scholarly journals Genetic prodrug activation therapy (GPAT) in two rat prostate models generates an immune bystander effect and can be monitored by magnetic resonance techniques

Gene Therapy ◽  
2001 ◽  
Vol 8 (7) ◽  
pp. 557-567 ◽  
Author(s):  
J D Eaton ◽  
M J A Perry ◽  
S M Todryk ◽  
R A Mazucco ◽  
R S Kirby ◽  
...  

Author(s):  
Rakhi Dhankhar ◽  
Anubhuti Kawatra ◽  
Aparajita Mohanty ◽  
Pooja Gulati

Abstract:: Enzyme prodrug therapy has gained momentum in the recent years due to their ability to improve therapeutic index (benefits versus toxic side-effects) and efficacy of chemotherapy in cancer treatment. Inactive prodrugs used in this system are converted into active anti-cancerous drugs by enzymes, specifically within the tumor cells. This therapy involves three components namely prodrug, enzyme and gene delivery vector. Past reports have clearly indicated that the choice of enzyme used, is the major determinant for the success of this therapy. Generally, enzymes from non-human sources are employed to avoid off-target toxicity. Exogenous enzymes also give a better control to the clinician regarding the calibration of treatment by site-specific initiation. Amongst these exo-enzymes, microbial enzymes are preferred due to their high productivity, stability and ease of manipulation. The present review focuses on the commonly used microbial enzymes particularly cytosine deaminase, nitroreductase, carboxypeptidase, purine nucleoside phosphorylase in prodrug activation therapy. Various aspects viz. source of the enzymes, types of cancer targeted, mode of action and efficacy of the enzyme/prodrug system, efficient vectors used and recent research developments of each of these enzymes are comprehensively elaborated. Further, the results of the clinical trials and various strategies to improve their clinical applicability are also discussed.



2000 ◽  
Vol 3 (S1) ◽  
pp. S10-S10
Author(s):  
JD Eaton ◽  
IA Clarke ◽  
H Pandha ◽  
AG Dalgleish ◽  
RS Kirby


1999 ◽  
Vol 880 (1 CELL AND MOLE) ◽  
pp. 319-325 ◽  
Author(s):  
A. S. RIGG ◽  
N. R. LEMOINE




1998 ◽  
Vol 23 (3) ◽  
pp. 279
Author(s):  
L.-A. Martin ◽  
H.S. Pandha ◽  
K. Sikora


2010 ◽  
Vol 4 ◽  
pp. MRI.S6028 ◽  
Author(s):  
Katarina Stenman ◽  
Izabella Surowiec ◽  
Henrik Antti ◽  
Katrine Riklund ◽  
Pär Stattin ◽  
...  

The use of magnetic resonance spectroscopy (MRS) for the detection of in-vivo metabolic perturbations is increasing in popularity in Prostate Cancer (PCa) research on both humans and rodent models. However, there are distinct metabolic differences between species and prostate areas; a fact making general conclusions about PCa difficult. Here, we use High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HRMAS NMR) spectroscopy to provide tissue specific identification of metabolites and their relative ratios; information useful in providing insight into the biochemical pathways of the prostate. As our NMR-based approach reveals, human and rat prostate tissues have different metabolic signatures as reflected in numerous key metabolites, including citrate and choline compounds, but also aspartate, lysine, taurine, glutamate, glutamine, creatine and inositol. In general, distribution of these metabolites is not only highly dependent on the species (human versus rat), but also on the location (lobe/zone) in the prostate tissue and the sample pathology; an observation making HRMAS NMR of intact tissue samples a promising method for extracting differences and common features in various experimental prostate cancer models.



The Lancet ◽  
1997 ◽  
Vol 350 (9094) ◽  
pp. 1793-1794 ◽  
Author(s):  
LA Martin ◽  
R Vile ◽  
NR Lemoine ◽  
K Sikora ◽  
HS Pandha


1997 ◽  
Vol 3 (8) ◽  
pp. 359-366 ◽  
Author(s):  
Anne Rigg ◽  
Karol Sikora


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