Page 30 - 2014 Printable Abstract Book
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S01 NORMAL TISSUE TOXICITY: RECENT FINDINGS AND DIRECTIONS
The normal tissue effects that can occur following radiation exposure have far-reaching consequences.
This symposium will provide an overview of the progress that has been made in this field and, most
excitingly, offer insights into some of the directions that are being explored currently in this important
area of research.
(S101) Death, inflammation and tissue microenvironment: past, present and future directions in normal
2
2
2
2
1
tissue research. Jacqueline P. Williams ; Kerry O'Banion ; John Olschowka ; Edith Lord ; Julie Ryan ; James
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1
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Palis ; Laura Calvi ; and Jacob N. Finkelstein James P. Wilmot Cancer Center, Rochester, NY and
2
University of Rochester Medical Center, Rochester, NY
The acute and delayed normal tissue effects that can occur following radiation exposure have far-
reaching consequences: for example, as part of radiation therapy-related treatment, the risk of radiation-
induced effects in critical tissues and organs limits practitioners’ ability to deliver curative doses and
affects the quality of life in the growing populations of cancer survivors; there are suggestions by some
that the risk of long-term neurodegenerative and carcinogenic outcomes resulting from even the low
doses and dose rates of galactic cosmic rays should potentially limit, or even, prevent man’s exploration
of space; finally, in light of the risk of a major radiological or nuclear event as part of an ongoing terrorist
threat, significant government resources have been expended to improve survival of the acute effects of
irradiation, although our experience to date suggests that, in many of these victims, mortality will
nonetheless occur due to our current inability to mitigate the subsequent late injury.
Decades of work have provided a plethora of hypotheses as to how and why radiation induces such a
broad spectrum of outcomes. These have included the classic target theory, suggesting that effects were
a consequence of cell loss in critical cell populations. The frequent presence of chronic inflammation has
led some to investigate the role of inflammation in normal tissue effect progression. Both chronic
oxidative stress and microvascular-related hypoxia have been implicated as critical factors. However, to
date, none of the identified mechanisms have provided the “silver bullet” allowing us to abrogate or even
mitigate the, often devastating, endpoints. Fortunately, investigators are beginning to offer insights into
some of the underlying causes of radiation-induced late effects, offering opportunities for mitigation and
treatment. Some of the directions that have been and are currently being explored will be discussed.
(S102) Therapeutic radiation produces significant articular cartilage and joint degeneration. Jeffrey S.
Willey, Wake Forest University School of Medicine, Winston Salem, NC
Premature joint failure and decreased mobility are major sources of morbidity among childhood
cancer survivors who receive total body irradiation (TBI) as preconditioning for stem cell transplantation;
the relative risk of premature joint replacement is 54 times greater than for siblings. Clinical reports
describe early degenerative changes in joints after TBI, but fail to follow progressive articular cartilage
degeneration to early adulthood where the risk of joint replacement is significant. We have characterized
28 | P a g e
The normal tissue effects that can occur following radiation exposure have far-reaching consequences.
This symposium will provide an overview of the progress that has been made in this field and, most
excitingly, offer insights into some of the directions that are being explored currently in this important
area of research.
(S101) Death, inflammation and tissue microenvironment: past, present and future directions in normal
2
2
2
2
1
tissue research. Jacqueline P. Williams ; Kerry O'Banion ; John Olschowka ; Edith Lord ; Julie Ryan ; James
2
2
1
2
Palis ; Laura Calvi ; and Jacob N. Finkelstein James P. Wilmot Cancer Center, Rochester, NY and
2
University of Rochester Medical Center, Rochester, NY
The acute and delayed normal tissue effects that can occur following radiation exposure have far-
reaching consequences: for example, as part of radiation therapy-related treatment, the risk of radiation-
induced effects in critical tissues and organs limits practitioners’ ability to deliver curative doses and
affects the quality of life in the growing populations of cancer survivors; there are suggestions by some
that the risk of long-term neurodegenerative and carcinogenic outcomes resulting from even the low
doses and dose rates of galactic cosmic rays should potentially limit, or even, prevent man’s exploration
of space; finally, in light of the risk of a major radiological or nuclear event as part of an ongoing terrorist
threat, significant government resources have been expended to improve survival of the acute effects of
irradiation, although our experience to date suggests that, in many of these victims, mortality will
nonetheless occur due to our current inability to mitigate the subsequent late injury.
Decades of work have provided a plethora of hypotheses as to how and why radiation induces such a
broad spectrum of outcomes. These have included the classic target theory, suggesting that effects were
a consequence of cell loss in critical cell populations. The frequent presence of chronic inflammation has
led some to investigate the role of inflammation in normal tissue effect progression. Both chronic
oxidative stress and microvascular-related hypoxia have been implicated as critical factors. However, to
date, none of the identified mechanisms have provided the “silver bullet” allowing us to abrogate or even
mitigate the, often devastating, endpoints. Fortunately, investigators are beginning to offer insights into
some of the underlying causes of radiation-induced late effects, offering opportunities for mitigation and
treatment. Some of the directions that have been and are currently being explored will be discussed.
(S102) Therapeutic radiation produces significant articular cartilage and joint degeneration. Jeffrey S.
Willey, Wake Forest University School of Medicine, Winston Salem, NC
Premature joint failure and decreased mobility are major sources of morbidity among childhood
cancer survivors who receive total body irradiation (TBI) as preconditioning for stem cell transplantation;
the relative risk of premature joint replacement is 54 times greater than for siblings. Clinical reports
describe early degenerative changes in joints after TBI, but fail to follow progressive articular cartilage
degeneration to early adulthood where the risk of joint replacement is significant. We have characterized
28 | P a g e
