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1
Åström, P. (Pirjo). "Regulatory mechanisms mediating matrix metalloproteinase-8 effects in oral tissue repair and tongue cancer." Doctoral thesis, Oulun yliopisto, 2014. http://urn.fi/urn:isbn:9789526206103.
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Abstract Tissue repair and cancer progression involve similar mechanisms, including degradation of extracellular matrix in which matrix metalloproteinases (MMPs) play essential roles. The action of MMPs is important in normal physiological processes but MMPs also contribute to various pathological conditions. MMP-8 belongs to a family of collagenases with a diverse set of substrates. MMP-8 action is involved in skin wound healing and in various human cancers. The function of MMP-8 in cancer appears to be highly complex and varies depending on the cancer type and location. Little is known about the involvement of MMP-8 in oral physiology and pathology. The aim of this study was to clarify the role of MMP-8 in oral tissue repair and oral tongue squamous cell carcinoma (OTSCC). Studies with MMP-8 deficient mice revealed that the function of MMP-8 in tissue repair is highly dependent on the spatial aspects. In alveolar bone, MMP-8 increased inflammation and affected collagen metabolism. In tongue wounds, MMP-8 impaired early healing and reduced transforming growth factor (TGF) -β1 levels. This study also revealed the protective role of MMP-8 in OTSCC patients, in agreement with previous studies indicating positive features of MMP-8 in cancer. Low MMP-8 level and high vascular endothelial growth factor (VEGF) -C levels in tumors correlated with worse prognosis in these patients. In mouse tongue fibroblast cell cultures, MMP-8 reduced TGF-β1 signaling molecule phosphorylated Smad2 levels and impaired the collagen contraction ability. TGF-β1, apoptosis factor Fas-ligand (Fas-L) and estrogen receptors (ERs) were identified as novel MMP-8 substrates. In OTSCC cell cultures, MMP-8 impaired cell migration and invasion. Diminished TGF-β1 levels were involved in the defective migration of MMP-8 overexpressing cells. Moreover, MMP-8 affected the expression of MMP-9, MMP-1, cathepsin-K, VEGF-C and TGF-β1. In mouse models of OTSCC, MMP-8 protected against tumor development but was not able to prevent metastasis formation. The main findings of this study were that 1) MMP-8 action in tissue repair depends on the site of the injury and 2) in OTSCC, MMP-8 has tumor suppressive effects, but in mouse, MMP-8 does not inhibit metastasis formation. In addition, 3) four novel MMP-8 substrates (TGF-β1, Fas-L, ER-α and -β) were identified that may explain the spatial and diverse roles of MMP-8Tiivistelmä Kudosvaurioiden paranemiseen ja syövän etenemiseen liittyy useita samankaltaisia mekanismeja. Molemmissa toimivat soluvälitilan muokkaamiseen osallistuvat proteaasit, joista matriksin metalloproteinaaseilla (MMP) on tärkeä merkitys; ne osallistuvat lukuisiin elimistön keskeisiin fysiopatologisiin prosesseihin. Kollagenaasi MMP-8 muokkaa monentyyppisiä molekyylejä. Se on mukana ihohaavan paranemisessa ja useissa syövissä. MMP-8:n toiminta syöpätiloissa on hyvin moninainen riippuen syöpätyypistä ja sijainnista. Väitöstutkimuksessa selvitettiin MMP-8:n merkitystä suun kova- ja pehmytkudosvaurioprosesseissa sekä kielisyövässä, joissa se on ollut tuntematon. MMP-8 poistogeenisillä hiirillä tehdyissä pehmyt- ja kovakudoshaavoissa MMP-8:n vaikutusmekanismit riippuivat kohdekudoksesta. Alveoliluun paranemisen yhteydessä MMP-8 lisäsi tulehdusta ja osallistui kollageenin muokkaamiseen. Akuutin kielihaavan paranemisessa MMP-8 hidasti haavan umpeutumista ja vähensi transformoivan kasvutekijä-β1:n (TGF-β1) määrää. Kuten useissa muissakin syövissä, myös kielisyövässä todettiin MMP-8:lla olevan suojaava vaikutus. Potilaan ennuste huononi, jos kasvainsolukon matala MMP-8-taso yhdistyi korkeaan verisuonten kasvutekijä-C:n (VEGF-C) määrään. Hiiren kielen normaaleissa fibroblastiviljelmissä MMP-8 vähensi TGF-β1:n solunsisäistä signalointia välittävän fosforyloidun Smad2:n määrää sekä solujen kykyä supistaa kollageenikiekkoja. Koeputkessa MMP-8 pilkkoi TGF-β1:tä, estrogeenireseptoreja (ER) ja apoptoositekijä Fas-ligandia (Fas-L). Ihmisen kielikarsinoomasoluviljelmissä korkea MMP-8:n määrä vähensi solujen migraatiota ja invaasiota sekä muutti MMP-1:n, MMP-9:n, katepsiini-K:n, TGF-β1:n ja VEGF-C:n ilmentymistä. Migraation heikentyminen MMP-8:aa tuottavissa soluissa johtui osin vähentyneestä TGF-β1:n määrästä. Hiiren kokeellisissa kielisyövissä MMP-8 hidasti syövän muodostumista mutta ei estänyt etäpesäkkeiden muodostusta. Tässä väitöskirjatutkimuksessa on kolme päälöydöstä: 1) MMP-8:n vaikutus kudoksen paranemisprosessiin riippuu vauriokohdasta, 2) MMP-8 on kielisyövän kehittymisessä puolustuksellinen molekyyli, mutta sen lisääntynyt tuotto ei hiirikokeissa estänyt etäpesäkkeiden muodostusta, 3) MMP-8:lle löydettiin neljä uutta kohdemolekyyliä (TGF-β1, Fas-L, ER-α ja -β), joiden muokkaus saattaa osin selittää MMP-8:n monipuoliset kudos- ja prosessispesifit vaikutukset
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Sgaramella, Nicola. "Squamous cell carcinoma of the oral tongue : studies of biomarkers connected to human papillomavirus infection, epithelial to mesenchymal transition and locoregional metastatis." Doctoral thesis, Umeå universitet, Patologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-134567.
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Background: Oral Tongue Squamous Cell Carcinoma (OTSCC) is the most frequent and aggressive carcinoma in the head and neck region. Its incidence has increased during the last decades, especially in young patients (≤40 years) mainly female. These young patients have either not been exposed to the traditional risk factors for this disease, or have a much reduced duration of exposure than the typical OTSCC patient. The reasons behind this increasing incidence remain unknown. The aims of this thesis were to analyse the presence and possible role of human papillomavirus (HPV) in oral tongue cancer in correlation with its surrogate marker p16 and its receptor syndecan-1. Other aims were to evaluate expression of EMT (epithelial to mesenchymal transition) - related markers, such as E-cadherin, β-catenin, CK5 and CK19, and to address the potential predictive role of podoplanin in the loco-regional metastatic process. Clinical parameters including age, sex, geographical distribution, relapse, tumour staging and grading were also investigated for a possible correlation with biomarker expression and prediction of survival rate and therapeutic strategy. Materials and methods: More than one hundred samples of OTSCC coming from two University Hospitals of two different countries (Sweden and Italy) were analysed. HPV presence was evaluated by in situ hybridisation for detection of the high-risk HPV 16 and indirectly by immunohistochemistry (IHC) of its surrogate marker p16. Expression of the HPV receptor syndecan-1 and the EMT biomarkers E-cadherin, β-catenin, CK5, CK19 were also evaluated by immunohistochemistry. Samples were scored using a quick score (QS), taking both number and intensity of cells stained into account. Podoplanin expression was investigated at both protein and RNA level. Results: Tumour size and lymph node metastasis correlated to both overall and disease-free survival. Despite variable expression of the syndecan-1 receptor, HPV 16 was not detected in any sample analysed, excluding a possible association with p16, which was expressed in 33% of the cases. All EMT-related markers were commonly expressed in tongue cancer. Data showed E-cadherin to be an independent prognostic factor with higher expression associated with poor overall survival. Notably, E-cadherin, β-catenin and CK5 directly correlated to each other. Multivariate analysis of clinical data demonstrated that age of the patient is an independent prognostic factor with younger patients showing a worse survival rate. Patients younger than 40 years also showed significantly higher expression of podoplanin. Data for geographic distribution revealed a difference in expression of E-cadherin between Swedish and Italian patients. Conclusions: In contrast to SCC of the base of the tongue and the tonsil, HPV is not present in OTSCC, excluding HPV infection as a risk factor. Higher levels of E-cadherin and young age is associated with poor survival in OTSCC patients. The different frequency of EMT markers seen between Swedish and Italian patients suggests an important role for the environment and the geographical area in the onset of different molecular patterns of OTSCC.
