性.

  3. 樟氨磷汀治疗颈胸上段食管癌放射性食管炎的效果与护理

    Institute of Scientific and Technical Information of China (English)

    张占香

    2009-01-01

    @@ 食管癌是常见的恶性肿瘤之一,颈段和上胸段食管癌对放射治疗敏感,可首选的根治性放疗.近年来随着放疗技术的迅速提高,使食管癌的控制率得到较大的改善,但与肿瘤放疗相关的放射性损伤不仅限制了放疗的强度、降低了治疗的效果,也严重影响着患者的生活质量,甚至危及生命.为减轻放疗对患者正常组织的损伤,我们采用氨磷汀(Amifostin)作为放疗中正常组织的保护剂,以减轻放射性损伤.

  4. 氨磷汀对草酸铂和氟脲嘧啶脱氧核苷肾毒性的保护作用

    Institute of Scientific and Technical Information of China (English)

    李丽; 刘宝瑞; 钱晓萍

    2003-01-01

    @@ 氨磷汀(Amifostine)是美国FDA批准上市的第一个泛细胞保护剂.其作用机理是它是一种有机硫代磷酸化合物,正常组织对其摄取迅速而代谢缓慢,肿瘤组织则有缓慢摄取,结果正常组织因有高浓度氨磷汀而起到清除因化放疗产生的氧自由基作用,但不影响放化疗的抗肿瘤作用.国外研究证明[1~4]:氨磷汀对化疗药物所引起的肾毒性、骨髓毒性保护作用尤为明显,并对耳毒性、粘膜毒性、心脏毒性和放疗引起的口腔干燥综合症也有防护作用.我们利用上述优点对一名晚期肺癌患者进行治疗.

  5. Radioprotectors in radiotherapy - advances in the potential application of phytochemicals.

    Science.gov (United States)

    Szejk, Magdalena; Kołodziejczyk-Czepas, Joanna; Żbikowska, Halina Małgorzata

    2016-01-01

    Radiotherapy, in addition to chemotherapy, is currently the primary method of cancer treatment based on destruction of malignant cells by ionizing radiation. Unfortunately, it also affects normal cells, which is associated with negative consequences for a patient. Radioprotectors are compounds used to prevent/protect the non-tumor cells from the harmful effects of radiation. To play their role these compounds should meet several criteria; among others, they should significantly protect normal cells from radiation without changing the tumor cell radiosensitivity. In general, agents used to alter normal tissue toxicity from radiation can be broadly divided into three categories based on timing of delivery in relation to radiation: chemical radioprotectors, mitigators, and treatment. These groups include a diverse range of synthetic compounds in terms of their structure and protective mechanisms. The aminoradiothiol amifostine is the only radioprotectant approved in clinical application. However, its use is limited due to toxicity concerns (it may cause hypotension). Natural compounds, derived from plants, meet all criteria of the ideal radioprotector. They exert their protective actions against adverse effects of ionizing radiation by several mechanisms. Plant compounds that show radioprotective activity include flavonoids and phenolic acids, stilbenes, lycopene, alkaloids, peptides, polysaccharides, and phytohormones. Garlic, green tea, apples, citrus, and ginger are examples of constituents of the human diet that contain radioprotective substances. PMID:27356603

  6. New strategies for the prevention of radiation injury. Possible implications for countering radiation hazards of long-term space travel

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.; Kumar, S.; Whitnall, M. [Armed Forces Radiobiology Research Inst., Bethesda, MD (United States). Radiation Casualty Management] [and others

    2002-12-01

    New strategies for the prevention of radiation injuries are currently being explored with the ultimate aim of developing globally radioprotective, nontoxic pharmacologics. The prophylactic treatments under review encompass such diverse pharmacologic classes as novel immunomodulators, nutritional antioxidants, and cytokines. An immunomodulator that shows promise is 5-androstenediol (AED), a well-tolerated, long-acting and rostene steroid with broad-spectrum radioprotective attributes that include not only protection against acute tissue injury, but also reduced susceptibility to infectious agents, as well as reduced rates of neoplastic transformation. Other potentially useful radioprotectants currently under study include the nutraceutical vitamin E and analogs, a chemically-engineered cytokine, interleukin-1{beta}, and a sustained-release formulation of an aminothiol, amifostine. Results suggest that a new paradigm is evolving for the prophylaxes of radiation injuries, based on use of newly identified, nontoxic, broad-spectrum prophylactic agents whose protective action may be leveraged by subsequent postexposure use of cytokines with organ-specific reparative functions. (author)

  7. Novel Recombinant Protein FlaA N/C Protects against Radiation Injury via NF-κB Signaling.

    Science.gov (United States)

    Xu, Ying; Wu, Dongming; Fan, Yuanchun; Li, Peigeng; Du, Hongfei; Shi, Jiao; Wang, Dan; Zhou, Xiaoping

    2016-01-01

    There are few safe and effective drugs available that protect healthy tissue against radiation-induced damage, highlighting the need to develop such radioprotective agents. We investigated the mechanism underlying the protective effects of the novel, recombinant, flagellin-like protein FlaA N/C against radiation-induced tissue damage in female BALB/c mice. FlaA N/C treatment increased the levels of several pro-proliferative cytokines while inhibiting apoptosis and reducing inflammation. These effects were accompanied by activation of the nuclear factor κB signaling pathway via direct interaction of FlaA N/C with Toll-like receptor 5, as well as enhanced survival of mice after total-body irradiation compared to that observed with treatment with amifostine, a radioprotective agent that is currently being used in clinical practice. These results indicate that FlaA N/C could be further explored as a possible protector of damage to healthy tissue during radiotherapy. PMID:26789847

  8. Radio-induced neuropathology: from early effects to late sequelae. Rat behavioural and metabolic studies after sublethal total body irradiation; Neuropathologie radio-induite: des effets precoces aux sequelles tardives. Etudes comportementales et metaboliques chez le rat apres irradiation globale subletale

    Energy Technology Data Exchange (ETDEWEB)

    Martigne, A.P.

    2010-05-15

    The radioresistance dogma of Central Nervous System (CNS) is now obsolete. Recent progress in neuroscience allow us to reconsider the radiation-induced cognitive dysfunctions observed after radiation therapy or after a nuclear accident, and to devise appropriate diagnostic and therapeutic means. We have developed a Rat model to study the effects of total body irradiation at a sublethal dose (4.5 Gy). This leads to impaired learning and memory of a task being acquired during the first month - which is prevented by administration of a radioprotector (amifostine) - while it does not appear to affect retrograde memory. Early, an apoptotic wave occurs in the sub-ventricular zone, 5 to 9 hours after exposure, while neuro-genesis is suppressed. Two days after irradiation, the metabolic study conducted by NMR HRMAS (High Resolution Magic Angle Spinning) suggests the presence of cerebral oedema and the study of brain lipids in liquid NMR confirms the membrane damages (elevated cholesterol and phospholipids). The lipid profile is then normalized while a gliosis appears. Finally, 1 month post-irradiation, the elevation of GABA, an inhibitory neurotransmitter, in 2 separate brain structures, occurs simultaneously with a taurine decrease in the hippocampus that lasts 6 months. Our integrated model allows validating bio-markers measurable in vivo NMR spectroscopy - the next experimental stage - and testing new radiation-protective agents. (author)

  9. Risks and management of radiation exposure.

    Science.gov (United States)

