SPM Receptor Expression and Localization in Irradiated Salivary Glands

2021 ◽  
Vol 69 (8) ◽  
pp. 523-534
Author(s):  
Harim Tavares dos Santos ◽  
Kihoon Nam ◽  
Jason P. Hunt ◽  
Luke O. Buchmann ◽  
Marcus M. Monroe ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Salivary Gland ◽  
Salivary Glands ◽  
Artificial Saliva ◽  
Receptor Expression ◽  
Lipid Mediator ◽  
Resolution Of Inflammation ◽  
Ductal Cells ◽  
Alternative Measures ◽  
And Function

Radiation therapy–mediated salivary gland destruction is characterized by increased inflammatory cell infiltration and fibrosis, both of which ultimately lead to salivary gland hypofunction. However, current treatments (e.g., artificial saliva and sialagogues) only promote temporary relief of symptoms. As such, developing alternative measures against radiation damage is critical for restoring salivary gland structure and function. One promising option for managing radiation therapy–mediated damage in salivary glands is by activation of specialized proresolving lipid mediator receptors due to their demonstrated role in resolution of inflammation and fibrosis in many tissues. Nonetheless, little is known about the presence and function of these receptors in healthy and/or irradiated salivary glands. Therefore, the goal of this study was to detect whether these specialized proresolving lipid mediator receptors are expressed in healthy salivary glands and, if so, if they are maintained after radiation therapy–mediated damage. Our results indicate that specialized proresolving lipid mediator receptors are heterogeneously expressed in inflammatory as well as in acinar and ductal cells within human submandibular glands and that their expression persists after radiation therapy. These findings suggest that epithelial cells as well as resident immune cells represent potential targets for modulation of resolution of inflammation and fibrosis in irradiated salivary glands.

scholarly journals Neurofibromin expression by normal salivary glands

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Eloá Borges Luna ◽  
Pâmella Pinho Montovani ◽  
Rafaela Elvira Rozza-de-Menezes ◽  
Karin Soares Cunha
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Acinar Cells ◽  
Staining Intensity ◽  
Neurofibromatosis 1 ◽  
Tissue Type ◽  
Sublingual Gland ◽  
Minor Salivary Glands ◽  
Expression Levels ◽  
Ductal Cells

AbstractIntroductionNeurofibromin, a protein encoded by theNF1gene, is mutated in neurofibromatosis 1, one of the most common genetic diseases. Oral manifestations are common and a high prevalence of hyposalivation was recently described in individuals with neurofibromatosis 1. Although neurofibromin is ubiquitously expressed, its expression levels vary depending on the tissue type and developmental stage of the organism. The role of neurofibromin in the development, morphology, and physiology of salivary glands is unknown and a detailed expression of neurofibromin in human normal salivary glands has never been investigated.AimTo investigate the expression levels and distribution of neurofibromin in acinar and ductal cells of major and minor salivary glands of adult individuals without NF1.Material and methodTen samples of morphologically normal major and minor salivary glands (three samples of each gland: parotid, submandibular and minor salivary; and one sample of sublingual gland) from individuals without neurofibromatosis 1 were selected to assess neurofibromin expression through immunohistochemistry. Immunoquantification was performed by a digital method.ResultsNeurofibromin was expressed in the cytoplasm of both serous and mucous acinar cells, as well as in ducts from all the samples of salivary glands. Staining intensity varied from mild to strong depending on the type of salivary gland and region (acini or ducts). Ducts had higher neurofibromin expression than acinar cells (p = 0.003). There was no statistical association between the expression of neurofibromin and the type of the salivary gland, considering acini (p = 0.09) or ducts (p = 0.50) of the four salivary glands (parotid, submandibular, minor salivary, and sublingual gland). Similar results were obtained comparing the acini (p = 0.35) and ducts (p = 0.50) of minor and major salivary glands. Besides, there was no correlation between the expression of neurofibromin and age (p = 0.08), and sex (p = 0.79) of the individuals, considering simultaneously the neurofibromin levels of acini and duct (n = 34).ConclusionNeurofibromin is expressed in the cytoplasm of serous and mucous acinar cells, and ductal cells of salivary glands, suggesting that this protein is important for salivary gland function.

