Sensitivity of Salivary Glands to Radiation: from Animal Models to Therapies

Grundmann, Oliver; Mitchell, Geoffrey C.; Limesand, Kirsten H.

doi:10.1177/0022034509343143

Cited by 224 publications

(275 citation statements)

References 100 publications

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“…36 The salivary gland has long been known to exhibit a paradoxically acute sensitivity to radiation therapy. 47,82,83 The loss of terminally differentiated secretory cells after radiation has been suggested to occur through radical-mediated damage of secretory granules 84 or the plasma membrane. 44 A process common to both of these phenomena is the formation of hydroxyl radicals from the irradiation of water, which subsequently abstracts hydrogens from unsaturated fatty acids in the plasma membrane and generates peroxyl radicals that propagate through adjacent fatty acids molecules, resulting in membrane destabilization.…”

Section: Resultsmentioning

confidence: 99%

“…31,42,43 In this work, methods have been explored to encapsulate, culture, and characterize primary SMG cells within PEG hydrogels, with the long-term goal of developing a tissue engineering approach for the salivary gland. Due to the sensitivity of salivary gland cells to reactive oxygen species (ROS), [44][45][46][47][48] we examined the effects of two forms of radical-mediated hydrogel polymerization: chain addition methacrylate-based polymerizations and step-growth thiol-ene polymerizations on primary SMG cells. PEG hydrogels are bioinert, 26 and they lack cell-matrix and cell-cell interactions that are commonly utilized to maintain survivability of sensitive cell types.…”

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confidence: 99%

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Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

Shubin

Felong

Graunke

et al. 2015

Tissue Engineering Part A

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More than 40,000 patients are diagnosed with head and neck cancers annually in the United States with the vast majority receiving radiation therapy. Salivary glands are irreparably damaged by radiation therapy resulting in xerostomia, which severely affects patient quality of life. Cell-based therapies have shown some promise in mouse models of radiation-induced xerostomia, but they suffer from insufficient and inconsistent gland regeneration and accompanying secretory function. To aid in the development of regenerative therapies, poly(ethylene glycol) hydrogels were investigated for the encapsulation of primary submandibular gland (SMG) cells for tissue engineering applications. Different methods of hydrogel formation and cell preparation were examined to identify cytocompatible encapsulation conditions for SMG cells. Cell viability was much higher after thiol-ene polymerizations compared with conventional methacrylate polymerizations due to reduced membrane peroxidation and intracellular reactive oxygen species formation. In addition, the formation of multicellular microspheres before encapsulation maximized cell-cell contacts and increased viability of SMG cells over 14-day culture periods. Thiol-ene hydrogel-encapsulated microspheres also promoted SMG proliferation. Lineage tracing was employed to determine the cellular composition of hydrogel-encapsulated microspheres using markers for acinar (Mist1) and duct (Keratin5) cells. Our findings indicate that both acinar and duct cell phenotypes are present throughout the 14 day culture period. However, the acinar:duct cell ratios are reduced over time, likely due to duct cell proliferation. Altogether, permissive encapsulation methods for primary SMG cells have been identified that promote cell viability, proliferation, and maintenance of differentiated salivary gland cell phenotypes, which allows for translation of this approach for salivary gland tissue engineering applications.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

Shubin

Felong

Graunke

et al. 2015

Tissue Engineering Part A

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“…87,88 Direct tissue damage may be related to p53-related apoptosis due to the development of reactive oxygen species leading to DNA damage and reduced insulin-like growth factor production. 89,90 RT has a dramatic effect on salivary function when the glands are within the RT field. The serous acini are initially more sensitive to RT.…”

Section: Rt-induced Xerostomia and Hyposalivationmentioning

confidence: 99%

Oral complications of cancer and cancer therapy

Epstein

Thariat

Bensadoun

et al. 2012

CA A Cancer J Clinicians

431

356

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Answer questions and earn CME/CNEOral complications resulting from cancer and cancer therapies cause acute and late toxicities that may be underreported, underrecognized, and undertreated. Recent advances in cancer treatment have led to changes in the incidence, nature, and severity of oral complications. As the number of survivors increases, it is becoming increasingly recognized that the aggressive management of oral toxicities is needed to ensure optimal long‐term oral health and general well‐being. Advances in care have had an impact on previously recognized oral complications and are leading to newly recognized adverse effects. Here, the authors briefly review advances in cancer therapy, including recent advances in surgery, oral care, radiation therapy, hematopoietic cell transplantation, and medical oncology; describe how these advances affect oral health; and discuss the frequent and/or severe oral health complications associated with cancer and cancer treatment and their effect upon long‐term health. Although some of the acute oral toxicities of cancer therapies may be reduced, they remain essentially unavoidable. The significant impact of long‐term complications requires increased awareness and recognition to promote prevention and appropriate intervention. It is therefore important for the primary oncologist to be aware of these complications so that appropriate measures can be implemented in a timely manner. Prevention and management is best provided via multidisciplinary health care teams, which must be integrated and communicate effectively in order to provide the best patient care in a coordinated manner at the appropriate time. CA Cancer J Clin 2012. © 2012 American Cancer Society.

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“…The protein content of whole saliva derives from the three major paired salivary glands, which comprise the contralateral major (parotid, submandibular and sublingual) and minor salivary glands (4). The protein composition of whole saliva depends on the circadian rhythm, diet, age, gender and physiological status of the individual (5).…”

Section: Introductionmentioning

confidence: 99%

Novel possibilities in the study of the salivary proteomic profile using SELDI-TOF/MS technology

et al. 2016

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Abstract. There is currently an increasing interest in exploring human saliva to identify salivary diagnostic and prognostic biomarkers, since the collection of saliva is rapid, non-invasive and stress-free. Diagnostic tests on saliva are common and cost-effective, particularly for patients who need to monitor their hormone levels or the effectiveness of undergoing therapies. Furthermore, salivary diagnostics is ideal for surveillance studies and in situations where fast results and inexpensive technologies are required. The most important constituents of saliva are proteins, the expression levels of which may be modified due to variations of the cellular conditions. Therefore, the different profile of proteins detected in saliva, including their absence, presence or altered levels, is a potential biomarker of certain physiological and/or pathological conditions. A promising novel approach to study saliva is the global analysis of salivary proteins using proteomic techniques. In the present study, surface-enhanced laser desorption/ionization-time-of-flight/mass spectrometry (SELDI-TOF/MS), one of the most recent proteomic tools for the identification of novel biomarkers, is reviewed. In addition, the possible use of this technique in salivary proteomic studies is discussed, since SELDI technology combines the precision of matrix-assisted laser desorption/ionization-TOF/MS proteomic analysis and the high-throughput nature of protein array analysis.

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Sensitivity of Salivary Glands to Radiation: from Animal Models to Therapies

Cited by 224 publications

References 100 publications

Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

Oral complications of cancer and cancer therapy

Novel possibilities in the study of the salivary proteomic profile using SELDI-TOF/MS technology

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