Objective To examine mitomycin-C (MMC)-induced apoptosis in an ex vivo mode
l of superficial TCC, and relate it to the in vivo response to chemotherapy
.
Materials and methods Dose- and time-response curves were constructed to de
termine the optimal conditions for the induction of apoptosis by MMC in an
ex vivo model of superficial bladder cancer. Subsequently, 41 individual tu
mours were exposed to MMC in the model and the effects assessed by measurin
g of apoptosis before and after chemotherapy. The relationships between tum
our grade and stage and the intrinsic and induced apoptotic counts were det
ermined. In tandem, in a clinical study, the relationship between in vivo r
esponse of a marker tumour to MMC and the ex vivo induction of apoptosis wa
s determined.
Results In the ex vivo model, apoptosis was induced at a MMC concentration
of 0.5 mg/mL after an incubation time of 8 h. In 41 tumours the intrinsic a
poptotic index (AI) was higher with increased grade and stage of tumour (P
= 0.048). There was no correlation between the intrinsic AI and the AI afte
r treatment with MMC (induced AI). In 21 tumours (51%) the induced AI did n
ot increase above a predetermined response threshold and these tumours were
considered resistant to MMC. Resistance to MMC was related to tumour grade
(P = 0.037) with a trend for G3 pT1 tumours to be resistant to the therapy
. There was a significant association between ex vivo sensitivity and in vi
vo marker tumour response (P = 0.02).
Conclusions Apoptosis is differentially induced in an ex vivo incubation mo
del of superficial TCC by MMC and evidence suggests that this response matc
hes that seen in vivo. The measurement of apoptosis before therapy does not
predict the apoptotic response of a tumour to chemotherapy. The ability to
undergo apoptosis correlates with clinical outcome.