    Yamamoto, Loren G

    2013-09-01

    High-energy ionizing radiation is harmful. Low-level exposure sources include background, occupational, and medical diagnostics. Radiation disaster incidents include radioactive substance accidents and nuclear power plant accidents. Terrorism and international conflict could trigger intentional radiation disasters that include radiation dispersion devices (RDD) (a radioactive dirty bomb), deliberate exposure to industrial radioactive substances, nuclear power plant sabotage, and nuclear weapon detonation. Nuclear fissioning events such as nuclear power plant incidents and nuclear weapon detonation release radioactive fallout that include radioactive iodine 131, cesium 137, strontium 90, uranium, plutonium, and many other radioactive isotopes. An RDD dirty bomb is likely to spread only one radioactive substance, with the most likely substance being cesium 137. Cobalt 60 and strontium 90 are other RDD dirty bomb possibilities. In a radiation disaster, stable patients should be decontaminated to minimize further radiation exposure. Potassium iodide (KI) is useful for iodine 131 exposure. Prussian blue (ferric hexacyanoferrate) enhances the fecal excretion of cesium via ion exchange. Ca-DTPA (diethylenetriaminepentaacetic acid) and Zn-DTPA form stable ionic complexes with plutonium, americium, and curium, which are excreted in the urine. Amifostine enhances chemical and enzymatic repair of damaged DNA. Acute radiation sickness ranges in severity from mild to lethal, which can be assessed by the nausea/vomiting onset/duration, complete blood cell count findings, and neurologic symptoms. PMID:24201986

  10. Treatment of oral mucositis due to chemotherapy

    Science.gov (United States)

    Bagán-Sebastián, José V

    2016-01-01

    Introduction The management of oral mucositis is a challenge, due to its complex biological nature. Over the last 10 years, different strategies have been developed for the management of oral mucositis caused by chemotherapy in cancer patients. Material and Methods An exhaustive search was made of the PubMed-Medline, Cochrane Library and Scopus databases, crossing the key words “oral mucositis”, “prevention” and “treatment” with the terms “chemotherapy” and “radiotherapy” by means of the boolean operators “AND” and “NOT”. A total of 268 articles were obtained, of which 96 met the inclusion criteria. Results Several interventions for the prevention of oral mucositis, such as oral hygiene protocols, amifostine, benzidamine, calcium phosphate, cryotherapy and iseganan, among others, were found to yield only limited benefits. Other studies have reported a decrease in the appearance and severity of mucositis with the use of cytoprotectors (sucralfate, oral glutamine, hyaluronic acid), growth factors, topical polyvinylpyrrolidone, and low power laser irradiation. Conclusions Very few interventions of confirmed efficacy are available for the management of oral mucositis due to chemotherapy. However, according to the reviewed literature, the use of palifermin, cryotherapy and low power laser offers benefits, reducing the incidence and severity of oral mucositis – though further studies are needed to confirm the results obtained. Key words:Chemotherapy-Induced Oral Mucositis Treatment. PMID:27034762

  11. Human Anti-Oxidation Protein A1M—A Potential Kidney Protection Agent in Peptide Receptor Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    Jonas Ahlstedt

    2015-12-01

    Full Text Available Peptide receptor radionuclide therapy (PRRT has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ methods to protect the kidneys during PRRT. Today, infusion of positively charged amino acids is the standard method of kidney protection. Other methods, such as administration of amifostine, are still under evaluation and show promising results. α1-microglobulin (A1M is a reductase and radical scavenging protein ubiquitously present in plasma and extravascular tissue. Human A1M has antioxidation properties and has been shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. It has recently been shown in mice that exogenously infused A1M and the somatostatin analogue octreotide are co-localized in proximal tubules of the kidney after intravenous infusion. In this review we describe the current situation of kidney protection during PRRT, discuss the necessity and implications of more precise dosimetry and present A1M as a new, potential candidate for renal protection during PRRT and related targeted radionuclide therapies.

  12. Protective effect of allium sativum ethanol extract on cultured human lymphocytes against electron beam radiation

    International Nuclear Information System (INIS)

    The development of radioprotective agent has been the subject of intense research because exposure to ionizing radiation causes DNA damage which may cause mutation and ultimately leads to cancer, on the other hand radiotherapy has become an integral part in treatment of cancer which uses ionizing radiations like X rays, gamma rays to kill the cancer cells. Amifostine is a well-known radioprotector which is clinically approved. There are many other radioprotectors like cysteine, cystamine, serotine but they are not used because of its normal tissue toxicity. Allium sativum is commonly known as garlic which has already been reported for its medicinal properties. In this study we evaluated radioprotection property of Allium sativum on DNA damage caused by electron beam radiation in cultured human lymphocytes. Allium sativum ethanol extract was used for this study. Cell viability was performed by MTT assay. DNA damage was assessed by comet assay parameters. The cultured lymphocytes were incubated with different concentrations 10, 50 and 100 μg/mL of Allium sativum extracts for 2, 4, 6 and 24 hour time intervals. Treatment of lymphocytes with various concentration of Allium sativum extract resulted in significant decrease in the level of DNA damage (Percentage tail DNA 6%) and increase in cell viability 93% (p>0.05) compare to the radiation control group. Results of this study revealed that Allium sativum protects cultured lymphocytes when exposed to electron beam radiation at its sub lethal dose. (author)

  13. Bisbenzimidazole - DMA: a potential radioprotector mitigates DNA damage in radiotherapy

    International Nuclear Information System (INIS)

    Ionizing radiation causes radiolysis of cellular water, generating reactive oxygen species (ROS), causing DNA damage. Radioprotectors protect the normal cells from the unwanted radiation damage. Since the beginning of the nuclear era, despite extensive research on the development of radioprotectors from natural and synthetic compounds, success has been limited. The only clinically acceptable radioprotector, amifostine, has inherent dose-limiting toxicities and has therefore stimulated extensive search for nontoxic, effective, and alternative radioprotectors. We have developed a cytoprotective radioprotector DMA, having a bisbenzimidazole nucleus. Relative quantitation of gene expression of the identified proteins and their interacting partners led to the identification of MAP3K14 (NFB inducing kinase) as one of the plausible target. Subsequently, over expression and knock down of MAP3K14 suggested that DMA affects NFB inducing kinase mediated phosphorylation of IKKα and IKK both alone and in the presence of ionizing radiation. Our results demonstrated 3.62 fold increase in NFB activation in DMA treated cells as compared to control cells. This activation was further increased by 5.8 fold in drug + radiation (50 μM + 8.5 Gy) treated cells in comparison to control. We observed 51% radioprotection in untreated cells that attenuated to 17% in siRNA NIK treated U87 cells at 24h. In addition we studied the effects of DMA on the radiation and transcriptional response of HEK293 cell lines also. Our results, suggested that the treatment of DMA increased the level of phosphorylated AKT in HEK cells in presence of radiation, and this was consistent with the alteration of DNA-PKcs. Our findings were further confirmed by the increased phosphorylation levels of GSK3, a substrate of activated AKT in DMA treated cells. (author)

  14. Protective Effect of Lycium ruthenicum Murr. Against Radiation Injury in Mice

    Directory of Open Access Journals (Sweden)

    Yabin Duan

    2015-07-01

    Full Text Available The protective effect of Lycium ruthenicum Murr. against radiation injury was examined in mice. Kunming mice were randomly divided into a control group, model group, positive drug group and L. ruthenicum high dose (8 g/kg, L. ruthenicum middle dose (4 g/kg, L. ruthenicum low dose (2 g/kg treatment groups, for which doses were administered the third day, seventh day and 14th day after irradiation. L. ruthenicum extract was administered orally to the mice in the three treatment groups and normal saline was administered orally to the mice in the control group and model group for 14 days. The positive group was treated with amifostine (WR-2721 at 30 min before irradiation. Except for the control group, the groups of mice received a 5 Gy quantity of X-radiation evenly over their whole body at one time. Body weight, hemogram, thymus and spleen index, DNA, caspase-3, caspase-6, and P53 contents were observed at the third day, seventh day, and 14th day after irradiation. L. ruthenicum could significantly increase the total red blood cell count, hemoglobin count and DNA contents (p < 0.05. The spleen index recovered significantly by the third day and 14th day after irradiation (p < 0.05. L. ruthenicum low dose group showed a significant reduction in caspase-3 and caspase-6 of serum in mice at the third day, seventh day, and 14th day after irradiation and L. ruthenicum middle dose group experienced a reduction in caspase-6 of serum in mice by the seventh day after irradiation. L. ruthenicum could decrease the expression of P53. The results showed that L. ruthenicum had protective effects against radiation injury in mice.

