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Ribozyme-Mediated Reversal of Human Pancreatic Carcinoma Phenotype

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Bone Marrow Transplantation

Summary

Point mutations in the ras gene have been found in approximately 90% of human pancreatic carcinomas. These alterations can be used as potential targets for specific ribozyme-mediated reversal of the malignant phenotype. We have evaluated the efficacy of a hammerhead ribozyme directed against codon 12 (GUU) of the activated K-ras gene in a Capan-1 human pancreatic carcinoma cell line using different delivery systems. Our results have demonstrated that the anti-Kras ribozyme cloned into the pHß plasmid was able to efficiently suppress K-ras gene expression and to inhibit the proliferation of transfected Capan-1 cells. In contrast, the anti-K-ras ribozyme was less efficient against the Capan-1 cells when cloned into a pLNCX retroviral plasmid. In addition, our results showed that adenoviral-mediated expression of the ribozyme RNA was more effective than the two other plasmid vectors. Our studies have characterized different viral and non-viral delivery systems for the therapeutic application of an anti-K-ras ribozyme against a human pancreatic carcinoma cell line. In the near future, ribozymes could emerge as important therapeutic agents against human malignancies, and optimal delivery systems are necessary to achieve maximal gene therapy benefit.

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Authors and Affiliations

  1. Section of Biochemical Pharmacology, Department of Medical Oncology, City of Hope National Medical Center, Montana Building,1500 East Duarte Road, Duarte, California, 91010, USA

    Hiroshi Kijima, David Y. Bouffard & Kevin J. Scanlon

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  1. Hiroshi Kijima
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  2. David Y. Bouffard
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  3. Kevin J. Scanlon
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Editor information

Editors and Affiliations

  1. First Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570, Japan

    Susumu Ikehara M.D., Ph.D. (Professor) (Professor)

  2. International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162, Japan

    Fumimaro Takaku M.D., Ph.D. (President) (President)

  3. Department of Pediatrics, All Children’s Hospital, University of South Florida, 801 Sixth Street South, Box 753, St. Petersburg, FL, 33701, USA

    Robert A. Good M.D., Ph.D., D.Sc., FACP (Distinguished Research Professor, University of South Florida, Head of Allergy and Clinical Immunology) (Distinguished Research Professor, University of South Florida, Head of Allergy and Clinical Immunology)

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© 1996 Springer-Verlag Tokyo

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Kijima, H., Bouffard, D.Y., Scanlon, K.J. (1996). Ribozyme-Mediated Reversal of Human Pancreatic Carcinoma Phenotype. In: Ikehara, S., Takaku, F., Good, R.A. (eds) Bone Marrow Transplantation. Springer, Tokyo. https://doi.org/10.1007/978-4-431-68320-9_20

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  • DOI: https://doi.org/10.1007/978-4-431-68320-9_20

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-68322-3

  • Online ISBN: 978-4-431-68320-9

  • eBook Packages: Springer Book Archive

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