Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amifostine was developed as a radio- and chemoprotective agent. It has shown protection against whole-body irradiation, and myelo- and nephrotoxicity of cytotoxic agents both in experimental and clinical studies. Some experimental trials revealed an influence of amifostine on tumor growth or the activity of cytotoxic drugs under certain circumstances. Therefore, it was the aim of our work to evaluate the pharmacological potential of amifostine in a preclinical in vivo situation with human xenotransplanted neuroblastomas. Human neuroblastoma cells (IMR5-75 and Kelly) were grown s.c. as xenografts in nude mice to palpable sizes (approximately 4 x 5 mm). Then the animals received 200 mg/kg amifostine i.p. and were treated 30 min later with one of the following cytotoxic drugs: cyclophosphamide, doxorubicin, cisplatin, ifosfamide, vincristine and etoposide. Amifostine as the only treatment did not influence the growth of the neuroblastomas IMR5-75 and Kelly. We observed no side effects of the compound itself. In no case did amifostine interact significantly with the antitumor effect of any cytostatic used in combination. However, amifostine mitigated the body weight loss induced by vicristine and the leukopenia induced by cyclophosphamide, cisplatin or ifosfamide, respectively. The side effects of the remaining cytostatics were--if observed at all--unchanged. We conclude that amifostine did not influence the tumor growth of xenotransplanted neuroblastomas and did not reduce the antineoplastic activity of the tested cytostatic drugs. Further investigation of amifostine as a protectant from side effects of chemotherapy in a clinical setting is warranted.
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PMID:Effects of amifostine (WR-2721, ethyol) on tumor growth and pharmacology of cytotoxic drugs in human xenotransplanted neuroblastomas. 907 13

Amifostine (WR-2721) is currently being investigated as a potential protector of normal tissues during chemotherapy in adult and pediatric cancer patients. The marked reduction of bone marrow and renal toxicity by amifostine is well documented, but data are lacking whether the anticancer activity of cytostatic drugs is also preserved in neuroblastoma as the second most common pediatric malignancy. We investigated the cytotoxic effect of six drugs on two neuroblastoma cells lines chosen for their presence or absence of N-myc amplification and PGY1 overexpression: IMR-5 (N-myc 25 x, PGY1-negative), CHP-100 (N-myc 1x, PGY1-positive) in vitro in the presence and absence of WR-2721 and its active metabolite WR-1065 using the monolayer proliferation assay. Doxorubicin, vincristine, etoposide, cisplatin, 4-hydroperoxycyclophosphamide and 4-hydroperoxyifosfamide were equally cytotoxic with and without preincubation of WR-2721 (14 mM) or WR-1065 (40 microM) as shown by virtually identical dose-response curves and ID50 values. We conclude that WR-2721 and WR-1065 did not reduce the cytostatic activity of six commonly used drugs on neuroblastoma cell lines in vitro.
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PMID:Effects of WR-2721 (amifostine) and its metabolite WR-1065 on the antiproliferative activity of chemotherapeutic agents on neuroblastoma cells in vitro. 914 9

Amifostine [WR-2721; H2N-(CH2)3-NH-(CH2)2-S-PO3H2] is used as a protecting agent in the chemotherapy of neuroblastoma. It is supposed that Amifostine will be transformed into its active form, the free thiol (WR-1065), easier by normal cells than by tumour cells. Analytical capillary isotachophoresis was used to determine the dephosphorylation of Amifostine in serum and on neuroblastoma cells and peripheral blood cells. Furthermore, the biological effects of Amifostine and its free thiol, on cell proliferation of neuroblastoma cells were measured in combination with Carboplatin. It was found that neuroblastoma cells did not split phosphate less efficiently than normal peripheral blood cells. Furthermore, neither Amifostine (as expected) nor the free thiol (not expected according to the theory) were able to inhibit the effects of Carboplatin. Therefore, the current hypothesis concerning the mode of action of Amifostine must be questioned.
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PMID:Isotachophoretic determination of phosphate splitting from Amifostine and p-nitrophenyl phosphate in serum and neuroblastoma cells. 1032 42

Amifostine (Ethyol, WR-2721) has been clinically used in combination with high dose therapy of neuroblastoma stage 4 with melphalan, carboplatin and VP-16 in 14 patients. The amifostine group was compared to a historical control group of 24 comparably-treated patients. There were no significant differences regarding the time of hematological recovery, the duration of hospitalization, the duration of antibiotic treatment and the extent of renal toxicity. However, in contrast to four patients of the control group, no patient in the amifostine group developed such severe mucositis that artificial ventilation became necessary. Pretreatment of neuroblastoma cell lines for 30 minutes with amifostine and the free thiol(WR-1065) did not reduce the cytotoxic effects of melphalan, carboplatin and VP-16. Evidence was obtained that the uptake of the activated thiol could be achieved by a polyamine transporter. Taken together, the data do not support the use of amifostine in high dose chemotherapy of neuroblastoma prior to autologous stem cell transplantation. However, amifostine may be more effective in conventional neuroblastoma therapy where protection of bone marrow stem cells is necessary.
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PMID:Effect of amifostine on neuroblastoma during high dose chemotherapy: in vivo and in vitro investigations. 1120

Nephrotoxicity is observed in 30% of patient's treated with chemotherapy schedules based on cisplatin analogues. Ethyol (amiphostin) was used as a protectant of kidney in 3 paediatric patients with neoplastic disease. Two patients suffered from Wilms tumour. One of them, a 5 month old boy presented with agenesis of the right kidney and stage II tumour in the left kidney. Bilateral Wilms tumour was recognised in a 6 year old girl. In both cases glomerular filtration was diminished. The third patient was a girl aged 5 who had isolated relapse of neuroblastoma in the central nervous system. Primary treatment caused nephrotoxic complications such as Fanconi syndrome and diminished glomerular filtration (66 ml/min). In these 3 cases Ethyol was used every lime before analogues of cisplatin were given. Tolerance and the effect of this protectant were good.
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PMID:[Application of Ethyol during chemotherapy in patients with impaired kidney function. Description of three cases]. 1200 47

Cisplatin in higher doses have been used routinely in the treatment of childhood tumours including neuroblastoma and germ cell tumors. Amifostine, a broad-spectrum cytoprotector of normal tissues, has been approved by U.S. Food and Drug Administration for use in patients receiving cisplatin. Such administration of amifostine has been reported to reduce cisplatin-related toxicities in some studies, but not all. The authors report a case of severe toxicity with cisplatin in a girl with epithelial cell carcinoma of the ovary despite the use of amifostine.
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PMID:Severe neurotoxicity, ototoxicity and nephrotoxicity following high-dose cisplatin and amifostine. 1602 Jan 36