The Role of Autophagy in Salivary Gland Dysfunction Following Targeted Head and Neck Radiation

Persistent Link:
http://hdl.handle.net/10150/301532
Title:
The Role of Autophagy in Salivary Gland Dysfunction Following Targeted Head and Neck Radiation
Author:
Morgan-Bathke, Maria Elizabeth
Issue Date:
2013
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Head and neck cancer is one of the most common cancers worldwide. The current standard of care for head and neck cancer includes surgical resection of the tumor followed by chemoradiation. This targeted head and neck radiation causes dysfunction of the salivary glands, which leads to xerostomia, mucositis, dysphagia, dental caries, and malnutrition. These side effects greatly decrease patient quality of life and increase their financial responsibility. Current therapies available to ameliorate these negative side effects are expensive, only provide short-term relief, and many of them have negative side effects of their own. Therefore, another therapy is needed to prevent salivary gland dysfunction or restore its function following targeted head and neck radiation. Autophagy is a homeostatic cellular mechanism that could be targeted as a therapeutic mechanism in the salivary glands following targeted head and neck radiation. Autophagy is a catabolic process necessary to maintain cellular homeostasis. It has been shown to play a beneficial role in a variety of disease states including diabetes mellitus, obesity, and cancer. The role of autophagy in the response of cancerous tissue to radiation has been vastly studied. However, the role autophagy plays in normal tissue response to radiation remains poorly understood and much more research in this area is needed.Atg5^(f/f);Aqp5-Cre mice have a conditional knockout of Atg5, a gene necessary for autophagy, in the salivary glands. These mice have unchanged baseline levels of apoptosis, proliferation, and stimulated salivary flow rates when compared to wild-type mice. Therefore, they are a useful model to investigate the role of autophagy in the response of the salivary glands to targeted head and neck radiation. These Atg5^(f/f);Aqp5-Cre autophagy-deficient mice display increased radiosensitivity following targeted head and neck radiation. Furthermore, post-therapy use of CCI-779, a rapalogue and inducer of autophagy, allowed for restoration of salivary gland function following targeted head and neck radiation. Taken together, these results implicate autophagy as playing a beneficial role in normal salivary function following radiation. Therefore, autophagy could be utilized by normal salivary gland tissue following targeted head and neck radiation to maintain salivary gland function.
Type:
text; Electronic Dissertation
Keywords:
head and neck cancer; radiation; salivary gland; Nutritional Sciences; autophagy
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Nutritional Sciences
Degree Grantor:
University of Arizona
Advisor:
Limesand, Kirsten H.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleThe Role of Autophagy in Salivary Gland Dysfunction Following Targeted Head and Neck Radiationen_US
dc.creatorMorgan-Bathke, Maria Elizabethen_US
dc.contributor.authorMorgan-Bathke, Maria Elizabethen_US
dc.date.issued2013-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractHead and neck cancer is one of the most common cancers worldwide. The current standard of care for head and neck cancer includes surgical resection of the tumor followed by chemoradiation. This targeted head and neck radiation causes dysfunction of the salivary glands, which leads to xerostomia, mucositis, dysphagia, dental caries, and malnutrition. These side effects greatly decrease patient quality of life and increase their financial responsibility. Current therapies available to ameliorate these negative side effects are expensive, only provide short-term relief, and many of them have negative side effects of their own. Therefore, another therapy is needed to prevent salivary gland dysfunction or restore its function following targeted head and neck radiation. Autophagy is a homeostatic cellular mechanism that could be targeted as a therapeutic mechanism in the salivary glands following targeted head and neck radiation. Autophagy is a catabolic process necessary to maintain cellular homeostasis. It has been shown to play a beneficial role in a variety of disease states including diabetes mellitus, obesity, and cancer. The role of autophagy in the response of cancerous tissue to radiation has been vastly studied. However, the role autophagy plays in normal tissue response to radiation remains poorly understood and much more research in this area is needed.Atg5^(f/f);Aqp5-Cre mice have a conditional knockout of Atg5, a gene necessary for autophagy, in the salivary glands. These mice have unchanged baseline levels of apoptosis, proliferation, and stimulated salivary flow rates when compared to wild-type mice. Therefore, they are a useful model to investigate the role of autophagy in the response of the salivary glands to targeted head and neck radiation. These Atg5^(f/f);Aqp5-Cre autophagy-deficient mice display increased radiosensitivity following targeted head and neck radiation. Furthermore, post-therapy use of CCI-779, a rapalogue and inducer of autophagy, allowed for restoration of salivary gland function following targeted head and neck radiation. Taken together, these results implicate autophagy as playing a beneficial role in normal salivary function following radiation. Therefore, autophagy could be utilized by normal salivary gland tissue following targeted head and neck radiation to maintain salivary gland function.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjecthead and neck canceren_US
dc.subjectradiationen_US
dc.subjectsalivary glanden_US
dc.subjectNutritional Sciencesen_US
dc.subjectautophagyen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineNutritional Sciencesen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorLimesand, Kirsten H.en_US
dc.contributor.committeememberBurd, Randyen_US
dc.contributor.committeememberThomson, Cynthiaen_US
dc.contributor.committeememberLimesand, Kirsten H.en_US
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