Human Kallikrein 14 (Klk14) Expression in Salivary Gland Tumors

2010 ◽  
Vol 25 (1) ◽  
pp. 32-37 ◽  
Author(s):  
Nelly N. Hashem ◽  
Thomas W. Mara ◽  
Mohamed Mohamed ◽  
Irene Zhang ◽  
Kevin Fung ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Malignant Tumors ◽  
Expression Profiles ◽  
Staining Technique ◽  
Tumor Stage ◽  
Salivary Gland Tumors ◽  
Immunoperoxidase Staining ◽  
Clinical Parameters ◽  
Ductal Cells

Objective To analyze the expression of human kallikrein 14 (KLK14) in salivary gland tumors. Methods A standard immunoperoxidase staining technique was used to assess the expression profile of KLK14 in normal salivary glands and tumors including pleomorphic adenoma (PA; n=17), adenoid cystic carcinoma (ACC; n=13) and mucoepidermoid carcinoma (MEC; n=9). Tumor stage, grade, patient age and gender, and site of occurrence were recorded. These clinical parameters were correlated with KLK14 levels in malignant tumors. The expression profiles for KLK3, 5, 6, 8 and 13 were also retrieved. Results Normal salivary glands, PA, ACC and MEC showed strong expression of KLK14 in ductal and non-ductal cells. Both PA and ACC showed higher KLK14 levels than normal glands and MEC tissues. There were no statistically significant associations between levels of KLK14 and clinical parameters. Conclusions The differences in the levels of KLK14 suggest that KLKs may aid in the differential diagnosis of salivary gland tumors. The coexpression of KLKs suggests their possible involvement in an enzymatic pathway activated in salivary gland. KLK14 may be a promising new biomarker in salivary gland tumors.

scholarly journals Epigenetic Modification as a Regulatory Mechanism for Spatiotemporal Dynamics of ANO1 Expression in Salivary Glands

2019 ◽  
Vol 20 (24) ◽  
pp. 6298 ◽  
Author(s):  
Yonghwan Shin ◽  
Sang-Woo Lee ◽  
Eun Namkoong ◽  
Woojin An ◽  
Jong-Ho Lee ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Differential Expression ◽  
Expression Pattern ◽  
Dna Methyltransferase ◽  
Epigenetic Modification ◽  
Critical Role ◽  
Cpg Islands ◽  
Ductal Cells ◽  
Differential Expression Pattern

Anoctamin1 (ANO1), a calcium activated chloride channel, is known to play a critical role in salivary secretion. In the salivary gland, ANO1 is expressed exclusively in the acinar cells, with no expression in the ductal cells. However, the mechanisms that determine this distinctive cell type-dependent expression pattern of ANO1 remain unknown. In this study, we discovered that the cell-dependent expression of ANO1 during salivary gland organogenesis is regulated by DNA methylation of ANO1 CpG islands. ANO1 CpG islands in e12 embryonic submandibular glands (eSMG) are highly methylated, but those in e14 eSMG or adult SMG are significantly unmethylated. The differential expression pattern of ANO1 in duct and acini is defined at e14. Artificial demethylation by treatment with the demethylating agent 5-aza-2’-deoxycytidine (5-Aza-CdR), induced the expression of ANO1 in both the ductal cell line Human Submandibular Gland (HSG) and in the duct cells of adult mouse SMG. During the trans-differentiation in Matrigel of duct-origin HSG cells into acinar-like phenotype, significant demethylation of ANO1 CpG islands is observed. This may be due to the reduced expression of DNA methyltransferase (DNMT) 3a and 3b. These results suggest that the differential expression of ANO1 in salivary glands during organogenesis and differentiation is mainly regulated by epigenetic demethylation of the ANO1 gene.

scholarly journals Morphologic Characteristics of the Submandibular Salivary Gland of the Collared Peccary (Tayassu Tajacu)

2018 ◽  
Vol 35 (02) ◽  
pp. 116-121
Author(s):  
Gabriela de Souza Reginato ◽  
Cristina de Sousa Bolina ◽  
Moacir Franco Oliveira ◽  
Sonia Regina Yokomizo Almeida ◽  
Ii-sei Watanabe ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Salivary Gland ◽  
Salivary Glands ◽  
Secretory Granules ◽  
Morphological Characteristics ◽  
Acinar Cells ◽  
Collagen Fibers ◽  
Submandibular Salivary Gland ◽  
Ductal Cells ◽  
Collared Peccary

