Page 249 - 2014 Printable Abstract Book
P. 249
(PS4-24) Selective amino acid mixture decreases chronic lung complications in irradiated mice. Liangjie
1
2
1
1
1
Yin, MS ; Rejeesh Menon, MD ; Sreekala Prabhakaran, MD ; Mei Zhang, MD ; Walter O'Dell, PhD ; Paul
1
1
Okunieff, MD ; Sadasivan Vidyasagar, MD, PhD, University of Florida Shands Cancer Center, Gainesville,
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1
FL and Department of Pediatrics, Division of Pediatric Pulmonology, University of Florida, Gainesville, FL
Introduction: Radiotherapy affects normal lung tissue and can cause acute and chronic lung injury.
It disrupts the alveolar-capillary barrier and interferes with fluid and electrolyte transfer in the lungs,
resulting in increased fluid leakage that may contribute to increased lung stiffness and long-term fibrosis.
A select set of amino acids (lysine, glycine, tryptophan, tyrosine, aspartic acid, isoleucine, threonine,
valine, and serine) that led to increased electrolyte absorptive capacity, decreased paracellular
permeability, and decreased plasma interleukin 1β was found to mitigate radiation-induced
gastrointestinal (GI) toxicity. The GI and respiratory epithelium have a similar set of transporters; thus, we
hypothesized a similar effect in lung tissues. Hypothesis: Early supportive therapy using the amino acid
mixture decreases chronic lung complications following irradiation. Methods: NIH Swiss mice were
irradiated (8 Gy) and gavaged using the amino acid mixture (300 µL/day) started 24 hours after irradiation
and continued for 2 weeks. Normal saline was used as a control. The pulmonary function test was
performed with a noninvasive unrestrained technique using whole body plethysmography (EMMS
solutions, Hants, UK). Mice were placed in the plethysmograph to measure respiratory frequency, tidal
volume, expiratory and inspiratory times, and peak inspiratory and expiratory flows. A Sanco Medical
desktop cone-beam micro CT 35 was used to study the extent of pulmonary fibrosis. Results: Tidal volume
was reduced in irradiated mice as compared to nonirradiated mice ( 260.0 ± 10.0 vs 231 ± 20 µl ); however,
tidal volume was increased in treated mice as compared to irradiated controls ( 290 ± 20 vs 230 ± 20 µl ).
The treated group had improved exhalation time (88 ± 0.3 vs 102 ± 0.6 ms) and increased relaxation time
(41±0.1 vs 53 ± 0.2 ms) as compared to irradiated controls. The micro CT scans per-formed on anesthetized
animals showed increased lung density after irradiation, but with amino acid treatment the lung fields
showed improved radiological clearance. Conclusion: Early supportive therapy using a select set of amino
acids protected against radiation-induced chronic lung injury. Study was funded by Enterade USA LLC.
(PS4-25) Hedgehog inhibitor GANT61 sensitizes prostate cancer cells to ionizing radiation. Annelies
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2
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1
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Gonnissen ; Sofie Isebaert ; Chad McKee ; Ruth Muschel ; and Karin Haustermans, Laboratory of
Experimental Radiotherapy, Department of Oncology, KU Leuven & Radiation Oncology, University
1
Hospitals Leuven, Leuven, Belgium and Department of Oncology, Gray Institute for Radiation Oncology
2
and Biology, University of Oxford, Oxford, United Kingdom
Background: Increasing evidence suggests that the Hedgehog (Hh) pathway plays a crucial role in the
development of prostate cancer (PCa) as well as in the progression to more aggressive and therapy-
resistant disease states. Moreover, recent data suggest that Hh signaling is associated with radiation
resistance. Inhibition of Hh signaling could therefore represent a promising therapeutic strategy for PCa.
Aim: Investigation of the Hh pathway inhibitor GANT61 as a radiosensitizing agent in prostate cancer cells.
