Page 370 - 2014 Printable Abstract Book
P. 370
spontaneous leukemia rate from 10% to 0%. Treatment with Yel002 following IR accelerates the recovery
of the hematopoietic cells after sub-lethal exposures. In addition, treatment with Yel002 reduces EMS,
MMS, UV, and cigarette smoke extract as well as nitrogen mustard induced toxicity as well as genotoxicity
showing a broad application spectrum. It also prolongs live of cells in a senescence assay. In addition Atm
deficient mice live 16 weeks longer with weekly injection of Yel002 which is about 12 years in human life
expectancy. In addition, Yel002 complements a zebrafish model of Diamond Blackfan Anemia. It works in
yeast, CHO cells, different human cells, mice and zebrafish. Toxicity has not been observed in neither in
vitro nor in vivo administrations. Overall, Yel compounds have much potential as stockpile therapies for
radiation-induced lethality and cancer: they are highly effective when administered up to 24hours post
exposure, they reduce radiation-induce sequelae such as leukemia, and appear to have an acceptable
toxicity profile.
1
(PS7-31) Control of brain tumor response to irradiation by MMP2 expression. Ching-Fang Yu ; Li-Chu
3
2
1
Chin ; Ying-Chieh Yang ; Ji-Hong Hong ; Chi-Shiun Chiang , National Tsing Hua University, Hsinchu,
1
1
2
Taiwan ; National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan ; and Chang-Gung
3
Memorial Hospital, Taoyuan, Taiwan
Glioma is frequently resistant to radiation therapy (RT) due to their intrinsic radioresistance and
the invasive growth natures. The matrix metalloproteinase-2 (MMP-2) has been associated with invasion
properties in gliomas and is a maker of poor prognosis. Using an invasive murine astrocytoma tumor cell
line, ALTS1C1, and a MMP2 specific lentiviral-shRNA approach, we found that the suppression of MMP2
expression decreased the invasive ability of tumor cells, but up-regulated DNA repair pathways.
Although MMP2 suppression tumors (MMP2kd) were more resistant to the cytotoxicity of irradiation in
both in vitro and in vivo orthotopic tumor models, the Kaplan-Meier survival curve shows that mice-
bearing MMP2kd tumors still had longer surviving time than mice-bearing ALTS1C1 tumors even after 15
Gy of single dose of whole brain irradiation. In conclusion, this study indicates that glioma response to
RT is governed by at least two tumor intrinsic factors, the radiosensitivity and invasiveness. These two
factors might be in reciprocal signal transduction pathways and partially explain the difficulty of glioma
therapy. (This study was supported by NHRI-EX103-10132BI grant)
(PS7-32) Underground laboratories as an opportunity to study Natural Environmental Ionizing Radiation
effects: The Cosmic Silence project experience. Emiliano Fratini 1; 2 ; Mariafausta Fischietti 1; 3 ; Giustina
1
1
5
3;4
Simone ; Edoardo Alesse 3; 4 ; Francesca Zazzeroni ; Pamela J. Sykes ; Luigi Satta ; and Maria Antonella
1
2;6
Tabocchini , Museo Storico della Fisica e Centro Studi e Ricerche Enrico Fermi, Roma, Italy ; INFN Roma1-
2
3
4
Gr.coll.Sanità, Roma, Italy ; L’Aquila University, L’Aquila, Italy ; INFN-LNGS, Gr.coll.UNIAQ, Italy ; Flinders
5
University, Bedford Park, Adelaide, Australia ; and Istituto Superiore di Sanità, Roma, Italy 6
The underground Gran Sasso National Laboratory (LNGS) of the Italian Istituto Nazionale di
Fisica Nucleare (INFN), provides a very low radiation environment. It was constructed to study very rare
events such as proton decay or solar neutrino detection. In this underground laboratory, shielded by at
least 1400 m of overburden, the cosmic radiation is almost absent, the neutron flux is reduced by a factor
3
of 10 with respect to the external values due to the small amount of the Uranium and Thorium content
of the dolomite rocks of the mountain and the γ radiation is particularly low; the mountain being of
368 | P a g e
of the hematopoietic cells after sub-lethal exposures. In addition, treatment with Yel002 reduces EMS,
MMS, UV, and cigarette smoke extract as well as nitrogen mustard induced toxicity as well as genotoxicity
showing a broad application spectrum. It also prolongs live of cells in a senescence assay. In addition Atm
deficient mice live 16 weeks longer with weekly injection of Yel002 which is about 12 years in human life
expectancy. In addition, Yel002 complements a zebrafish model of Diamond Blackfan Anemia. It works in
yeast, CHO cells, different human cells, mice and zebrafish. Toxicity has not been observed in neither in
vitro nor in vivo administrations. Overall, Yel compounds have much potential as stockpile therapies for
radiation-induced lethality and cancer: they are highly effective when administered up to 24hours post
exposure, they reduce radiation-induce sequelae such as leukemia, and appear to have an acceptable
toxicity profile.
