Prerequisites for effective adenovirus mediated gene therapy of colorectal liver metastases in the rat using an intracellular neutralizing antibody fragment to p21-Ras
| Autor: | M R de Vries, B. van Etten, A. M. M. Eggermont, Timo L.M. ten Hagen, T Huet, G Ambagtsheer |
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| Přispěvatelé: | Surgery |
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty animal structures Genetic enhancement ras oncogene Biology In Vitro Techniques Antibodies Metastasis Viral vector Adenoviridae Proto-Oncogene Proteins p21(ras) Hepatic Artery In vivo medicine Tumor Cells Cultured Animals Experimental Therapeutics Infusions Parenteral Neoplasm Metastasis Neutralizing antibody Infusions Intravenous Oncogene isolated liver perfusion Liver Neoplasms Cancer Transfection adenovirus Genetic Therapy medicine.disease gene therapy hepatic artery infusion Rats Perfusion Oncology Colonic Neoplasms Cancer research biology.protein liver metastases |
| Zdroj: | British Journal of Cancer British Journal of Cancer, 86(3), 436-442. Nature Publishing Group |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | 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. British Journal of Cancer (2002) 86, 436–442. DOI: 10.1038/sj/bjc/6600089 www.bjcancer.com © 2002 The Cancer Research Campaign |
| Databáze: | OpenAIRE |
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