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Rodrigues, Priscila Campioni 1984. "Myofibroblast distribution in oral dysplasias and squamous cell carcinoma and evaluation of clinicopathological factors associated with prognosis of squamous cell carcinoma of tongue = Distribuição de miofibroblastos em lesões orais displásicas e carcinomas espinocelulares e avaliação das características clínico-patológicas associadas ao prognóstico do carcinoma espinocelular de língua." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288716.
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Orientador: Ricardo Della ColettaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: Embora várias características histopatológicas e moleculares tenham sido propostas como fatores prognósticos do carcinoma espinocelular (CEC) oral, nenhuma ainda é utilizada rotineiramente. Estudos prévios demonstraram que a presença de miofibroblastos no estroma de CECs orais é associada a um pior prognóstico e que pacientes jovens apresentam tumores com comportamento biológico distinto quando comparado ao de pacientes idosos. Os objetivos deste estudo foram 1) avaliar a influência das características demográficas, clínicas e histopatológicas no prognóstico dos CECs de língua, 2) avaliar a frequência de miofibroblastos em displasias orais (leve, moderada e severa), CECs (lesões bem diferenciadas e pobremente diferenciadas) e carcinomas verrucosos (uma variante bem diferenciada do CEC oral) e comparar a frequência destas células com hiperplasias fibrosas (HF) e 3) comparar a densidade de miofibroblastos entre CEC orais de pacientes jovens (<40 anos) e pacientes idosos (>45 anos). Para determinar a influência das características clínicas, demográficas e histopatológicas (risco histológico de Brandwein-Gensler) no prognóstico dos CECs de língua, um estudo retrospectivo com 202 pacientes foi realizado. A detecção de miofibroblastos foi realizada por reações de imuno-histoquímica para a isoforma ? da actina de músculo liso (?-SMA) em HFs com epitélio normal (n=29), displasias (n=69), CECs bem diferenciados (n=19), CECs pobremente diferenciados (n=18) e carcinomas verrucosos (n=8). A comparação entre CECs de pacientes jovens e de pacientes idosos foi realizada em um segundo grupo contendo 29 amostras pareadas para localização, estádio clínico e graduação histológica. A análise multivariada de Cox revelou que estádio T, estádio N e recorrência foram fatores independentes das sobrevidas global, específica e livre de doença para os pacientes com CEC de língua. O risco histológico não correlacionou com o prognóstico destes pacientes. HFs e displasias orais não apresentam miofibroblastos, enquanto que 62,2% dos CECs demonstraram miofibroblastos no estroma tumoral. A presença de miofibroblastos foi significantemente mais frequente nos CECs pobremente diferenciados em comparação aos CECs bem diferenciados ou aos carcinomas verrucosos. Não houve diferença estatisticamente significante entre a densidade de miofibroblastos nos CECs de pacientes jovens e idosos. Os resultados deste estudo demonstram que as características clínicas são melhores fatores preditivos para o prognóstico do CEC de língua do que o risco histológico e que a presença de miofibroblastos não é associada com displasias orais, mas tumores pobremente diferenciados apresentam uma densidade significantemente maior que tumores bem diferenciados. O estudo revelou também que a presença de miofibroblastos no estroma dos CECs de língua não diferencia entre tumores em pacientes jovens e idosos
Abstract: Although several histopathological and molecular features have been proposed as prognostic factors of the oral squamous cell carcinoma (OSCC), any is routinely used. Previous studies have demonstrated that the presence of myofibroblasts in the stroma of the OSCC is associated with a worse prognosis and that young patients have tumors with a particular biological behavior when compared with older patients. The aims of this study were 1) to evaluate the influence of the demographics, clinical and histopathological features in the prognostic of SCC of tongue, 2) to determine the frequency of myofibroblasts in the oral dysplasias (mild, moderate and severe), OSCC (well differentiated and poorly differentiated) and verrucous carcinoma (a well differentiated variant of the OSCC) and compare the density of this cell with fibrous hyperplasias and 3) to compare the density of myofibroblasts among OSCC of young patients (< 40 years) and older patients (> 45 years). To determine the influence of the clinical, demographic and histopathological (histologic risk of Brandwein-Gensler) features in the prognostic of SCCs of tongue, a retrospective study was realized with 202 patients. Myofibroblasts were detected by immunohistochemical analysis of ? smooth muscle actin (?-SMA) in fibrous hyperplasia with normal epithelium (n=29), oral dysplasias (n=69), well differentiated OSCC (n=19), poorly differentiated OSCC (n=18) and verrrucous carcinoma (n=8). The comparison between OSCC affecting young patients and older patients was realized in a second group containing 29 samples paired to localization, clinical stage and histological differentiation. Cox multivariate analysis revealed that the T stage, N stage and recurrence were independent factors of overall survival, disease-especific survival and disease-free survival. The histologic risk was not correlated with the prognostic of the patients. Fibrous hyperplasia and oral dysplasias did not show myofibroblasts in the stroma. The presence of myofibroblasts was higher in the poorly differentiated OSCCs when compared with well differentiated OSCC or with verrucous carcinomas. No significant differences existed between the presence of stromal myofibroblasts of OSCC affecting young and old individuals. The results of this study demonstrated that the clinical features were best predictive factors to the SCC of tongue prognostic than the histologic risk, and the presence of myofibroblasts was not associated with the oral dyspasias. However the poorly differentiated tumors demonstrated a higher expression of myofibroblasts than well differentiated tumors. The study also revealed that the presence of myofibroblasts in the OSCC not show differences among young and older patients
Mestrado
Patologia
Mestra em Estomatopatologia
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Sundquist, E. (Elias). "The role of tumor microenvironment on oral tongue cancer invasion and prognosis." Doctoral thesis, Oulun yliopisto, 2018. http://urn.fi/urn:isbn:9789526217659.