1
(PS7-31) Control of brain tumor response to irradiation by MMP2 expression. Ching-Fang Yu ; Li-Chu
3
2
1
Chin ; Ying-Chieh Yang ; Ji-Hong Hong ; Chi-Shiun Chiang , National Tsing Hua University, Hsinchu,
1
1
2
Taiwan ; National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan ; and Chang-Gung
3
Memorial Hospital, Taoyuan, Taiwan
Glioma is frequently resistant to radiation therapy (RT) due to their intrinsic radioresistance and
the invasive growth natures. The matrix metalloproteinase-2 (MMP-2) has been associated with invasion
properties in gliomas and is a maker of poor prognosis. Using an invasive murine astrocytoma tumor cell
line, ALTS1C1, and a MMP2 specific lentiviral-shRNA approach, we found that the suppression of MMP2
expression decreased the invasive ability of tumor cells, but up-regulated DNA repair pathways.
Although MMP2 suppression tumors (MMP2kd) were more resistant to the cytotoxicity of irradiation in
both in vitro and in vivo orthotopic tumor models, the Kaplan-Meier survival curve shows that mice-
bearing MMP2kd tumors still had longer surviving time than mice-bearing ALTS1C1 tumors even after 15
Gy of single dose of whole brain irradiation. In conclusion, this study indicates that glioma response to
RT is governed by at least two tumor intrinsic factors, the radiosensitivity and invasiveness. These two
factors might be in reciprocal signal transduction pathways and partially explain the difficulty of glioma
therapy. (This study was supported by NHRI-EX103-10132BI grant)
(PS7-32) Underground laboratories as an opportunity to study Natural Environmental Ionizing Radiation
effects: The Cosmic Silence project experience. Emiliano Fratini 1; 2 ; Mariafausta Fischietti 1; 3 ; Giustina
1
1
5
3;4
Simone ; Edoardo Alesse 3; 4 ; Francesca Zazzeroni ; Pamela J. Sykes ; Luigi Satta ; and Maria Antonella
1
2;6
Tabocchini , Museo Storico della Fisica e Centro Studi e Ricerche Enrico Fermi, Roma, Italy ; INFN Roma1-
2
3
4
Gr.coll.Sanità, Roma, Italy ; L’Aquila University, L’Aquila, Italy ; INFN-LNGS, Gr.coll.UNIAQ, Italy ; Flinders
5
University, Bedford Park, Adelaide, Australia ; and Istituto Superiore di Sanità, Roma, Italy 6
The underground Gran Sasso National Laboratory (LNGS) of the Italian Istituto Nazionale di
Fisica Nucleare (INFN), provides a very low radiation environment. It was constructed to study very rare
events such as proton decay or solar neutrino detection. In this underground laboratory, shielded by at
least 1400 m of overburden, the cosmic radiation is almost absent, the neutron flux is reduced by a factor
3
of 10 with respect to the external values due to the small amount of the Uranium and Thorium content
of the dolomite rocks of the mountain and the γ radiation is particularly low; the mountain being of
368 | P a g e