Materials and methods: Two PCa cell lines (PC3Luc, 22Rv1) were treated with 0, 1 or 10µM of GANT61
and effects on cell survival, proliferation and radiation sensitivity was investigated by means of
Sulforhodamine B (SRB) assays, bromodeoxyuridine (BrdU) assays and colony assays. The effect on gene
and protein expression (qRT-PCR/Western blotting), cell cycle distribution (flow cytometry, PI staining)
247 | P a g e
1
2
1
1
1
Yin, MS ; Rejeesh Menon, MD ; Sreekala Prabhakaran, MD ; Mei Zhang, MD ; Walter O'Dell, PhD ; Paul
1
1
Okunieff, MD ; Sadasivan Vidyasagar, MD, PhD, University of Florida Shands Cancer Center, Gainesville,
2
1
FL and Department of Pediatrics, Division of Pediatric Pulmonology, University of Florida, Gainesville, FL
Introduction: Radiotherapy affects normal lung tissue and can cause acute and chronic lung injury.
It disrupts the alveolar-capillary barrier and interferes with fluid and electrolyte transfer in the lungs,
resulting in increased fluid leakage that may contribute to increased lung stiffness and long-term fibrosis.
A select set of amino acids (lysine, glycine, tryptophan, tyrosine, aspartic acid, isoleucine, threonine,
valine, and serine) that led to increased electrolyte absorptive capacity, decreased paracellular
permeability, and decreased plasma interleukin 1β was found to mitigate radiation-induced
gastrointestinal (GI) toxicity. The GI and respiratory epithelium have a similar set of transporters; thus, we
hypothesized a similar effect in lung tissues. Hypothesis: Early supportive therapy using the amino acid
mixture decreases chronic lung complications following irradiation. Methods: NIH Swiss mice were
irradiated (8 Gy) and gavaged using the amino acid mixture (300 µL/day) started 24 hours after irradiation
and continued for 2 weeks. Normal saline was used as a control. The pulmonary function test was
performed with a noninvasive unrestrained technique using whole body plethysmography (EMMS
solutions, Hants, UK). Mice were placed in the plethysmograph to measure respiratory frequency, tidal
volume, expiratory and inspiratory times, and peak inspiratory and expiratory flows. A Sanco Medical
desktop cone-beam micro CT 35 was used to study the extent of pulmonary fibrosis. Results: Tidal volume
was reduced in irradiated mice as compared to nonirradiated mice ( 260.0 ± 10.0 vs 231 ± 20 µl ); however,
tidal volume was increased in treated mice as compared to irradiated controls ( 290 ± 20 vs 230 ± 20 µl ).
The treated group had improved exhalation time (88 ± 0.3 vs 102 ± 0.6 ms) and increased relaxation time
(41±0.1 vs 53 ± 0.2 ms) as compared to irradiated controls. The micro CT scans per-formed on anesthetized
animals showed increased lung density after irradiation, but with amino acid treatment the lung fields
showed improved radiological clearance. Conclusion: Early supportive therapy using a select set of amino
acids protected against radiation-induced chronic lung injury. Study was funded by Enterade USA LLC.
(PS4-25) Hedgehog inhibitor GANT61 sensitizes prostate cancer cells to ionizing radiation. Annelies
1
2
1
1
2
Gonnissen ; Sofie Isebaert ; Chad McKee ; Ruth Muschel ; and Karin Haustermans, Laboratory of
Experimental Radiotherapy, Department of Oncology, KU Leuven & Radiation Oncology, University
1
Hospitals Leuven, Leuven, Belgium and Department of Oncology, Gray Institute for Radiation Oncology
2
and Biology, University of Oxford, Oxford, United Kingdom
Background: Increasing evidence suggests that the Hedgehog (Hh) pathway plays a crucial role in the
development of prostate cancer (PCa) as well as in the progression to more aggressive and therapy-
resistant disease states. Moreover, recent data suggest that Hh signaling is associated with radiation
resistance. Inhibition of Hh signaling could therefore represent a promising therapeutic strategy for PCa.
Aim: Investigation of the Hh pathway inhibitor GANT61 as a radiosensitizing agent in prostate cancer cells.
Materials and methods: Two PCa cell lines (PC3Luc, 22Rv1) were treated with 0, 1 or 10µM of GANT61
and effects on cell survival, proliferation and radiation sensitivity was investigated by means of
Sulforhodamine B (SRB) assays, bromodeoxyuridine (BrdU) assays and colony assays. The effect on gene
and protein expression (qRT-PCR/Western blotting), cell cycle distribution (flow cytometry, PI staining)
247 | P a g e