  15. Melatonin can Ameliorate Radiation-Induced Oxidative Stress and Inflammation-Related Deterioration of Bone Quality in Rat Femur.

    Science.gov (United States)

    Çakir, Zelal Ünlü; Demirel, Can; Kilciksiz, Sevil Cagiran; Gürgül, Serkan; Zincircioğlu, S Burhanedtin; Erdal, Nurten

    2016-06-01

    The aim of the present study was to evaluate the radioprotective effects of melatonin on the biomechanical properties of bone in comparison to amifostine (WR-2721). Forty Sprague Dawley rats were divided equally into 5 groups namely; control (C), irradiation (R; single dose of 50 Gy), irradiation + WR-2721 (R + WR-2721; irradiation + 200 mg/kg WR-2721) radiation + melatonin 25 mg/kg (R + M25; irradiation + 25 mg/kg melatonin), and radiation + melatonin 50 mg/kg (R + M50; irradiation + 50 mg/kg melatonin). In order to measure extrinsic (organ-level mechanical properties of bone; the ultimate strength, deformation, stiffness, energy absorption capacity) and intrinsic (tissue-level mechanical properties of bone; ultimate stress, ultimate strain, elastic modulus, toughness) features of the bone, a three-point bending (TPB) test was performed for biomechanical evaluation. In addition, a bone mineral density (BMD) test was carried out. The BMD and extrinsic properties of the diaphyseal femur were found to be significantly higher in the R + M25 group than in group R (p < 0.05). A significant increase was observed in R + M50 (p < 0.05) in comparison to group R in the cross-sectional area of the femoral shaft and elastic modulus parameter. The protective effect of melatonin was similar to that of WR-2721. Thus, biomechanical quality of irradiated bone can be ameliorated by free radical scavenger melatonin. PMID:27052631

  16. Radioprotective Effect of Moderate Wine Consumption in Patients With Breast Carcinoma

    International Nuclear Information System (INIS)

    Purpose: Given the high cost and side effects of radioprotective agents such as amifostine, attention has been focused on potentially equally effective but less expensive and toxic natural substances. We evaluated the potential radioprotective effects of wine in preventing skin toxicity in patients with breast cancer. Methods and Materials: Before treatment, the medical history and habits of patients were assessed and the information recorded in their clinical folders. Patients were divided into three groups based on the dose/fractionation scheme used: control group, 60.4 Gy (standard technique); Modulated Accelerated Radiotherapy in Adjuvant treatment of breast cancer (MARA)-1 protocol group, 44 Gy (concomitant boost to tumoral bed); and MARA-2 protocol group, 60 Gy (concomitant boost to tumoral bed). The impact of the following variables on acute skin toxicity was evaluated by chart review: radiotherapy protocol, planning target volume (PTV), comorbidity (e.g., hypertension and diabetes), hemoglobin level before therapy, adjuvant hormone therapy, adjuvant chemotherapy, cigarette smoking, and drinking habits. Results: The study population consisted of 348 patients. More severe skin toxicity was significantly associated with the radiotherapy protocol (p < 0.001) and median PTV (p = 0.005). In addition, the incidence of acute toxicity of Grade 2 or greater was higher in patients without alcohol intake (38.4% vs. 22.3%, p = 0.021). The daily amount of alcohol intake also influenced the incidence of skin toxicity, with an incidence of 38.4% in patients with no wine intake, 31.8% in patients drinking half a glass per day, 13.6% in patients drinking one glass per day, and 35.0% in patients drinking two glasses per day. Multivariate analysis showed that wine intake, PTV, and radiotherapy protocol were all significantly correlated with acute toxicity. Conclusions: Our results indicate that wine may have a radioprotective effect; however, prospective studies are needed to

  17. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Rolleman, Edgar J.; Melis, Marleen; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, V 220, Rotterdam (Netherlands); Boerman, Otto C. [Radboud University Hospital, Department of Nuclear Medicine, Nijmegen (Netherlands)

    2010-05-15

    This review focuses on the present status of kidney protection during peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues. This treatment modality for somatostatin receptor-positive tumours is limited by renal reabsorption and retention of radiolabelled peptides resulting in dose-limiting high kidney radiation doses. Radiation nephropathy has been described in several patients. Studies on the mechanism and localization demonstrate that renal uptake of radiolabelled somatostatin analogues largely depends on the megalin/cubulin system in the proximal tubule cells. Thus methods are needed that interfere with this reabsorption pathway to achieve kidney protection. Such methods include coadministration of basic amino acids, the bovine gelatin-containing solution Gelofusine or albumin fragments. Amino acids are already commonly used in the clinical setting during PRRT. Other compounds that interfere with renal reabsorption capacity (maleic acid and colchicine) are not suitable for clinical use because of potential toxicity. The safe limit for the renal radiation dose during PRRT is not exactly known. Dosimetry studies applying the principle of the biological equivalent dose (correcting for the effect of dose fractionation) suggest that a dose of about 37 Gy is the threshold for development of kidney toxicity. This threshold is lower when risk factors for development of renal damage exist: age over 60 years, hypertension, diabetes mellitus and previous chemotherapy. A still experimental pathway for kidney protection is mitigation of radiation effects, possibly achievable by cotreatment with amifostine (Ethylol), a radiation protector, or with blockers of the renin-angiotensin-aldosterone system. Future perspectives on improving kidney protection during PRRT include combinations of agents to reduce renal retention of radiolabelled peptides, eventually together with mitigating medicines. Moreover, new somatostatin analogues with lower

  18. Protective effect of oleanolic acid on oxidative injury and cellular abnormalities in doxorubicin induced cardiac toxicity in rats.

    Science.gov (United States)

    Goyal, Sameer N; Mahajan, Umesh B; Chandrayan, Govind; Kumawat, Vivek S; Kamble, Sarika; Patil, Pradip; Agrawal, Yogeeta O; Patil, Chandragouda R; Ojha, Shreesh

    2016-01-01

    The prevention of doxorubicin (Dox) induced cardiotoxicity may be co-operative to recover future Dox treatment. The aim of this study was to explore the cardioprotective effects of oleanolic acid (OA), an antioxidant agent, on Dox induced cardiotoxicity. OA is a triterpenoid compound, which exist widely in plant kingdom in free acid form or as a glycosidic triterpenoids saponins. Cardiotoxicity was induced in Wistar rats with single intravenous injection of doxorubicin at dose of 67.75 mg/kg i.v for 48 hrs. At 12 hrs of interval following Dox administration the cardioprotective effect of OA (1.5 mg/kg, i.v.) and Amifostine (AMF) (90 mg/kg i.v., single dose prior 30 min) were evaluated. Induction of cardiotoxicity was confirmed by increase in systolic, diastolic, mean arterial pressures, maximal positive rate of developed left ventricular pressure (+LVdP/dtmax, an indicator of myocardial contraction), maximal negative rate of developed left ventricular pressure (-LVdP/dtmax, a meter of myocardial relaxation) and an increase in left ventricular end-diastolic pressure (LVEDP, a marker of pre-load). Cardiac markers in such as CK-MB, LDH and alterations in ECG. Dox administration showed alteration in Biochemical parameters and endogenous antioxidants. Administration of OA Showed maximal protection against Dox induced cardiac toxicity as observed by reduction in blood pressure, prevention of left ventricular function and attenuation of biochemical and antioxidant parameters. Based on the findings, its concluded that OA can be used as an adjuvant with Dox therapy in treating cancers. PMID:27069540

  19. Minutes of the 25. meeting of the European Society for Therapeutic Radiology and Oncology (ESTRO); Compte-rendu de la 25. reunion de l'European Society for Therapeutic Radiology and Oncology (ESTRO)

    Energy Technology Data Exchange (ETDEWEB)

    Mazeron, J.J. [Groupe Hospitalier de la Pitie-Salpetriere, APHP, Service de Radiotherapie Oncologique, 75 - Paris (France)