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Abstract Oral tongue squamous cell carcinoma (OTSCC) is the most common cancer of the oral cavity. The 5-year mortality of OTSCC remains at about 50%. The tumor microenvironment (TME) is now recognized as an important factor in cancer progression and metastasis, as well as a tool for prognostication. The aim of this study was to elucidate the roles of TME hypoxia and soluble factors on cancer cell migration and invasion, and the prognostic value of two extracellular matrix (ECM) molecules: tenascin-C (TNC) and fibronectin (FN). Hypoxia was studied using oral squamous cell carcinoma cells in migration and invasion assays. Invasion assays were carried out using a 3D-myoma invasion method. Similarly, the effect of soluble factors as well as ECM alterations were studied using the myoma model: the effect of soluble factors was studied by rinsing the myoma discs prior to experiments, and ECM alterations by lyophilizing and rehydrating. ECM was further studied by analyzing the prognostic value of TNC and FN from OTSCC samples. The effect of hypoxia was shown to be OTSCC cell line dependent: the effect of hypoxia on migration and invasion was increased in aggressive cell lines. Additionally, the response to hypoxia was altered in rinsed tissue. Tissue rinsing media were analyzed and factors affecting cell motility were found. The TME was found to be pivotal for cancer invasion: invasion was impaired in non-neoplastic tissue. Furthermore, changes in the ECM by lyophilization and rehydration led to a change in the invasion mechanism. High expression of stromal TNC and FN were excellent prognosticators in early-stage OTSCC. In conclusion, the present study highlighted the role of various TME components in cancer cell invasion as well as prognostication in OTSCC. Additionally, this study provided feasible tools for more precise diagnosis of early-stage OTSCCTiivistelmä Liikkuvan kielen levyepiteelikarsinooma (OTSCC) on suuontelon yleisin syöpä. Viiden vuoden kuolleisuus OTSCC:an on edelleen noin 50 %. Kasvaimen mikroympäristön (TME) tiedetään nykyään olevan tärkeässä roolissa syövän kehityksessä ja etäpesäkkeiden muodostuksessa, sekä tarjoavan työkaluja ennusteiden laadintaan. Tämän tutkimuksen tarkoituksena oli selvittää TME:n hypoksian ja liukoisten tekijöiden vaikutusta syöpäsolujen liikkumiseen ja invaasioon ympäröivään kudokseen, sekä tutkia kahden solunulkoisen matriksin (ECM) proteiinin, tenaskiini-C:n (TNC) ja fibronektiinin (FN), vaikutusta OTSCC:n ennusteeseen. Hypoksian vaikutusta tutkittiin käyttäen suun levyepiteelikarsinoomasoluja liikkuvuus- ja invaasiokokeissa. Invaasiokokeissa hyödynnettiin kolmiulotteista ihmisen myoomaan perustuvaa invaasiomallia. Myös liukoisten tekijöiden ja ECM:n muutosten vaikutusten tutkimisessa käytettiin myoomamallia: liukoisten tekijöiden vaikutusta tutkittiin huuhtomalla myoomakiekot ennen niiden käyttämistä, ja ECM:n muutosten vaikutusta kylmäkuivaamalla ja uudelleen nesteyttämällä myoomakiekot. ECM:ia tutkittiin myös analysoimalla TNC:n ja FN:n värjäytyvyyden merkitystä OTSCC:n ennusteessa. Hypoksian vaikutus osoittautui solulinjariippuvaiseksi: hypoksia lisäsi kielisyöpäsolujen liikkuvuutta ja invaasiota eniten aggressiivisimmilla solulinjoilla. Lisäksi solujen vaste hypoksialle oli erilainen huuhdotussa kudoksessa. Huuhteluliuos analysoitiin ja siitä löydettiin solujen liikkumiseen vaikuttavia tekijöitä. TME:n havaittiin olevan ratkaisevassa roolissa syöpäsolujen invaasiossa: syöpäsolut eivät kyenneet invasoitumaan lainkaan ei-neoplastiseen kudokseen. Lisäksi muutosten ECM:ssä havaittiin johtavan muutoksiin solujen käyttämässä invaasion mekanismissa. Strooman TNC:n ja FN:n värjäytyvyyden todettiin olevan erinomaisia ennustekijöitä aikaisen vaiheen OTSCC:ssa. Tiivistettynä voidaan todeta, että tämä tutkimus alleviivasi useiden TME:n komponenttien vaikutusta syövän invaasiolle ja ennusteelle OTSCC:ssä. Lisäksi se tarjoaa käyttökelpoiset työkalut (TNC ja FN) tarkemmalle diagnostiikalle aikaisen vaiheen OTSCC:ssä
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Väyrynen, O. (Otto). "Factors affecting aggressive oral tongue cancer invasion and development of in vitro models for chemoradiotherapy assay." Doctoral thesis, Oulun yliopisto, 2019. http://urn.fi/urn:isbn:9789526222813.
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Abstract Tumor associated macrophages (TAMs) are linked to the invasion of oral tongue squamous cell carcinoma (OTSCC). We modified THP-1 leukemia cells to M1 (inflammatory), M2 (TAM-like) and R848 (imidazoquinoline-treated) type macrophages in order to examine their interactions with OTSCC-cells (HSC-3) by using different kinds of in vitro migration and invasion models. We observed that interaction of TAM-resembling M2-type macrophages with HSC-3 cells induced invasion and migration, whereas the influence of M1 macrophages reduced them. Patient response to chemoradiotherapy is highly reliant on the characteristics such as the aggressiveness and stage of the cancer. Therefore, new methods for treatment testing are needed in order to design personalized therapies. We tested the applicability and consistency of human TME mimicking tissue methods for analyzing the effects of chemoradiation using commercial OTSCC cell lines. Based on our trials, both our human uterine leiomyoma tissue -based matrix models provide viable platforms for future in vitro chemoradiotherapy testing. Conventionally pro-tumorigenic activities of matrix metalloproteinase (MMP)9 have been linked with oral squamous cell carcinoma, but recently its tumor-suppressor role has also been revealed. Our study provides strong evidence that MMP9 also has an anti-invasive effect in OTSCC and is a potential mediator of the protective effects of arresten in tongue cancer cellsTiivistelmä Makrofageilla on yhteys kielen levyepiteelikarsinooman invaasioon eli syöpäkasvaimen tunkeutumiseen ympäröivään kudokseen. Tutkimuksessamme muokkasimme ihmisen THP-1 leukemiasoluja kemiallisesti tulehdusreittejä aktivoiviksi M1-makrofageiksi, kasvaimeen liittyvien makrofagien kaltaisiksi M2-makrofageiksi sekä imidatsokinoliini-käsitellyiksi R848-makrofageiksi. Tarkoituksenamme oli tutkia makrofagien ja kielisyöpäsolujen vuorovaikutuksia erilaisilla in vitro migraatio- ja invaasiomalleilla. Anti-inflammatoristen, syövän etenemistä edesauttavien TAM-makrofagien kaltaisiksi erilaistetut M2-tyypin makrofagit lisäsivät HSC-3 kielikarsinoomasolujen invaasiota ja migraatiota, kun taas M1-tyypin makrofagien vaikutus oli päinvastainen. Potilaan vaste kemosädehoitoon riippuu syöpäkasvaimen ominaisuuksista, kuten syöpäsolujen aggressiivisuudesta ja syövän levinneisyysasteesta. Tämän vuoksi on tarve uusille menetelmille, joiden avulla voidaan ottaa huomioon potilaan sekä syöpätyypin yksilölliset ominaisuudet hoitoa suunniteltaessa. Testasimme syöpäkasvaimen mikroympäristöä mallintavien, ihmiskudokseen perustuvien menetelmien käyttökelpoisuutta ja luotettavuutta kemosädehoidon vaikutusten arvioimiseen. Testiemme perusteella myoomakudokseen pohjautuvat menetelmät voivat auttaa kemosädehoidon vaikutusten testauksessa. Matriksin metalloproteinaasi (MMP) 9:n on pitkään uskottu olevan yksinomaan syövän etenemistä edesauttava molekyyli. Viimeaikaisissa tutkimuksissa on myös havaittu, että MMP9:llä voi olla syövältä suojaavia vaikutuksia. Tutkimme MMP9:n vaikutusta kielisyöpäsoluihin ja havaitsimme, että MMP9:llä on myös invaasiota hillitseviä vaikutuksia. Lisäksi MMP9 saattaa toimia verisuonten muodostumista estävän arresten-molekyylin syövältä suojaavien mekanismien välittäjänä
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Carvalho, Larissa Kim Higashi de. "Avaliação dos efeitos pró apoptóticos da fosfoetanolamina sintética e da formulação lipossomal DODAC/FOS em células de carcinoma espinocelular da cavidade oral." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5160/tde-31072017-132005/.
