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PubMed2001

The utility of SPECT in determining the relationship between radiation dose and salivary gland dysfunction after radiotherapy.

Salivary gland scintigraphy (SGS) is used to depict salivary gland dysfunction after radiotherapy (RT). The aim of this study was to investigate the utility of SGS combined with single photon emission computed tomography (SPECT). Twenty-one patients with a carcinoma of head and neck underwent SGS before and 1 month after RT. After injection of 370 MBq 99Tcm-pertechnetate, a biplanar dynamic acquisition (12 x 1 min) was started, followed by a SPECT acquisition during 4 min. Carbachol was then injected and a second dynamic study (16 x 1 min) was performed, again followed by a SPECT acquisition. The salivary excretion fraction (SEF) was calculated both from the geometric mean planar image for each parotid and from the SPECT data for each transverse plane through the parotids. The RT-induced changes in the SEF (dSEF) were correlated with the mean radiation dose calculated using tomography-based dosimetry. The mean radiation dose to the parotids was 44 Gy (range 4.4-68.1 Gy). The mean range of the variation in radiation dose to the transverse slices within the parotids of a patient was 24 Gy (range 6.2-51.9 Gy). Considering all transverse planes through the parotids in all patients, a linear correlation was found between the dSEF calculated using SGS-SPECT and the radiation dose (r=0.45, P=0.0001). Thirteen patients had a variation in radiation dose within the parotids of more than 20 Gy. In nine of these a significant intra-individual correlation between radiation dose and the dSEF of the transverse parotid slices was found (r range 0.55-0.97; P value range 0.037-0.0001). In conclusion, SGS-SPECT can be used for monitoring radiation-induced parotid gland dysfunction. It offers the unique possibility for the assessment of intra-individual dose-dysfunction curves in patients with large variations in the radiation dose within the parotids.

Adult↗
PubMed1985

Salivary gland malignancies in children.

Malignant salivary gland neoplasms in children are rare. Such tumors usually occur in the parotid gland of older children. Sixteen cases of major salivary gland malignancy are reviewed, 14 occurring in the parotid gland and two in the submandibular gland. Adenoid cystic carcinoma was the most common malignancy encountered, occurring in five patients; four have died of disease. Low-grade mucoepidermoid carcinoma occurred in three patients and all remain alive and free of disease. An assorted variety of other cancers occurred in eight patients. One child died of reticulum cell sarcoma of the parotid gland, and two children have died of adenocarcinoma. The remaining five patients remain alive and free of disease. Salivary gland malignancies in children appear to have similar biological activity as those occurring in adults. Such tumors must be treated according to the same principles generally accepted for management of salivary gland malignancies in adults.

Adenocarcinoma↗
PubMed1988

Perinatal salivary gland tumours (embryomas).

Epithelial salivary gland tumours presenting in the first month of life (perinatal tumours) are exclusively of major salivary gland origin and predominantly of the parotid gland. Approximately 25 per cent of these rare tumours have been histologically and/or biologically malignant. Except for an occasional pleomorphic and monomorphic adenoma, the majority of the tumours are proliferations suggesting a tumourous arrest of maturation of the salivary gland anlage, hence their designation as embryomas. A case report of an embryoma of the parotid is presented, accompanied by a review of the literature.

Humans↗
PubMed1999

In vitro transformation of cell lines from human salivary gland tumors.

Explanted cells from salivary gland tumors are particularly difficult to propagate in vitro and not efficiently immortalized by agents such as simian virus 40. Human papillomavirus 16 (HPV16) has been widely used to transform cells of epithelial origin, but its use for salivary gland cell transformation has not been described. In this study, we employed viral constructs containing the E6/E7 genes of HPV16 to infect and stably transform 9 salivary gland tumor cell cultures. Four of the tumor cell cultures were derived from benign tumors and 5 from malignant tumors. All of the original cell cultures were diploid; however, 6 contained subpopulations of cells with structural abnormalities. All 9 cell cultures were successfully transformed, and 8 were immortalized. The resulting cell lines have decreased serum requirements, exhibit a high proliferation rate, are E6/E7-positive and form colonies in soft agar. Immuno-histochemical and molecular studies confirmed that the transformed cells were indeed epithelial/myoepithelial in origin. All of the transformed cell lines had a diploid or near-diploid karyotype, and 2 contained the original translocated chromosomes in all cells. Our report represents a new application of the E6/E7 system in immortalizing salivary gland cell cultures, resulting in retention of the cellular features found in the native tissue without a general destabilization of the karyotype. These types of tissue culture resources should prove useful for positional cloning and functional studies of genes involved in salivary gland oncogenesis.

