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[Differentiation therapy for salivary gland tumors].

A neoplastic human salivary intercalated duct cell line, HSG and its derivative HSG-AZA1 cells with a myoepithelial cell phenotype and HSG-AZA3 cells with an acinar cell phenotype, which were induced by treatment of HSG cells with 5-azacytidine, have been used in our laboratory as models for studying mechanisms regulating cytodifferentiation in salivary glands as well as for developing differentiation therapy for salivary gland tumors. Consequently, it has been shown that the treatment of HSG, HSG-AZA1 and HSG-AZA3 cells with various differentiation agents results in cellular differentiation into myoepithelial, acinar or neuronal cells as well as keratinizing squamous cells, chondrocytes, and osteoblast, with a concomitant decrease of anchorage-independent and anchorage-dependent growths in addition to decreased tumorigenicity in nude mice. It was also found that the treatment of an adenoid cystic carcinoma of the maxillary sinus with adoptive immunotherapy involving intra-arterial injection of LAK cells and IL-2 in combination with radiotherapy, resulted in bone formation in the treated tumor, which was then replaced completely by lamellar bone tissue with myxomatous stroma. These findings may suggest the potential usefulness of differentiation therapy in human salivary gland tumors.

Animals↗

[Differential diagnosis of squamous epithelial carcinoma of the salivary glands].

Primary squamous cell carcinomas (SCC) of the salivary glands are localized predominantly in the major salivary glands and must be distinguished from metastases of extraglandular SCC of the skin, especially the head and neck area. Squamous cell metaplasia in non-tumourous diseases of the salivary gland (e.g. necrotizing sialometaplasia) as well as in benign or malignant salivary gland tumours (e.g. metaplastic Warthin tumour) can simulate SCC. Other differential diagnostic problems are the structural variants of SCC which develop predominantly in the minor salivary glands, but not in the major salivary glands. Special types include the very rare adenoid SCC with pseudoglandular structures as the result of acantholysis, the biphasic adenosquamous carcinoma with differentiation as SCC and adenocarcinoma, the biphasic basaloid squamous carcinoma with a structure as SCC and solid basaloid carcinoma (analogous to the solid type of adenoid-cystic carcinoma) and the poorly differentiated mucoepidermoid carcinoma (grade III) with biphasic structure of undifferentiated epidermoid and intermediate cells as well as inclusion of small groups of mucous-producing goblet cells. The differential diagnostic criteria are analysed concerning prognosis and treatment.

Carcinoma, Squamous Cell↗

Occurrence and some properties of eledoisin in extracts of posterior salivary glands of Eledone.

The posterior salivary glands of Eledone, alone among the tissues of this molluscan species, contain eledoisin, an endecapeptide with activity on blood vessels and extravascular smooth muscles. The salivary glands of Octopus vulgaris and O. macropus lack the polypeptide. Eledoisin is present, in amounts ranging from 20 to 160 mug/g fresh tissue, at all stages of growth and in every season; however, conspicuous differences in the eledoisin content were observed in different groups of animals. Eledoisin is fairly stable in intact salivary glands stored on ice. The most suitable solvent for its extraction is 70 to 80% methanol. Better results are also obtained with boiling diluted acetic acid, than with ethanol, whereas extraction with acetone gives unsatisfactory yields. Eledoisin is stable in neutral or slightly acid medium, but is rapidly destroyed by strong acids and even more rapidly by strong alkalis. It is quickly and completely inactivated by chymotrypsin, and somewhat more slowly and incompletely by trypsin. Carboxypeptidase is ineffective. Passage of crude salivary extracts of Eledone through an alumina column yields preparations of eledoisin which may be considered pure from a biological point of view.

Acetic Acid↗

Diet and the risk of salivary gland cancer.

