Page 378 - 2014 Printable Abstract Book
P. 378
to expose patients to high doses of radiation without damaging normal brain tissues and/or preventing
cognitive dysfunction. Therefore, it is important to develop novel therapeutics that sensitize cancer cells
in order to make them more susceptible to radiation therapy and most importantly prevent relapse of the
disease. Preliminary data showed that a 23 amino acid synthetic peptide drug known as TP508
(Chrysalin©), increased RT-induced tumor shrinkage of brain tumors in mice and did not interfere with
radio-sensitivity on cancer cells in vitro. Therefore, our goal was to determine whether TP508 could
prevent/delay tumor relapse of brain cancer cells post-RT and whether it specifically sensitizes cancer
stem cells which are known to be responsible for cancer relapse. Given that cancer stem cells are known
to be required to initiate tumor growth and proliferation, Medulloblastoma (Daoy) and Glioblastoma (U-
87 MG) cells were grown as 3D spheroids in vitro to select for the growth of stem cells. Primary
neurospheres were treated on day 5 with either saline or TP508 (1mg/mL), and exposed to radiation
(10Gy) on day 7 using a Cs137 source. Cells were then dissociated and replated as secondary spheroids
on day 8 to examine the relapse potential of these cells. Daily images were taken and neurospheres were
counted and assessed for viability. In addition, spheroids were analyzed by western blot analysis and
immunofluorescent staining for the stemness (CD133/LGR5/CD44/DCLK1/Sox-2), proliferative (PCNA) and
apoptotic potential of these cells.Based on our findings, TP508 prevented the formation of secondary
spheroids post-RT in Daoy cells but not in U-87 MG. The lack of effect on U-87 MG may be due to the fact
that U-87 MG are more malignant and therefore may require a higher radiation dose or TP508 dose in
order to obverse any effects. Cell viability in Daoy cells treated with TP508 was significantly lower than
the control group. In addition, the proliferative potential and stem cell expression in the spheres were
TP508 seems to be preventing and/or delaying relapse of brain tumor stem cells in vitro. The peptide may
likely be sensitizing the cancer stem cells to radiation; this finding demonstrates that TP508 may perhaps
be used as a novel therapeutic tool in combination to RT for treating brain cancer patients and improving
clinical outcome. This work was supported by NCI Contract # HHSN261201300076C to DC.
1
(PS7-44) Development of the NASA Space Cancer Risk Model -2015. Blake Rowedder ; Myung-Hee Y.
1
1
2
Kim ; and Francis A. Cucinotta , University of Nevada Las Vegas, Las Vegas, NV and USRA Division of Life
2
Sciences, Houston, TX
The NASA Space Cancer Risk (NSCR) model developed by Cucinotta et al. (2013) was reviewed by
the National Research Council in 2012 and received NASA’s Software of the Year Award in 2013. NSCR-
2012 introduced a new approach to radiation quality factors (QFs) using track structure theory to define
probability distribution functions to estimate QF-uncertainties and their contributions to overall
uncertainties in radiation risk estimates. Another development was the introduction of a never-smoker
model to be used for assessing cancer risks of astronauts. NSCR-2014 (Cucinotta et al.) extended NSCR-
2012 to consider uncertainties due to potentially increased lethality of high LET induced tumors (heavy
ions and neutrons) compared to background or low LET tumors, a model of never-smokers of normal
weight, and made estimates of non-cancer risk contributions to lifetime radiation fatality risks. In this
report we will describe new developments to be included in NSCR-2015 including the use of a new more
accurate model of the galactic cosmic ray (GCR) environment, and a new Monte-Carlo approach to space
radiation transport in shielding and tissue. NSCR-2015 will rely extensively on parallel processing using the
GCR Event-Based Risk (GERM) code of particle transport replacing the use of the deterministic HZETRN
transport code. We will discuss our parallel processing approach and applications of NSCR-2015 to assess
secondary cancers in Hadron therapy.
