In vitro and in vivo studies on the action of BW502U83, an arylmethylaminopropanediol.
BW502U83, an arylmethylaminopropanediol (AMAP), showed to be partially cross-resistant in a P-glycoprotein-positive and in a P-glycoprotein-negative, doxorubicin-resistant cell line, while no cross-resistance was noticed in a cisplatin-resistant cell line. Interstrand cross-links were not observed, but BW502U83 induced extensive DNA strand breaks. In a feasibility study the effect of intra-arterially BW502U83 was tested. One patient with a hepatocellular carcinoma showed partial remission and signs of a tumor lysis syndrome, another patient with a hepatocellular carcinoma improved clinically. A patient with soft tissue sarcoma had stable disease. Transient increase in SGOT, SGPT and LDH were observed, but no systemic side effects.
van der Graaf
W T
WT
Division of Medical Oncology, University Hospital, Groningen, The Netherlands.
Zijlstra
J G
JG
de Vries
E G
EG
Nethersell
A B
AB
Mulder
N H
NH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000873:Anthracenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001692:Biological Transport; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects; D018432:Drug Resistance, Multiple; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007269:Injections, Intra-Arterial; D007364:Intercalating Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D010386:Pelvic Neoplasms / Q000188:drug therapy; D012509:Sarcoma / Q000188:drug therapy; D014407:Tumor Cells, Cultured / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000873:Anthracenes; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007364:Intercalating Agents; D009363:Neoplasm Proteins; C066521:502U83