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Major salivary gland tumours were studied for the presence of hormone receptors for oestrogen and progesterone. Of the eight salivary gland tumours exhibiting varied histology, none showed high affinity receptors for oestrogen or progesterone. Salivary tissue from four patients with non-neoplastic salivary gland disease was also studied and found not to contain high affinity receptor sites. The absence of hormone receptors in these glands suggests that such tumours are not dependent on endocrine function.
Undifferentiated salivary carcinomas are defined as primary epithelial malignant neoplasms that are devoid of any phenotypic expression by light microscopy that would allow them to be otherwise classified. A clinicopathologic study of sixteen so-defined carcinomas of the major salivary glands is presented. The carcinomas are unquestionably high-grade malignant neoplasms. Ten of the sixteen patients were dead because of their disease within 4 1/2 years of histologic diagnosis. Cell size and ultrastructural features have little bearing on prognosis. The single most important clinicopathologic factor relating to patient outcome is size of the primary neoplasm. All patients with carcinomas larger than 4 cm died, and these carcinomas had nearly two times the incidence of perineural invasion, extrasalivary extension, and locoregional failure of control.
Submaxillary salivary gland tissue from large White, Göttingen miniature and Meishan (Chinese) breeds of pig, and European wild boars, was incubated with [35S]methionine. The radiolabelled amino acid was incorporated into protein in all incubations as demonstrated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Specifically [35S]methionine was predominantly incorporated into the alpha- and beta-charge isomers of pheromaxein, a 16-androstene steroid-binding protein, as shown by SDS-PAGE in combination with vertical isoelectric focusing on polyacrylamide slab gels. The synthesis of pheromaxein occurred in submaxillary gland tissue from both sexes, including tissues stored frozen at -70 degrees C for long periods. There was little evidence for pheromaxein synthesis in parotid gland tissue or skeletal muscle. Total protein, pheromaxein and total 16-androstenes were determined in the submaxillary gland cytosols of six mature Göttingen miniature boars and a positive correlation was found between these glandular constituents. The amounts of endogenous pheromaxein relative to total protein in the submaxillary gland cytosols (range 10.3-18.0%), together with the predominant synthesis of this protein in vitro, indicate that pheromaxein is a major protein produced in porcine submaxillary glands, particularly in those of the male.
Salivary glands have proven to be unusual but valuable target sites for multiple clinical gene transfer applications. Access to salivary glands for gene transfer is easy. Multiple studies in animal models have yielded proofs of concept for novel treatments for damaged salivary glands following therapeutic irraditation, in Sjögren's syndrome, and for gene therapeutics systemically by way of the blood-stream and locally in the oral cavity and upper gastrointestinal tract.
The acinar salivary glands of cockroaches receive a dual innervation from the subesophageal ganglion and the stomatogastric nervous system. Acinar cells are surrounded by a plexus of dopaminergic and serotonergic varicose fibers. In addition, serotonergic terminals lie deep in the extracellular spaces between acinar cells. Excitation-secretion coupling in cockroach salivary glands is stimulated by both dopamine and serotonin. These monoamines cause increases in the intracellular concentrations of cAMP and Ca(2+). Stimulation of the glands by serotonin results in the production of a protein-rich saliva, whereas stimulation by dopamine results in saliva that is protein-free. Thus, two elementary secretory processes, namely electrolyte/water secretion and protein secretion, are triggered by different aminergic transmitters. Because of its simplicity and experimental accessibility, cockroach salivary glands have been used extensively as a model system to study the cellular actions of biogenic amines and to examine the pharmacological properties of biogenic amine receptors. In this review, we summarize current knowledge concerning the aminergic control of cockroach salivary glands and discuss our efforts to characterize Periplaneta biogenic amine receptors molecularly.
An IgG2a mouse monoclonal antibody (MoAb) to the human salivary gland adenocarcinoma cell line HSG, 5B/10, has been generated in our laboratory. In the current study, the antitumor effects mediated by MoAb 5B/10 in human salivary gland adenocarcinoma (HSG)-bearing nude mice or the antibody-dependent cell-mediated cytotoxicity (ADCC) against HSG cells using human peripheral blood mononuclear cells (PBMC) as effector cells were examined. In addition, effects of the streptococcal preparation OK-432 on the growth of HSG tumors or on the MoAb 5B/10-mediated cellular cytotoxicity were studied. MoAb 5B/10 mediated an ADCC reaction against HSG cells that were insensitive to NK cells but not to the reaction of antibody and complement-mediated cytotoxicity. The coexistence of MoAb 5B/10 and OK-432 caused marked augmentation of cytotoxic effects. Treatment of OK-432-stimulated PBMC with antiasialo Gm1 antiserum plus complement but not with silica particles resulted in a significant decrease of cytotoxic effects as compared with relevant controls. the nude mice inoculated intraperitoneally with HSG cells and treated with MoAb 5B/10, OK-432, or (especially) a combination of the two had significantly prolonged survival times as compared with untreated controls. Moreover, spleen cells from the tumor-bearing mice treated with OK-432 alone or a combination of MoAb 5B/10 and OK-432 were found to carry high levels of effector cell activity in the MoAb 5B/10-mediated cytotoxicity assay using HSG cells as targets.