Introduction Most salivary glands is located on the inside and around the oral cavity, and are divided into major and minor salivary glands. The aim of the present study was to describe the structural and ultrastructural morphological characteristics of the lingual tissue of the submandibular glands of the collared peccary (Tayassu tajacu). Materials and Methods The submandibular glands (n = 10) of adult male collared peccaries ( T. tajacu) were used for histological and ultrastructural analysis. The techniques used were light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Results The submandibular salivary glands of the collared peccary (T. tajacu) showed a capsule formed by a connective tissue containing the acinus and duct cells. Histologically, the nuclei located at the basal region of the cells was observed. The light polarized microscopy clearly showed the presence of type I and type III collagen. In the SEM image, the submandibular salivary gland revealed a round aspect separated in several lobules with bundles of collagen fibers. The vibratome sections showed the groupings of acinar cells, with intermingled secretory ducts containing vessels of different diameters. The secretory granules were noted in the apical portion of the acinar and ductal cells. The thick bundles of collagen fibers formed a glandular capsule and were identified around of the acinar and ductal cells in three-dimensional SEM images. The TEM images showed a number of secretory granules, especially in the apical region of the cytoplasm of the acinar cells and in the basal portion of the nuclei. The granular endoplasmic reticulum area, the euchromatic nuclei and the cytoplasmic projections may be seen. Mucous acinar cells separated by fine collagen fibers were also observed. Conclusion The morphological characteristics of the submandibular gland of the collared peccary is similar to that of other mammals with the same eating habits and habitat.

Peculiar histopathological features in minor salivary gland in lupus erythematosus

Lupus ◽  
2018 ◽  
Vol 27 (10) ◽  
pp. 1706-1711 ◽  
Author(s):  
S B Bologna ◽  
M M S Nico ◽  
G Florezi ◽  
W S Cavalcante ◽  
S V Lourenço
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Lupus Erythematosus ◽  
Inflammatory Infiltrate ◽  
Minor Salivary Gland ◽  
Control Group ◽  
Minor Salivary Glands ◽  
Vacuolar Degeneration ◽  
Ductal Cells ◽  
American College Of Rheumatology

Salivary glands (SGs) can be affected by lupus erythematosus (LE). Many authors debate whether this condition is a secondary manifestation of Sjögren syndrome (SS) or a glandular aspect of LE. The present study investigated the histopathological aspects of biopsied minor salivary glands from LE patients to analyze their peculiar features that lead to xerostomia. Twenty-three minor labial salivary gland (MLSG) cases were included in the study; the diagnosis of LE was rendered according to the American College of Rheumatology criteria. Twenty-three healthy MLSGs were used as a control, for comparison. Regarding lupus MLSG, the presence of hyalinization and thickening of ductal basement membrane, perivascular inflammatory infiltrate, epithelial spongiosis with no ductal lymphocytic aggression, vacuolar degeneration of the ductal cells and acinar serous metaplasia were statistically significant compared to the control group. In the LE group, there was a statistically significant correlation between acinar atrophy and acinar fibrosis; acinar atrophy and ductal ectasia; acinar fibrosis and ductal ectasia; ductal atrophy and ductal spongiosis with no lymphocytic focus, interstitial inflammatory infiltrate intensity and vasculitis as well as vascular thrombi and vasculitis. There were no morphological differences between the three subtypes of lupus analyzed. Minor salivary glands from patients diagnosed with LE present peculiar histopathological changes and may be a multisystemic presentation.

Direct in vivo adenovirus-mediated gene transfer to salivary glands

1994 ◽  
Vol 266 (6) ◽  
pp. G1146-G1155 ◽  
Author(s):  
A. Mastrangeli ◽  
B. O'Connell ◽  
W. Aladib ◽  
P. C. Fox ◽  
B. J. Baum ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Gene Transfer ◽  
Salivary Glands ◽  
De Novo ◽  
Recombinant Adenovirus ◽  
Salivary Gland Cell ◽  
Immunodeficient Mice ◽  
Ductal Cells ◽  
Adenovirus Vectors

Gene transfer to the salivary glands holds the potential for the therapy of salivary gland disorders and for delivery of therapeutic proteins to the mouth and upper gastrointestinal tract. Administration of the recombinant adenovirus vectors Ad.RSV beta gal [coding for the intracellular protein beta-galactosidase (beta-Gal)] and Ad alpha 1AT [coding for human alpha 1-antitrypsin (alpha 1-AT), a secreted protein] to salivary gland cell lines in vitro demonstrated exogenous gene expression. Retrograde ductal injection of the Ad.RSV beta gal vector to rat salivary glands in vivo resulted in beta-Gal expression in acinar and ductal cells. Exposure of submandibular glands in vivo to Ad alpha 1AT resulted in expression of alpha 1-AT mRNA transcripts, de novo synthesis of alpha 1-AT, and secretion in the saliva. To evaluate the feasibility of adenovirus-mediated gene transfer to human glands, human minor salivary glands were infected ex vivo with Ad.RSV beta gal, and implanted into severe combined immunodeficient mice. Evaluation of the human tissue demonstrated beta-Gal activity. These observations demonstrate that adenovirus vectors are capable of direct delivery of genes to the salivary glands, suggesting a variety of possible gene therapy applications.