    2007-05-15

    Four parts are treated in this article. Cancers of the O.R.L. sphere, prostate cancers, rectum cancer and breast cancer. About the O.R.L. sphere it is question of recurrences, and how to optimize a second radiotherapy with or without a combined chemotherapy. The fractionation of irradiation, the side effects (toxicity) and the use of amifostine are studied. For the prostate cancer, the question was about the use or not of a boost following the first radiotherapy. The tests were between a radiotherapy of 55 Grays in twenty fractions in the prostate or a reduced dose of 35.7 Grays in thirteen fractions, then a boost of high dose rate brachytherapy of 17 Grays in two fractions. The conditions of the choice for patients are exposed. No difference has been found between the two therapies in term of toxicity. The results plaid for the boost of brachytherapy. The part relative to the rectum cancer concerns the study of radiotherapy validity before surgery. The conclusion is in favour of a short radiotherapy before surgery in comparison with a postoperative chemoradiotherapy delivered in the selected cases among patients operated with mesorectum excision. About the last part devoted to the breast cancer, it concerns a comparison made by the Danish Cancer Group between mastectomy and mastectomy followed by radiotherapy. The results of a test of the European Society for Therapeutic Radiology and Oncology called boost versus non boost. Finally the rule to practice a total irradiation of the mammary gland after conservative surgery of breast cancer is reconsidered. (N.C.)

  20. Radioprotectors and Tumors: Molecular Studies in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Gayle Woloschak, David Grdina

    2010-03-10

    This proposal investigated effects of radiation using a set of archival tissues. Main interests of this proposal were to investigate effects of irradiation alone or in the presence or radioprotectors; to investigate these effects on different tissues; and to use/develop molecular biology techniques that would be suitable for work with archived tissues. This work resulted in several manuscripts published or in preparation. Approach for evaluation of gene copy numbers by quantitative real time PCR has been developed and we are striving to establish methods to utilize Q-RT-PCR data to evaluate genomic instability caused by irradiation(s) and accompanying treatments. References: 1. Paunesku D, Paunesku T, Wahl A, Kataoka Y, Murley J, Grdina DJ, Woloschak GE. Incidence of tissue toxicities in gamma ray and fission neutron-exposed mice treated with Amifostine. Int J Radiat Biol. 2008, 84(8):623-34. PMID: 18661379, http://informahealthcare.com/doi/full/10.1080/09553000802241762?cookieSet=1 2. Wang Q, Paunesku T and Woloschak GE. Tissue and data archives from irradiation experiments conducted at Argonne National Laboratory over a period of four decades, in press in Radiation and Environmental Biophysics. 3. Alcantara M, Paunesku D, Rademaker A, Paunesku T and Woloschak GE. A RETROSPECTIVE ANALYSIS OF TISSUE TOXICITIES IN B6CF1 MICE IRRADIATED WITH FISSION NEUTRONS OR COBALT 60 GAMMA RAYS: Gender modulates accumulation of tissue toxicities caused by low dose rate fractionated irradiation; in preparation; this document has been uploaded as STI product 4. Wang Q, Paunesku T Wanzer B and Woloschak GE. Mitochondrial gene copy number differences in different tissues of irradiated and control mice with lymphoid cancers; in preparation 5. Wang Q, Raha, S, Paunesku T and Woloschak GE. Evaluation of gene copy number differences in different tissues of irradiated and control mice; in preparation

  1. Strategies for protection against exposure to ionizing radiation

    International Nuclear Information System (INIS)

    Radiations are known to be mutagenic, carcinogenic and cyto-lethal depending on the total dose, dose rate, quality of radiation and many other factors related to the person exposed. Therefore strategies for protection against exposure to ionizing radiations have to be accordingly planned. Radioprotection, though remains prophylactic in principle, includes mitigating and therapeutic modalities also. Initially, the central theme of biological radioprotection has been to protect against radiation-induced lethality and to optimize radiotherapy of tumours; the emphasis has now extended to cover many more situations of planned and unplanned nature. The central dogma of radioprotection work has been antioxidant action, which is relevant indeed against low LET radiation. The increasing understanding of the mechanism of radiation damage, however, permitted the advent of newer agents of both synthetic and natural origin. Sulfhydryl compounds like cysteamine, AET, Amifostine and endogenous molecules like GSH, SOD etc have been very important agents. Molecules like cytokines, immunomodulators, anti-inflammatory agents, angiotensin converting enzymes, metallo-elements and metallothionins, DNA ligands and Calcium antagonists have also been investigated recently. Unfortunately, no single agent could yield desired results especially due to toxicity at their radioprotective concentration. This led to the emergence of combinational modality where two or more agents working with different mechanisms could synergistically complement radioprotective action.. Recently, herbal extracts and dietary agents, which are the natural combinations of a large number of compounds that have important attributes to counter the damaging effects of ionizing radiations, have gained world-wide interest.. These agents have been found to be less toxic. Decorporation of radionuclei and protection against low dose chronic exposures like space flights and long haul inter-continental flights need to be

  2. An Odyssey of cytoprotective bisbenzimidazole as therapeutic agent for human well being

    International Nuclear Information System (INIS)

    Radiotherapy is utilized by 80% patients as a part of their treatment to most prevalent disease like cancer. Ionizing radiation causes radiolysis of water, generation of ROS and has deleterious effect penetrating the living tissues resulting in the-transfer of radiation energy to the biological materials. Radioprotectors protect the normal cells from the unwanted radiation damage. Since the beginning of the nuclear era, despite extensive research on the development of radioprotectors from natural and synthetic compounds, success has been limited. The only clinically acceptable radioprotector, amifostine, has inherent dose-limiting toxicities and has therefore stimulated extensive search for nontoxic, effective, and alternative radioprotectors. We have developed a cytoprotective radioprotector DMA, having a bisbenzimidazole nucleus. Relative quantitation of gene expression of the identified proteins and their interacting partners led to the identification of NFkB inducing kinase (NIK) as one of the plausible target. Subsequently, over expression and knock down of NIK suggested that DMA affects NFkB inducing kinase mediated phosphorylation of IKKα and IKKβ both alone and in the presence of ionizing radiation. We observed 51% radioprotection in untreated cells that attenuated to 17% in siRNA NIK treated U87 cells at 24h. Further studies concluded that the Coactivation of AKT/NFkB triggered by DMA, is a reason behind protection against ionizing radiation-induced apoptosis of normal cells, and this was consistent with the alteration of DNA-PKcs. Pharmacokinetic (PK) evaluations and bioavailability measurements proved superior in vivo efficacy, higher AUCs, greater residence time of DMA. (author)

  3. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues

    International Nuclear Information System (INIS)

    This review focuses on the present status of kidney protection during peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues. This treatment modality for somatostatin receptor-positive tumours is limited by renal reabsorption and retention of radiolabelled peptides resulting in dose-limiting high kidney radiation doses. Radiation nephropathy has been described in several patients. Studies on the mechanism and localization demonstrate that renal uptake of radiolabelled somatostatin analogues largely depends on the megalin/cubulin system in the proximal tubule cells. Thus methods are needed that interfere with this reabsorption pathway to achieve kidney protection. Such methods include coadministration of basic amino acids, the bovine gelatin-containing solution Gelofusine or albumin fragments. Amino acids are already commonly used in the clinical setting during PRRT. Other compounds that interfere with renal reabsorption capacity (maleic acid and colchicine) are not suitable for clinical use because of potential toxicity. The safe limit for the renal radiation dose during PRRT is not exactly known. Dosimetry studies applying the principle of the biological equivalent dose (correcting for the effect of dose fractionation) suggest that a dose of about 37 Gy is the threshold for development of kidney toxicity. This threshold is lower when risk factors for development of renal damage exist: age over 60 years, hypertension, diabetes mellitus and previous chemotherapy. A still experimental pathway for kidney protection is mitigation of radiation effects, possibly achievable by cotreatment with amifostine (Ethylol), a radiation protector, or with blockers of the renin-angiotensin-aldosterone system. Future perspectives on improving kidney protection during PRRT include combinations of agents to reduce renal retention of radiolabelled peptides, eventually together with mitigating medicines. Moreover, new somatostatin analogues with lower

