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PubMed2001

Enhancing effects of fibroblast growth factor on the proliferation of salivary gland carcinoma cells and salivary gland carcinogenesis.

The proliferation of mouse submandibular gland carcinoma YT-12 cells was stimulated by endothelial cell growth factor (ECGF)/bovine brain-derived acidic fibroblast growth factor (aFGF) and recombinant human aFGF. To determine whether aFGF was capable of modifying salivary gland carcinogenesis, the effect of brain-derived aFGF was examined in vivo. Mice in Groups 1 and 2 were injected with 9,10-dimethyl-1,2-benzanthracene (DMBA) into the left submandibular gland, and then Group 1 mice received bovine brain-derived aFGF and Group 2 mice received vehicle subcutaneously for 10 weeks. Group 3 and 4 mice received either bovine brain-derived aFGF or vehicle only. Sixteen weeks after the start of the experiment, the incidence of submandibular gland carcinomas in Group 1 was significantly greater than that in Group 2. Immunohistochemical study indicated that ducts in the normal submandibular glands and carcinomas showed positive staining with anti-aFGF antibody. Immunoblot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the expression of aFGF in these tissues. FGF receptor (FGFR)-1 and FGFR-4 were detectable in the mouse submandibular glands and carcinomas. These findings suggest that bovine brain-derived aFGF stimulates the proliferation of submandibular gland carcinoma cells and promotes mouse submandibular gland carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1976

Classification of the pathohistology of diseases of the salivary glands - review of 2,600 cases in the Salivary Gland Register.

Three major disease groups emerge from a classification of the pathohistology of 2,600 salivary gland preparations in the salivary gland register (from 1965 to 1974): salivary gland tumors (41%), salivary gland inflammations (26%), and sialadenosis (6%). Mucoceles (2%) and salivary gland cysts (1.5%) are seen less often. It is diagnostically important that lymph node changes in the area of the salivary glands (lymphadenitis, lymphomas, etc.) are worked up under suspicion of a primary salivary gland disease. Sialadenosis involves a primary, vegetative neuropathy, which is accompanied by enlargement of acinar cells. Under the heading of chronic sialdenitis, we fine 50% socalled Küttner tumors of the submandibular gland, 21% chronic relapsing parotitis, 14% chronic inflammations of the minor salivary glands and the sublingual gland, and 12% immune sialadenitis (myoepithelial sialadenitis in Sjögren's syndrome and epitheloid cell sialadenitis in Heerfordts syndrome). A more than average number of immune sialadenitis cases develop into malignant lymphomas (4 cases in the salivary gland register). The 1,067 tumor cases containing of 929 epithelial tumors (87%), 89 mesenchymal tumors (hemangiomas, lymphangiomas, lipomas, neurofibromas, sarcomas) and 49 metastases or periglandular tumors. Epithelial tumors were grouped on the basis of the World Health Organization (WHO) classification. Benign tumors (71.5%) consisted of pleomorphic adenomas (51.5%) and monomorphic adenomas (50%). After the pleomorphic adenomas, cystadenolymphomas (over 10%) represented the most frequent benign salivary gland tumor. On the basis of epithelial and stromal differentiation, pleomorphic adenomas were subdividied into four subtypes (stroma-rich and stroma-poor adenomas). The malignant tumors consisted of acinar cell tumors (2.5%), mucoepidermoid tumors (6%), and carcinomas at various levels of differentiation (adenoid-cystic carcinomas, 6.5%; adenocarcinomas, 2%; squamous cell carcinomas, 2%; carcinomas in pleomorphic adenomas, 4%; miscellaneous carcinomas - salivary duct carcinomas, clear-cell carcinomas, undifferentiated carcinomas, 5.5%). Differences in age and sex distribution, localization, malignity metastases, recidivism, et

Adenoma↗
PubMed2003

MUC1 and MUC2 expression in salivary gland tumors and in non-neoplastic salivary gland tissue.

