scholarly journals Indomethacin Treatment Post-irradiation Improves Mouse Parotid Salivary Gland Function via Modulation of Prostaglandin E2 Signaling

2021 ◽  
Vol 9 ◽  
Author(s):  
Kristy E. Gilman ◽  
Jean M. Camden ◽  
Lucas T. Woods ◽  
Gary A. Weisman ◽  
Kirsten H. Limesand
Keyword(s):  
Salivary Gland ◽  
Parotid Gland ◽  
Salivary Glands ◽  
Prostaglandin E ◽  
Loss Of Function ◽  
Salivary Gland Function ◽  
Post Irradiation ◽  
Gland Cells ◽  
Study Results ◽  
Gland Function

Annually, >600,000 new cases of head and neck cancer (HNC) are diagnosed worldwide with primary treatment being surgery and radiotherapy. During ionizing radiation (IR) treatment of HNC, healthy salivary glands are collaterally damaged, leading to loss of function that severely diminishes the quality of life for patients due to increased health complications, including oral infections and sores, cavities, and malnutrition, among others. Therapies for salivary hypofunction are ineffective and largely palliative, indicating a need for further research to uncover effective approaches to prevent or restore loss of salivary gland function following radiotherapy. Previous work in our lab implicated prostaglandin E2 (PGE2) as an inflammatory mediator whose release from radiation-exposed cells promotes salivary gland damage and loss of function. Deletion of the P2X7 purinergic receptor for extracellular ATP reduces PGE2 secretion in irradiated primary parotid gland cells, and salivary gland function is enhanced in irradiated P2X7R–/– mice compared to wild-type mice. However, the role of PGE2 signaling in irradiated salivary glands is unclear and understanding the mechanism of PGE2 action is a goal of this study. Results show that treatment of irradiated mice with the non-steroidal anti-inflammatory drug (NSAID) indomethacin, which reduces PGE2 production via inhibition of cyclooxygenase-1 (COX-1), improves salivary gland function compared to irradiated vehicle-treated mice. To define the signaling pathway whereby PGE2 induces salivary gland dysfunction, primary parotid gland cells treated with PGE2 have increased c-Jun N-terminal Kinase (JNK) activation and cell proliferation and reduced amylase levels and store-operated calcium entry (SOCE). The in vivo effects of blocking PGE2 production were also examined and irradiated mice receiving indomethacin injections have reduced JNK activity at 8 days post-irradiation and reduced proliferation and increased amylase levels at day 30, as compared to irradiated mice without indomethacin. Combined, these data suggest a mechanism whereby irradiation-induced PGE2 signaling to JNK blocks critical steps in saliva secretion manifested by a decrease in the quality (diminished amylase) and quantity (loss of calcium channel activity) of saliva, that can be restored with indomethacin. These findings encourage further attempts evaluating indomethacin as a viable therapeutic option to prevent damage to salivary glands caused by irradiation of HNC in humans.

Mathematical evaluation of post-radiotherapy salivary gland function using salivary gland scintigraphy

2021 ◽  
Author(s):  
Tomohiro Itonaga ◽  
Koichi Tokuuye ◽  
Ryuji Mikami ◽  
Akira Shimizu ◽  
Hiroki Sato ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Conformal Radiotherapy ◽  
Head And Neck Carcinoma ◽  
Salivary Gland Function ◽  
Salivary Gland Scintigraphy ◽  
Radiotherapy Group ◽  
Tolerance Dose ◽  
Gland Function ◽  
Mathematical Evaluation

Objective: Xerostomia is the most common treatment-related toxicity after radiotherapy (RT) for head and neck carcinoma, reducing the quality of life of patients due to a decrease in salivary gland function. Methods: Salivary gland scintigraphy was performed to quantitatively evaluate the salivary gland functions in patients undergoing RT. It was done chronologically for 62 salivary glands of 31 patients before RT and retested 12 months later. Results: The salivary gland functions of most patients deteriorated post-RT and recovered when the radiation dose to the salivary gland was not high. The mean dose to the salivary gland was found to be the most reliable factor in deteriorating salivary gland function, and the tolerance dose was determined to be 46 Gy. The recovery rate of salivary gland function after 1 year of RT was 72% in the RT alone group (n = 10), 56% in the conformal radiotherapy group (n = 15), and 44% in the bioradiotherapy group (n = 6). Conclusion: Scintigraphy revealed that the salivary glands recovered from post-RT hypofunction when decreased doses were administered. The determined tolerance dose of 46 Gy may guide the approach to minimizing associated xerostomia in RT. Advances in knowledge: In this study, the average tolerated dose to the salivary glands was 46 Gy.