Antigens, Differentiation↗
PubMed1995

Postirradiated submandibular gland: a potential model to study salivary gland radioprotection and tumourigenesis.

Theoretical reserve cells located in the intercalated and excretory ducts are postulated to be responsible for salivary gland tumourigenesis, with acinar cells playing no role in this process. Animal models, one using low-dose radiation to rat submandibular glands, indicate that this hypothesis is incorrect. Few human models have been devised to demonstrate and verify this theory. Submandibular glands in the field of ionizing radiation, as external-beam radiotherapy for head and neck tumours, were examined using an immunocytochemical technique and an antibody to proliferating cell nuclear antigen (PCNA), a specific marker for cycling cells. In the nonirradiated gland, nuclei positive for PCNA were seen in acinar as well as ductal cells of all types. Six months post irradiation, human submandibular glands show increased proliferative rates in both ductal and acinar cells that are significantly greater than control glands (p = .012). Based on this regenerative capacity, postirradiated human submandibular glands might serve as a model to investigate various treatment modalities for the prevention of radiation damage to acinar cells and the consequent patient morbidity that develops due to xerostomia. As well, these results suggest that even in humans, acinar cells are potential targets for carcinogenic agents and that current histogenic concepts for salivary gland tumourigenesis are incorrect.

Adult↗
PubMed2005

[Evaluation of sialometry and minor salivary gland biopsy in classification of Sjögren's Syndrome patients].

UNLABELLED: Sjögren's Syndrome is an autoimmune disease of the exocrine glands, mainly salivary and lachrymal glands. There is no gold standard test for diagnosis. AIM: evaluation of the importance of minor salivary gland biopsy and sialometry, isolated or associated, as methods for classification of Sjögren's Syndrome. STUDY DESIGN: Transversal cohort. PATIENTS AND METHOD: Seventy-two patients that reported dry mouth from January 1997 to September 2003 were investigated and classified, based on the established criteria. Non-stimulated sialometry was performed by the swab technique. Histopathology exams were evaluated for the presence of inflammatory focus. RESULTS: Non-stimulated sialometry and minor salivary gland biopsy presented different sensitivities for primary Sjögren's Syndrome and for secondary Sjögren's Syndrome. Focal sialadenitis with higher focus score was characteristic of primary Sjögren's Syndrome. Biopsy and sialometry were compared and it was observed that specificity and positive predictive value of biopsy were higher. Comparing biopsy and biopsy associated with sialometry, it was observed that biopsy had higher sensitivity and negative predictive value. Specificity of biopsy associated with sialometry was higher. Comparing sialometry and biopsy associated with sialometry, it was observed that biopsy associated with sialometry presented higher positive predictive value and higher specificity. Sialometry's sensitivity was higher. CONCLUSIONS: Sialometry and biopsy tests presented different performances in primary Sjögren's Syndrome and secondary Sjögren's Syndrome; the positivity of the association of both tests increases the specificity for Sjögren's Syndrome (95%).

Arthritis, Rheumatoid↗
PubMed2006

Expression of the Na+-HCO3- cotransporter and its role in pHi regulation in guinea pig salivary glands.