The expression of MUC1 and MUC2 was studied in salivary gland tumors and non-neoplastic salivary gland tissue. Formalin-fixed paraffin-embedded specimens from 101 patients (21 pleomorphic adenomas (PA), 22 Warthin's tumors (WT), 26 adenoid cystic carcinomas (ACC), 13 acinic cell adenocarcinomas (ACA), 9 mucoepidermoid carcinomas (MC), and 10 specimens of non-neoplastic parotid and submandibular gland tissue) were immunostained. All salivary gland tumors expressed MUC1. A strong immunoreactivity was noted in WT and MC, a moderate in ACC and ACA, and a weak in PA. Strong expression of MUC2 was noted in all WT, moderate expression in MC, and weak expression in PA and ACA. All cases of ACC except for two were negative for MUC2. In general, MUC1 expression was stronger than that of MUC2. Non-neoplastic salivary gland tissue revealed a moderate MUC1 and MUC2 expression in excretory ducts and a strong expression in striated ducts. The apical plasma membrane of some serous acini expressed MUC1. Mucous acini were negative for both antigens. No change in immunoreactivity was noted in cases of chronic sclerosing sialadenitis. In conclusion, the different expression pattern of MUC1 and MUC2 in salivary gland neoplasia may be of additional value for the classification of salivary gland tumors.

Adenolymphoma↗
PubMed1999

Assessment of salivary gland dysfunction following chemoradiotherapy using quantitative salivary gland scintigraphy.

PURPOSE: To assess chemoradiotherapy-induced salivary gland dysfunction using quantitative salivary gland scintigraphy (QSGS), and whether QSGS is capable of predicting the grade of persistent salivary dysfunction after chemoradiotherapy. METHODS: From a time-activity curve using a stimulation test, the washout rate (WR) calculated was assessed. All glands (n = 155) were classified into four groups: a no-therapy group (n = 18), a chemotherapy alone group (n = 31), a radiotherapy alone group (n = 50), and a chemoradiotherapy group (n = 56). Subjective descriptions of xerostomia were recorded 1 year after the completion of the treatment period, and the 32 glands subjected to irradiation with or without chemotherapy were assessed. RESULTS: The WR values were significantly lower in glands that received chemoradiotherapy than in glands treated with radiotherapy alone (mean: 0.75 x 10(-3), n = 40 vs. 0.22, n = 36, p < 0.015), but there was no significant difference in the WR values between the no-therapy group and the chemotherapy alone group. The mean values of WR were lower in the chemoradiotherapy glands than in the radiotherapy alone glands in each of cumulative dose ranges of 1-20, 21-30, and 31-60 Gy. With regard to recovery from xerostomia, the WR values at a cumulative dose range of 20 to 40 Gy were significantly lower in the not improved group (-0.418, n = 16) than in the improved group (0.245, n = 16) (p < 0.0001). CONCLUSION: Chemotherapy per se has no or little adverse effect on salivary function, but combination chemotherapy can deteriorate radiation-induced injury of the salivary glands. QSGS appears useful in predicting the grade of persistent xerostomia following chemoradiotherapy.

Adolescent↗
PubMed2001

Expression of volume-sensitive Cl(-) channels and ClC-3 in acinar cells isolated from the rat lacrimal gland and submandibular salivary gland.

1. The expression of ClC-3 was examined in rat lacrimal gland and submandibular salivary gland cells using RT-PCR and Western analysis. Whole-cell patch clamp methods were used to investigate the expression of volume-sensitive anion channels in acinar cells isolated from these tissues. 2. Expression of mRNA encoding ClC-3, and ClC-3 protein, was found in rat submandibular gland by RT-PCR and Western analysis. Rat lacrimal gland cells, however, did not appear to express mRNA encoding for ClC-3, nor the ClC-3 protein. 3. Volume-sensitive anion conductances were observed in both rat lacrimal gland and submandibular salivary gland acinar cells. The conductance was of a similar size in the two cell types, but was much slower to activate in the lacrimal cells. 4. The properties of the conductances in lacrimal and submandibular cells were similar, e.g. halide selectivity sequence (P(I) > P(Cl) > P(aspartate)) and inhibition by 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid, 5-nitro-2-(3-phenylpropylamino)-benzoate and tamoxifen. 5. The data suggest that the expression of ClC-3 is not an absolute requirement for the activity of volume-sensitive anion channels in rat lacrimal gland acinar cells.