Epithelial-Myoepithelial Carcinoma of Salivary Glands

1992 ◽  
Vol 101 (6) ◽  
pp. 540-542 ◽  
Author(s):  
John G. Batsakis ◽  
Adel K. El-Naggar ◽  
Mario A. Luna
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Cell Population ◽  
Phenotypic Expression ◽  
Myoepithelial Cells ◽  
Salivary Gland Neoplasms ◽  
Myoepithelial Carcinoma ◽  
Parotid Glands ◽  
Ductal Cells ◽  
Epithelial Myoepithelial Carcinoma

Epithelial-myoepithelial carcinomas comprise approximately 1 % of all salivary gland neoplasms. They are preponderantly tumors of the parotid glands with a relatively low mortality but a decided locoregional aggressiveness. Histopathologically, the carcinomas are characterized by a dual cell population of epithelial (ductal) cells and myoepithelial cells. These cells vary in their dominance and phenotypic expression

scholarly journals Aldehyde dehydrogenase 3A1 activation prevents radiation-induced xerostomia by protecting salivary stem cells from toxic aldehydes

2018 ◽  
Vol 115 (24) ◽  
pp. 6279-6284 ◽  
Author(s):  
Julie P. Saiki ◽  
Hongbin Cao ◽  
Lauren D. Van Wassenhove ◽  
Vignesh Viswanathan ◽  
Joshua Bloomstein ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Salivary Glands ◽  
Aldehyde Dehydrogenase ◽  
Neck Cancer ◽  
Common Side Effect ◽  
Loss Of Function ◽  
And Function

Xerostomia (dry mouth) is the most common side effect of radiation therapy in patients with head and neck cancer and causes difficulty speaking and swallowing. Since aldehyde dehydrogenase 3A1 (ALDH3A1) is highly expressed in mouse salivary stem/progenitor cells (SSPCs), we sought to determine the role of ALDH3A1 in SSPCs using genetic loss-of-function and pharmacologic gain-of-function studies. Using DarkZone dye to measure intracellular aldehydes, we observed higher aldehyde accumulation in irradiated Aldh3a1−/− adult murine salisphere cells and in situ in whole murine embryonic salivary glands enriched in SSPCs compared with wild-type glands. To identify a safe ALDH3A1 activator for potential clinical testing, we screened a traditional Chinese medicine library and isolated d-limonene, commonly used as a food-flavoring agent, as a single constituent activator. ALDH3A1 activation by d-limonene significantly reduced aldehyde accumulation in SSPCs and whole embryonic glands, increased sphere-forming ability, decreased apoptosis, and improved submandibular gland structure and function in vivo after radiation. A phase 0 study in patients with salivary gland tumors showed effective delivery of d-limonene into human salivary glands following daily oral dosing. Given its safety and bioavailability, d-limonene may be a good clinical candidate for mitigating xerostomia in patients with head and neck cancer receiving radiation therapy.

Radiation-Associated Carcinoma of the Salivary Glands a Controlled Study

1981 ◽  
Vol 90 (2) ◽  
pp. 107-108 ◽  
Author(s):  
Harry R. Maxon ◽  
Eugene L. Saenger ◽  
Stephen R. Thomas ◽  
Margaret L. Shafer ◽  
C. Ralph Buncher ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Salivary Gland ◽  
Head And Neck ◽  
Salivary Glands ◽  
Radiation Field ◽  
Controlled Study ◽  
External Radiation ◽  
Significant Excess ◽  
Benign Diseases ◽  
External Radiation Therapy

Five hundred fifty-four persons were evaluated who had received external radiation therapy for benign diseases of the head and neck in childhood and whose salivary glands were presumably included in the radiation field. A significant excess of salivary gland cancers were noted when they were compared to 958 nonirradiated control subjects.

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