Continuous or bolus chemotherapy with 5-fluoro-2?-deoxyuridine in transplanted experimental liver tumors?

Riemenschneider, Th.; Ruf, C.; Späth, G; Stuhldreier, G.; Elmouaouy, A

doi:10.1007/bf00391496

Cited by 5 publications

(1 citation statement)

References 18 publications

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“…Repetitive locoregional administration of drugs can be achieved by regional infusions via the hepatic artery (Riemenschneider et al, 1988;Miyazaki et al, 1993;Kemeny et al, 1994). Thus repeated delivery of adenoviral vectors via the hepatic artery may further increase the efficacy of transfection.…”

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Prerequisites for effective adenovirus mediated gene therapy of colorectal liver metastases in the rat using an intracellular neutralizing antibody fragment to p21-Ras

et al. 2002

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Ras mutations are present in 40 -50% of colorectal cancers. Inactivating this oncogene may therefore reduce proliferation capacity. In order to target ras we studied the transduction efficacy and anti tumour activity of an adenoviral vector expressing an intracellular, neutralizing single chain antibody to p21-ras (Y28). In in vitro studies transfection levels of the K-ras mutated rat colon carcinoma cell line CC531 were studied using the LacZ marker gene. In our in vivo liver metastases model different routes of administration were evaluated to determine which regimen resulted in the best transfection levels and tumour responses: intravenous injection, intratumoural injection, isolated liver perfusion, or hepatic artery infusion. CC531 cells are readily transfected in vitro, resulting in significant inhibition of tumour cell proliferation by the Y28 construct. Intravenous injection did not result in any measurable transfection. Intratumoural injection resulted only in the transfection of tumour cells along the needle track. IHP as well as single HAI achieved low transfection levels of tumour tissue. Expression of Y28 was demonstrated in tumours after IT injection, HAI and IHP. Whereas, repeated HAI's clearly achieved expression in and around tumour associated vessels. Only five times repeated HAI's with Y28 resulted in a tumour response: in all animals tumour growth was inhibited, and in three rats out of eight a complete regression of the liver tumours was observed.

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Prerequisites for effective adenovirus mediated gene therapy of colorectal liver metastases in the rat using an intracellular neutralizing antibody fragment to p21-Ras

et al. 2002

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The Rationale of Intraarterial Chemotherapy of Liver Cancer

Schlag

Hohenberger

1989

Drug Delivery in Cancer Treatment II

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Arterial, portal or combined arterio-portal regional chemotherapy in experimental liver tumours?

Riemenschneider

Ruf

Kratzsch

et al. 1992

J Cancer Res Clin Oncol

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The most appropriate route for regional administration of chemotherapeutic drugs to liver tumours was studied in a standardized rodent model: cells of Novikoff hepatoma were transplanted into the central liver lobe of Sprague-Dawley rats. From day 5 to day 12 after transplantation, the liver was continuously perfused with 420 mg/kg 5'-fluoro-2-deoxyuridine by subcutaneous osmotic micropumps via the hepatic artery (n = 20), the portal vein (n = 20) or both vessels together (n = 12). The tumour multiplication factor (TMF) and the vascularization of the tumour were evaluated. Arterial and combined infusion led to a highly significant reduction in TMF, but combined infusion was not more effective than arterial alone. Portal infusion had no significant effect. There was no correlation between vascularization and tumour response in arterial infusion, but a strong correlation in portal infusion. Thus chemotherapy via the portal route may be effective in selected tumours with considerable portal vascularisation.

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Continuous or bolus chemotherapy with 5-fluoro-2?-deoxyuridine in transplanted experimental liver tumors?

Cited by 5 publications

References 18 publications

Prerequisites for effective adenovirus mediated gene therapy of colorectal liver metastases in the rat using an intracellular neutralizing antibody fragment to p21-Ras

Prerequisites for effective adenovirus mediated gene therapy of colorectal liver metastases in the rat using an intracellular neutralizing antibody fragment to p21-Ras

The Rationale of Intraarterial Chemotherapy of Liver Cancer

Arterial, portal or combined arterio-portal regional chemotherapy in experimental liver tumours?

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