Animals↗
PubMed2004

Salivary agglutinin/DMBT1SAG expression is up-regulated in the presence of salivary gland tumors.

Salivary agglutinin (SAG) is encoded by the gene Deleted in Malignant Brain Tumors 1 (DMBT1) and represents the salivary variant of DMBT1 (DMBT1(SAG)). While SAG is a bona fide anti-caries factor, DMBT1 was proposed as a candidate tumor-suppressor for brain, digestive tract, and lung cancer. Though DMBT1(SAG) is expressed in the salivary glands, its expression in salivary gland tumors is unknown. Here we analyzed DMBT1(SAG) expression in 20 salivary gland tumors and 14 tumor-flanking tissues by immunohistochemistry. DMBT1(SAG) in salivary gland tumors resembles the changes of expression levels known from DMBT1 in tumors in other cancer types. Particularly, DMBT1(SAG) was up-regulated in 10/14 tumor-flanking tissues, and a strong staining of the luminal content in the tumor and/or the tumor-flanking tissue was observed in 14/20 cases. This suggests that, in addition to its role in caries defense, SAG may serve as a potential tumor indicator and/or tumor suppressor in salivary gland tissue.

Agglutinins↗
PubMed1981

Radionuclide salivary gland imaging.

Salivary gland imaging with 99mTc as pertechnetate provides functional information concerning trapping and excretion of the parotid and submandibular glands. Anatomic information gained often adds little to clinical evaluation. On the other hand, functional information may detect subclinical involvement, which correlates well with biopsy of the minor labial salivary glands. Salivary gland abnormalities in systemic disease such as sarcoidosis, rheumatoid arthritis, lupus erythematosus, and other collagenvascular disorders may be detected before they result in the clinical manifestaions of Sjögren's syndrome. Such glands, after initially demonstrating increased trapping in the acute phase, tend to have decreased trapping and failure to discharge pertechnetate in response to an appropriate physiologic stimulus. Increased uptake of gallium-67 citrate often accompanies these findings. Inflammatory parotitis can be suspected when increased perfusion is evident on radionuclide angiography with any agent. The ability of the salivary gland image to detect and categorize mass lesions, which result in focal areas of diminished activity such as tumors, cysts, and most other masses, is disappointing, while its ability to detect and categorize Warthin's tumor, which concentrates pertechnetate, is much more valuable, although not specific.

Adenolymphoma↗
PubMed1984

Radioiodide uptake in brain, CSF, thyroid, and salivary glands of audiogenic seizure mice.

DBA/2J (DBA) mice are susceptible to audiogenic seizures (ASs) in an age-dependent manner. Anion transport as measured by radioiodide uptake was determined in thyroid gland, salivary gland, skeletal muscle, cerebral cortex, cerebellum, brainstem, and CSF from these mice at various ages. Anion transport was also determined in C57BL/6J(C57) mice, an AS-resistant strain. In thyroid, DBA mice had an enhanced ability to concentrate iodide at 21 days of age when they have maximal AS susceptibility, as compared with the same-aged C57 mice. This difference in thyroid function was less marked at 40 days of age, when DBA mice are less AS susceptible, and was absent at 110 days of age, when DBA mice are AS resistant. In brain, differences in iodide uptake were also noted between these two strains of mice at 21 days of age. DBA mice had an increased concentration of iodide in CSF, an indication that they have a defect in the transport of iodide out of the CSF across the choroid plexus. In addition, DBA mice had a lower ratio of cerebral cortex to CSF iodide, which suggests that DBA mice have a defect in the transport of this anion into cerebral cortical cells from brain interstitial fluid. These differences in iodide transport in brain decreased with age as the AS susceptibility of DBA mice decreased. These results suggest a relation between anion transport in thyroid gland, cerebral cortex, and choroid plexus and AS susceptibility in DBA mice at 21 days of age.

