Biomaterial Database

Vasopressin selectively increases 5-fluorouracil uptake by colorectal liver metastases following hepatic artery bolus infusion. 1998

D W Dietz, and S Casillas, and S C Jones, and J W Milsom

Department of General Surgery, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio, 44195, USA.

BACKGROUND Poor drug uptake secondary to the hypovascularity of colorectal liver metastases may partially explain their limited response to hepatic artery chemotherapy. Vasoconstrictors can increase tumor perfusion but their effect on drug uptake has not been well-characterized. The aim of this study was to determine whether vasopressin could selectively increase tumor uptake of 5-FU. METHODS A syngeneic rat model of colorectal liver metastases was used. Control group rats underwent a 60-s hepatic artery infusion of 14C-5-FU (30 mCi/150 microL). Treatment group rats had vasopressin (60 mIU/kg, dose determined in pilot study) added to the 14C-5-FU infusion. Mean systemic arterial pressure was minimally affected. Tumor:liver (T/L UR) and tumor center:periphery (C/P UR) 5-FU uptake ratios were determined using quantitative autoradiography techniques. Differences in tumor size (< or > 4 mm) and location (superficial vs deep) were accounted for. Statistical analysis was by repeated measures ANOVA (P = 0.01 significant). RESULTS A total of 161 tumors in 18 rats was analyzed. T/L URs were significantly higher in the treatment group compared to controls for tumors <4 mm (1.72 +/- 0.14 vs 0.70 +/- 0.16, P <0.001), tumors >4 mm (0.99 +/- 0.15 vs 0.45 +/- 0.16, P = 0.01), deep tumors (1.17 +/- 0.13 vs 0.68 +/- 0.15, P = 0.01), and superficial tumors (1.54 +/- 0. 15 vs 0.47 +/- 0.17, P <0.001). C/P URs did not differ significantly between the groups. CONCLUSIONS The results of this study show that vasopressin selectively enhances the uptake of 5-FU by colorectal liver metastases in a rat model of hepatic artery infusion. This may represent a promising strategy for improving tumor response rates and patient survival.

UI	MeSH Term	Description	Entries
D007269	Injections, Intra-Arterial	Delivery of drugs into an artery.	Injections, Intraarterial,Intra-Arterial Injections,Intraarterial Injections,Injection, Intra-Arterial,Injection, Intraarterial,Injections, Intra Arterial,Intra Arterial Injections,Intra-Arterial Injection,Intraarterial Injection
D008113	Liver Neoplasms	Tumors or cancer of the LIVER.	Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D008297	Male		Males
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
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
D005472	Fluorouracil	A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.	5-FU,5-FU Lederle,5-FU Medac,5-Fluorouracil,5-Fluorouracil-Biosyn,5-HU Hexal,5FU,Adrucil,Carac,Efudex,Efudix,Fluoro-Uracile ICN,Fluoroplex,Fluorouracil Mononitrate,Fluorouracil Monopotassium Salt,Fluorouracil Monosodium Salt,Fluorouracil Potassium Salt,Fluorouracil-GRY,Fluorouracile Dakota,Fluorouracilo Ferrer Far,Fluoruracil,Fluracedyl,Flurodex,Haemato-FU,Neofluor,Onkofluor,Ribofluor,5 FU Lederle,5 FU Medac,5 Fluorouracil,5 Fluorouracil Biosyn,5 HU Hexal,Dakota, Fluorouracile,Fluoro Uracile ICN,Fluorouracil GRY,Haemato FU
D006499	Hepatic Artery	A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum.	Arteries, Hepatic,Artery, Hepatic,Hepatic Arteries
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000964	Antimetabolites, Antineoplastic	Antimetabolites that are useful in cancer chemotherapy.	Antineoplastic Antimetabolites
D014662	Vasoconstrictor Agents	Drugs used to cause constriction of the blood vessels.	Vasoactive Agonist,Vasoactive Agonists,Vasoconstrictor,Vasoconstrictor Agent,Vasoconstrictor Drug,Vasopressor Agent,Vasopressor Agents,Vasoconstrictor Drugs,Vasoconstrictors,Agent, Vasoconstrictor,Agent, Vasopressor,Agents, Vasoconstrictor,Agents, Vasopressor,Agonist, Vasoactive,Agonists, Vasoactive,Drug, Vasoconstrictor,Drugs, Vasoconstrictor