OBJECTIVE: Amifostine (Ethyol(R)), an organic thiophosphate, has shown the ability to protect normal, but not neoplastic, tissues from the damaging effects of chemotherapy and radiotherapy in various kinds of cancers. This study was designed to determine ifostine could reduce the serious hematologic and nephrologic toxicities associated with cisplatin based combination chemotherapy in gynecologic cancer patients. PATIENTS AND METHODS: Forty patients who received cisplatin-based combination chemotherapy were randomized into two groups. They received chemotherapy with or without pretreatment of amifostine before each course. The occurrence of hematologic and renal toxicities were evaluated. Stastical analysis was done by independent t-test and Chi-square test. RESULTS: Hematologic toxicity was evaluated with nadir count of neutrophil and platelet. The nadir count of neutrophil was 2034.2+/-1199.20/microliter in group with pretreatment using amifostine vs 1070.85+/-472.66/microliter in control group (p<0.01). Platelet count was not statistically different. (p<0.16) Grade 3 neutropenia was observed in nine (45%) patients in pretreatment group vs four (20%) patients with control group (p<0.09). Grade 4 neutropenia occurred in one patient only in control group. Renal toxicity was evaluated by serum creatinine and creatinine clearance. Protracted serum creatinine elevation was not significant in both groups. (p<0.14) Reduction of creatinine clearance was less in patients with pretreatment (p<0.01). There were no significant side reactions in subjects using amifostine. CONCLUSION: Pretreatment with amifostine reduces the neutropenia and nephrotoxicity associated with cisplatin-based combination chemotherapy with gynecologic cancer patients.
Amifostine* ; Blood Platelets ; Cisplatin ; Creatinine ; Drug Therapy ; Drug Therapy, Combination* ; Humans ; Neutropenia ; Neutrophils ; Platelet Count ; Radiotherapy

OBJECTIVE: Amifostine (Ethyol(R)), an organic thiophosphate, has shown the ability to protect normal, but not neoplastic, tissues from the damaging effects of chemotherapy and radiotherapy in various kinds of cancers. This study was designed to determine ifostine could reduce the serious hematologic and nephrologic toxicities associated with cisplatin based combination chemotherapy in gynecologic cancer patients. PATIENTS AND METHODS: Forty patients who received cisplatin-based combination chemotherapy were randomized into two groups. They received chemotherapy with or without pretreatment of amifostine before each course. The occurrence of hematologic and renal toxicities were evaluated. Stastical analysis was done by independent t-test and Chi-square test. RESULTS: Hematologic toxicity was evaluated with nadir count of neutrophil and platelet. The nadir count of neutrophil was 2034.2+/-1199.20/microliter in group with pretreatment using amifostine vs 1070.85+/-472.66/microliter in control group (p<0.01). Platelet count was not statistically different. (p<0.16) Grade 3 neutropenia was observed in nine (45%) patients in pretreatment group vs four (20%) patients with control group (p<0.09). Grade 4 neutropenia occurred in one patient only in control group. Renal toxicity was evaluated by serum creatinine and creatinine clearance. Protracted serum creatinine elevation was not significant in both groups. (p<0.14) Reduction of creatinine clearance was less in patients with pretreatment (p<0.01). There were no significant side reactions in subjects using amifostine. CONCLUSION: Pretreatment with amifostine reduces the neutropenia and nephrotoxicity associated with cisplatin-based combination chemotherapy with gynecologic cancer patients.
Amifostine* ; Blood Platelets ; Cisplatin ; Creatinine ; Drug Therapy ; Drug Therapy, Combination* ; Humans ; Neutropenia ; Neutrophils ; Platelet Count ; Radiotherapy

Amifostine ; pharmacology ; Animals ; Benzene ; toxicity ; Blood ; drug effects ; Blood Cell Count ; Male ; Mice ; Random Allocation

Myelodysplastic syndrome (MDS) is one of the most prevalent haematological malignancies originating from haemopoietic stem/progenitor cells. MDS characterized by morbid haematopoiesis of bone marrow and peripheral blood cell reduction and mainly occurs in the elders. The dangerous factors of MDS include chemotherapy, radiotherapy, benzene, other organic solvent, immune depressants and so on. Following the recent progress of medical sciences, a large number of new regimens of chemotherapy, radiotherapy and immune therapy against carcinomas generate and lead the development of therapeutics for malignancies. It is worried that the incidence of MDS still increases year by year and the patient age becomes younger. Although many agents are used to MDS, curative effect is not as good as expect. Amifostine, a kind of pancytoprotector also used in treatment of MDS. This review summarizes the mechanism of amifostine in MDS therapy which possesses a challenge binding with the current related investigations.
Amifostine ; therapeutic use ; Humans ; Myelodysplastic Syndromes ; drug therapy ; Radiation-Protective Agents ; therapeutic use

