zinostatin and Pheochromocytoma

A 48-year-old woman developed hepatic metastases from malignant pheochromocytoma resected 8 years previously. Angiography revealed multiple tumor stains in the liver. Transcatheter oily chemoembolization using styrenomaleic acid neocarzinostatin and iodized oil was performed. The patient complained of severe right upper quadrant pain immediately following the transcatheter oily chemoembolization. Necrotizing cholecystitis developed on the 4th day post-transcatheter oily chemoembolization, hepatic infarction on the 12th day, and a biloma on the 19th day. Despite the administration of antibiotics and percutaneous transhepatic drainage, neither the volume of drainage nor the size of the biloma decreased. Biliary reconstruction was performed using a metallic stent, which decreased the size of the biloma.

Topics: Adrenal Gland Neoplasms; Adrenalectomy; Angiography; Antibiotics, Antineoplastic; Bile Duct Diseases; Bile Ducts, Intrahepatic; Chemoembolization, Therapeutic; Drug Combinations; Female; Follow-Up Studies; Humans; Iodized Oil; Liver Abscess; Liver Neoplasms; Magnetic Resonance Imaging; Middle Aged; Pheochromocytoma; Zinostatin

Bcl-2 overexpression has been shown to be protective against apoptosis induced by a variety of mechanistically diverse chemotherapeutic drugs. Recently, oxygen radical species have been implicated in the process of apoptosis, and Bcl-2 has been proposed to exert its protective effect by altering the redox state of the cell. Unlike most other chemotherapeutic agents, naturally occurring enediynes are rendered more cytotoxic in the presence of a higher reducing potential, because as prodrugs, they require reduction for activation. We demonstrate herein that induction of Bcl-2 expression in PC12 cells potentiates the induction of apoptosis and differentiation by the enediyne neocarzinostatin. In contradistinction, Bcl-2 abrogates the induction of apoptosis and differentiation by the autoactivating enediyne, enediyne-5, and the non-enediyne chemotherapeutic agent, cisplatin. We further demonstrate that enediyne potentiation by Bcl-2 is related to an increase in cellular glutathione. The present studies suggest that enediynes that require reductive activation might be critically useful agents in the therapy of tumors such as neuroblastomas and estrogen-responsive breast cancers, the resistance of which is related to up-regulation of Bcl-2.

Topics: Adrenal Gland Neoplasms; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Apoptosis; Buthionine Sulfoximine; Cell Differentiation; Cells, Cultured; Cisplatin; Methionine Sulfoximine; Neoplasm Proteins; Oxidation-Reduction; Pheochromocytoma; Prodrugs; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Rats; Transfection; Zinostatin