Patterns of salivary HCO(3)(-) secretion vary and depend on species and gland types. However, the identities of the transporters involved in HCO(3)(-) transport and the underlying mechanism of intracellular pH (pH(i)) regulation in salivary glands still remain unclear. In this study, we examined the expression of the Na(+)-HCO(3)(-) cotransporter (NBC) and its role in pH(i) regulation in guinea pig salivary glands, which can serve as an experimental model to study HCO(3)(-) transport in human salivary glands. RT-PCR, immunohistochemistry, and pH(i) measurements from BCECF-AM-loaded cells were performed. The amiloride-sensitive Na(+)/H(+) exchanger (NHE) played a putative role in pH(i) regulation in salivary acinar cells and also appeared to be involved in regulation in salivary ducts. In addition to NHE, NBC also played a role in pH(i) regulation in both acini and ducts. In the parotid gland, NBC1 was functionally expressed in the basolateral membrane (BLM) of acinar cells and the luminal membrane (LM) of ducts. In the submandibular gland, NBC1 was expressed only in the BLM of ducts. NBC1 expressed in these two types of salivary glands takes up HCO(3)(-) and is involved in pH(i) regulation. Although NBC3 immunoreactivity was also detected in submandibular gland acinar cells and in the ducts of both glands, it is unlikely that NBC3 plays any role in pH(i) regulation. We conclude that NBC1 is functionally expressed and plays a role in pH(i) regulation in guinea pig salivary glands but that its localization and role are different depending on the type of salivary glands.

Animals↗
PubMed1985

Myoepithelial cells in salivary gland tumors. An immunohistochemical study.

Normal salivary glands and 55 salivary gland tumors were examined by immunostaining (immunoperoxidase [IMP] and immunofluorescence [IMF]) to identify myoepithelial cells (MCs) and speculate on their role in the histogenesis of the tumors. The classic (C) MCs of normal salivary glands stained by IMP with antibodies to cytokeratin and S100 protein and stained by IMF with the same antibodies and with antibodies to vimentin and actin. Modified (M) MCs of pleomorphic adenomas stained positively by IMP and IMF with all of the preceding antibodies. In many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas, variable numbers of CMCs and MMCs stained positively by IMP with anti-cytokeratin and anti-S100 protein antibodies. No MCs were detected in adenolymphomas or acinic cell carcinomas. We believe that MCs play a major role in the histogenesis of pleomorphic adenomas and may also be important in many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas.

Actins↗
PubMed1990

Immunohistopathological properties of pleomorphic adenoma in salivary gland.

Fifty-eight salivary gland pleomorphic adenomas and 5 normal salivary glands were studied immunohistochemically with respect to intermediate filaments (keratin, desmin, and vimentin), actin and S-100 protein to observe the cellular differentiation of these tumor cells. Normal myoepithelial cells showed positive immunostaining for actin, vimentin and S-100 protein. Pleomorphic adenomas expressed keratin, vimentin and S-100 protein to various degrees, but only a few tumor cells of pleomorphic adenoma revealed actin. The results indicate that the tumor cells of pleomorphic adenoma show a bipolar differentiation capability of both epithelial and mesenchymal origins, although normal myoepithelial cells show only mesenchymal characteristics. The findings also support previous reports using light and electron microscopy, and also contribute to more precise diagnosis and a better understanding of the histogenesis of this tumor.

Actins↗
PubMed2003

Systemic and mucosal antibody responses following retroductal gene transfer to the salivary gland.

Gene transfer to salivary glands by retrograde perfusion of the salivary duct has been shown to result in production of the encoded protein. We sought to determine if this technique would be useful for genetic immunization. In studies that compare delivery of DNA to either the salivary gland (SG) or muscle (im), mean plasma IgG and IgA titers obtained following SG delivery were 46- and 86-fold greater, respectively, than those following im delivery. We also tested the hypothesis that SG vaccination could generate mucosal responses in sites proximal and distal to DNA administration. SG-treated animals produced specific antibodies within saliva, vaginal fluid, and lung washes as well as demonstrating robust specific responses in Peyer's patches. In a test of functional immunity, animals vaccinated with DNA by SG retrograde perfusion were significantly more resistant to the effects of lethal anthrax challenge than im DNA-vaccinated animals. These data suggest that SG genetic immunization may offer advantages over conventional routes of vaccination.