  4. Effect of benzene on the inhibition rate of cell proliferation and investigation of relevant protective factors%苯对细胞增殖抑制率的影响及保护因素探讨

    Institute of Scientific and Technical Information of China (English)

    钟东明; 蔡静怡; 肖云; 李庆华; 朱如芳

    2013-01-01

    Objective To explore the effect of benzene on the inhibition rate of proliferation of bone marrow mononudear cells and investigate the relevant protective factors.Methods The experiment included four groups:blank control group,(0.25,3.5,20μmol/L) benzene group,(0.25,3.5,20μmol/L) benzene + (2,10,50pg/mL) amifostine group,(0.25,3.5,20μmol/L) benzene+serum group,the inhibition of proliferation of bone marrow mononuclear cell would be tested and calculated by the cell proliferation assay (CCK-8 method).Results High concentrations of benzene could highly inhibit cell proliferation than the low or medium concentrations groupa (P < 0.01);The inhibition rate of cell proliferation were corresponding reduced in(3.5,0.25μmol/L)Benzene + serum group than that in benzene group (P<0.05 or P<0.01); but there was no significant difference between the 20μmol/L Benzene + serum group and the benzene group (P>0.05).Significant differences were noticed between(0.25,3.5,20μmol/L) benzene +(50,10,2ug/ml)amifostine group and the benzene ones (P<0.01 or P<0.05).Conclusion The inhibition rate of cell proliferation will increase with the increase of benzene concentration,and there is a dose-dependent effect in toxicity of benzene; The serum and amifostine may reduce the toxicity of benzene on cell proliferation and they perhaps act as a protectant for benzene poisoning cells.%目的 探讨苯对骨髓单个核细胞增殖抑制率的影响,同时了解血清及氨磷汀能否作为保护因素减轻苯对细胞的影响.方法 实验分四组:空白对照组、(0.25、3.5、20μmol/L)苯组、(0.25、3.5、20μmol/L)苯+(2、10、50μg/mL)氨磷汀组、(0.25、3.5、20μmol/L)苯+血清组,通过细胞增殖检测(CCK-8法)并计算骨髓单个核细胞增殖抑制率.结果 高浓度苯组较低、中浓度苯组更能抑制细胞增殖(P<0.01);(3.5、0.25μmol/L)苯+血清组细胞增殖抑制率均较相对应浓度的苯组减少(P<0.05或P<0.01);但20μmol

  5. Radioprotective efficacy and cytogenetic effect of an organoselenium derivative: an in vitro evaluation in Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    With increase in applications of ionizing radiation in medical practices (radiotherapy and nuclear medicine) and also potential accidental exposures to ionizing radiation in various areas of radiation applications such as industrial, nuclear power plants and applications in armed forces, the development of effective radio protector is of great significance and need. The present study was designed to evaluate the in vitro radioprotective efficacy and cytogenetic effect of a novel synthetic organoselenium compound, 3,3'-Diselenodipropionic acid (DSePA), a diselenide and a derivative of selenocystine against damage induced by exposure to 60Co gamma radiation. We have made an attempt to reduce biological damage to as low a level as reasonably possible. The study was carried out by pretreatment (2 hr before irradiation) of test compound to exponentially grown CHO cell cultures at concentrations from 0 to 10 μg/ml. The results have shown that all concentrations tested reduced radiation-induced chromosomal damage compared with cells with no treatment. Maximum protection against radiation damage was observed at the concentration of 2 to 3 μg/ml. The reduction in cytogenetic damage with the radiation dose administered reached to 48%, which represents a significant reduction in gamma-ray induced chromosomal damage. This degree of protection is comparable with that obtained with amifostine, a radioprotective compound used in radiotherapy which is the only FDA approved drug, but characterized by its high cyto-toxicity. DSePA inhibited radiation-induced lipid peroxidation, measured as decrease in thiobarbituric acid reactive substances (TBARS) indicating protective effects on the cellular membrane system. In addition, DSePA treatment scavenged the free radicals and prevented the depletion of glutathione (GSH) level thus protected CHO cells from free-radical-induced oxidative stress. Our results also reflected that DSePA induced the rate of proliferation and attenuated the

  6. Radioprotective cerium oxide nanoparticles: Molecular imaging investigations of conps' pharmacokinetics, efficacy, and mechanisms of action

    Science.gov (United States)

    McDonagh, Philip Reed Wills, III

    Cerium oxide nanoparticles (CONPs) are being investigated for several anti-oxidant applications in medicine. One of their most promising applications is as a radioprotective drug, an area of research in need due to the severe side effects from radiation therapy. In this work, the potential of CONPs as a radioprotective drug is examined using four criteria: favorable biodistribution/pharmacokinetics, low toxicity, ability to protect normal tissue from radiation damage, and lack of protection of tumor. The mechanisms of action of CONPs are also studied. Biodistribution was determined in radiolabeled CONPs with surface coatings including citrate, dextran T10-amine (DT10-NH2), dextran T10-polyethylene glycol (DT10-PEG), dextran T10-sulfobetaine (DT10-SB) and poly(acrylic acid) (PAA), and compared to uncoated. 89Zr was incorporated into CONPs for positron emission tomography (PET) imaging and ex vivo tissue analysis in tumor bearing mice. Compared to uncoated [ 89Zr]CONPs, coated [89Zr]CONPs showed improved biodistribution, including significantly enhanced renal clearance of PAA- [89Zr]CONPs. The toxicity of CONPs was evaluated in vitro and in vivo, with low toxicity at therapeutic doses. After clinically mimetic radiation therapy, pre-treatment of mice with coated and uncoated CONPs showed greater than 50% reduction of cell death in normal colon tissue, comparable to the clinically available radioprotective drug amifostine. Tumor control after irradiation of spontaneous colon tumors was unchanged with PAA-CONP pre-treatment, while citrate, DT10-PEG, and uncoated CONP pre-treatment had slightly less tumor control. Xenograft tumors were irradiated after pH normalizing treatment with sodium bicarbonate and PAA-CONP pre-treatment. Treatment of these tumors showed slightly less tumor control than irradiation alone or PAA-CONP plus irradiation, demonstrating that the acidic pH of the tumor microenvironment may be the basis of preventing CONPs' radioprotective properties in

  7. Terapêutica citoprotetora em pacientes tratados com quimio e/ou radioterapia anti neoplásica Cytoprotective therapy in patients treated with chemotherapy and/or antineoplasic radiotherapy

    Directory of Open Access Journals (Sweden)

    Cármino A. Souza

    2000-08-01

    Full Text Available Nos últimos anos, vários agentes citoprotetores têm sido desenvolvidos para proteger células normais dos efeitos tóxicos da quimioterapia e radioterapia. O agente citoprotetor ideal seria aquele capaz de permitir a intensificação da dose dos quimioterápicos; proteger um amplo espectro de órgãos e tecidos quando do tratamento com diversos fármacos quimioterápicos; conferir proteção específica aos tecidos normais; preservar o efeito anti-tumoral e ter pequena e/ou controlável toxicidade e efeitos colaterais. Um citoprotetor deve ser administrado antes da quimioterapia citotóxica, ao contrário dos fatores estimuladores de colônia e do Leucovorin, que são administrados após quimioterapia como resgate à medula óssea e estimular a sua recuperação. Do ponto de vista prático existem três agentes citoprotetores: dois citoprotetores quimio-específicos (Dexrazoxane e Mesna e um citoprotetor de amplo espectro (Amifostina. Os autores discutem as principais propriedades e utilidades destas drogas utilizadas em Onco Hematologia.In recent years, cytoprotective agents have been developed to protect normal cells from the toxic effects of chemotherapy and radiotherapy. The ideal cytoprotectant is that which is able to allow intensification of chemotherapy; protects a broad spectrum of normal tissues and organs when used with a variety of chemotherapeutic agents; confers specific protection for normal tissues; preserves anti tumour activity and has little or manageable toxicity of its own. A cytoprotectant is administered prior to cytotoxic therapy, in contrast to the colony stimulant factors and Leucovorin, which are administered after chemotherapy to rescue the bone marrow and stimulate haematological recovery. Currently there are three cytoprotectors: two chemotherapy-specific (Dexrazoxane and Mesna and one broad-spectrum (Amifostine. The authors discuss the main properties and usefulness of these drugs in Oncohematology.