376 | P a g e
cognitive dysfunction. Therefore, it is important to develop novel therapeutics that sensitize cancer cells
in order to make them more susceptible to radiation therapy and most importantly prevent relapse of the
disease. Preliminary data showed that a 23 amino acid synthetic peptide drug known as TP508
(Chrysalin©), increased RT-induced tumor shrinkage of brain tumors in mice and did not interfere with
radio-sensitivity on cancer cells in vitro. Therefore, our goal was to determine whether TP508 could
prevent/delay tumor relapse of brain cancer cells post-RT and whether it specifically sensitizes cancer
stem cells which are known to be responsible for cancer relapse. Given that cancer stem cells are known
to be required to initiate tumor growth and proliferation, Medulloblastoma (Daoy) and Glioblastoma (U-
87 MG) cells were grown as 3D spheroids in vitro to select for the growth of stem cells. Primary
neurospheres were treated on day 5 with either saline or TP508 (1mg/mL), and exposed to radiation
(10Gy) on day 7 using a Cs137 source. Cells were then dissociated and replated as secondary spheroids
on day 8 to examine the relapse potential of these cells. Daily images were taken and neurospheres were
counted and assessed for viability. In addition, spheroids were analyzed by western blot analysis and
immunofluorescent staining for the stemness (CD133/LGR5/CD44/DCLK1/Sox-2), proliferative (PCNA) and
apoptotic potential of these cells.Based on our findings, TP508 prevented the formation of secondary
spheroids post-RT in Daoy cells but not in U-87 MG. The lack of effect on U-87 MG may be due to the fact
that U-87 MG are more malignant and therefore may require a higher radiation dose or TP508 dose in
order to obverse any effects. Cell viability in Daoy cells treated with TP508 was significantly lower than
the control group. In addition, the proliferative potential and stem cell expression in the spheres were
TP508 seems to be preventing and/or delaying relapse of brain tumor stem cells in vitro. The peptide may
likely be sensitizing the cancer stem cells to radiation; this finding demonstrates that TP508 may perhaps
be used as a novel therapeutic tool in combination to RT for treating brain cancer patients and improving
clinical outcome. This work was supported by NCI Contract # HHSN261201300076C to DC.
1
(PS7-44) Development of the NASA Space Cancer Risk Model -2015. Blake Rowedder ; Myung-Hee Y.
1
1
2
Kim ; and Francis A. Cucinotta , University of Nevada Las Vegas, Las Vegas, NV and USRA Division of Life
2
Sciences, Houston, TX
The NASA Space Cancer Risk (NSCR) model developed by Cucinotta et al. (2013) was reviewed by
the National Research Council in 2012 and received NASA’s Software of the Year Award in 2013. NSCR-
2012 introduced a new approach to radiation quality factors (QFs) using track structure theory to define
probability distribution functions to estimate QF-uncertainties and their contributions to overall
uncertainties in radiation risk estimates. Another development was the introduction of a never-smoker
model to be used for assessing cancer risks of astronauts. NSCR-2014 (Cucinotta et al.) extended NSCR-
2012 to consider uncertainties due to potentially increased lethality of high LET induced tumors (heavy
ions and neutrons) compared to background or low LET tumors, a model of never-smokers of normal
weight, and made estimates of non-cancer risk contributions to lifetime radiation fatality risks. In this
report we will describe new developments to be included in NSCR-2015 including the use of a new more
accurate model of the galactic cosmic ray (GCR) environment, and a new Monte-Carlo approach to space
radiation transport in shielding and tissue. NSCR-2015 will rely extensively on parallel processing using the
GCR Event-Based Risk (GERM) code of particle transport replacing the use of the deterministic HZETRN
transport code. We will discuss our parallel processing approach and applications of NSCR-2015 to assess
secondary cancers in Hadron therapy.
376 | P a g e