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Os carcinomas de cabeça e pescoço correspondem a 10% de todos dos tumores malignos, destes aproximadamente 40% se manifestam na boca e 90% correspondem ao carcinoma espinocelular. Os principais agentes carcinogênicos relacionados ao câncer bucal são o tabaco e o álcool. A cirurgia é o tratamento de eleição para o carcinoma de boca seguido dos tratamentos quimio e radioterápicos. O uso de lipossomas como vetor de quimioterápicos abre grandes perspectivas para o tratamento do câncer, pois possibilitam maior eficácia, reduzindo a toxicidade e a dosagem do fármaco. Neste projeto foram avaliados os efeitos pró apoptóticos \"in vitro\" da fosfoetanolamina sintética (FOS) e da sua formulação lipossomal DODAC/FOS em duas linhagens celulares de carcinoma espinocelular de língua humano, SCC-9 e SCC-25. A FOS, a formulação lipossomal DODAC/FOS e o carreador DODAC vazio apresentam diferentes significados em seu potencial citotóxico. A FOS aumentou significativamente a formação de lipoperóxidos pela membrana celular nas maiores concentrações estudadas. A análise das fases do ciclo celular mostrou aumento significativo da população de células com DNA fragmentado em ambas as linhagens celulares induzindo a morte celular por apoptose com aumento da expressão de Bad, Bax, citocromo c e diminuição de Bcl-2, como também alterou o potencial elétrico mitocondrial promovendo a ativação da caspase-3. A FOS e a formulação lipossomal DODAC/FOS induziram retração dos filamentos de actina e fragmentação do DNA. O conjunto de resultados mostra que o composto FOS e a sua formulação lipossomal DODAC/FOS atuam nos efeitos citotóxicos e antitumoral promovidos por estes alquilfosfoésteres, sendo capazes de induzir a morte celular por apoptose em diferentes apresentaçõesHead and neck carcinomas account for 10% of all malignant tumors, approximately 40% of these tumors manifest in the mouth and 90% correspond to squamous cell carcinoma. The main carcinogenic agents related to oral cancer are tobacco and alcohol. Surgery is the treatment of choice for oral carcinoma followed by chemo and radiotherapeutic treatments. The use of liposomes as a vector of chemotherapy offers great prospects for treatment of cancer, as they allow greater efficacy, reducing the toxicity and the dosage of drug. In this project, in vitro pro apoptotic effects of synthetic phosphoethanolamine (Pho-S) and DODAC/Pho-S liposomal formulation were evaluated in two human tongue squamous cell carcinoma cell lines, SCC-9 and SCC-25. Pho-S, DODAC/Pho-S liposomal formulation and the empty DODAC carrier have different meanings in their cytotoxic potential. Pho-S significantly increased the formation of lipoperoxides by cell membrane in higher concentrations studied. Analysis of the cell cycle phases showed a significant increase in the cell population with fragmented DNA in both cell lines inducing apoptosis cell death with increase expression of Bad, Bax, cytochrome c and decrease of Bcl-2, as well as altered the potential mitochondrial activation promoting caspase-3 activation. Pho-S and the DODAC/Pho-S liposomal formulation induced retraction of the actin filaments and DNA fragmentation. The set of results shows that the Pho-S compound and its liposomal formulation DODAC/Pho-S act on the cytotoxic and antitumor effects promoted by these alkylphosphoesters, being able to induce cell death by apoptosis in different presentations
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Silveira, Ericka Janine Dantas da. "Carcinoma epiderm?ide de l?ngua :correla??o cl?nica, histol?gica e imuno-histoqu?mica." Universidade Federal do Rio Grande do Norte, 2004. http://repositorio.ufrn.br:8080/jspui/handle/123456789/17105.
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Previous issue date: 2006-05-19Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior
Oral squamous cell carcinoma is the most common malignant neoplasm in oral cavity. Several studies have been carried out to establish biologic behaviour criteria of this neoplasm. Thus, the purpose of this experiment was to performe a clinic, morphologic and immunohistochemical analysis, by the expression of cytokeratins 7, 10, 13, 14, 16 and 19 in 30 cases of tongue squamous cell carcinoma from the files of Dr. Luiz Ant?nio Hospital (Natal-RN). It was verifeid of the immunoexpression the correlation clinic estadiament and histologic gradation system proposed by Bryne (1998), in order to investigate the use of these intermediate filaments as an indicator of tumour progression. Data was collected from the patients file and it was observed that information regarding sex, age and race was resemble to the literature. Data obtained from disease evolution, clinic estadiament, metastasis and expression of cytokeratins 7, 10, 13, 14, 16 and 19 was submited to statistical analysis (Test K2), which showed that only the histologic gradation didn t demonstrated significant correlation to the clinic variables. The expression the cytokeratins presented variation in the analysed tumours. CK 10 expression showed significant correlation to metastasis, and the presence of CK 16 was related to disease evolution (obit/remission) and also with the T3 and T4 of TNM. These results evidenced that metastasis and TNM showed a good efficacy as a prognostic indicator. The histologic gradation proposed by Bryne (1998) didn t reflect the biologic behaviour of the studied tongue squamous cell carcinoma, and the analysis of some intermediate filaments of cytokeratins seems to reflect the biologic behaviour and agressivity of some oral squamous cell carcinoma
O carcinoma epiderm?ide oral ? a neoplasia maligna mais freq?ente na cavidade oral. Muitas pesquisas desenvolvidas visam estabelecer crit?rios que determinem o comportamento biol?gico dessa neoplasia, assim, objetivou-se com esse trabalho realizar uma an?lise cl?nica, morfol?gica e imuno-histoqu?mica atrav?s da express?o das citoqueratinas 7, 10, 13, 14, 16 e 19 em 30 casos de carcinoma epiderm?ide de l?ngua retirados dos arquivos do Hospital Dr. Luiz Ant?nio (Natal-RN), correlacionando essa express?o ao estadiamento cl?nico e grada??o histol?gica de malignidade proposto por Bryne (1998), com o intuito de verificar a utiliza??o destes filamentos intermedi?rios como indicadores de progress?o tumoral. Ap?s a an?lise cl?nica das informa??es contidas nos prontu?rios desses pacientes verificamos que os dados referentes a sexo, idade e ra?a se assemelham aos da literatura pertinente. Os dados obtidos em rela??o ao desfecho da doen?a, estadiamento cl?nico, presen?a de met?stase, grada??o histol?gica de malignidade, e express?o das citoqueratinas 7, 10, 13, 14, 16 e 19 foram submetidos a an?lise estat?stica (teste Qui2), observando-se que somente a grada??o histol?gica de malignidade n?o apresentou correla??o significativa com as vari?veis cl?nicas estudadas. A express?o dessas citoqueratinas foi variada nos tumores analisados. A express?o da CK 10 mostrou correla??o estatisticamente significativa com a presen?a de met?stase, a presen?a da CK 16 correlacionou-se ao desfecho da doen?a (?bito/remiss?o) e ainda aos est?gios III e IV do TNM. Esses resultados evidenciaram que a met?stase e o estadiamento cl?nico (TNM) mostraram boa efetividade como indicadores de progn?stico. O sistema de grada??o histol?gica de malignidade proposto por Bryne (1998) n?o refletiu o comportamento biol?gico dos carcinomas epiderm?ides de l?ngua estudados, e a an?lise de alguns filamentos intermedi?rios de citoqueratinas parece refletir o comportamento biol?gico e agressividade dos carcinomas epiderm?ides orais
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Jonsson, Eva Lindell. "Biomolecular markers in head and neck cancer." Doctoral thesis, Uppsala universitet, Öron-, näs- och halssjukdomar, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-306126.
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Head and neck cancer is a heterogeneous group of tumours, of which certain subgroups such as cancer of the mobile tongue frequently are associated with a relatively poor prognosis due to the high risk of regional failure and mortality rates that haven’t improved in a significant way over the last 3 decades, despite advancements in both diagnostics and treatment. Today we lack means to assess the biological aggressiveness of each individual tumour, which varies largely. Treatment comprises of surgery with additional radiotherapy and medical therapies in more advanced tumours. The focus in this thesis is on molecular biomarker expression in head and neck cancer and especially in association with radiotherapy. Increased knowledge paves the way to a more individualized cancer treatment aiming for better outcome and less overtreatment and sequelae. The aims of this thesis was: To map the effects of radiotherapy in both tumour and adjacent tissue for the possible markers hyaluronan, EGFR and mast cells. To investigate whether the expression of hyaluronan in the epithelium and connective tissue stroma and EGFR in the tumour correlates with the risk for developing cervical metastasis in N0 patients, and to find out whether the 3-year tumour-specific survival rates correlates with the expression of HA in the epithelium and EGFR in the tumour. To establish an animal model for radiation-induced mucositis and to use that model to examine the pattern of invading inflammatory cells. To investigate whether the expression of podoplanin in tongue cancer correlates with the risk for cervical metastasis and to determine whether the total amount of lymph vessels in the diagnostic biopsy has any impact on the clinical outcome. To investigate the differences in the metabolome of tongue cancer cell lines with different radiosensitivity. The most important findings of this thesis were: The expression of EGFR and hyaluronan hade the same pattern of expression in both tumour and adjacent tissues before radiotherapy. The expression of EGFR was increased in the epithelium of the adjacent tissue close to the tumour after radiotherapy. The intensity of the staining of hyaluronan was correlated to the 3-year survival rates in patients with tongue cancer. An experimental model for radiation-induced oral mucositis in rat was established and in this model a temporal pattern of macrophage invasion with two different subtypes of macrophages was found. There were no correlation between the expression of podoplanin in the tumour tissue and the cervical metastasis rate in patients with tongue cancer, but the younger patients were more likely to have a higher expression of podoplanin in their tumour than elder patients. Tongue cancer cell lines with different radiosensitivity respond to irradiation with different patterns of metabolic expressions.
