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Published on: July 30, 2018
Studies on in vivo gene transfer in pituitary tumors using herpes-derived and adenoviral vectors
Néstor G Carri1, Yolanda E Sosa, Oscar A Brown
1Multidisciplinary Institute of Cell Biology, La Plata, Argentina.
Abstract:
Suicide gene therapy has met limited success for the treatment of rat pituitary tumors. In order to determine the cause of primary pituitary tumor resistance to suicide gene therapy, we studied the transgene expression of an adenoviral (Ad.RSV.beta gal.nls) and a herpes simplex virus-derived (tsK/beta-gal) vector, both harboring the beta-galactosidase reporter gene in rat prolactinomas. Rats carrying experimental prolactinomas received bilateral 1 microl intrapituitary injections of either saline (saline group), 5 x 10(5) plaque-forming units (pfu) tsK/beta-gal (HSV Group) or 5 x 10(5) pfu Ad.RSV.beta gal.nls (RAd Group). Two or seven days later the tumors were examined. Macroscopic inspection of glands injected with either vector showed that the tissue expressing beta-gal was concentrated at the ventral area around the site reached by the tip of the needle. Almost no transgene expression was observed in other sites. Cellularity and lactotrophic cell density was not affected by saline or virus injection. In the injected areas, apoptotic levels were (x +/-S.E.M.): 9.3+/-0.5, 22.1+/-1.1 and 31.7+/-1.4%, for the saline, RAd and HSV groups, respectively. Serum prolactin and growth hormone levels were not affected by virus injection. We conclude that the low diffusibility of viral suspensions in the pituitary tissue may constitute a significant obstacle for achieving full remission of in situ pituitary tumors in rats.
Insights
Limited success in suicide gene therapy for rat pituitary tumors is due to poor viral vector diffusion. This study investigated transgene expression and apoptosis in rat prolactinomas after viral vector injection.
Area of Science:
- Oncology
- Gene Therapy
- Endocrinology
Background:
- Suicide gene therapy shows limited efficacy for pituitary tumors.
- Understanding resistance mechanisms is crucial for improving treatment outcomes.
Purpose of the Study:
- To investigate the cause of primary pituitary tumor resistance to suicide gene therapy.
- To evaluate transgene expression and apoptosis following viral vector delivery in rat prolactinomas.
Main Methods:
- Adenoviral (Ad.RSV.beta gal.nls) and herpes simplex virus-derived (tsK/beta-gal) vectors expressing beta-galactosidase were used.
- Vectors were injected into rat prolactinomas, with saline as a control.
- Transgene expression, cellularity, lactotrophic cell density, and apoptosis were assessed.
Main Results:
- Beta-galactosidase expression was localized to the injection site, with poor diffusion throughout the pituitary tumor.
- Apoptotic levels increased significantly in vector-injected groups compared to saline.
- Serum prolactin and growth hormone levels remained unaffected by the injections.
Conclusions:
- Limited diffusion of viral suspensions within pituitary tissue is a major obstacle for effective suicide gene therapy in pituitary tumors.
- Further strategies are needed to enhance vector distribution for successful in situ tumor treatment.