Evaluation of salivary gland function in allergic rhinitis patients by [99mTc] pertechnetate salivary gland scintigraphy

Open Medicine ◽  
2010 ◽  
Vol 5 (2) ◽  
pp. 246-250
Author(s):  
Ozgur Yoruk ◽  
Bedri Seven ◽  
Erhan Varoglu ◽  
Harun Ucuncu ◽  
Ali Sahin ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Salivary Gland ◽  
Salivary Glands ◽  
Healthy Controls ◽  
Time Activity ◽  
Salivary Gland Function ◽  
Salivary Gland Scintigraphy ◽  
99Mtc Pertechnetate ◽  
Significant Difference ◽  
Gland Function

AbstractThe purpose of this study was to compare the quantitative parameters of salivary gland functions in patients with allergic rhinitis and healthy volunteers using [99mTc] pertechnetate salivary gland scintigraphy. Thirty-six patients with allergic rhinitis (14 males and 22 females, mean age 30.6 ± 5.2 years) and thirty-nine healthy controls (18 males and 21 females, mean age 32.2 ± 5.6 years) were evaluated. Dynamic salivary gland scintigraphy was performed after intravenous administration of 185 MBq (5 mCi) of [99mTc] pertechnetate for 25 minutes. Lemon juice was used to stimulate the salivary glands. On the basis of the time-activity curves, the following glandular function parameters were calculated for the parotid and submandibular salivary glands: uptake ratio, maximum accumulation, and ejection fraction. Statistically, all the functional parameters of the parotid and submandibular glands obtained for the allergic rhinitis patients were significantly lower than those of the healthy controls group (p < 0.05). This study demonstrated that there was a significant difference in salivary gland function between patients with allergic rhinitis and healthy controls, which can easily be evaluated by [99mTc] pertechnetate salivary gland scintigraphy.

Sialoscintigraphy – Shopworn or Bestselling? A Traditional Procedure with New Prominent Role in Theranostics and Immuno-Oncology

2020 ◽  
Vol 59 (05) ◽  
pp. 375-380
Author(s):  
Barbara Kreppel ◽  
Florian C. Gaertner ◽  
Markus Essler
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Clinical Relevance ◽  
Checkpoint Inhibitors ◽  
Dental Health ◽  
Nuclear Imaging ◽  
Salivary Gland Function ◽  
Traditional Procedure ◽  
Gland Function

AbstractSialoscintigraphy has been used in nuclear imaging for almost sixty years. It allows functional assessment and quantification of all large salivary glands. Physiological function of the salivary glands is essential for the preservation of the oral mucosa, the sense of taste and dental health. Impaired salivary gland function may lead to reduced or even absent salivation resulting in various complaints such as loss of taste reducing quality of life. During the recent years clinical relevance of assessment of salivary gland function has been rising. As novel radiopharmaceuticals such as 225Ac-PSMA or 177Lu-PSMA may cause damage to the salivary glands in a subset of patients, reliable methods for quantification of salivary gland function are vital for therapy planning and follow-up. Standardized protocols for the implementation and interpretation of this procedure are necessary to achieve comparable results from individual theranostic centers and to facilitate multicenter trials. Sialocintigraphy is also of clinical relevance for immunooncology. Treatments with checkpoint inhibitors such as Ipilimumab or Nivulomab frequently cause autoimmune disorders affecting the salivary glands that may lead to reduced production of saliva and finally loss of taste. Therefore, standardized procedure protocols for sialoscintigraphy are also important for general oncology.Here we suggest a protocol for sialoscintigraphy that may be used as standard in centers for theranostics or immunooncology and discuss the potential future role of this traditional procedure.

scholarly journals An AAV2/5 Vector Enhances Safety of Gene Transfer to the Mouse Salivary Gland

2012 ◽  
Vol 91 (4) ◽  
pp. 382-386 ◽  
Author(s):  
R.N. Geguchadze ◽  
L. Machen ◽  
L. Zourelias ◽  
P.H. Gallo ◽  
M.J. Passineau
Keyword(s):  
Salivary Gland ◽  
Gene Transfer ◽  
Salivary Glands ◽  
Expression Level ◽  
High Dose ◽  
Clinical Parameters ◽  
Aav Vector ◽  
Salivary Gland Function ◽  
Submandibular Salivary Glands ◽  
Gland Function