  8. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Retrospective Evaluation

    Directory of Open Access Journals (Sweden)

    Özlem Dicle

    2009-03-01

    Full Text Available Background and Design: Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN are severe drug reactions characterized by an extensive skin rash with blisters and exfoliation, accompanied by mucositis. The aim of this paper was to evaluate demographic and clinical features, prognosis and treatment in our patient group.Material and Method: A total of 20 consecutive patients with SJS and TEN diagnosed between 2000 and 2008 in our hospital were retrospectively analyzed.Results: Among the 20 cases, 3 had SJS (15%, 5 had SJS-TEN overlap (25% and 12 had TEN (60%. Oral mucosae was the most commonly affected site (%95 which was followed by conjunctivae ( 85% while all mucosal surfaces were affected in 2 patients. Causative drugs, anticonvulsive drugs (5 cases, sulfasalazine and non-steroidal anti-inflammatory drugs (6 cases, allopruninol (2 cases, anti-cancer therapy drugs (3 cases, amifostine (1 case and ampicillin (1 case, were identified in 18 patients. Five of 20 patients died of severe sepsis and irreversible multiple organ failure. The age above 60 years, percentage of epidermal detachment above 70% of body surface area and associated malignancy were found to be statistically correlated with poor prognosis (p=0.035, p=0.005, p=0.015; respectively. Fourteen patients were treated with short courses of medium-dose corticosteroids. An objective response to corticosteroids therapy was observed in all patients and the survival rate was 100%. The mean delay between occurrence of eruption and the withdrawal of suspected drug was 2.2 days and the first dose of corticosteroids was 3.4 days.Conclusion: In our patients, the suspected causative agents were the most frequently implicated high-risk drugs for the disease. Old age, extensive skin lesions and associated malignancy were found to be correlated with poor prognosis. Our treatment results indicate that beside rapid withdrawal of suspected drug short courses of medium-dose corticosteroids may

  9. Protection of radiation-induced DNA damage in albino rats by Zingiber Montanum extract

    International Nuclear Information System (INIS)

    The tropical ginger, Zingiber montanum (J. König) A. Dietr, has potentials in scavenging free radicals and affording protection from radiation-induced chromosomal aberrations. The present investigation aims at determining antioxidant and radioprotective properties of the rhizome extract. Sulphur free radical, DPPH and superoxide scavenging assays were carried out for assessing antioxidant activities. Radiation-induced (500 cGy) DNA damage in pBR322 in vitro could be significantly reduced upto 71% (P < 0.05) by treatment with 60% ethanol extract (20 μg). Acute toxicity of the 60% ethanol extract was determined and suitable injectable dose was selected for intra-peritoneal administration in albino rats (Rattus norvegicus). The LD50 of extract calculated for 72 hrs was found to be 2.9 g/kg, and maximum tolerated dose (MTD) of rhizome extract was 1.3 g/kg. Rhizome extract (0.5 g/kg) in 60% ethanol was intra-peritoneally injected to albino rats and exposed to 100, 300 and 500 cGy. Radioprotective effect of the extract was determined by alkaline single cell comet assay. Significant reduction (P < 0.05) of comet DNA (68%) and length (61%)in rat bone marrow cells was observed at a radiation dose of 500 cGy. The results demonstrate that tropical ginger possess free radical scavenging properties and can protect bone marrow cells from radiation-induced DNA damages. The results on radiation induced DNA damage using plasmid pBR322 DNA obviously justify that the extract at a low dose can protect DNA from undergoing strand breakage due to gamma radiation exposure. Versatility of Zingiber montanum in different chemical assays in terms of its radical scavenging potential shows that this non-conventional food plant as a lot of potential in maintaining human health through dietary supplementation as nutraceutical. This candidate plant also can possibly be a promising candidate in clinical radiotherapy perhaps as a substitute of or the well-know radioprotector amifostine. (author)

  10. DF-1, A Nontoxic Carbon Fullerene Based Antioxidant, is Effective as a Biomedical Countermeasure Against Radiation

    Science.gov (United States)

    Theriot, Corey A.; Casey, Rachael; Conyers, Jodie; Wu, Honglu

    2010-01-01

    A long-term goal of radiation research is the mitigation of inherent risks of radiation exposure. Thus the study and development of safe agents, whether biomedical or dietary, that act as effective radioprotectors is an important step in accomplishing this long-term goal. Some of the most effective agents to date have been aminothiols and their derivatives. Unfortunately, most of these agents have side effects such as nausea, vomiting, hypotension, weakness, and fatigability. For example, nausea and emesis occur in most patients treated with WR-2721 (Amifostine), requiring the use of effective antiemetics, with hypotension being the dose-limiting side effect in patients treated. Clearly, the need for a radioprotector that is both effective and safe still exists. Development of biocompatible nano-materials for radioprotection is a promising emerging technology that could be exploited to address the need to minimize biological effects when exposure is unavoidable. Testing free radical scavenging nanoparticles for potential use in radioprotection is exciting and highly relevant. Initial investigations presented here demonstrate the ability of a particular functionalized carbon fullerene nanoparticle, (DF-1), to act as an effective radioprotector. DF-1 was first identified as the most promising candidate in a screen of several functionalized carbon fullerenes based on lack of toxicity and antioxidant therapeutic potential against oxidative injuries (i.e. organ reperfusion and ionizing radiation). Subsequently, DF-1 has been shown to reduce chromosome aberration yield and cell death, as well as overall ROS levels in human lymphocytes and fibroblasts after exposure to gamma radiation and energetic protons while demonstrating no associated toxicity. The dose-reducing factor of DF-1 at LD50 is nearly 2.0 for gamma radiation. In addition, DF-1 treatment also significantly prevented cell cycle arrest after exposure. Finally, DF-1 markedly attenuated COX2 upregulation in cell

  11. Anticancer drug-induced kidney disorders.

    Science.gov (United States)

    Kintzel, P E

    2001-01-01

    Nephrotoxicity is an inherent adverse effect of certain anticancer drugs. Renal dysfunction can be categorised as prerenal uraemia, intrinsic damage or postrenal uraemia according to the underlying pathophysiological process. Renal hypoperfusion promulgates prerenal uraemia. Intrinsic renal damage results from prolonged hypoperfusion, exposure to exogenous or endogenous nephrotoxins, renotubular precipitation of xenobiotics or endogenous compounds, renovascular obstruction, glomerular disease, renal microvascular damage or disease, and tubulointerstitial damage or disease. Postrenal uraemia is a consequence of clinically significant urinary tract obstruction. Clinical signs of nephrotoxicity and methods used to assess renal function are discussed. Mechanisms of chemotherapy-induced renal dysfunction generally include damage to vasculature or structures of the kidneys, haemolytic uraemic syndrome and prerenal perfusion deficits. Patients with cancer are frequently at risk of renal impairment secondary to disease-related and iatrogenic causes. This article reviews the incidence, presentation, prevention and management of anticancer drug-induced renal dysfunction. Dose-related nephrotoxicity subsequent to administration of certain chloroethylnitrosourea compounds (carmustine, semustine and streptozocin) is commonly heralded by increased serum creatinine levels, uraemia and proteinuria. Additional signs of streptozocin-induced nephrotoxicity include hypophosphataemia, hypokalaemia, hypouricaemia, renal tubular acidosis, glucosuria, aceturia and aminoaciduria. Cisplatin and carboplatin cause dose-related renal dysfunction. In addition to increased serum creatinine levels and uraemia, electrolyte abnormalities, such as hypomagnesaemia and hypokalaemia, are commonly reported adverse effects. Rarely, cisplatin has been implicated as the underlying cause of haemolytic uraemic syndrome. Pharmaceutical antidotes to cisplatin-induced nephrotoxicity include amifostine, sodium

