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2011HigginsJAPhD.pdf (3.69 MB)

The Impact of Chemoprevention on Treatment Regimens for Non-Muscle Invasive Bladder Cancer

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posted on 2011-07-15, 13:20 authored by Jennifer Ann Higgins
Chemoprevention is becoming a highly promising approach to lowering the incidence of cancers. There is, however, insufficient data to determine whether these agents are safe to be used alongside established treatment regimens such as chemotherapy. Non-muscle invasive bladder cancer is readily treatable with surgery (TURBT), yet there is a high rate of recurrence (~60%), 20-30% of patients recurring with the muscle invasive form of the disease, making it a good candidate for chemopreventive intervention. Anthocyanins are one example of dietary compounds currently under investigation as chemopreventive agents. They have been found excreted in the urine of mice at levels capable of causing 50% growth inhibition in cancer cell lines, making them potential bladder cancer chemopreventive agents. Mirtoselect, a standardised bilberry extract containing a mixture of 15 different anthocyanins, was investigated in vitro as a potential chemopreventive agent for bladder cancer alongside chemotherapeutic agent mitomycin C (MMC). Mirtoselect itself was found to inhibit cell survival and growth, causing significant a decrease in clonogenic cell survival, as well as causing an increase in apoptosis in two of the bladder cancer cell lines investigated. In combined studies mirtoselect pre-treatment did not inhibit the effects of MMC in measures of growth, cell survival, apoptosis, cell cycle distribution or DNA damage. In fact, there was a mirtoselect dependent increase in MMC-induced crosslinks, an enhancement of MMCs anti-proliferative effects at low concentrations of mirtoselect and in some instances apoptosis was greater than additive. Furthermore mirtoselect was shown to enhance the DNA damaging effects of radiation. Mirtoselect itself appears to be a good chemopreventive candidate for non-muscle invasive bladder cancer. In combination it does not appear to interfere with the cytotoxic actions of MMC, potentially enhancing its effects, and could also provide a therapeutic advantage in radiotherapy, therefore warranting further investigation for use in clinic.

History

Supervisor(s)

Jones, George; Brown, Karen

Date of award

2011-05-01

Awarding institution

University of Leicester

Qualification level

  • Doctoral

Qualification name

  • PhD

Language

en

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