Migration Stimulating Factor (MSF) is an oncofoetal protein which is constitutively produced by both epithelial and stromal cells during foetal development, not expressed by the majority of their normal adult counterparts, but re-expressed during pathological processes such as cancer and wound healing. Scotland has the highest occurrence of oral cancers in the UK; the incidence is still increasing, but patient survival remains very poor. The expression of MSF in oral tumours has not been previously reported. The aims of this study were: • To determine the effects of MSF on the migration of oral tumour cell lines and normal stromal cells in culture (chapter 3), • To ascertain the possible presence, diagnostic and prognostic value of MSF in oral squamous cell carcinoma (OSCC; chapter 4), and salivary gland tumours (SGT; chapter 5). • To identify the putative MSF receptors in oral tumour cell lines (chapter 6). For tissue culture studies, the effects of rhMSF (wild type and mutant proteins) were examined on human cell lines TYS, HSG, Endo 742 and FSF44. These cells were derived from OSCC, SGT, microvascular endothelial cells and skin fibroblasts, respectively. For ex-vivo studies, paraffin embedded archival specimens of OSCC and SGT were stained with specific MSF antibodies and the level of staining was assessed by consensus of 2-4 independent observers. The association between MSF expression and patient survival was determined by Kaplan-Meier and log-rank tests. Results presented in this thesis indicate that TYS and HSG cells secrete bioactive MSF in culture. rhMSF stimulated the migration of these tumour cells. The use of mutant proteins demonstrated marked differences among the cells examined: Five bioactive motifs (4x IGD and 1x HEEGH) were required for MSF bioactivity on TYS and HSG cells, whereas only one of these motifs was required for Endo 742 and two for FSF44. MSF+aa and MSF-aa showed the same migration-stimulating activity, but differ in their interaction with the MSF-inhibitor Neutrophil Gelatinase-Asscciated Lipocalin (NGAL). NGAL was shown to bind to and inhibit MSF+aa, but not MSF-aa. The bioactivity of MSF+aa and MSF-aa was inhibited by Insulin-like Growth Factor Binding Protein-7 (IGFBP7), MSF-function-neutralising antibody and antibody to the integrin avß3. This integrin was identified in the cell membrane material bound to MSF, suggesting that avß3 is a receptor for MSF.

Apesar da incidência relativamente baixa, as neoplasias de glândulas salivares (NGSs) constituem um grupo de doenças caracterizado pela notável heterogeneidade em sua apresentação clínica, histológica e comportamento biológico, abrigando um fator de extrema relevância a despeito de seu prognóstico: a ocorrência de metástases, considerada a principal intercorrência relacionada à mortalidade em pacientes oncológicos. Neste estudo, analisamos as características clínicas e histopatológicas de pacientes diagnosticados com metástases à distância de carcinomas de glândulas salivares tratados no A.C. Camargo Cancer Center, São Paulo, no período de 1970 a 2010. Investigamos alterações fenotípicas entre os tumores primários e tumores metastáticos de glândulas salivares, a partir do estudo da caracterização do padrão de expressão de citoqueratinas, procurando identificar a associação entre a expressão destes antígenos a fatores de risco, ou não, ao potencial metastático à distância e sua importância prognóstica. A casuística total compreendeu 43 pacientes diagnosticados com metástase à distância, com a média de idade de 42.5 anos sendo a glândula parótida o órgão primário mais acometido, e os pulmões o sítio metastático mais incidente. O tipo histológico mais comumente relacionado à metástase foi o carcinoma adenoide cístico. A análise imunoistoquímica da expressão de citoqueratinas fora realizada em 10 neoplasias primárias e 10 metastáticas, as quais revelaram um padrão fenotípico similar no tumor primário e no tumor metastático, apresentando a evidenciação majoritária de células luminais de estruturas ductais. A perda de expressão dos marcadores em áreas tumorais periféricas, adjacentes ao parênquima pulmonar, corrobora a predição de alteração do citoesqueleto das células neoplásicas, possivelmente promovendo uma maior capacidade de migração das células neoplásicas. / Salivary gland neoplasms consist of a notorious group of malignancies best known for its clinical features, biological behavior and histological heterogeneity. An important facto related to prognosis is distant metastasis (uncommon in salivary gland tumors). Cytokeratins (CK) are important differentiation markers frequently used for diagnosis processes. Its employment may be useful to identify metastatic disease. In this study, a retrospective evaluation was performed on patients undergoing treatment for metastatic salivary glands tumors between 1970 and 2010, from A.C. Camargo Cancer Center, São Paulo, Brazil. Demographic data and histopathological specimens were obtained from the medical records. Investigation of the expression of cytokeratins in primary and metastatic salivary gland neoplasms was performed and correlated with their phenotypical patterns. Forty three eligible patients were obtained from the database. Parotid gland represented the primary tumor site most frequently related to metastasis. Lung was the most common metastatic site. Adenoid cystic carcinoma was the histological type more frequently associated to metastatic disease. Immunohistochemistry analysis was performed in 10 primary salivary gland tumors and 10 metastatic salivary gland neoplasms. CK expression patterns were similar in both primary and metastatic neoplams, except for the tumor periphery in close contact with lung parenchyma. Cytokeratins were absent in the invasive front of metastatic lesions, and this may be related to an increased capacity of tumor cells migration and proliferation.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (p. 119-136).