Cancer of the major salivary glands is relatively rare, and little is known about its etiology. The only established risk factors are radiation exposure and a prior cancer. The role of diet in the development of salivary gland tumors has not been addressed previously. The results from a population-based case-control study conducted in the greater San Francisco-Monterey Bay area examining the association between dietary intake and salivary gland cancer risk are presented. Of 199 cases diagnosed with salivary gland tumors between 1989 and 1993, 150 (75%) were interviewed. Nine cases were subsequently excluded based on review of pathology specimens. Of 271 controls identified through random-digit dialing and the Health Care Finance Administration files, 191 (70%) were interviewed. Eight cases and seven controls who over- or underreported dietary intake were excluded from analysis. Vitamin C intake of > 200 mg/day compared with < or = 100 mg/day was associated with a 60% decrease in salivary gland cancer risk (odds ratio (OR) = 0.40, 95% confidence interval (CI) 0.22-0.70). Inverse associations observed for carotene, vitamin E, and fiber from fruits and vegetables were diminished when adjusted for vitamin C intake. Fiber from been sources was associated with a 51% decrease in risk after adjusting for vitamin C intake (OR = 0.49, 95% CI 0.26-0.92 for > 1.4 g/day compared with < or = 0.4 g/day). Cholesterol intake was associated with elevated risk (OR = 1.67, 95% CI 1.2-2.4 for a 10% increase in calories from cholesterol). These findings suggest that preventive strategies developed for common chronic diseases, such as increased consumption of fruits and vegetables and limiting foods high in cholesterol, also may be effective in preventing these rare tumors.

Adult↗

A novel secreted endonuclease from Culex quinquefasciatus salivary glands.

Previous analysis of the salivary gland transcriptome of Culex quinquefasciatus showed the potential presence of an endonuclease with sequence similarities to shrimp, crab and two tsetse salivary proteins. Indeed, not only was the cloned cDNA shown to encode an active double-stranded endonuclease, but also the same activity was demonstrated to be secreted by salivary glands of Cx. quinquefasciatus. Preliminary studies with salivary gland extracts confirmed the presence of a highly active nuclease. This enzyme was shown to be present in the saliva of female mosquitoes by allowing starved mosquitoes to probe DNA-containing agarose gel. The recombinant Cx. quinquefasciatus endonuclease (CuquEndo) produced in mammalian cells showed no sequence specificity for DNA substrate except that it only cleaves double-stranded DNA. Recombinant Cx. quinquefasciatus endonuclease was active in the presence of Mg(2+) ions at pH 7.0-8.0, but no endonuclease activity was detected in the presence of calcium ions. The final hydrolysis products of this enzyme, detected by ion exchange chromatography, yielded DNA fragments ranging form 8-12 base pairs. Although endonucleases have been associated with a variety of cellular functions, their role in mosquito saliva is not clear. This female-specific secreted endonuclease may assist blood meal intake by lowering the local viscosity created by the release of host DNA in the bite site and/or acting as an indirect anticoagulant factor by producing a defibrotide-like mixture of DNA haptamers.

Amino Acid Sequence↗

Differential inhibitory effect of 5-fluorouridine on RNA labelling in dipteran salivary gland cells.

In Chironomus salivary glands, 5-fluorouridine inhibits labelling of ribosomal RNA. The drug does not prevent labelling of other types of RNA- like heterodisperse messenger-like RNA, 75-S RNA of Balbiani ring origin and 4-S RNA, which furthermore are exported to cytoplasm. The potential use of this drug for the study of RNA metabolism in insect salivary glands can be compared with the use of low doses of actinomycin D in cultured mammalian cells.

Diptera↗

Potentiation by spiperone and other butyrophenones of fluid secretion by isolated salivary glands of ixodid ticks.

Isolated salivary glands from the ixodid tick, Amblyomma hebraeum Koch are stimulated to secrete fluid when exposed to dopamine (DA), the maximum response occurring at 10(-6) M. Spiperone, and a number of other butyrophenone derivatives, although lacking intrinsic activity, are able to potentiate the secretion elicited by supramaximal concentrations of DA; this potentiation by spiperone is evident at concentrations in the femtomolar range. Tranylcypromine, a potent, competitive inhibitor of monoamine oxidase (MAO) in tick salivary gland homogenates, has both intrinsic activity and potentiates DA-induced salivation. The fact that spiperone potentiates ergometrine-induced salivation that the prime mechanism of the butyrophenone effect is not by inhibiting catecholamine catabolism. The results also suggest that the receptor for DA and that for butyrophenones are distinct sites. Droperidol, benperidol and bromperidol, all potent neuroleptic drugs, failed (at 10(-9) M) to potentiate salivation. By contrast, R951, R27275 and R1187 (all at 10(-9) M) were very effective potentiators on the salivary gland system, despite the fact that they lack the basic structural requirements for neuroleptic activity. These results suggest that the butyrophenone site in tick salivary glands is different from butyrophenone binding sites in mammalian CNS.

Animals↗

[Clinical analysis of sixteen cases of lymphoepithelial carcinoma of salivary gland].