Acoustic Stimulation↗
PubMed2004

Transplantation of cultured salivary gland cells into an atrophic salivary gland.

Patients with dry mouth have been treated with salivary substitutes and/or medications such as pilocarpine or cevimeline hydrochloride. These treatments temporarily relieve their symptoms and induce salivation from residual tissue. However, no treatment is available for the purpose of regenerating an atrophic gland. In this study, the feasibility of a cell transplantation therapy for the atrophic submandibular glands was investigated in rats. Further, the potential of cell differentiation into a useful phenotype was assessed by immunohistochemistry together with cell tracking with the fluorescent dye PKH 26. Rat submandibular glands were excised, and the salivary gland epithelial cells were cultured for 3 weeks with 3T3 cells as a feeder layer. Ductal ligation of the submandibular gland was employed to generate an atrophic gland. One week after the operation, the ligation was removed, and the cultured cells labeled with PKH 26 were injected into the atrophic submandibular glands. As a control, the cultured cells were also injected into normal submandibular glands. Two weeks after cell transplantation, the transplanted cells were detectable in both the experimental and control groups. The cells were clustered in the connective tissue between the lobules. Four weeks after transplantation, the labeled cells were detectable in the experimental group but not in the control group. In the atrophic glands, the scattered transplanted cells were observed over a broad area of the gland but localized mainly around the acini and ductal region. Immunostaining results showed a possible involvement of the transplanted cells in ductal regeneration, while neither myoepithelial nor acinar differentiations were observed within the 4 weeks since transplantation. This study demonstrated that cell transplantation to the salivary gland is feasible, and that the transplanted cells were selectively attracted to and remained in the damaged area without affecting normal tissue.

3T3 Cells↗
PubMed2000

Correlation between quantitative salivary gland scintigraphy and salivary secretion rates in children and young adults treated for hematological, malignant and metabolic diseases.

OBJECTIVES: To study the correlation between whole salivary secretion rates and different variables from the radionuclide time-activity curve and to determine a reliable region for background correction in salivary gland scintigraphy. METHODS: Salivary gland scintigraphy (SGS) was performed before bone marrow transplantation or more than 4 years later in 23 patients aged 13.5 (s.d. 4.9) years. Unstimulated and stimulated whole salivary secretion rates were measured before SGS. Six different methods for background correction were evaluated. RESULTS: The unstimulated secretion rate was significantly correlated (P < 0.05) with the percentage stimulated secretion (S) and reaccumulation-slope (RS) after stimulation. The stimulated secretion rate was significantly correlated with RS, S and down-slope (DS). The temporal region above the parotid glands and the area above the thyroid gland was used for subtraction of background radiation for the parotid and submandibular glands respectively showed a strong correlation between repeated measurements of the variables analysed. The mean maximum uptake was 0.73-1.34% of total dose injected. CONCLUSIONS: The salivary scintigraphic variables which correlated more strongly with salivary secretion rates were RS, S and DS. The temporal region above the parotid gland and the area above the thyroid gland can be used reliably for correction background radiation in the analysis of the time-activity curve in SGS of the parotid and submandibular glands respectively.

Adolescent↗
PubMed1990

A review of the proliferative capacity of major salivary glands and the relationship to current concepts of neoplasia in salivary glands.