Radioactive iodine (131I) targets the thyroid gland and has been proven to play an effective role in the treatment of differentiated thyroid cancers. However, this radioisotope is simultaneously absorbed on the salivary glands where it is concentrated and secreted into the saliva. Dose related damage to the salivary parenchyma results from the 131I irradiation. Salivary gland swelling and pain, usually involving the parotid, can be seen. The symptoms may develop immediately after a therapeutic dose of 131I and/or months later and progress in intensity with time. Prevention of the 131I-induced sialadenitis includes the use of sialagogic agents to enhance the transit time of the 131I through the salivary glands. However, many studies are not available to delineate the efficacy of this approach. Recently, amifostine has been advocated to prevent the effects of irradiation. Treatment of the varied complications that may develop encompass numerous approaches and include gland massage, sialagogic agents, duct probing, antibiotics, mouthwashes, good oral hygiene, and adequate hydration.
Amifostine ; Anti-Bacterial Agents ; Iodine ; Massage ; Mouthwashes ; Oral Hygiene ; Radioactivity ; Saliva ; Salivary Glands ; Sialadenitis* ; Thyroid Gland

Adult ; Aged ; Amifostine ; therapeutic use ; Benzene ; poisoning ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; chemically induced ; drug therapy

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 internet-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 11 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.
Amifostine ; pharmacology ; Computational Biology ; Gene Expression ; drug effects ; Gene Expression Profiling ; methods ; Humans ; Microarray Analysis ; Molecular Sequence Annotation

Amifostine ; pharmacology ; Anemia, Aplastic ; chemically induced ; pathology ; prevention & control ; Animals ; Benzene ; toxicity ; Dose-Response Relationship, Drug ; Male ; Mice

BACKGROUND: S-2-(3 aminoprophlamino) ethylphosphorothioic acid (WR-2721) is one of the radical scavenging thiols. We tested its protective effects in the reperfused heart. MATERIAL AND METHOD: The experimental setup was the constant pressure Langendorffs perfusion system. We investigated the radical scavenging properties of this compound in isolated rat hearts which were exposed to 20 minutes ischemia and 20 minutes reperfusion. Four experimental groups were used:group I, control, Amifostine 50 mg (1 mL) peritoneal injection 30 minutes before ischemia (group II), Amifostine 10 mg (0.2 mL) injection during ischemia through coronary artery (group III),and Amifostine 50 mg (1 mL) peritoneal injection 2 hrs before ischemia (group IV). The experimental parameters were the levels of latate, CK-MB, and adenosine deaminase (ADA) in frozen myocardium, the quantity of coronary flow,and left ventricular developed pressure, and it's dp/dt. Statistical analysis was performed using repeated measured analysis of variance and student t-test. RESULT: The coronary flow of group II and IV were less than group I and III at equilibrium state but recovery of coronary flow at reperfusion state of group II, III, and IV were more increased compared with group I. The change of systolic left ventricular devoloping pressure of group II and IV were less than control group at equilibrium state, which seemed to be the influence of the pharmacological hypotensive effect of amifostine. But it was higher compared with group I at reperfusion state. The lactic acid contents of group II were less than control group in frozen myocardium. (Group I was 0.20 0.29 mM/g vs Group II, which was 0.10 0.11 mM/g). The quantity of CK-MB in myocardial tissue was highest in group IV (P=0.026 I: 120.0 97.8 U/L vs IV: 242.2 79.15 U/L). The adenosine deaminase contents in the coronary flow and frozen myocardium were not significantly different among each group. CONCLUSION: Amifostine seemed to have significant cardioprotective effect during ischemia and reperfusion injuries of myocardium.
Adenosine Deaminase ; Amifostine* ; Animals ; Coronary Vessels ; Free Radical Scavengers ; Heart* ; Humans ; Ischemia ; Lactic Acid ; Myocardium ; Perfusion ; Rats* ; Reperfusion ; Reperfusion Injury ; Sulfhydryl Compounds

PURPOSE: The pattern of radioprotection by the combined use of low dose amifostine plus IL-1beta was investigated in mice exposed to an acute whole-body radiation dose of 10 Gy. MATERIALS AND METHODS: Male ICR mice were divided into the control group, the irradiation-only group, the high dose amifostine (400 mg/kg i.p. 30 min before irradiation) group, and the low dose amifostine (200 mg/kg i.p. 30 min before irradiation) plus IL-1beta (5 microgram/kg i.p. 20 h before irradiation) group. The radioprotective effects were evaluated using TUNEL assay and microcolony survival assay at jejunal crypt, bone marrow cell count and CBC in peripheral blood, and survival analysis up to 30 days following irradiation. RESULTS: The apoptotic index (p=0.987), surviving crypt number (p=0.484), and the number of WBCs (p=0.226), RBCs (p=0.544), and platelets (p=0.157) were not significantly different between the high dose amifostine group and the low dose amifostine plus IL-1beta group, although the bone marrow cell count was higher in the combination group. The irradiation-only group was dead within 15 days. However, the survival rate at 30 days in the high dose amifostine and the low dose amifostine plus IL-1beta pretreatments were 61% and 66%, respectively. Moreover, the differences between the two groups were insignificant for both 10 days (p=0.9461) and 30 days (p=0.8030). CONCLUSION: These results indicate that the low dose amifostine plus IL-1beta may be applied as a non-toxic radioprotector, while the high dose amifostine, known as the strongest radioprotector, however, had toxic side effects.
Amifostine* ; Animals ; Bone Marrow Cells ; Humans ; In Situ Nick-End Labeling ; Interleukin-1* ; Interleukin-1beta* ; Interleukins* ; Male ; Mice ; Mice, Inbred ICR ; Radiation Protection ; Survival Analysis ; Whole-Body Irradiation