Animals↗
PubMedDate not supplied

Papillary cystadenoma: a rare tumor of the minor salivary glands.

Papillary cystadenoma of the minor salivary glands is a rare benign neoplasm that clinically resembles mucous cysts. Characteristic histological features are diagnostic. However, salivary gland histology is particularly difficult to interpret. Primarily, as further clinical and histological differential diagnoses have to take into account the well-differentiated cystic mucoepidermoid carcinoma and the papillary cystic type of acinic cell carcinoma, both malignant neoplasms of the salivary glands. We report on a 39 year old female with a bluish cystic lesion at the buccal mucosa, which occurred 14 years after the excision of a similar appearing, histologically proven mucous retention cyst at the same location. The histology of this tumor, however, revealed a papillary cystadenoma. Although rare, benign and malignant salivary gland neoplasms occur in minor salivary glands, and are clinically indistinguishable from mucous retention cysts. The dermatologist should be familiar with these differential diagnoses, since different therapeutic consequences result from an early diagnosis obtained by excision and histological examination of oral cystic tumors.

Adult↗
PubMed1982

The influence of calcium on the control of fluid secretion in the cockroach salivary gland.

When cockroach salivary glands are bathed in calcium-free medium the basal rate of fluid secretion increases from about 1 nl/min to about 10 nl/min; maintained dopamine stimulation elicits a further rise in secretory rate which gradually declines. Evidence is presented which indicates that magnesium is unable to substitute for calcium in this system. When calcium is returned to the bathing solution after a period of calcium deprivation there is a transient increase in secretory rate. Stimulation of the glands in certain conditions which inhibit the secretory response leads to some kind of calcium-dependent active state in the secretory cells which can outlast the interaction of the agonist with its receptors. It is concluded that stimulus-secretion coupling in this gland involves a calcium-dependent second messenger system.

Animals↗
PubMed1982

Localization of S-100 protein and glial fibrillary acidic protein-related antigen in pleomorphic adenoma of the salivary glands.

Pleomorphic adenoma of the salivary glands was studied by the peroxidase-antiperoxidase method and Ouchterlony's double diffusion for the presence of so-called nervous system-specific proteins, S-100 protein, glial fibrillary acidic protein (GFAP), and astroprotein. Positive immunostaining for S-100 protein was observed in tumor cells of epithelial, myxomatous, and chondroid areas. An immunodiffusion test confirmed its presence in the tumor. Normal salivary glands were also stained with anti-S-100 serum, but the reaction was less intense than that of tumor. Specific immunostaining for GFAP and astroprotein was found in a small number of cells of myxomatous and chondroid areas and occasionally in cells in epithelial areas. An immunodiffusion test suggests that the GFAP-related antigen of the pleomorphic adenoma showing a minor heterogeneity of antigenic determinants is almost identical with GFAP. Normal salivary glands did not stain with GFAP or astroprotein antisera, nor did they react with anti-GFAP serum by immunodiffusion. Thus, the S-100 protein and GFAP-related antigen may be actively synthesized in adenoma cells during the course of tumor development. In addition, the GFAP-related antigen is considered to be a tumor-associated antigen of pleomorphic adenoma of the salivary glands.

Adenoma, Pleomorphic↗
PubMed1999

Evidence of a phenotypically determined ductal cell lineage in mouse salivary glands.