This study was designed to improve AAV-mediated gene transfer to the murine submandibular salivary glands. Our first aim was to utilize AAV pseudotype vectors, containing the genetic elements of the canonical AAV2, packaged within capsids of AAV serotypes 5, 8, and 9. Having determined that this pseudotyping increased the efficiency of gene transfer to the glands by several orders of magnitude, we next asked whether we could reduce the gene transfer inoculum of the pseudotype while still achieving gene transfer comparable with that achieved with high-dose AAV2. Having achieved gene transfer comparable with that of AAV2 using a pseudotype vector (AAV2/5) at a 100-fold lower dose, our final objective was to evaluate the implications of this lower dose on two pre-clinical parameters of vector safety. To evaluate systemic toxicity, we measured AAV vector sequestration in the liver using qPCR, and found that the 100-fold lower dose reduced the vector recovered from the liver by 300-fold. To evaluate salivary gland function, we undertook whole-proteome profiling of salivary gland lysates two weeks after vector administration and found that high-dose (5 × 109) AAV altered the expression level of ~32% of the entire salivary gland proteome, and that the lower dose (5 × 107) reduced this effect to ~7%.

scholarly journals Disease-Induced Changes in Salivary Gland Function and the Composition of Saliva

2021 ◽  
pp. 002203452110048
Author(s):  
G.B. Proctor ◽  
A.M. Shaalan
Keyword(s):  
Salivary Gland ◽  
Sjögren Syndrome ◽  
Healthy Population ◽  
Sjogren Syndrome ◽  
Salivary Gland Function ◽  
Salivary Gland Dysfunction ◽  
Gland Function ◽  
And Function ◽  
The Impact ◽  
Saliva Composition

Although the physiological control of salivary secretion has been well studied, the impact of disease on salivary gland function and how this changes the composition and function of saliva is less well understood and is considered in this review. Secretion of saliva is dependent upon nerve-mediated stimuli, which activate glandular fluid and protein secretory mechanisms. The volume of saliva secreted by salivary glands depends upon the frequency and intensity of nerve-mediated stimuli, which increase dramatically with food intake and are subject to facilitatory or inhibitory influences within the central nervous system. Longer-term changes in saliva secretion have been found to occur in response to dietary change and aging, and these physiological influences can alter the composition and function of saliva in the mouth. Salivary gland dysfunction is associated with different diseases, including Sjögren syndrome, sialadenitis, and iatrogenic disease, due to radiotherapy and medications and is usually reported as a loss of secretory volume, which can range in severity. Defining salivary gland dysfunction by measuring salivary flow rates can be difficult since these vary widely in the healthy population. However, saliva can be sampled noninvasively and repeatedly, which facilitates longitudinal studies of subjects, providing a clearer picture of altered function. The application of omics technologies has revealed changes in saliva composition in many systemic diseases, offering disease biomarkers, but these compositional changes may not be related to salivary gland dysfunction. In Sjögren syndrome, there appears to be a change in the rheology of saliva due to altered mucin glycosylation. Analysis of glandular saliva in diseases or therapeutic interventions causing salivary gland inflammation frequently shows increased electrolyte concentrations and increased presence of innate immune proteins, most notably lactoferrin. Altering nerve-mediated signaling of salivary gland secretion contributes to medication-induced dysfunction and may also contribute to altered saliva composition in neurodegenerative disease.

Terminal duct adenocarcinomas of the parotid gland

1995 ◽  
Vol 109 (5) ◽  
pp. 466-468 ◽  
Author(s):  
Bonnie L. Kemp ◽  
John G. Batsakis ◽  
Adel K. El-Naggar ◽  
Sophia N. Kotliar ◽  
Mario A. Luna
Keyword(s):  
Salivary Gland ◽  
Parotid Gland ◽  
Salivary Glands ◽  
Minor Salivary Gland ◽  
Low Grade ◽  
Minor Salivary Glands ◽  
Biological Behaviour ◽  
Parotid Neoplasms ◽  
Clinicopathological Study

AbstractThe major salivary glands are considered to rarely be the sites of primary terminal duct adenocarcinomas, a neoplasm with a considerable predilection for origin from intraoral minor salivary glands. We present a clinicopathological study of 22 terminal duct adenocarcinomas of the parotid gland, the largest single series to date. A comparison between the parotid neoplasms and over 200 minor salivary gland terminal duct adenocarcinomas indicates there is little difference in biological behaviour and confirms the low-grade quality of the carcinomas, regardless of site of origin.

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