BACKGROUND & OBJECTIVE: Lymphoepithelial carcinoma of salivary gland is a rare and special kind of malignant tumor, and has seldom been reported. This study was to summarize the clinical features, treatment and curative effect of this disease according to our experiences. METHODS: Clinical data of 16 patients with pathologically confirmed primary lymphoepithelial carcinoma of salivary gland, treated in Cancer Center of Sun Yat-sen University from Jan. 1990 to Sep. 2004, were retrospectively analyzed, and survival analysis was performed with Kaplan-Meier method. RESULTS: The 16 patients with lymphoepithelial carcinoma of salivary gland accounted for 3.6% of all the patients diagnosed as malignant tumors of salivary gland simultaneously in our center. All patients had tumors occurred in unilateral gland, aged 15-57 years, with the female to male ratio of 1:1. All patients were from southern China. Except for 1 patient, the rest 15 had Epstein-Barr virus (EBV) serological tests. The positive rates of EBV-VCA-IgA, EBV-EA-IgA, and EBV-DNA enzyme were 93.3%, 66.7%, and 86.7%, respectively. All patients were treated with surgery, of which 9 received surgery only, 5 received surgery plus postoperative radiotherapy, 1 received surgery plus postoperative chemoradiotherapy, 1 received surgery plus chemotherapy. Four (25.0%) patients had postoperative pathology-proved ipsilateral cervical lymph node metastasis. The 1-, 3-, and 5-year survival rates of the 16 patients were 86.15%, 48.46%, and 24.23%. CONCLUSIONS: Although lymphoepithelial carcinoma of salivary gland is poorly differentiated, the prognosis of this disease is good. Complete resection plus postoperative radiotherapy is possibly accommodating.

Adolescent↗

Analysis of c-erbB-2 amplification in salivary gland tumours by differential polymerase chain reaction.

DNA samples extracted from 22 normal salivary glands, 38 salivary pleomorphic adenomas and 20 other salivary gland neoplasms were screened for amplification of the c-erbB-2 oncogene by a differential polymerase chain reaction (PCR). The samples were PCR amplified with primers specific for the c-erbB-2 oncogene and for a reference gene (interferon-gamma). A breast carcinoma cell line SKBR-3 known to contain c-erbB-2 amplification was used as positive control. Following gel electrophoresis, the intensity of the amplified DNA bands was determined by laser densitometry and the level of amplification of the c-erbB-2 oncogene was assessed from the intensity of the c-erbB-2 specific band relative to that of the interferon-gamma band. Of all the tumours detected, only the two poorly differentiated adenocarcinomas, two of the pleomorphic adenomas and one of the Warthin's tumours showed gene amplification at levels comparable to the breast carcinoma cell line. None of the normal salivary gland tissues was found to have amplification. Within the group of pleomorphic adenomas the average level of amplification was not significantly different from that observed in the normal salivary gland, or in total genomic DNA from unrelated tissue (P < or = 0.001, determined by a general linear model of statistical analysis). These results indicate that amplification of the c-erbB-2 oncogene is infrequent in salivary neoplasia. Thus, gene amplification alone cannot account for the high prevalence of c-erbB-2 overexpression demonstrated previously in salivary gland tumours. When present, c-erbB-2 amplification may be associated with a more aggressive behaviour.

Adenoma↗

Salivary duct carcinoma in major and minor salivary glands. A clinicopathological analysis of four cases.

Salivary duct carcinomas are an uncommon but distinct group of highly malignant salivary gland tumours. We report the clinical course, pathological findings and surgical treatment of this tumour in 4 patients. In one patient an intraductal tumour developed in a minor salivary gland, while in the other three patients, a major salivary gland was involved by an infiltrating salivary duct carcinoma. We point out the highly aggressive biological behaviour of the tumour when occurring in the major salivary glands, in contrast to the benign course of the intraductal carcinoma in the minor salivary gland.

Adenocarcinoma, Papillary↗

Tick salivary glands: function, physiology and future.

The salivary glands are the organs of osmoregulation in ticks and, as such, are critical to the biological success of ticks both during the extended period off the host and also during the feeding period on the host. Absorption of water vapour from unsaturated air into hygroscopic fluid produced by the salivary glands permit the tick to remain hydrated and viable during the many months between blood-meals. When feeding, the tick is able to return about 70% of the fluid and ion content of the blood-meal into the host by salivation into the feeding site. This saliva also contains many bioactive protein and lipid components that aid acquisition of the blood-meal. The salivary glands are the site of pathogen development and the saliva the route of transmission. The importance of the multifunctional salivary glands to tick survival and vector competency makes the glands a potential target for intervention. Here we review the cell biology of tick salivary glands and discuss the application of new approaches such as expressed sequence tag projects and RNA interference to this important area in the field of tick and tick-borne pathogen research.

