1. Int J Cancer. 2010 Jan 15;126(2):583-8.

Use of Xanthinol Nicotinate as a co-treatment for radio- and chemo-therapy in
experimental tumors.

Segers J, Crokart N, Danhier P, Grégoire V, Jordan BF, Gallez B.

Louvain Drug Research Institute, Université Catholique de Louvain, Brussels,
Belgium.

The tumor micro-environment plays a key role in the tumor resistance to cytotoxic
treatments. It has been demonstrated that it is possible to modulate the tumor
microenvironment to potentiate anti-cancer therapy. Here, we made the hypothesis 
that the vasoactive agent xanthinol nicotinate (XN) could be an important
modulator of the tumor perfusion and oxygenation. Using functional non invasive
techniques (in vivo EPR oximetry and dynamic contrast enhanced MRI), we were able
to define a time window in which tumor oxygenation, flow and permeability were
significantly increased in the TLT tumor model implanted in muscles of mice. As a
consequence of the alleviation of tumor hypoxia, we found out that XN was able to
radiosensitize the tumors when applying 10 Gy of X-Rays during the reoxygenation 
of the tumors (enhancement in radiation response of 1.4). Moreover, the
administration of cyclosphosphamide (50 mg/kg) used as a chemotherapeutic agent
was more efficient when applying the treatment after XN administration
(enhancement in response to chemotherapy of 2.7). These results show the
importance of the dynamic evolution of the tumor microenvironment on the response
to treatments, and that XN is an efficient modulator of the tumor hemodynamics
that may potentiate cytotoxic treatments.

PMID: 19585554 [PubMed - indexed for MEDLINE]