Cockroach salivary glands are innervated by dopaminergic and serotonergic neurons. Both transmitters elicit saliva secretion. We studied the distribution pattern of neurons containing gamma-aminobutyric acid ( GABA) and their physiological role. Immunofluorescence revealed a GABA-immunoreactive axon that originates within the subesophageal ganglion at the salivary neuron 2 (SN2) and this extends within the salivary duct nerve towards the salivary gland. GABA-positive fibers form a network on most acinar lobules and a dense plexus in the interior of a minor fraction of acinar lobules. Co-staining with anti-synapsin revealed that some putative GABAergic terminals seem to make pre-synaptic contacts with GABA-negative release sites. Many putative GABAergic release sites are at some distance from other synapses and at distance from the acinar tissue. Intracellular recordings from isolated salivary glands have revealed that GABA does not affect the basolateral membrane potential of the acinar cells directly. When applied during salivary duct nerve stimulation, GABA enhances the electrical response of the acinar cells and increases the rates of fluid and protein secretion. The effect on electrical cell responses is mimicked by the GABA(B) receptor agonists baclofen and SKF97541, and blocked by the GABAB receptor antagonists CGP52432 and CGP54626. These findings indicate that GABA has a modulatory role in the control of salivation, acting presynaptically on serotonergic and/or dopaminergic neurotransmission.

The aim of the present thesis was to find a test for prediction of caries activity which would be useful in routine clinical work.Correlations between oral health, general health, food habits and socioeconomic conditions were investigated in 4- and 8-year-old children. It was found that the salivary secretion rate and the prevalence of oral lactobacilli were factors which might be useful in caries prediction.In 5- and 8-year-old children negative correlations between caries frequency and secretion rate, pH and buffer effect of saliva were demonstrated. However, these parameters showed a wide range of variation.A dip-slide test (Dentocult®), for determination of the number of lactobacilli in saliva, were investigated. The test proved to be reliable for determining of the number of lactobacilli in saliva.The clinical use of information on salivary secretion rate and number of lactobacilli in saliva in prediction of caries activity was examined in 115 14-year-old children over a period of 64 weeks. The number of lactobacilli in saliva, but not the salivary secretion rate, was correlated to caries activity. The number of lactobacilli in saliva seems to reflect the frequency of ingested fermentable carbohydrates and indirectly the risk for initiation of carious lesions. However, when the lactobacillus test is used it is important that there are no such areas of microbial retention on the teeth, as open cavities, poorly executed conservations, dentures or orthodontic bands. The lactobacillus test would make it possible to individualize prophylactic caries treatment. / <p>Annan ISSN på omslaget och titelblad (ISSN 0934-7532).</p><p>Härtill 5 delarbeten.</p> / digitalisering@umu