Animals↗

[Toxicity and tetramine contents of salivary glands from carnivorous gastropods].

Salivary glands from 29 species of marine carnivorous gastropods in nine families were examined for lethal activity against mice and tetramine content. Mouse lethality was assayed by intravenous injection of buffer extracts into mice, and was detected in 14 species. Heat-stability tests confirmed that toxins in four species were thermolabile, while those in eight species were thermostable. Based on the tetramine contents determined by the colorimetric method using methanolic extracts, the thermostable toxins in seven species (Neptunea eulimatalamellosa, N. vinosa, N. arthritica, N. bulbacea, N. intersculpta f. pribiloffensis, N. intersculpta f. frater pilsbry and Hemifusus tuba) were considered to be tetramine contained at high levels (more than 900 micrograms/g salivary gland), but that in one species (Buccinum opisthoplectum) appeared to be a low-molecular-weight compound differing from tetramine. It is interesting that one (Hemifusus tuba) of the seven species containing high amounts of tetramine belongs to the family Melongenidae, although the other six Neptunea species are members of the family Buccinidae, as expected from previous studies.

Animals↗

[Imaging in major salivary gland diseases]

Most of the salivary glands diseases are characterized only by a few distinct clinical patterns. Medical history and clinical examination are still considered of great relevance. However, in order to obtain a definite diagnosis, imaging techniques are required in most of the cases. Salivary glands ultrasonography (US) is the technique to be used as the first because US can easily differentiate calculosis, inflammatory diseases and tumors. Sonography is also frequently needed to perform needle aspiration or biopsy (FNAC). Sialography should be used essentially for assessing chronic sialoadenitis as well as Sjögren's syndrome. At present, Magnetic Resonance sialography should be preferred because of the greater sensibility in diagnosing inflammatory diseases of the salivary glands. It allows to evaluate both intraglandular oedema and nodules, so that incannulation of the salivary duct is not required. Computer Tomography (CT) and Magnetic Resonance imaging (MR) are useful when neoplasm are suspected, particularly if deep areas of the gland, which cannot be visualized by US, are involved. Sequential scintigraphy is currently employed for assessing the functional status of all the 4 major salivary glands and evaluating the chronic evolution of glandular damage.

Journal Article↗

Characterization of primary translation products from ovine and rat salivary gland mRNAs.

Ovine and rat salivary gland mRNAs have been prepared and their translation products characterized. A 60 kD translation product from ovine submaxillary and sublingual gland mRNAs is identical in mass to the ovine apomucin. Two additional ovine translation products, 25 and 40 kD, are specific to mucin-producing salivary glands. Four rat mRNA translation products are encoded by mucin-producing salivary glands (38, 44, 67, 69 kD). These polypeptides were not detected in the parotid gland mRNAs, a serous gland. Each of these products has a high level of [3H]serine incorporation, a characteristic of mucins. The nature of these products suggests that they are mucins or mucin-like and that their molecular weights should approximate that of the corresponding apomucins.

Animals↗

Relative paucity of gross genetic alterations in myoepitheliomas and myoepithelial carcinomas of salivary glands.

The diagnosis of salivary gland myoepithelioma, an entity with heterogeneous cytomorphology and inconsistent immunophenotype, rests on conventional histology. However, the clinical course cannot be predicted reliably from cytomorphological and immunophenotypic analysis. The present study determined the immunophenotype of a representative series of 12 myoepitheliomas and 21 malignant myoepitheliomas. Among the seven markers tested, antibodies against cytokeratins 5/6, S-100 protein, and vimentin produced the most consistent reactivity profile. Comparative genomic hybridization (CGH) profiles of 12 myoepitheliomas showed chromosomal losses in three of 12 cases. In myoepithelial carcinomas, however, ten of 19 tissues investigated by CGH lacked detectable cytogenetic aberrations. In five cases, aberrations involved chromosome 8, in line with observations in salivary gland carcinomas of other differentiation. One case that was represented in three separately localized manifestations of the disease proved informative as to the relevance of gross aberration for tumour development, as these tumours differed in their CGH profiles. Staining for cytokeratins 5/6 is a useful addition to the established immunohistological marker panel in the work-up of myoepitheliomas, because of its reliable expression in most cases and because it may underline the epithelial nature of the lesion. CGH proved to be of limited value as a diagnostic adjunct; the presence of numerous gross cytogenetic aberrations should raise the suspicion of malignancy. The low frequency of aberrations detectable by CGH in overtly malignant myoepithelial neoplasms suggests that gross cytogenetic alterations were acquired in the course of tumour progression and points to the relevance of genetic changes not resolved by CGH.

