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

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

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

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

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

To study the effects of S-2-(3-aminopropylamino) ethyl phosphorothioic acid (WR-2721, amifostine) on proliferation inhibition and apoptosis of HL-60 human leukemia cell line, the cell apoptosis rate of HL-60 was determined by annexin V/PI double staining method. Cell proliferation and chemotherapy sensitivity were analyzed with XTT assay, and the changes of cell cycle were observed through flow cytometry. The results showed that WR-2721 could significantly inhibit HL-60 cell proliferation. After treatment (30 min, 37 degrees C) with WR-2721, the sensitivity of HL-60 cells to VP16 was enhanced, and the IC(50) descended from 52.5 micro g/ml to 40.5 microg/ml. After 72 hours treatment of HL-60 cells with WR-2721, the early apoptotic cells (annexin V-FITC positive/PI negative) were increased from (5.5 +/- 1.9)% to (48.5 +/- 8.4)% (P < 0.001), late apoptotic cells (annexin V-FITC positive/PI positive) were increased from (1.2 +/- 0.5)% to (39.0 +/- 4.0)% (P < 0.001), and HL-60 cells were arrested in G(2)-M phase. In conclusion, WR-2721 treatment can enhance HL-60 cell chemotherapy sensitivity to VP16, inhibit proliferation, induce apoptosis and accumulation of cells in G(2)-M phase.
Amifostine ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Drug Synergism ; Etoposide ; pharmacology ; HL-60 Cells ; Humans

The aim of this study was to investigate the curative effect of amifostine (AMF) combined with recombinant human erythropoietin (rhEPO) on the aged patients with myelodysplastic syndrome. Two aged MDS patients (one aged 91; another 86) were treated with amifostine and rhEPO over a period of 4 weeks. The results showed that a short-term curative effect was observed and transfusion interval was prolonged in both patients after 4 week treatment with 5 x 0.4 g AMF plus 3 x 6,000 U rhEPO per week. The reticulocyte count in MDS-RA patient returned to normal at first week of treatment and still remained in normal level for 4 weeks; leukocyte, hemoglobin and platelet values in peripheral blood of MDS-RCMD patient obviousby increased, the abnormally increased reticulocyte value displayed a decrease trend after amifostine plus rh-EPO treatment. In conclusion, amifostine plus rhEPO may have a good therapeutic effect for aged MDS patients, and its clinical long-term curative effect still needs further evaluation.
Aged ; Aged, 80 and over ; Amifostine ; therapeutic use ; Drug Therapy, Combination ; Erythropoietin ; therapeutic use ; Humans ; Male ; Myelodysplastic Syndromes ; drug therapy ; Recombinant Proteins ; Time Factors ; Treatment Outcome