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highly contrasted scintigraphic imaging of SRC in vivo.
Quantitative analysis of scintigraphic scans evidenced a
significant decrease in tracer uptake in treated animals
compared to controls at day 17 (p<0.02). This decrease was
still maintained at day 30. We posit that changes in 99mTc-
NTP 15–5 uptake reflect a decrease in the PG content of
tumour tissue as a result of a cytotoxic effect of Mel-AQ.
The decrease in PG content of Mel-AQ-treated tumours
was confirmed by biochemical assay of tumour tissue and
Alcian blue staining of histological SRC slices. These
results suggest that Mel-AQ treatment could trigger the
“downregulation synthesis” of PG in chondrosarcoma
tissue in vivo, as already described for other chemotherapy
approaches [27].
Conclusion
Cartilage tumours continue to present orthopaedic oncolo-
gists with therapeutic challenges. Malignant cartilaginous
tumours are generally unresponsive to chemotherapy, with
the result that the 5-year survival rate of high-grade
chondrosarcoma is only 29% [5]. Based on its high binding
capacity to proteoglycans, quaternary ammonium conjugat-
ed with melphalan alkylating agent was synthesized, and its
potential antitumour activity in chondrosarcoma was tested
and characterized in vitro and in vivo. The differential in
vitro antitumour activity (tumour chondrocytes versus
normal chondrocytes) of Mel-AQ, its ability to inhibit
tumour cell growth in vivo, and its good tolerance in
animals make Mel-AQ a promising candidate for further
work to develop an urgently needed efficacious treatment of
chondrosarcoma.
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Chaplin DJ, Double JA, Everitt J, Farningham DA, Glennie MJ,
Kelland LR, Robinson V, Stratford IJ, Tozer GM, Watson S,
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of animals in cancer research. Br J Cancer 102:1555–1577
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Gouin F (2002) Bone remodelling and tumour grade modifica-
tions induced by interactions between bone and swarm rat
chondrosarcoma. Histol Histopathol 17:1103–1111
Financial support Institut National du Cancer (NoRO7022NN),
Ligue Contre le Cancer Auvergne Région, Innovation Regional Fund
(FRI2, OSEO), State-Region Planning Contract (CPER)
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