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Browsing by Subject "xenograft models"

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  • Nieminen, Jonna (2010)
    Prostate cancer is one of the most common cancers in the developed countries. Prostate cancer is slowly progressing cancer but can transform into aggressive disease and metastasize. Metastases are the major cause of mortality. Androgens play an important role in the pathogenesis of prostate cancer and prostate tumors are usually dependent on androgens. Thus the aim of the treatment is to eliminate testicular androgens by surgical or medical castration and/or block the effect of androgens on the prostate with antiandrogens. Prostate cancer and new therapies to treat the disease are being investigated vigorously. Numerous in vivo models of prostate cancer have been developed. Androgen responsive animal models mimic prostate cancer more closely. There are many animal species that may be used to model prostate cancer but mouse is no doubt the most useful. Tumor models can be created by inoculating human cancer cells or solid parts of tumors into immune deficient mice. Orthotopic prostate tumor models reflect the abnormal cancer cell-stroma interactions occuring in prostate cancer. Transgenic mouse models are becoming more and more common in the research of prostate cancer. Transgenic models are able to model the initiation and progression of the disease more realistically. Growth of the orthotopic tumor is difficult to monitor without measuring serum prostate specific antigen (PSA) concentrations or using specific imaging methods. Imaging techniques, such as optical imaging, are being utilized in different in vivo models of prostate cancer. The objective of the experimental part of this thesis was to optimize bioluminescence imaging method in androgen responsive cell line LNCaP-luc2 in orthotopic model of prostate cancer. Bioluminescence imaging is based on a reaction catalyzed by a luciferase which is expressed by the tumor cells. In the ATP-dependent reaction luciferase enzyme oxidizes its substrate, luciferin, and produces light. In addition, the purpose of this study was to examine the effects of medical therapy and castration on tumor growth. Bioluminescence imaging enabled noninvasive, real-time and longitudinal monitoring of the growth of prostate tumors in this model. Quantification of the tumors with bioluminescence measurement was faster than with ultrasound sonography. It was also possible to monitor the growth of the tumors more often with bioluminescence imaging than with PSA measurements. Bioluminescence imaging was found to correlate better with serum PSA concentrations than with the actual size of the tumor. However prostate tumor size was noted to correlate better with PSA concentrations than with bioluminescence imaging in this study. Medical treatment or castration was found to have no effect on the size of the tumors when measured with bioluminescence imaging. The larger size of the tumors than expected was the probable reason for this. Bioluminescence imaging is not suitable for large or necrotic tumors because this imaging method can only be applied in living cells. In addition, a successful luciferin injection is essential for the proper utilization of bioluminescence imaging in this model. More studies are needed to validate the model for example in proving the effects of the medical therapies.