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advocated and tested in experimental systems. Targeting of suppressor genes requires
their reactivation and gene or suppressor protein transfer. Gene transfer would be
accomplished incorporating the therapeutic genes into viral (bacteriophage) and
plasmid vectors. These can be delivered into the cells using nanotechnology. Virus
or plasmid vectors can be incorporated into nanocapsules. Attempts have also been
made to permeate the cell membrane with therapeutic proteins to allow the cell to
regain suppressor function. Again the therapeutic protein is subject to intracellular
degradation and also administration via enteric and injectable modes is impractical.
With both therapeutic gene and protein transfers a major problem would be achiev-
ing target specificity. So gene therapy obviously faces many strategic as well as tacti-
cal logistic problems to be effective in patient management.
Gene transfer studies relating to nm23 are not many. Transfer of a plasmid carry-
ing nm23-H1 by electroporation into T24 cells has been reported to reduce in vitro
cell motility and increased the sensitivity of the transfectants to cisplatin ( http://www.
medical-res-papers.com/urologic-surgery/5741 ) . A full description of this work is not
available for proper assessment. Nm23-H1 protein that can permeate the cell mem-
brane has been designed. Li et al. (2006) used an adenovirus vector to transfer nm23-
H1 into a high metastatic variant ovarian cancer cell line and found that this resulted
in a 60% reduction in the number of animals developing liver metastases when cells
carrying nm23-H1 were introduced intraperitoneally. They claimed a reduction in
metastatic deposition as estimated from the extent of involvement of liver tissue. The
reliability of this mode of determining extent of spread could not be evaluated in the
absence of adequate illustration. However, the host animals did survive considerably
longer with nm23-H1 than the controls. More recently poly-l-lysine-modified iron
oxide nanoparticles (IONP-PLL) have been used to transfer the gene into host cells.
Injection of transfected cells by the intravenous route reduced their lung colonisation
as well as enhanced host survival time when gene transfer was combined with cyclo-
phosphamide treatment (Li et al., 2009f). It is needless to say nm23-H1 does in fact
influence intercellular and substratum adhesion, so the observed effect on lung colo-
nisation does not necessarily reflect a true and proper diminution of the metastatic
process. Tumour cell lines into which the protein was introduced showed reduction in
the incidence of lung metastases, reduced pre-existing metastatic load and enhanced
survival of hosts carrying tumours (Lim et  al., 2011). These studies are laudable
per se , but it is a long shot to pre-clinical or clinical testing.
Upregulation of nm23 by Medroxyprogesterone Acetate
With the identification of such a broad spectrum of biological effects of nm23,
upregulating the expression of nm23 has to be considered as a viable therapeutic
option. As noted earlier, both oestrogen and progesterone regulate and influence the
expression nm23-H1 and nm23-H2. Progesterone upregulates the expression of nm-
23H2 (Syed et  al., 2005). MPA (medroxyprogesterone acetate) was suggested for
clinical testing for its ability to upregulate nm23 and inhibit metastatic dissemination
of murine tumour models (Palmieri et al., 2005, 2006). MPA might also inhibit cell
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