Page 197 - Vitamin D and Cancer
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184                                                  S.A. Mazzilli et al.

            with 1,25(OH) D  post UV-B exposure only. The treatment of 1,25(OH) D  pre and
                        2  3                                         2  3
            post UV-B exposure appeared to reduce the amount of DNA damage as measured
            by the number of cyclobutane pyrimidine dimers (CPDs) formed. Further examina-
            tion into the efficacy of vitamin D as a preventive agent is required, however the
            current  study  begins  to  shed  a  positive  light  for  a  preventive  mechanism  for
            melanoma.
              Retinoblastoma is common in children that has relatively high cure rates [32].
            However, although treatments are successful they are often destructive and may
            cause visual impairment, thus finding methods to prevent progression may reduce
            the impairments associated with treatment. A study by Albert et al. examines the
            potential for the use of 1,25(OH) D  in the prevention of retinoblastoma in a trans-
                                      2  3
            genic  mouse  model  of  retinoblastoma  [33].  The  retinoblastoma  transgenic  mice
            express SV40 T antigen in the retina, which inactivates the p 105  protein resulting
                                                               Rb
            in the formation of ocular tumors beginning at 14 weeks of age [34]. 8–10 week old
            mice were treated with either 0.05 mg or 0.025 mg of 1,25(OH) D  five times a
                                                                 2  3
            week for 5 weeks then sacrificed at 5 months age. In mice treated with high dose
            1,25(OH) D , 20% had no evidence of disease while the remaining had organ con-
                   2  3
            fined disease. In the mice treated with low dose 1,25(OH) D , 13% had no evidence
                                                          2  3
            of disease. In contrast, all untreated mice formed bilateral disease that involved
            large invading tumors. This model clearly demonstrates that 1,25(OH) D  inhibits
                                                                     2  3
            the growth and local extension of retinoblastoma, suggesting a potential preventive
            role for vitamin D for retinoblastoma.



            8.2.6   Summary


            Overall  the  preclinical  studies  support  a  chemopreventive  role  for  vitamin  D  in
            cancer. More studies are needed to understand the impact of vitamin D deficiency
            on  cancer  initiation  and  progression.  Likewise,  more  information  is  needed  to
            define sufficient levels of vitamin D necessary to achieve an anticancer benefit as
            well as defining the optimal levels for achieving the greatest anticancer benefit.
            A greater understanding of the molecular mechanism by which vitamin D exerts its
            chemopreventive effects and defining the molecular phenotype of the target cells
            that respond to vitamin chemoprevention therapy will enhance our ability to effec-
            tively utilize vitamin D and its analogs to reduce the incidence and impact of can-
            cers in the clinic.



            8.3   Clinical Prevention Trials


            While the epidemiology of vitamin D status has been associated with lower cancer
            rates, supported by preclinical research, there have been only a few clinical preven-
            tion trials in humans that appear in the literature. These trials are included in the
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