  12. Radioprotectors in Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nair, C.K.K. [Bhabha Atomic Research Centre, Mumbai (India); Parida, D.K.; Nomura, Taisei

    2001-03-01

    This review article focuses on clinically relevant radioprotectors and their mechanisms of radioprotection. Radiotherapy is the most common modality of human cancer therapy. Obtaining optimal results requires a judicious balance between the total dose of radiotherapy delivered and the threshold limit of critical surrounding normal tissues, and the normal tissues need to be protected against radiation injury to obtain better tumor control by using a higher dose. For this reason, radiation-protective agents play an important role in clinical radiotherapy. Radiation-protective agents can be classified into three groups: radioprotectors, adaptogens, and absorbents. The first group generally consists of sulfhydryl compounds and other antioxidants. They include several myelo-, entero-, and cerebro-protectors. Adaptogens act as promotors of radioresistance. They are natural protectors that offer chemical protection against low levels of ionizing radiation. Absorbents protect organs from internal radiation and chemicals. They include drugs that prevent incorporation of radioiodine by the thyroid gland and absorption of radionuclides. This article thoroughly describes the properties, mechanisms of action, and perspectives on clinical application of the following categories of radioprotectors: sulfhydryl compounds (e.g., cysteine, cysteamine, glutathione, AET, WR 2127, and other WR-compounds), antioxidants (e.g., tempace, Hoechst 33342, vitamin A, E, and C, TMG, melatonin), angiotensin-converting enzyme (ACE) inhibitors (e.g., captopril, elanopril, penicillamine, pentoxifylline, L-158, 809), cytoprotective agents (mesna, dexrazoxane, and amifostin), metalloelements (e.g., manganese chloride, cadmium salts, bismuth subnitrate), immunomodulators (gamma-interferon, polysaccharides AM5, AM218, heat-killed lactobacillus cells, broncho-vaxom, trehalose dicorynomycolate, and AS101), lipopolysaccharides and prostaglandins, plant extracts and compounds isolated from plants (curcmin

  13. A survey of techniques to reduce and manage external beam radiation-induced xerostomia in British oncology and radiotherapy departments

    Energy Technology Data Exchange (ETDEWEB)

    Macknelly, Andrew [Norfolk and Norwich University Hospital (United Kingdom); Day, Jane [Faculty of Health, Wellbeing and Science, University Campus Suffolk, Waterfront Building, Neptune Quay, Ipswich (United Kingdom)], E-mail: j.day@ucs.ac.uk

    2009-11-15

    Xerostomia is the most common side effect of external beam radiotherapy to the head and neck [Anand A, Jain J, Negi P, Chaudhoory A, Sinha S, Choudhury P, et-al. Can dose reduction to one parotid gland prevent xerostomia? - A feasibility study for locally advanced head and neck cancer patients treated with intensity-modulated radiotherapy. Clinical Oncology 2006;18(6):497-504.]. A survey was carried out in British oncology departments to determine what treatment regimes, to minimise xerostomia, are used for patients with head-and-neck cancers treated with external beam radiotherapy. A semi-structured questionnaire consisting of both quantitative and qualitative questions was designed that asked departments which of the identified methods they used, why a method might not be currently employed, and whether its use had ever been considered. The study found that there are wide disparities between the techniques employed by oncology departments to avoid and reduce xerostomia in patients with cancers of the head and neck. The National Institute of Clinical Health and Excellence, [National Institute for Clinical Health and Excellence (NICE). Improving outcomes in head and neck cancers: the manual. London: Office of Public Sector Information; 2004.] for example, recommends that patients are given dental care and dietary advice but some departments did not appear to be doing this. Less than half of departments stated that they offer complementary therapies and less than 40% prescribed pilocarpine, a saliva-stimulant. Only two respondents stated that they use amifostine, a radioprotector, during radiotherapy treatment to the head and neck. The results also suggested a move toward using Intensity Modulated Radiotherapy (IMRT) for treating head-and-neck cancers which offers better normal tissue sparing than three-dimensional conformal radiotherapy. [Anand A, Jain J, Negi P, Chaudhoory A, Sinha S, Choudhury P, et al. Can dose reduction to one parotid gland prevent xerostomia

  14. 血栓通对顺铂肾损伤大鼠的肾功能和氧化指标的影响%Effect of Xueshuantong on Renal Function and Oxidation Indexes in Cisplatin-induced Nephroxicity Rats

    Institute of Scientific and Technical Information of China (English)

    席加喜; 刘晓霞; 杨玉芳; 张春花; 刘华钢

    2012-01-01

    目的:研究血栓通对顺铂肾损伤大鼠肾功能的保护作用和其对损伤大鼠氧化指标的影响.方法:采用顺铂(0.5 mg·kg-1)尾静脉注射的方法制造顺铂肾毒性模型.将72只大鼠随机分为6组,空白组、模型组、安磷汀阳性药物组、血栓通低剂、中、高剂量组(15.63,31.35,62.70 mg·kg-1).分别给药处理10d后,观察大鼠24 h尿蛋白量、尿N-乙酰β-D氨基葡萄糖苷酶NAG,血清中肌酐、尿素氮,肾组织匀浆中超氧化物歧化酶(SOD)活性、谷胱甘肽过氧化物酶(GSH-Px)活性、丙二醛(MAD)含量及肾组织的病理变化.结果:与模型组比较,各治疗组大鼠血肌酐、血清尿素氮,24h尿蛋白量、尿NAG的含量明显降低,肾组织匀浆中SOD活性、GSH-Px活性明显增高,MAD含量明显降低(P <0.01,P<0.05);肾脏的病理变化明显减轻.结论:血栓通能有效改善顺铂肾损伤大鼠肾功能,降低肾组织氧化水平,减轻肾脏的病理变化,对大鼠顺铂肾损伤有保护作用.%Objective: To study the protective effect of Xueshuantong against cisplatin-induced nephrotoxicity. Method; Female SD rats were randomly divided into six groups; normal saline (NS) group, model group, positive control group and the high dose group, middle dose group and low dose group of Xueshuantong, with 12 rats in each group. The model rats with nephrotoxicity were duplicated with injection of cisplatin by vena caudalis. Rats in model group, positive control group and the high dose group, middle dose group and low dose group of Xueshuantong were treated by amifostine, 0. 1 mg · kg-1, Xueshuantong, 15. 63 , 31. 35, 62.70 mg-kg-1 once a day. The changes of serum creatinine (SCr), blood urea nitrogen (BUN), W-acetyl-beta-D glucosa minidase (NAG), urine protein/24 h, the content of malondialdehyde ( MD A) and the activity of superoxide dismutase (SOD) , glutathione peroxidase (GSH-Px) were measured and renal structure was observed after 10 days of

  15. Antiradiation Vaccine: Technology Development- Radiation Tolerance,Prophylaxis, Prevention And Treatment Of Clinical Presentation After Heavy Ion Irradiation.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

    irradiation was generated in heavy ion (Fe56) accelerator - UTI. Heavy Ion linear transfer energy - 2000- 2600 KeV -mkm, 600 MeV -92U. Absorbed Dose - 3820 Rad. Experimental Design: Rabbits from all groups were irradiated by heavy ion accelerator. Group A: control-10 rabbits; Group B: placebo-5 rabbits; Group C: Radioprotectant Cystamine (50 mg-kg)-5 rabbits, 15 minutes before irradiation - 5 rabbits; Group D: Radioprotectant Gammafos (Amifostine 400mg -kg ) - 5 rabbits; Group E: Antiradiation Vaccine: subcutaneus administration or IM - 2 ml of active substance, 14 days before irradiation Results: Group A 100% mortality within two hours after heavy ion irradiation with clinical symptoms of Acute Cerebro- and Cardio-Vascular Radiation syndromes. Group B 100% mortality within 15 hours following irradiation. Group C 100% mortality within 14-15 hours after irradiation. Group D 100% mortality within 15-16 hours after irradiation. In groups A- D registered the development of acute radiation cerebrovascular and cardiovascular syndromes and also extensive burns. of skin produced rapid death. Group E -100% mortality in 280-290 hours (12 days) following heavy ion irradiation with animals exhibiting a combination or individual forms of Acute Cerebrovascular, Cardiovascular, and Gastrointestinal forms and focal skin burns. Discussion Antiradiation vaccine and immune-prophylaxis is an effective method of neutralization of Radiation Toxins. Vaccination before irradiation extended survival time after irradiation with heavy ions from two hours up to 300 hours. Clinical signs, clinical features, symptoms were somewhat attenuated. Degree of clinical forms of Acute Radiation Syndromes were diminished in their clinical manifestation and severity. Groups A-D demonstrated extremely severe level of Cerebrovascular and Cardiovascular forms of Acute Radiation Syndromes and lethality 100% was registered in short time after irradiation. Radiation induced burns in this groups (with Cutaneous sub