Surgery for salivary gland tumors requires technical skill, competence in head and neck anatomy, and a familiarity with a variety of tumors. Benign salivary tumors at all sites should be 100 percent curable, with a local recurrence rate of less than five percent; these local failures should be curable with further surgery. The majority of parotid tumors are benign. Sixty-two percent of patients with malignant parotid tumors will be alive at five years, 54 percent at 10 years, and 47 percent at 15 years. These survival rates for malignant parotid tumors are better than those for malignant tumors in the submaxillary and minor salivary glands and may be explained in part by the presence of a higher percentage of low-grade malignant tumors in the parotid gland. Since most submaxillary gland tumors are malignant, they are more dangerous than parotid tumors. A total of 80 percent of patients with submaxillary gland tumors die as a result of cancer. Almost all minor salivary gland tumors are malignant; curability relates to size, local extension, histology, and nodal metastases. Forty-five percent are alive at five years, and 21 percent at 15 years. Wide-field radical surgical excision is needed for malignant salivary tumors to minimize local recurrences and treatment failures. Future improvement in treatment results will be made possible by increased awareness of this group of tumors, earlier diagnosis when tumors are still small, more radical extirpation, and greater use of postoperative radiation therapy.
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Prior studies have identified Fibroblast Growth Factor-8 (Fgf8) as a possible proto-oncogene in mouse mammary tumorigenesis. We now report on the generation of two types of Fgf8 transgenic mice that each utilize the mouse mammary tumor virus (MMTV) promoter. The first transgene (MMTV-Fgf8b) results in the overexpression of the FGF8b isoform exclusively. Male and female MMTV-Fgf8b transgenic mice are viable and fertile. RNA for FGF8b is detected in mammary gland and salivary gland tissues of transgenic mice by Northern blot analysis. Nearly 85% of breeding transgenic female mice developed mammary lobular adenocarcinomas by 12 months of age, while no tumors developed in non-transgenic littermates. Salivary gland tumors occurred in some animals, always in association with mammary tumors. Several MMTV-Fgf8b transgenic mice had lung metastases at necropsy. The second transgene (MMTV-Fgf8) uses the entire Fgf8 gene and potentially encodes all FGF8 isoforms. Fgf8 is expressed by this transgene in several tissues in addition to those described above, notably the ovaries. The two MMTV-Fgf8 founders developed mammary ductal adenocarcinomas at five and eight months of age, and both displayed ovarian stromal hyperplasia. The founders expressing either transgene did not successfully nurse their pups. These results demonstrate that production of FGF8b, and possibly other FGF8 isoforms, in the mammary and salivary glands contributes to oncogenesis, and that ovarian expression results in stromal hyperplasia.
The minor salivary glands are important components of the oral cavity, present in most parts of the mouth, and their secretions directly bathe the tissues. Individual glands are usually in the submucosa between muscle fibres, and consist of groups of secretory endpieces made up of mucous acinar cells and serous or seromucous demilune cells. The ductal systems comprise intercalated ducts, intralobular ducts usually lacking basal striations, and excretory ducts opening directly through the mucosa Minor glands secrete highly glycosylated mucins, containing blood group determinants, and probably active in tissue lubrication and bacterial aggregation. They also secrete several antimicrobial proteins and immunoglobulins, and the lingual serous (von Ebner's) glands secrete digestive enzymes and proteins with possible taste perception functions. Minor gland morphology and function can conveniently be studied in the rat. There are substantial differences between major and minor salivary glands, as well as among the minor glands, in the nature and composition of their mucous and serous secretory products. The role of minor salivary glands in the function and defence of the oral cavity may be better understood as a result of new physiological and molecular methods applicable to samples of limited size and availability.