The classification of salivary gland tumors relies heavily on histogenetic postulates. One of these, the semipluripotential reserve cell theory, suggests that certain reserve cells in specific segments of the duct system of major and minor salivary glands are critical to the development of neoplasms in these glands. However, direct evidence in support of this hypothesis is unavailable. This survey of proliferative capacity in normal salivary gland is based on a review of data in the literature, our observations of DNA synthetic and mitotic activity in developing rat and human salivary gland, and autoradiographic studies of induced cell proliferation in rat salivary gland. Autoradiography of neonatal rat salivary gland after tritiated thymidine administration, and electron microscopy of these tissues, reveals that as well as duct basal cells, luminal cells at all levels of the duct system and even acinar cells are capable of DNA synthesis and mitosis. Indeed, in such studies, more luminal than basal cells are seen in mitosis. In adult rat salivary gland induced to undergo hyperplasia, more acinar cells than intercalated duct cells are in the S phase of the cell cycle. However, cycling cells were observed even in striated ducts and, importantly, both basal and luminal cells of major interlobular excretory ducts are also labeled. Similar findings are present in fetal and adult human salivary glands. From such observations, it is evident that dividing cells are not limited to basal cells of excretory ducts and luminal cells of intercalated ducts, so that there is no support for the semipluripotential bicellular reserve cell hypothesis. However, there is considerable evidence for a multicellular theory of tumor histogenesis; that is, any of the multiplicity of cell types in normal salivary gland have the potential to give use to any of the various types of tumor occurring in this organ.

Animals↗
PubMed2001

Focal lymphocytic infiltration in aging human palatal salivary glands: a comparative study with labial salivary glands.

Investigation of age-related prevalence of various types of focal lymphocytic infiltration (FLI) and degrees of histomorphologic changes was conducted on 120 biopsies of palatal and labial salivary glands (PSG and LSG, respectively) obtained from autopsy subjects free of salivary gland tumors/diseases. Biopsies were divided into young (<30 years, n=30), adult (30-60 years, n=45) and old (>60 years, n=45) age groups. A modified Chisholm & Mason grading system was used to record grades of FLI and a modified Greenspan et al. system was used to evaluate the severity of histomorphologic changes. The prevalence of FLI in PSG increased significantly from 10% in the young group to 46.6% in the old group (P=0.0012). No significant changes were found with aging in LSG. FLI was significantly more prevalent in the adult and old age groups in PSG as compared with LSG (P=0.015 and P=0.003, respectively). Both glands demonstrated significant histomorphologic changes among age groups (p<0.0001); however, these changes were significantly less common in the old age group in PSG as compared to LSG (P=0.003). In cases showing severe histomorphologic changes, FLI was not present. Therefore, FLI should not be considered as part of the deteriorating histomorphologic changes that are usually encountered in salivary glands with aging. The immunologic profile of these infiltrates should be further clarified to understand their role, both in physiologic and pathologic conditions.

Adult↗
PubMed2003

Expression of cathelicidin in human salivary glands.

BACKGROUND: Salivary secretions play a critical role in maintaining oral health via innate host defense mechanisms and secretion of secretory IgA. One of the antimicrobial peptides, LL-37, is the only cathelicidin protein that has yet been identified in humans. Cathelicidins are a family of peptides thought to provide an innate defensive barrier against a variety of potential microbial pathogens. OBJECTIVES: To examine the expression of cathelicidin in human salivary glands and to investigate up-regulation of cathelicidin in inflammatory conditions. DESIGN: Reverse transcriptase-polymerase chain reaction and immunohistochemical staining were performed on 20 salivary gland tissues, 10 from normal salivary glands and 10 from glands with chronic sialadenitis. RESULTS: Cathelicidin messenger RNA transcripts were detected in the tissues from the normal salivary glands and the glands with chronic sialadenitis. The level of cathelicidin messenger RNA in glands with chronic sialadenitis was significantly increased compared with that in normal salivary glands. Cathelicidin protein was expressed in the glandular epithelium of the normal salivary glands and the glands with chronic sialadenitis. CONCLUSION: The results indicate that cathelicidin might play an important role in innate host defense of human salivary glands.

Antimicrobial Cationic Peptides↗