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Nascimento, George Jo?o Ferreira do. "Associa??o entre polimorfismos funcionais nos genes da MMP-7 e MMP-9 e o perfil clinicopatol?gico do carcinoma epiderm?ide de l?ngua." Universidade Federal do Rio Grande do Norte, 2010. http://repositorio.ufrn.br:8080/jspui/handle/123456789/17145.
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Previous issue date: 2010-02-18Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico
Matrix metalloproteinase-7 (MMP-7) and -9 (MMP-9) modulate important functions strictly related to the development, invasion and metastasis of several human cancers among them the squamous cell carcinoma of the tongue (SCCT). However, individual genetic factors such as the functional single nucleotide polymorphisms (SNPs) influence the pattern of protein expression of these MMPs and thus may be related to the variability observed in the clinical behavior of patients with SCCT. In this context, the present cross-sectional study aimed to evaluate the association between the frequency of the functional SNPs MMP-7 -181 A/G and MMP-9 -1562 C/T and the clinical (age, gender and metastasis) and pathological (malignancy histological grading and immunohistochemistry expression) features of SCCT cases. Genotyping of these SNPs were performed by PCR-RFLP on DNA samples from 71 cases of SCCT and 60 individuals without cancer who constitute the control group. Among the results of this research, it was observed that the frequency of the polymorphic alleles MMP-7 -181 G and MMP-9 -1562 T in SCCT patients was 28% and 12%, respectively, and the frequency of the heterozygotes A/G (PR = 2.00; p < 0.001) and C/T (PR = 1.54; p = 0.014) were significantly higher in the patient group than in the controls. The prevalence of patients carrying the combination of SNPs studied was significantly associated with SCCT cases (PR = 2.00; p = 0.011) and metastasis (PR = 2.00; p < 0.001). Furthermore, with the frequency of SNPs analyzed, the age, gender, histological grading and immunoreactivity of MMP-7 and MMP-9 formed clinical and pathological parameters relevant to the identification of population subgroups more related to the development of SCCT and metastasis. Based on these results, it is suggested that the protein expression levels of MMP-7 and -9 substantially influence the balance between their pro- and anticancer biological functions and hence the clinicopathological profile of the squamous cell carcinoma of the tongue
As metaloproteinases da matriz extracelular-7 (MMP-7) e -9 (MMP-9) modulam importantes fun??es relacionadas ao desenvolvimento, invas?o e met?stase de diversos c?nceres humanos, dentre os quais o carcinoma epiderm?ide de l?ngua (CEL). Entretanto, fatores gen?ticos individuais, tais como polimorfismos de nucleot?deo ?nico (SNPs) funcionais, influenciam no padr?o de express?o proteica dessas MMPs, podendo estar relacionados ? variabilidade no comportamento cl?nico tumoral observado em pacientes com CEL. Neste contexto, o presente trabalho objetivou, atrav?s de an?lise em sec??o transversal, estudar a associa??o entre a frequ?ncia dos SNPs funcionais MMP-7 -181 A/G e MMP-9 -1562 C/T e as caracter?sticas cl?nicas (idade, sexo e met?stase) e patol?gicas (grada??o histol?gica e express?o imuno-histoqu?mica) em uma s?rie de casos de CEL. A genotipagem dos referidos SNPs foi executada por PCR-RFLP em amostras de DNA de 71 casos de CEL e de 60 indiv?duos sem c?ncer, que constitu?ram o grupo controle. Dentre os resultados da presente pesquisa, evidenciou-se que a frequ?ncia dos alelos polim?rficos MMP-7 -181 G e MMP-9 -1562 T nos pacientes com CEL foi de 28% e 12%, respectivamente, sendo as frequ?ncias dos heterozigotos A/G (RP = 2.00; p < 0.001) e C/T (RP = 1.54; p = 0.014) significativamente maiores neste grupo de pacientes que no grupo controle. A preval?ncia dos pacientes portadores da combina??o dos SNPs estudados associou-se significativamente aos casos de CEL (RP = 2.00; p = 0.011) e ? met?stase (RP = 2.00; p < 0.001). Ademais, junto ? frequ?ncia dos SNPs analisados, a idade, sexo, grada??o histol?gica e imunoexpress?o da MMP-7 e -9 constitu?ram par?metros clinicopatol?gicos relevantes para a identifica??o de subgrupos populacionais mais predispostos ao desenvolvimento do CEL e met?stase. Frente a estes resultados, sugere-se que os n?veis de express?o da MMP-7 e -9 influenciam consideravelmente no balan?o entre suas fun??es pr? e antineopl?sicas e, consequentemente, no perfil clinicopatol?gico do carcinoma epiderm?ide de l?ngua.
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Liu, Xiaobing. "Dysregulation of microRNAs in tongue squamous cell carcinoma." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/b40203499.
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Liu, Xiaobing, and 劉小兵. "Dysregulation of microRNAs in tongue squamous cell carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40203499.
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Murphy, Justin Thomas. "Radioresistance in oral squamous cell carcinoma." Thesis, University of Hull, 2008. http://hydra.hull.ac.uk/resources/hull:770.
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Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer accounting for approximately 6% of all cancers worldwide. However the distribution across the globe varies considerably. The majority of small tumours of the oral cavity and upper aerodigestive tract, in the absence of metastatic disease, can be successfully treated with surgery or radiotherapy. Despite this most small tumours of the oral cavity are now treated with surgery as the primary treatment modality with radiotherapy being reserved for adjuvant therapy, palliation or in patients unfit for surgery. Radiotherapy is also used in cases where there is doubt about the completeness of resection and where adverse histological characteristics are present. Unfortunately, on average about 10% of tumours treated in this way are resistant to radiotherapy, developing tumour recurrence within the original radiotherapy field during the ensuing 12 months. Patients with radioresistant tumours are not only receiving a therapy that is unnecessary but are also being put at risk of potentially serious complications, e.g. osteoradionecrosis of the cervical spine. The primary aim of this thesis was to investigate the mechanism of radioresistance and create an in vitro model of a radioresistant oral squamous cell carcinoma. The methods of cell culture, microarray analysis and immunohistochemistry were employed to this end. Two novel radioresistant cell lines, PE-CAPJ41RR and PE-CAPJ49RR, were created and a number of targets identified using microarray analysis. Immunohistochemistry was used to investigate the relationship EGFR, Bcl-2, BAX and COX-2 had with radiotherapy response.
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Ash, Cecil Samuel. "Mandibular invasion in oral squamous cell carcinoma." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq23202.pdf.
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Sun, Li. "Molecular cytogenetics of oral squamous cell carcinoma." Click to view the E-thesis via HKUTO, 2002. http://sunzi.lib.hku.hk/HKUTO/record/B38627887.
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Lim, Kue Peng. "Fibroblasts in human oral squamous cell carcinoma." Thesis, University of Bristol, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.503859.
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The tumour microenvironment is known to play an important role in tumour development and progression. The diversity and role of stromal fibroblasts in human oral cancer, however, is unknown. In this study, fibroblasts were oral cancer, however, is unknown. In this study, fibroblasts were isolated from cultures of normal oral mucosa, oral epithelial dysplasia and mortal and immortal oral carcinomas, the latter malignancy being genetically unstable. Using global gene expression profiling, we demonstrated that fibroblasts clustered according to their tissue of origin.
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Sun, Li, and 孫莉. "Molecular cytogenetics of oral squamous cell carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B36544267.
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Yap, Lee Fah. "Molecular characterization of oral squamous cell carcinoma." Thesis, University of Bristol, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.435716.
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Kim, Hyung Jun. "Surgical management of oral squamous cell carcinoma infiltrating mandible." Diss., lmu, 2008. http://nbn-resolving.de/urn:nbn:de:bvb:19-98143.
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Sawair, F. A. "Prognostic indicators of outcome for oral squamous cell carcinoma." Thesis, Queen's University Belfast, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390863.
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Gemenetzidis, Emilios. "The role of FOXM1 in oral squamous cell carcinoma." Thesis, Queen Mary, University of London, 2010. http://qmro.qmul.ac.uk/xmlui/handle/123456789/492.