Salivary glands in aquatic larvae of Chironomus are responsible for formation of a fiber that larvae use to construct feeding tubes. Major constituents of this fiber include a family (the sp-I family) of high Mr (1 X 10(6) secretory polypeptides. Because of our interest in the polypeptide composition and polymerization of the salivary fiber we conducted a survey of the electrophoretic pattern of sp-I components found in salivary glands obtained from individual larvae. The survey encompassed ten strains of Chironomus tentans, three strains of Chironomus pallidivittatus and four strains of Chironomus thummi. Salivary glands from C. tentans and C. pallidivittatus contained at least four sp-I components (sp-Ia, sp-Ib, sp-Ic and sp-Id) that behave identically with regard to their electrophoretic mobility and detectability when larvae were exposed to galactose or glycerol. Sp-I components in C. thummi were generally fewer and not directly comparable by electrophoretic mobility to sp-I components in the other two species. During this survey two important alterations were observed in the electrophoretic pattern of sp-I components obtained from C. tentans and C. pallidivittatus. First, all four sp-I components exhibited, with a low frequency, double bands that appeared as slow-versus-fast electrophoretic variants of a particular component. Secondly, the relative steady-state level of each sp-I component fluctuated in comparison to other sp-I components in the same extract. This fluctuation varied such that any one sp-I component might appear as a single prominent component.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: We have previously shown that specific enhancement in acinar cells of proteolytic activity induced by tumor necrosis factor alpha (TNFalpha) may be responsible for the destruction of the acinar structure in the salivary glands of patients with Sjögren's syndrome. Because matrix metalloproteinase 9 (MMP-9) is regulated by nuclear factor kappaB (NF-kappaB), we investigated the effect of a super-repressor form of inhibitor of nuclear factor kappaBalpha (srIkappaBalpha) on the suppression of TNFalpha-induced MMP-9 production in acinar cells. METHODS: Two srIkappaBalpha complementary DNA (cDNA)-transfected acinar cell clones (ACMT-6 and ACMT-7) and 1 empty vector-transfected cell clone (ACpRc-1) were established. After treatment of cell clones with TNFalpha, the expression of MMP-9 was examined. In addition, the effect of TNFalpha on cell growth and the morphogenetic behavior of cell clones cultured on type IV collagen-coated dishes were examined. RESULTS: TNFalpha induced the production of MMP-9 in the ACpRc-1 cell clone, but greatly suppressed MMP-9 production in ACMT-6 and ACMT-7 clones. No apparent cytotoxic effect of TNFalpha treatment was observed in these cell clones. When ACpRc-1 cells were seeded on type IV collagen-coated dishes in the presence of both TNFalpha and plasmin, type IV collagen interaction with the cells was lost and the cells entered apoptosis. However, even when ACMT-6 and ACMT-7 cells were cultured under the same culture conditions as those for ACpRc-1, these cell clones attached to the substrate and grew consistently without showing apoptosis. Conclusion. These observations indicate that suppression of TNFalpha-induced MMP-9 production by the introduction of srIkappaBalpha cDNA corrected the aberrant in vitro morphogenesis of acinar cells grown on type IV collagen.
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Histogenetic concepts for salivary gland tumors are predicated on the presence of reserve or undifferentiated cells in normal glands, presumably the source for cell renewal and induction of tumors. Developing rat parotid gland, which remains fetal-like at birth, provides the opportunity to study differentiation and observe whether cytologically undifferentiated cells do or do not have functional indicators of specific differentiation pathways. Immunohistochemistry and immuno-electron microscopy, when applied to parotid gland at birth, at 12 days of age and in the adult gland, indicate that commitment to myoepithelial cell differentiation occurs prior to development of structural changes characteristic of these cells. Conversely, secretory granules are evident in differentiating acinar cells prior to synthesis of amylase. The results suggest that an appearance of undifferentiation does not confer reserve cell status either in the normal salivary gland or their tumors.
Evaluating salivary gland neoplasms is difficult because of the relatively low incidence of these lesions, their variable locations, and their multiple histologic cell types. Little has been reported on nodal metastases, whether manifest or occult, from these neoplasms. Ninety cases of salivary gland neoplasm are analyzed to provide a clearer understanding of the appropriate approach to occult salivary gland cervical metastases. Manifest regional metastases at the original presentation were absent in 72% (65/90). Few nodal metastases occurred after the primary tumor was controlled (2% [1/56]). Local recurrence (38% [34/90]) and distant metastases (25% [14/56]) were more common. Stage I and II disease was treated by surgical resection of the primary tumor alone; resection was combined with postoperative radiation therapy for stage III disease. Whenever the neck was entered for stage III disease, a conservative neck dissection was incorporated with the resection to reduce the postoperative irradiation field once the neck had been proved N, O histologically. Delayed nodal metastasis was treated by neck dissection alone.