Adult↗

Abnormal expression of Rb pathway-related proteins in salivary gland acinic cell carcinoma.

Salivary gland acinic cell carcinoma (ACC) is a relatively rare neoplasm, and limited information is available regarding its molecular pathogenesis. Because the deregulation of Rb pathway is common to most human tumors, we immunohistochemically investigated the expression of Rb pathway-related proteins, including Rb, Rb proteins phosphorylated at serine 780 and 795 (pRb-S780 and pRb-S795, respectively), cyclin D1, and p16INK4a in 18 cases of ACC. The expression of topoisomerase II-alpha and Ki-67 was also examined to evaluate cell proliferation. All the ACCs exhibited substantial numbers of positive cells against Rb antibody that recognizes both unphosphorylated and phosphorylated Rb proteins. The numbers of positive cells for pRb-S795 and cyclin D1 significantly increased in ACCs as compared with normal salivary glands. Double immunofluorescent staining demonstrated that pRb-S795 was colocalized with cyclin D1 in most tumor cells. However, neither significant change of the expression of Rb protein phosphorylated at serine 780 nor its colocalization with cyclin D1 was observed. The loss of p16INK4a is infrequent, but its expression was correlated with phosphorylated Rb proteins. Our results suggest that serine 795 but not serine 780 is the preferred phosphorylation site induced by cyclin D1. This phosphorylation appeared to be critical for inactivation of Rb-mediated growth suppression and may play an important role in the pathogenesis of ACC.

Adolescent↗

Serial cultivation of epithelial cells from human and macaque salivary glands.

To study the regulation of human salivary-type gene expression we developed cell culture systems to support the growth and serial cultivation of salivary gland epithelial and fibroblastic cell types. We have established 22 independent salivary gland epithelial cell strains from parotid or submandibular glands of human or macaque origin. Nineteen strains were derived from normal tissues and three from human parotid gland tumors. Both the normal and the tumor-derived salivary gland epithelial cells could be serially cultivated with the aid of a 3T3 fibroblast feeder layer in a mixture of Ham's F12 and Dulbecco's modified Eagle's media supplemented with fetal bovine serum, calcium, cholera toxin, hydrocortisone, insulin, and epidermal growth factor. Salivary gland epithelial cells cultured under these conditions conditioned to express the genes for at least two acinar-cell-specific markers at early passages. Amylase enzyme activity was detected in conditioned media from cultured rhesus parotid epithelial cells as late as Passage 5. Proline-rich-protein-specific RNAs were detected in primary cultures of both rhesus and human parotid epithelial cells. Neither amylase enzyme activity nor PRP-specific RNAs were detected in fibroblasts isolated from the same tissues. In addition, salivary gland epithelial cells cultured under our conditions retain the capacity to undergo dramatic morphologic changes in response to different substrata. The cultured salivary gland epithelial cells we have established will be important tools for the study of salivary gland differentiation and the tissue-specific regulation of salivary-type gene expression.

Amylases↗

Efficacy, risks, and limits of extracorporeal shock wave lithotripsy for salivary gland stones.

Stones of the salivary glands may cause recurrent swelling, ascending inflammation, and colic-like pain. Previously, in order to get rid of these stones, the gland usually had to be removed surgically in spite of the associated risks to adjacent structures, especially the facial nerve. We treated 104 salivary gland stones in patients 14 to 78 years old using the Storz Modulith SL 10 lithotripter. Each session (average 3.6 per patient) consisted of 1000 impulses at 2 Hz and 16 to 18 kV. No anesthesia was required. Earplugs were applied to patients being treated for parotid gland stones. With the aid of SWL and drug-induced salivation, 17 (59%) of the patients with parotid gland stones and 42 (56%) of those with submandibular gland stones obtained either total stone clearance or sufficient fragmentation to permit spontaneous passage. Four patients required surgery. The remaining patients are still being treated. The noninvasive SWL for salivary gland stones is noninvasive and painless and has a considerable success rate. It can be performed on an outpatient basis.

Acute Disease↗