Page 56 - 2014 Printable Abstract Book
P. 56
(S1101) Gold nanoparticles as radiosensitizers. Sunil Krishnan, MD Anderson Cancer Center, Houston, TX
An evolving body of recent literature alludes to the potential to sensitize tumors to radiation
therapy using metallic nanoparticles. In preclinical studies, the techniques that hold promise for eventual
clinical deployment are nanoparticle-assisted radiation dose enhancement and hyperthermic
radiosensitization. To understand the underlying nanoparticle-radiation interactions, computational
techniques offer an explanation for and predict the biophysical consequences at a nano-/meso-scopic
scale. Nonetheless, there are persisting gaps in knowledge relating to the molecular mechanism of action
of these radiosensitization approaches - some of these issues will be addressed. Since the literature
relating to the diverse disciplines involved in these efforts spans across multiple specialties (clinical
radiation oncology, radiation physics, radiation biology, nanotechnology, material science, biomedical
engineering, pharmacology, chemistry, and tumor biology) and numerous specialty journals, there is no
single compilation of extant research in this arena or forum for merging analogous concepts and
paradigms. This symposium will provide such a venue - my presentation will start with familiarizing the
audience with the potential applications of metallic nanoparticles in radiation therapy using specific
illustrative examples and begin to explore ways to understand the underlying mechanisms of the effects
observed.
(S1102) Focussed Ultrasound in Radiosensitization. Gregory Czarnota, Sunnybrook Health Sciences
Centre, Toronto, Canada
We have been investigating tested the hypothesis that microbubble agents in vivo may be used
apriori to cause endothelial cell perturbations thus causing "radiosensitization" of tumours. This research
has now been conducted in multiple murine and human tumour lines including bladder, breast,
fibrosarcoma and prostate cancer lines. We have also focussed investigations on potential mechanisms
which may account for interactions between the two forms of energy. Data have indicated synergistic
increases in tumour cell kill due to vascular disruption caused by the combined therapies that increased
when microbubbles were used in conjunction with radiation with increases of cell kill from 5% to over
50% with combined single treatments. Longitudinal experiments with multiple treatments have indicated
better therapeutic outcome with compared to single modality treatments. Immunohistochemistry has
indicated endothelial cell apoptosis and activation of the ceramide cell-death pathway to be caused by
microbubbles. Protecting the vasculature with bFGF or inhibiting the ceramide pathway chemically has
led to protective effects negating the effects of ultrasound-stimulated microbubbles. In addition,
experiments with genetically modified mice (Asmase -/-) compared to wild-type counterparts indicate the
role of the acid sphyingomelinase pathway as critical to this type of enhancement response. The particular
pathways activated by ultrasound-stimulated microbubbles are similar to those activated by radiation
with respect to membrane-related signalling of cellular stress. It may be possible that these pathways
activated by microbubbles synergize with other cancer therapies which can lead to the enhancement of
such therapies with ultrasound-based treatments.
54 | P a g e
An evolving body of recent literature alludes to the potential to sensitize tumors to radiation
therapy using metallic nanoparticles. In preclinical studies, the techniques that hold promise for eventual
clinical deployment are nanoparticle-assisted radiation dose enhancement and hyperthermic
radiosensitization. To understand the underlying nanoparticle-radiation interactions, computational
techniques offer an explanation for and predict the biophysical consequences at a nano-/meso-scopic
scale. Nonetheless, there are persisting gaps in knowledge relating to the molecular mechanism of action
of these radiosensitization approaches - some of these issues will be addressed. Since the literature
relating to the diverse disciplines involved in these efforts spans across multiple specialties (clinical
radiation oncology, radiation physics, radiation biology, nanotechnology, material science, biomedical
engineering, pharmacology, chemistry, and tumor biology) and numerous specialty journals, there is no
single compilation of extant research in this arena or forum for merging analogous concepts and
paradigms. This symposium will provide such a venue - my presentation will start with familiarizing the
audience with the potential applications of metallic nanoparticles in radiation therapy using specific
illustrative examples and begin to explore ways to understand the underlying mechanisms of the effects
observed.
(S1102) Focussed Ultrasound in Radiosensitization. Gregory Czarnota, Sunnybrook Health Sciences
Centre, Toronto, Canada
We have been investigating tested the hypothesis that microbubble agents in vivo may be used
apriori to cause endothelial cell perturbations thus causing "radiosensitization" of tumours. This research
has now been conducted in multiple murine and human tumour lines including bladder, breast,
fibrosarcoma and prostate cancer lines. We have also focussed investigations on potential mechanisms
which may account for interactions between the two forms of energy. Data have indicated synergistic
increases in tumour cell kill due to vascular disruption caused by the combined therapies that increased
when microbubbles were used in conjunction with radiation with increases of cell kill from 5% to over
50% with combined single treatments. Longitudinal experiments with multiple treatments have indicated
better therapeutic outcome with compared to single modality treatments. Immunohistochemistry has
indicated endothelial cell apoptosis and activation of the ceramide cell-death pathway to be caused by
microbubbles. Protecting the vasculature with bFGF or inhibiting the ceramide pathway chemically has
led to protective effects negating the effects of ultrasound-stimulated microbubbles. In addition,
experiments with genetically modified mice (Asmase -/-) compared to wild-type counterparts indicate the
role of the acid sphyingomelinase pathway as critical to this type of enhancement response. The particular
pathways activated by ultrasound-stimulated microbubbles are similar to those activated by radiation
with respect to membrane-related signalling of cellular stress. It may be possible that these pathways
activated by microbubbles synergize with other cancer therapies which can lead to the enhancement of
such therapies with ultrasound-based treatments.
54 | P a g e
