MacCullum Cancer Institute, Melbourne. In vivo experiments
were conducted by Ms F. Brook at ICP Firefly Pty Ltd.,
Sydney. Special thanks to Dr A. Bonin for his valuable
comments.
Notes and references
z Acute intraperitoneal toxicity is an adverse non-specific effect that
occurs in an animal within a short time after being injected with a
single dose of the drug (these effects are continually observed over a
defined period).
y Repeated intraperitoneal toxicity is an undesirable non-specific effect
that is observed in an animal within a short time frame after being
injected with several repeated doses of the drug over a defined period
(usually one to two weeks).
z A rough coat (generally considered a clinical sign of toxicity)
indicates that these mice were unwell and may have died within a
few days after this observation.
Fig. 3 Mean PC3 tumour volumes in Swiss SPF nude mice (Study 3)
treated with PHENSS (Group 1), CDDP (Group 2) and saline
(Group 3) (no. mice per group = 6).
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Table 2 Mean PC3 tumour weights in SPF Swiss nude mice (Study 3)
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3 P. J. O’Dwyer, J. P. Stevenson and S. W. Johnson, Clinical Status
of Cisplatin, Carboplatin, and Other Platinum-based Antitumour
Drugs, in Cisplatin. Chemistry and Biochemistry of a Leading
Anticancer Drug, ed. B. Lippert, Verlag Helvetica Chimica Acta,
Zurich, 1999, pp. 31–69.
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Mean tumour
No. of mice weight (ꢁ SD) (mg)
Group Test compound
1
2
3
PHENSS (16 mg kgꢃ1
)
6
29 ꢁ 14
26 ꢁ 7.0
44 ꢁ 24
CDDP (8 mg kgꢃ1
Saline
)
3 (3 died)
6
statistically significant due to wide variations in the tumour
volumes calculated (Fig. 3), although lower mean tumour
weights were observed for both the PHENSS and CDDP
treated groups when compared to the saline control Group 3
(35–40% decrease was observed). This trend in tumour weight
may also have some degree of biological significance.
Under the conditions of Study 3, PHENSS did not produce
obvious signs of toxicity in female SPF nude mice bearing the
PC3 tumour cell xenografts. Although treatment with
PHENSS did not significantly retard tumour growth over
the 20 day study period, a trend was observed in Group 1
with mice having lower tumour volumes and tumour weights
than the saline treated animals (Group 3). Study 3 was
terminated on day 20 due to the deaths of three mice in the
CDDP treated group (Group 2).
12 J. Reedijk, Proc. Natl. Acad. Sci. U. S. A., 2003, 100, 3611.
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The results of Study 3 suggest that the efficacy of PHENSS
should be further explored to determine if this compound can
produce a statistically significant antitumour effect (i.e., P o 0.05).
Small sample sizes used in Study 3 (n = 6) are likely to account
for large deviations in the measurements of body weights,
tumour weights and volumes, etc., thus having a large impact
on the variance of the data. An additional study over a longer
observation period (e.g. 50 days, or until a significant loss in
body weight is observed) with increased sample sizes and using
a lower treatment dose of CDDP (o8 mg kgꢃ1) may provide
a more accurate evaluation of the efficacy of PHENSS.
Further in vivo evaluation of PHENSS has been scheduled
for the near future.
Financial support from the Henry Bertie and Florence
Mabel Gritton Research Scholarship (USyd), Business Liason
Office (USyd), the UWS Research Grant and UWS Innova-
tion and Consulting is gratefully acknowledged. In vitro
experiments were conducted by Dr C. Cullinane of the Peter
27 N. Uchida, Y. Takeda, K. Hojo, R. Maekawa, K. Sugita and
T. Yoshioka, Eur. J. Cancer, 1998, 34, 1796.
ꢂc
This journal is The Royal Society of Chemistry 2008
Chem. Commun., 2008, 5613–5615 | 5615