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FOXM1 transcription factor regulates the expression of a multitude of genes, which are important for cell proliferation, mitosis, and differentiation. Although it is abundantly expressed in majority of human solid tumours, its role in early stages of human neoplasia remains unclear. Oral squamous cell carcinoma (OSCC) is characterized by sequential genomic alterations, which lead to invasive malignancy. In this study, it is shown that FOXM1 is significantly upregulated in early oral pre-malignant and OSCC tissues and cultured keratinocytes. Furthermore, the current study suggests that FOXM1B is the main isoform driving the cell cycle dependent expression of FOXM1, and that it is expressed mainly at the G2 phase of human epithelial keratinocytes. In an attempt to understand why FOXM1 precedes epithelial malignancy, the present study investigated 1) the genomic profile of FOXM1B overexpressing human epithelial keratinocytes, and 2) whether FOXM1B overexpression interferes with the innate program of keratinocyte differentiation, which is frequently reported as being the earliest oncogenic event in epithelial neoplasia. First, by using a high-resolution Affymetrix single nucleotide polymorphism (SNP) mapping technique, this study provides the first evidence that FOXM1B overexpression alone in primay human keratinocytes was sufficient to induce genomic instability, mainly in the form of copy number alterations. FOXM1B overexpression also cooperated with damaging agents relevant to human epidermal (UVB) and oral epithelial cancer (Nicotine), to promote genomic instability in human keratinocytes. Second, by using a 3D-organotypic culture model of oral mucosa, sustained overexpression of FOXM1 was found to induce a hyper-proliferative phenotype with suprabasal proliferation, exhibiting perturbed markers of epithelial differentiation such as cytokeratin 13 and filaggrin, resembling early oral dysplastic epithelium. Based on these observations it is hypothesised that aberrant upregulation of FOXM1B serves as a ‘first hit’ whereby cells acquire genomic instability, and an abnormal differentiation program. The latter event promotes epithelial proliferation at the expense of terminal differentiation, allowing sufficient time for the accumulation of additional genetic aberrations/mutations required for tumour promotion and expansion. The Role of FOXM1 in Oral Squamous Cell Carcinoma
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Qadir, Fatima. "Cellular and molecular signature of oral squamous cell carcinoma." Thesis, Queen Mary, University of London, 2018. http://qmro.qmul.ac.uk/xmlui/handle/123456789/39763.
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Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. It is a result of numerous aetiological factors such as genetic predisposition, smoking, excessive alcohol consumption and viruses such as the human papilloma virus. Due to late diagnosis it has a high mortality and morbidity rates which has remained unchanged over the last 5 decades. Currently no screening is available for high risk patients for better monitoring. Diagnosing OSCC relies on histopathology of biopsy tissue, reviewed for dysplasia and advancing lesions. Although the technique has been used for decades for successful diagnosis it fails to identify the molecular signature of OSCC which appears much before the visual signs. It also falls short in predicting the malignant transformation of pre-malignant oral lesions. Identifying the molecular and genetic changes leading to OSCC lesion will aid in more specific (quantitative) and early diagnosis of the disease reducing the financial burden of treating late-stage OSCC patients on the healthcare system. This study focuses on developing new adjuncts which can be used alongside histopathology for early diagnosis. There is a need to monitor high risk patients through non-invasive methods causing less patient discomfort. We therefore explored the potentials of exosomes which are extracellular vesicles secreted by normal and tumour cells. They can be isolated from body fluids such as blood and saliva. In cancer biology exosomes offer both diagnostic and therapeutic advantage. Their involvement in cell-cell communication indicates their influence in tumour development, progression, metastasis and therapeutic efficacy. Exosomes released by cancerous cells carry numerous biomarkers, which are passed on to healthy cells via microenvironment, causing stromal and angiogenic activation along with immune escape. In this study exosomes were successfully isolated from body fluids (blood, saliva and plasma) and cell line supernatant through ultracentrifugation and characterised by visual and particle size quantification techniques including Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM), Zetasizer and Nanosight Tracking Analysis (NTA). Exosomal specific membrane proteins were identified through Western blotting. 5 We report the presence of a potential protein biomarker located exclusively on the outer membrane of cancer exosomes. Since body fluids consist of a heterogeneous population of exosomes derived from multiple cell types, such surface biomarker can potentially be used to isolate OSCC exosomes. Characterisation of exosomal mRNA cargo was done using Agilent Bioanalyzer (for RNA quantity and quality assurance) and reverse transcription-quantitative PCR (RT-qPCR; for gene specific quantitation). Functional significance of exosomes was studied by transfecting normal oral keratinocyte cells with self and cancer-derived exosomes. Through gene-expression microarray and subsequent RT-qPCR verification, we report a panel of differentially expressed genes involved in essential cellular functions being modulated by exosome transfection. A previously developed molecular diagnostic system by our research group called quantitative malignancy index diagnostic system (qMIDS) based on FOXM1 oncogene and its downstream targets was validated on archival formalin fixed paraffin embedded OSCC patient biopsy samples. We report that qMIDS index successfully correlates with the disease stages including dysplasia, tumour and lymph node metastasis. Furthermore, through meta-analysis of 8 OSCC microarray studies we identified a panel of six genes including PLAU, FN1, CDCA5, CRNN, CLEC3B and DUOX1 (q6) which are able to identify two clinically distinct sub-groups of OSCC patient population. Through RT-qPCR the expression of q6 biomarkers was established in 100 OSCC biopsy samples. This information can be of immense importance in developing personalized treatment strategies based on the molecular makeup of the presenting tumour.
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supsavhad, wachiraphan. "Novel Molecular Targets for Feline Oral Squamous Cell Carcinoma." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1471628009.
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Davidson, Matthew Alexander. "Analysis of potential driver genes in oral squamous cell carcinoma." Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/9018/.
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The 5-year survival rate of head and neck squamous cell carcinoma (HNSCC) has remained at ~50% for over 50 years. HNSCC is categorised by multiple anatomical sites, but oral (oral SCC) and oropharyngeal squamous cell carcinoma (OPSCC) account for approximately 90% of all cases. At the time of writing, only one targeted agent, cetuximab (a monoclonal antibody targeting the epithelial growth factor receptor), has been approved for the treatment of recurrent/metastatic HNSCC. However, despite the high expression of EGFR in oral SCC tumour samples, the clinical benefit of cetuximab has been modest thus far. Using a phenotypic screening approach, I sought to identify putative therapeutic targets. A whole genome siRNA screen carried out using an aggressive patient-derived cell line (‘Liv7k’) in normoxic and hypoxic conditions provided the foundation for this project. In addition, a drug-repurposing screen tested the efficacy of 1,351 compounds, approved for cancer and non-cancer indications. A number of approaches were used to identify potential targets, including a whole genome siRNA screen in normoxic and hypoxic conditions, a drug-repurposing screen, and a data multiplexing approach combining the two screens with pathway analysis and datasets from The Cancer Genome Atlas and the International Cancer Genome Consortium. Genomic characterisation of oral cancer cell lines confirmed the importance of a previously identified frequently amplified region of chromosome three, which contains a number of driver genes in HNSCC. In addition, a differential susceptibility of oral SCC cells in hypoxia formed the basis of a line of inquiry centred on triglyceride and ether lipid metabolism. Finally, compound screening identified a dependence of oral SCCs on cysteinyl leukotriene signalling, which is involved in inflammatory conditions such as asthma.
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Liu, Wai-man Raymond, and 廖偉文. "Identification of microRNA-184 target genes in squamous cell carcinomaof tongue." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45208207.
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Emich, Helena. "Clinical implications of cancer stem cell properties in oral squamous cell carcinoma." Thesis, Queen Mary, University of London, 2014. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8479.