Polyacid modified composite resins (PMCR) are designed to combine the aesthetics of composites-resins with the fluoride release of glass-ionomers. Objectives: to compare the relative biostability and fluoride release of PMCR (F2000 [3M]; Dyract eXtra [DENTSPLY]) and a composite-resin (Z250 [3M]). Standardized samples were incubated in either buffer or human saliva derived esterases (HSDE) for up to 14 days. High- performance-liquid-chromatography revealed higher amounts of degradation products for all HSDE incubated groups, as compared with the buffer. Z250 samples released higher amounts of bishydroxypropoxyphenylpropane (Bis-HPPP) and triethylene-glycol-dimethacrylate (TEGDMA) than both PMCR. Dyract eXtra and F2000 samples released unique degradation products, respectively di-ester of 2-hydroxyethyl di-methacrylate with butane tetracarboxylic acid (TCB) and glyceryl dimethacrylate (GDMA). F2000 samples released more fluoride for both incubation periods in the presence of HSDE as compared with Dyract eXtra samples. Scanning electron microscopy analysis confirmed the greater degradation of both PMCR, as compared with Z250.

Background: Human salivary esterases have been shown to degrade dental resin composite restorations in vivo. Objective: To optimize in vivo protocols to recover biodegradation products and to compare the biostability of urethane-modified-bisGMA- (ubis) and bisGMA-based (bis) commercial resin composites. Methods: Class V and III composite restorations were placed in patients using adhesive and composite resin. Gingival crevicular fluid (GCF), plaque and a 2-minute oral rinse with 20% ethanol in saline (n=10) were collected immediately and 7-days after restoration placement. Samples were analyzed for biodegradation products using high performance liquid chromatography. The oral rinse protocol was then used to compare the bis and ubis composite resins (Z250, 3M; TPH, Dentsply) (n=58). Results and conclusions: The bisGMA composite matrix derived product, bishydroxypropoxyphenylpropane (BisHPPP) was only detected from oral rinse collected immediately after restoration placement. There was no statistical difference in the amount of bisHPPP collected from bis and ubis composite resins. This research was supported by CIHR (MOP 68947).

Background: Human salivary esterases have been shown to degrade dental resin composite restorations in vivo. Objective: To optimize in vivo protocols to recover biodegradation products and to compare the biostability of urethane-modified-bisGMA- (ubis) and bisGMA-based (bis) commercial resin composites. Methods: Class V and III composite restorations were placed in patients using adhesive and composite resin. Gingival crevicular fluid (GCF), plaque and a 2-minute oral rinse with 20% ethanol in saline (n=10) were collected immediately and 7-days after restoration placement. Samples were analyzed for biodegradation products using high performance liquid chromatography. The oral rinse protocol was then used to compare the bis and ubis composite resins (Z250, 3M; TPH, Dentsply) (n=58). Results and conclusions: The bisGMA composite matrix derived product, bishydroxypropoxyphenylpropane (BisHPPP) was only detected from oral rinse collected immediately after restoration placement. There was no statistical difference in the amount of bisHPPP collected from bis and ubis composite resins. This research was supported by CIHR (MOP 68947).

Polyacid modified composite resins (PMCR) are designed to combine the aesthetics of composites-resins with the fluoride release of glass-ionomers. Objectives: to compare the relative biostability and fluoride release of PMCR (F2000 [3M]; Dyract eXtra [DENTSPLY]) and a composite-resin (Z250 [3M]). Standardized samples were incubated in either buffer or human saliva derived esterases (HSDE) for up to 14 days. High- performance-liquid-chromatography revealed higher amounts of degradation products for all HSDE incubated groups, as compared with the buffer. Z250 samples released higher amounts of bishydroxypropoxyphenylpropane (Bis-HPPP) and triethylene-glycol-dimethacrylate (TEGDMA) than both PMCR. Dyract eXtra and F2000 samples released unique degradation products, respectively di-ester of 2-hydroxyethyl di-methacrylate with butane tetracarboxylic acid (TCB) and glyceryl dimethacrylate (GDMA). F2000 samples released more fluoride for both incubation periods in the presence of HSDE as compared with Dyract eXtra samples. Scanning electron microscopy analysis confirmed the greater degradation of both PMCR, as compared with Z250.

Thesis (Ph. D.)--University of Missouri--Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 108-125). Also available on the Internet.