The submandibular salivary gland of mice contains a parenchymal element, the granular duct, which matures peripubertally from the striated ducts. Granular duct cells also differentiate from intercalated ducts in the adult mouse submandibular gland. Using preproNGF-A as a signature protein of mature granular duct cells, this study inquired if phenotypic determination might have occurred earlier than the first signs of cellular differentiation. Results from RT-PCR indicate the presence of preproNGF-A transcripts at all postnatal stages of development of the submandibular glands, as well as in adult sublingual glands. The preproNGF-A transcript was also detected prenatally as early as embryonic day 17 in the submandibular/sublingual complex. Using an antibody directed specifically against the "pre" peptide, immunocytochemistry showed preproNGF-A localized in the granular ducts and striated ducts of the adult submandibular gland. In addition preproNGF-A was detected throughout the first order branches of the intercalated duct system. In the neonatal gland, preproNGF-A was found in the large tubules that differentiate to the striated ducts. The early appearance of preproNGF-A in the histological lineage that sequentially gives rise to striated ducts and then to granular ducts suggests that this lineage is phenotypically determined as early as birth. An undifferentiated stage of the phenotypically determined lineage also appears to be retained in the intercalated duct system to provide progenitors for subsequent differentiation in the adult gland. Throughout development of the sublingual gland, preproNGF-A was detectable in the striated ducts or in their predecessors, suggesting that they may also represent a phenotypically determined cell lineage similar to that of the submandibular gland.

Amino Acid Sequence↗
PubMed1998

Novel protection strategy against X-ray-induced damage to salivary glands.

Exposure of the major salivary glands to ionizing radiation often results in severe alterations in structure and function. The mechanism of these effects is still unknown, and no adequate prevention or treatment is yet available. The purpose of this study was to examine a mechanism based on the assumption that redox-active metal ions, which propagate the production of highly reactive free radicals, are responsible for the unique radiosensitivity of salivary glands. Zinc-desferrioxamine (Zn-DFO) was recently reported to be a very potent protector against the injuries induced by such metal ions in the vicinity of sensitive cellular targets. We chose to examine its protective potential against the damage to salivary glands induced by X rays. Head and neck irradiation (15 Gy) was delivered to rats 90 min after the intraperitoneal administration of 20 mg/kg Zn-DFO. This group was compared to two control groups, irradiated and nonirradiated. At 2 months after irradiation, both systemic and salivary parameters were analyzed. The results demonstrated that X irradiation induced a profound attenuation of body weight (30%) and a reduction of parotid gland saliva flow rate (74%), parotid gland weight (36%), submandibular gland/sublingual gland saliva flow rate (46%), and submandibular/sublingual gland weight (24%) (P < 0.01 for all parameters). The content of potassium in parotid gland saliva was increased by 46% (P < 0.01), while the protein content was unaltered. The increase in the potassium concentration of the saliva is considered to be another indication of salivary gland hypofunction. Administration of Zn-DFO prior to irradiation resulted in partial protection against radiation-induced injury to the parotid gland but not the submandibular gland. In the Zn-DFO-treated and irradiated group, the parotid gland saliva flow rate was reduced by 42%, the weight of the parotid gland was reduced by 13%, and the potassium concentration in the parotid gland saliva was increased by 21% (P < 0.05 for all parameters). These results give credence to the validity of the hypothesis which correlates radiation-induced damage of the salivary glands with the injurious role of intracellular redox-active metal ions. Furthermore, the results offer prospects in the clinical setting, as Zn-DFO is a modification of DFO, which is a clinically approved and widely used medication. Further examination of the clinical use of Zn-DFO is currently under way, focusing on its beneficial protective effect on healthy non-neoplastic tissue.

Animals↗
PubMed2005

[Tumors of the salivary glands].

Tumors of salivary glands arise mainly from the parotid gland. Magnetic Resonance Imaging (MRI) is mandatory not only to localize precisely the tumor within the gland but also to differentiate between benign and malignant neoplasms, in competition with cytology in fine-needle aspiration biopsy. Tumors without risk of transformation, such as adenolymphoma, are not systematically operated on. Indications of roentgenotherapy and irradiation volumes depend on histologic type, localisation and size of the tumor.

Adenolymphoma↗
PubMed1999

Benign salivary gland neoplasms.

Benign salivary gland neoplasms represent a diverse group of neoplasms with varied clinical behaviors. Successful management of these tumors depends on accurate clinical and diagnostic assessment, followed by appropriate therapeutic intervention. An appropriate understanding of the biologic behavior of each tumor type allows for development of an appropriate treatment plan tailored to the individual patient.

Diagnosis, Differential↗