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CD44 has been described as a marker of cancer stem cells in oral squamous cell carcinoma (OSCC). The main objective of this study was to characterise expression of CD44 in both fresh samples of human OSCC and in cell lines generated from them, and to examine its correlation with selected clinicopathological parameters of the tumours of origin. The epithelial fraction in 20 fresh OSCC samples was identified by the standard method using the negative selection technique with antibodies against non-tumour cells. A novel method of identifying the epithelial fraction, termed positive selection, was also developed and used for analysis of 14 additional OSCC samples. This new method, using epithelial-specific antibodies, led to a considerable improvement in the efficiency and the accuracy of the procedure. The frequency of CD44+ cells in the epithelial fraction of the tumour specimens was assessed by FACS and varied widely (3-97%). High frequency of CD44+ cells in tumour samples was found to be associated with high tumour grade, discohesive invasion front and presence of lymph node metastases (p<0.01, as calculated with Spearman’s ranked test and Fisher’s exact test). It was also observed, that the percentage of CD44+ cells changes when cells isolated from tumour samples are propagated in culture. Nearly all cells in cell lines generated from OSCC samples showed CD44 expression when analysed by FACS. However, a markedly higher level of CD44 expression (as assessed by median fluorescence intensity for cell surface CD44) was found for early passage cell lines generated from metastatic OSCC and lymph node metastases as compared to cell lines generated from nonmetastatic OSCC. These findings show that a high frequency of CD44+ cells in fresh OSCC tissue and a high level of CD44 expression in cultured OSCC cells correlate 11 with more aggressive tumour behaviour. These results might provide important information of prognostic and therapeutic value.
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Jonsson, Oskar, and Filip Papic. "Studies of Squamous Cell Carcinoma of the Tongue(TSCC), with Focus on Histological Factors." Thesis, Umeå universitet, Institutionen för odontologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-144078.
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Squamous cell carcinomas of the head and neck (SCCHN) is a diverse group of tumours includingtumours of the mouth, of which most are manifested in the tongue. Previous studies have shown that assessment of histological risk factors including worstpattern of invasion (WPOI) and lymphocytic response (LR) is of clinical relevance in treating SCCHN. It hasalsobeen suggested that evaluation of the inflammatory infiltrate could be of prognostic importance.The purpose of this study was to further investigate, analyze and map histological factors associated with TSCC.A total of 58biopsies fromtwo different ethnic groups,Swedish and Italian,were evaluated regarding factors like WPOI andLR. Results were thencorrelated to clinical data.Approximately halfof the patients, 53%, displayed patches ofdense lymphocytic infiltrate at the tumour interface. There was,however,no statistically relevant correlation seen between LR, recurrence of disease, survival rate or ethnicity. Considering WPOI, 83% of patients showed a tumour growth pattern withsmall invasive islands <15 cells (WPOI 4). No correlationbetween WPOI, recurrence of disease, survival rate, ethnicity or lymphocyticresponse was found.Our findings confirm that SSC of the tongue hasa very split patternof invasion. No conclusive result was found concerning inflammatory response and prognostic factors. Data collected showed that ethnic differences could potentiallybe of interest for further study of the prevalence of tongue SCC.
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Escriu, Carlos. "The role of Mst2 in oral squamous cell cancer progression." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708173.
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Sartor, Marina. "Analysis of G1 checkpoint components in Oral Squamous Cell Carcinoma (OSCC)." Thesis, King's College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325318.
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Rawal, Yeshwant B. "Pro and Antioxidant Modulation of the Oral Squamous Cell Carcinoma Phenotype." The Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=osu1419873714.
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Han, Byungdo B. "Chemoprevention of Oral Squamous Cell Carcinoma: Extending Therapeutic Parameters of Fenretinide." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429726539.
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Wilcock, Paul. "A systems biology approach for investigating oral squamous cell carcinoma (OSCC)." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/a-systems-biology-approach-for-investigating-oral-squamous-cell-carcinoma-oscc(8ec3728b-1928-450f-b467-76996fa970fb).html.
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A systems biology approach was adopted in order to assess various aspects of the disease oral squamous cell carcinoma. Three main aims were addressed; assess the ability of CoCl2 to mimic the hypoxic response in a eukaryotic cell line, assess the role of PDE4D in oral squamous cell carcinoma (OSCC) and the construction of a normoxic/hypoxic mathematical model to identify therapeutic targets.Cancer cells often acquire a revised metabolism which aids in initiation, survival and progression of the tumour. This is predominantly due to the transcription factor HIF-1 which is activated under hypoxic conditions. Certain compounds such as cobalt chloride (CoCl2) have been used extensively to inhibit the degradation of HIF-1α and simulate hypoxia. CoCl2 is likely to have off-target effects on metabolism; these effects were examined when exposing human telomerase reverse transcriptase (hTERT) cells to 100μM CoCl2. Gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS) based metabolomics were utilised in combination with ELISA assays for HIF-1α and ATP. Central metabolism was accurately mimicked when hTERT cells were subjected to 100μM CoCl2, however; it was apparent that this concentration of CoCl2 does not induce an equal extent of hypoxia as 1% oxygen. A number of off-target effects of CoCl2 were observed in secondary metabolism, specifically in lipids and fatty acids. In conclusion, CoCl2 should be used with caution as a hypoxic mimicker with the caveat that interpretation of results should be restricted to its effects on central metabolism.The transcription factor CREB has the ability to regulate approximately 4000 genes, a number of which are associated with cancer initiation and progression. Cyclic adenosine monophosphate (cAMP) is required to activate CREB and is partially regulated through its degradation via the enzyme phosphodiesterase type 4D (PDE4D). A homozygous deletion of PDE4D has been associated with OSCC; however; the exact consequence of this deletion has not been fully elucidated. PDE4D was knocked down in the OSCC cell line BicR16 and cellular proliferation, migration, resistance to ionising radiation and central metabolism was investigated using MTT, scratch, clonogenic and GC-MS, respectively. The knockdown resulted in an increase in proliferation, migration and radiation resistance suggesting the role of PDE4D as a TSG. Amino acids, cholesterol, fatty acids, carbohydrates and TCA intermediates were found to be altered in concentration.A mathematical model of glycolysis, TCA and glutaminolysis under normoxia and hypoxia was constructed through the amalgamation of two established models from the literature. New reactions, parameters and metabolite concentrations were added and unnecessary entities were deleted. COmplex PAthway SImulator (COPASI) was utilised to construct the model before validating the model using experimental data from the literature and steady state and flux analyses. Sensitivity analysis and a reduction in external glucose and glutamine were mimicked and the alterations in hypoxic and normoxic metabolism analysed. The reactions vCSII, vGS, vPGK and vGII were identified as potential therapeutic targets which may affect metabolism in hypoxia only. However, certain validation methods proved unsuccessful and hence the model requires further work before attempting the analyses again.
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Towle, Rebecca. "The molecular characterization of the progression of oral squamous cell carcinoma." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/59026.
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Oral squamous cell carcinoma (OSCC) is the most common subtype of head and neck cancer and has a relatively low five year survival rate of ~50%. One of the reasons for this high mortality rate is that patients are generally diagnosed at late stages. OSCC develops through a typical histological progression and although lesions in the oral cavity are visible at the premalignant stage, it is not possible to predict which lesions will progress based on histology alone. In-depth analysis of genome-wide molecular alterations may identify novel genes or pathways that can be used as biomarkers or therapeutic targets in order to improve survival rates of this disease.
In this thesis, I perform DNA methylation, gene expression and miRNA profiling on a panel of patient tissue samples, each with a paired adjacent normal, dysplasia and either a carcinoma in situ or squamous cell carcinoma, taken from a single contiguous disease field within a patient’s oral cavity. My hypotheses are that the epigenetic landscape of OSCC becomes progressively more deregulated throughout the different histological stages and that the most frequently altered molecular events identified at the dysplasia stage may be crucial for premalignant disease development and progression. A high level of deregulation in both methylation and miRNA patterns as the disease progresses is observed, and a number of highly frequent molecular events are identified. Several of these molecular events are then functionally validated to assess the ability to contribute to tumorigenesis in oral premalignant lesions.
Taken together, this thesis provides one of the most comprehensive epigenetic analyses of paired normal, dysplasia and CIS/SCC biopsies with regards to DNA methylation and miRNA profiling. In addition to providing a deeper insight into the molecular mechanisms at play within the premalignant lesions, we also validate the ability of these mechanisms to directly contribute to tumorigenesis.Medicine, Faculty of
Graduate
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Li, Chi-han Samson, and 李其翰. "Upregulation of microRNA 1290 in response to zebularine sensitizes tongue squamous cell carcinoma to cisplatin." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44523312.