  16. The optimal choice of medication administration route regarding intravenous, intramuscular, and subcutaneous injection

    Directory of Open Access Journals (Sweden)

    Jin JF

    2015-07-01

    Full Text Available Jing-fen Jin,1 Ling-ling Zhu,2 Meng Chen,3 Hui-min Xu,3 Hua-fen Wang,1 Xiu-qin Feng,1 Xiu-ping Zhu,3 Quan Zhou31Division of Nursing, 2VIP Care Ward, Division of Nursing, 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaBackground: Intravenous (IV, intramuscular (IM, and subcutaneous (SC are the three most frequently used injection routes in medication administration. Comparative studies of SC versus IV, IM versus IV, or IM versus SC have been sporadically conducted, and some new findings are completely different from the dosage recommendation as described in prescribing information. However, clinicians may still be ignorant of such new evidence-based findings when choosing treatment methods.Methods: A literature search was performed using PubMed, MEDLINE, and Web of Sciences™ Core Collection to analyze the advantages and disadvantages of SC, IV, and IM administration in head-to-head comparative studies.Results: “SC better than IV” involves trastuzumab, rituximab, antitumor necrosis factor medications, bortezomib, amifostine, recombinant human granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, recombinant interleukin-2, immunoglobulin, epoetin alfa, heparin, and opioids. “IV better than SC” involves ketamine, vitamin K1, and abatacept. With respect to insulin and ketamine, whether IV has advantages over SC is determined by specific clinical circumstances. “IM better than IV” involves epinephrine, hepatitis B immunoglobulin, pegaspargase, and some antibiotics. “IV better than IM” involves ketamine, morphine, and antivenom. “IM better than SC” involves epinephrine. “SC better than IM” involves interferon-beta-1a, methotrexate, human chorionic gonadotropin, hepatitis B immunoglobulin, hydrocortisone, and morphine. Safety, efficacy, patient preference, and pharmacoeconomics are four principles

  17. Toxicity and Radioprotective Effects of DF-1 and Carbon Nanotubes in Human Lung and Liver Cell Lines

    Science.gov (United States)

    Burgoyne, Madeline; Holtorf, Heidi; Huff, Janice; Moore, Valerie; Jeevarajan, Antony

    2007-01-01

    significant effect on the growth of the HepG2 cells by the nanotubes, and BHT-nanotubes. In order to examine the usefulness of the DF-1, nanotubes, and BHT-nanotubes in mediating the effects of radiation a clonogenic assay is being performed. The HF-19 cells were plated in different concentrations of the various compounds and exposed to varying amounts of radiation. The cells are being allowed to grow in a small enough concentration so that the ability of each cell to divide can be seen by the development of cell clusters. By comparing the irradiated control to the un-irradiated control the effects of radiation alone can be seen. By comparing the compound treated irradiated cells to the irradiated control the usefulness of each compound can be seen. It is thought that Amifostine, the positive control, will have more regularly dividing cells then the irradiated control, as will DF-1 and hopefully both nanotube materials as well.

  18. A survey of techniques to reduce and manage external beam radiation-induced xerostomia in British oncology and radiotherapy departments

    International Nuclear Information System (INIS)

    Xerostomia is the most common side effect of external beam radiotherapy to the head and neck [Anand A, Jain J, Negi P, Chaudhoory A, Sinha S, Choudhury P, et-al. Can dose reduction to one parotid gland prevent xerostomia? - A feasibility study for locally advanced head and neck cancer patients treated with intensity-modulated radiotherapy. Clinical Oncology 2006;18(6):497-504.]. A survey was carried out in British oncology departments to determine what treatment regimes, to minimise xerostomia, are used for patients with head-and-neck cancers treated with external beam radiotherapy. A semi-structured questionnaire consisting of both quantitative and qualitative questions was designed that asked departments which of the identified methods they used, why a method might not be currently employed, and whether its use had ever been considered. The study found that there are wide disparities between the techniques employed by oncology departments to avoid and reduce xerostomia in patients with cancers of the head and neck. The National Institute of Clinical Health and Excellence, [National Institute for Clinical Health and Excellence (NICE). Improving outcomes in head and neck cancers: the manual. London: Office of Public Sector Information; 2004.] for example, recommends that patients are given dental care and dietary advice but some departments did not appear to be doing this. Less than half of departments stated that they offer complementary therapies and less than 40% prescribed pilocarpine, a saliva-stimulant. Only two respondents stated that they use amifostine, a radioprotector, during radiotherapy treatment to the head and neck. The results also suggested a move toward using Intensity Modulated Radiotherapy (IMRT) for treating head-and-neck cancers which offers better normal tissue sparing than three-dimensional conformal radiotherapy. [Anand A, Jain J, Negi P, Chaudhoory A, Sinha S, Choudhury P, et al. Can dose reduction to one parotid gland prevent xerostomia

  19. Antiradiation Vaccine: Technology Development- Radiation Tolerance,Prophylaxis, Prevention And Treatment Of Clinical Presentation After Heavy Ion Irradiation.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

    irradiation was generated in heavy ion (Fe56) accelerator - UTI. Heavy Ion linear transfer energy - 2000- 2600 KeV -mkm, 600 MeV -92U. Absorbed Dose - 3820 Rad. Experimental Design: Rabbits from all groups were irradiated by heavy ion accelerator. Group A: control-10 rabbits; Group B: placebo-5 rabbits; Group C: Radioprotectant Cystamine (50 mg-kg)-5 rabbits, 15 minutes before irradiation - 5 rabbits; Group D: Radioprotectant Gammafos (Amifostine 400mg -kg ) - 5 rabbits; Group E: Antiradiation Vaccine: subcutaneus administration or IM - 2 ml of active substance, 14 days before irradiation Results: Group A 100% mortality within two hours after heavy ion irradiation with clinical symptoms of Acute Cerebro- and Cardio-Vascular Radiation syndromes. Group B 100% mortality within 15 hours following irradiation. Group C 100% mortality within 14-15 hours after irradiation. Group D 100% mortality within 15-16 hours after irradiation. In groups A- D registered the development of acute radiation cerebrovascular and cardiovascular syndromes and also extensive burns. of skin produced rapid death. Group E -100% mortality in 280-290 hours (12 days) following heavy ion irradiation with animals exhibiting a combination or individual forms of Acute Cerebrovascular, Cardiovascular, and Gastrointestinal forms and focal skin burns. Discussion Antiradiation vaccine and immune-prophylaxis is an effective method of neutralization of Radiation Toxins. Vaccination before irradiation extended survival time after irradiation with heavy ions from two hours up to 300 hours. Clinical signs, clinical features, symptoms were somewhat attenuated. Degree of clinical forms of Acute Radiation Syndromes were diminished in their clinical manifestation and severity. Groups A-D demonstrated extremely severe level of Cerebrovascular and Cardiovascular forms of Acute Radiation Syndromes and lethality 100% was registered in short time after irradiation. Radiation induced burns in this groups (with Cutaneous sub