Biomaterial Database

Effects of WR-2721 (amifostine) and its metabolite WR-1065 on the antiproliferative activity of chemotherapeutic agents on neuroblastoma cells in vitro. 1997

S Fulda, and W Oster, and F Berthold

Department of Pediatric Hematology and Oncology, Children's Hospital, University of Cologne, Germany.

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.

UI	MeSH Term	Description	Entries
D008624	Mercaptoethylamines	Ethylamines, including CYSTEAMINE, that contain a sulfhydryl group in their structure.
D009447	Neuroblastoma	A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)	Neuroblastomas
D011837	Radiation-Protective Agents	Drugs used to protect against ionizing radiation. They are usually of interest for use in radiation therapy but have been considered for other purposes, e.g. military.	Radiation Protectant,Radiation Protective Agent,Radiation-Protective Agent,Radiation-Protective Drug,Radioprotective Agent,Radioprotective Agents,Radioprotective Drug,Agents, Radiation-Protective,Radiation Protectants,Radiation Protective Agents,Radiation-Protective Drugs,Radiation-Protective Effect,Radiation-Protective Effects,Radioprotective Drugs,Agent, Radiation Protective,Agent, Radiation-Protective,Agent, Radioprotective,Agents, Radiation Protective,Agents, Radioprotective,Drug, Radiation-Protective,Drug, Radioprotective,Drugs, Radiation-Protective,Drugs, Radioprotective,Effect, Radiation-Protective,Effects, Radiation-Protective,Protectant, Radiation,Protectants, Radiation,Protective Agent, Radiation,Protective Agents, Radiation,Radiation Protective Drug,Radiation Protective Drugs,Radiation Protective Effect,Radiation Protective Effects
D001932	Brain Neoplasms	Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.	Brain Cancer,Brain Metastases,Brain Tumors,Cancer of Brain,Malignant Primary Brain Tumors,Neoplasms, Intracranial,Benign Neoplasms, Brain,Brain Neoplasm, Primary,Brain Neoplasms, Benign,Brain Neoplasms, Malignant,Brain Neoplasms, Malignant, Primary,Brain Neoplasms, Primary Malignant,Brain Tumor, Primary,Brain Tumor, Recurrent,Cancer of the Brain,Intracranial Neoplasms,Malignant Neoplasms, Brain,Malignant Primary Brain Neoplasms,Neoplasms, Brain,Neoplasms, Brain, Benign,Neoplasms, Brain, Malignant,Neoplasms, Brain, Primary,Primary Brain Neoplasms,Primary Malignant Brain Neoplasms,Primary Malignant Brain Tumors,Benign Brain Neoplasm,Benign Brain Neoplasms,Benign Neoplasm, Brain,Brain Benign Neoplasm,Brain Benign Neoplasms,Brain Cancers,Brain Malignant Neoplasm,Brain Malignant Neoplasms,Brain Metastase,Brain Neoplasm,Brain Neoplasm, Benign,Brain Neoplasm, Malignant,Brain Neoplasms, Primary,Brain Tumor,Brain Tumors, Recurrent,Cancer, Brain,Intracranial Neoplasm,Malignant Brain Neoplasm,Malignant Brain Neoplasms,Malignant Neoplasm, Brain,Neoplasm, Brain,Neoplasm, Intracranial,Primary Brain Neoplasm,Primary Brain Tumor,Primary Brain Tumors,Recurrent Brain Tumor,Recurrent Brain Tumors,Tumor, Brain
D002455	Cell Division	The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.	M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D004273	DNA, Neoplasm	DNA present in neoplastic tissue.	Neoplasm DNA
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004999	Amifostine	A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia.	Ethiofos,Gammaphos,APAETP,Amifostine Anhydrous,Amifostine Disodium Salt,Amifostine Monohydrate,Amifostine Monohydrochloride,Amifostine Trihydrate,Aminopropyl Aminoethylthiophosphate,Aminopropylaminoethylthiophosphate,Aminopropylaminoethylthiophosphoric Acid,Ethanethiol, 2-((3-aminopropyl)amino)-, dihydrogen phosphate (ester), trihydrate,Ethiofos Anhydrous,Ethyol,NSC-296961,S-(N-(3-Aminopropyl)-2-aminoethyl)thiophosphoric Acid,WR-2721,YM-08310,NSC 296961,NSC296961,WR 2721,WR2721,YM 08310,YM08310