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Korpi, J. (Jarkko). "Collagenase-2 (matrix metalloproteinase-8) in tongue squamous cell carcinoma, bone osteosarcoma, and wound repair." Doctoral thesis, University of Oulu, 2010. http://urn.fi/urn:isbn:9789514261046.
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Abstract
Degradation of extracellular matrix (ECM) and basement membrane (BM) are required both in normal physiological conditions such as wound healing and in pathological tissue remodelling such as chronic ulcers and cancers. Matrix metalloproteinases (MMPs) are an enzyme family, which can cleave most ECM and BM components. They are associated with physiological and pathological processes but their exact roles are still largely unknown.
The expression of MMP-8 and MMP-26 in acute and chronic human cutaneous wounds using histological and cell culture methods were investigated. MMP-8 was expressed in epithelial cells, neutrophils, and other inflammatory cells especially in chronic ulcers while in acute wounds MMP-8 expression was weak or absent. MMP-26 was temporarily present in acute wounds while it was strongly expressed in close vicinity to the BM in multiple cell types of most chronic ulcers. In vitro keratinocyte wound assay showed that MMP-8 and -26 were expressed in migrating cells.
Bone formation, collagen metabolism, and inflammation in MMP8-/- mice tooth extraction wounds and also periapical lesion formation were analysed. No differences between wild type or MMP-8-deficient mice in the new bone area or periapical lesion size were found. However, type III procollagen production was increased and inflammatory cell influx was decreased in MMP8-/- mice. In addition, Fas ligand (FasL) production was increased in mandibular alveolar mucosa but decreased in alveolar bone of MMP-8 deficient mice. MMP-8 was also found to cleave FasL in vitro.
A total of 90 human mobile tongue squamous cell carcinoma (SCC) samples were collected. Bryne’s malignancy scores, thickness of the SCCs, expression of microvessel density (CD31 and factor VIII), cyclooxygenase-2 (COX-2), the laminin-5 (currently termed laminin-332) γ2-chain, integrin αvβ6, estrogen receptor-α (ER-α), estrogen receptor-β (ER-β), and MMPs (-2, -7, -8, -9, -20, and -28) were analysed. The high expression of MMP-8 was associated with a better prognosis for the patients, particularly in females. In addition, tongue carcinoma formation in MMP8-/- mice was investigated. Tongue SCC developed more often in MMP8-/- female mice than wild type littermates. In addition, MMP-8 can cleave ER- α and -β and estrogen can induce MMP-8 production in vitro.
A total of 22 biopsies, 10 resection sections, and three lung metastases of 25 osteosarcoma patients samples were stained with MMP-2, -8, -13, -26, and tissue inhibitor of metalloproteinase-1 (TIMP-1) using immunohistological methods. Expression of these markers was mostly present in sarcoma cells but MMP-8 was not present in lung metastases. In resection sections, chemotherapy altered MMP-2, -8, and -13 expressions compared to biopsies. However, an association between the expression and prognosis of osteosarcoma patients could not been found.
In conclusion, MMP-8 seems to be an estrogen-related protective factor in tongue SCC and can regulate ECM and BM components and inflammation during wound healing. Further studies are needed to evaluate the exact function especially of MMP-8 in human osteosarcoma.
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Yoshikawa, Hiroto. "Feline oral squamous cell carcinoma| A comprehensive approach to improve treatment outcome." Thesis, Colorado State University, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3593468.
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Feline oral squamous cell carcinoma (SCC) is a devastating disease that responds poorly to traditional treatment modalities. The tumor location directly impacts the patient's ability to eat and drink, and immediate intervention to alleviate clinical signs is important. To design better treatment strategies it is paramount to understand the underlying biological behavior of this poorly defined tumor. This research takes a comprehensive approach in attempt to understand this disease. A number of assays have been developed and applied to elucidate underlying biology. New imaging modalities have been used to better stage the disease and define tumor location. Finally, patients were treated with a new radiation therapy modality, stereotactic radiation therapy (SRT), and outcome was correlated with the biological assays for potential predictive value.
The goal of the prospective study described in Chapter 2 was to compare gross tumor volume measurements using 18F-FDG PET vs. those using computed tomography (CT) for SRT planning in cats with oral SCC. Twelve cats with confirmed oral SCC underwent pretreatment 18F-FDG PET/CT. Gross tumor volumes based on contrast-enhanced CT and 18F-FDG PET were measured and compared between cats. Mean PET gross tumor volume was significantly smaller than mean CT gross tumor volume in the mandibular/maxillary SCC group (n=8, P=0.002) and for all cats (n=12, P=0.006), but not for cats with lingual/laryngeal SCC (n=4, P=0.57). Mismatch fraction analysis revealed that most of the lingual/laryngeal patients had a large region of high-18F-FDG activity outside of the CT gross tumor volume. This mismatch fraction was significantly greater in the lingual/laryngeal group than the mandibular/maxillary group ( P=0.028). The effect of poor spatial resolution of PET imaging was greater when the absolute tumor volume was small. Findings from this study indicated that 18F-FDG PET warrants further investigation as a supplemental imaging modality in cats with oral SCC because it detected presumed regions of primary tumor that were not detected on CT images.
For canine and feline patients with tumors in the head region, simultaneous irradiation of the primary tumor and mandibular and retropharyngeal lymph nodes (LNs) is often indicated. The purpose of this study described in Chapter 3 was to assess the reliability of a planning target volume (PTV) expansion protocol for secondary targets (LNs).
Information about the molecular biology of feline oral SCC is still limited. In Chapter 4, 22 archived tumor samples of feline oral SCC were evaluated to develop immunohistochemical assays and to determine if there was correlation to clinical parameters. Immunohistochemistry for Ki67, MVD, and EGFR was performed and scored. Patient survival information was obtained from the medical records. These molecular markers as well as MI were correlated with tumor locations and patient survival time. The 22 tumors showed wide variation in Ki67, MI, MVD, and EGFR. Tongue SCC expressed higher MVD than mandibular/maxillary SCC (P=0.088).
Cancer stem cell or tumor initiating cell (TIC) theory and telomere biology are actively studied fields in human head and neck (H&N) cancer. In feline oral SCC, which has been advocated as a feline model for human H&N cancer, our knowledge about the TIC and telomere/telomerase biology is limited. Protein expression levels of putative TIC markers of human H&N cancer, CD44 and Bmi-1, were immunohistochemically evaluated for their possible role as prognostic markers in 20 patients with feline oral SCC who underwent SRT. This patient population was part of a clinical trial and information relevant to PFI and ST was available. A combined technique of fluorescent in-situ hybridization and immunofluorescent staining was used to determine telomere length ratio (fractions of very short telomere/average length telomere in the putative cancer stem cells) in the putative TICs that were positive for CD44 and Bmi-1. This was also correlated with treatment outcome. (Abstract shortened by UMI.)
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Windrich, Martin. "Automatic quantification of speech intelligibility of adults with oral squamous cell carcinoma /." Erlangen, 2008. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000254063.
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Bergkvist, Gurå Therese. "Role of epidermal growth factor receptor in feline oral squamous cell carcinoma." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5542.
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Feline oral squamous cell carcinomas (FOSCCs) are locally aggressive tumours and a common cause of mortality and morbidity. Current treatment options are rarely successful and animals are frequently euthanised upon diagnosis due to their grave prognosis. Epidermal Growth Factor Receptor (EGFR) is a tyrosine kinase receptor which is frequently dysregulated in SCC of the head and neck (HNSCC) in man. Recent advances in human medicine have identified EGFR as a therapeutic target in HNSCC. In this study the role of EGFR in FOSCC was investigated. Sixty seven biopsy samples were immunohistochemically labelled for EGFR and Ki67, a proliferation marker. The tyrosine kinase region of feline EGFR was cloned and sequenced, and six small interfering RNAs (siRNAs) targeting the tyrosine kinase region were developed. The most effective siRNA as well as an EGFR specific tyrosine kinase inhibitor, gefitinib, was then used on a feline SCC cell line (SCCF1), and the effect of EGFR targeting alone, or in combination with irradiation, on the cell line was determined. The majority of the biopsy samples were labelled positively for EGFR and Ki67, and high proliferation corresponded with poor prognosis. The siRNA caused reduction in EGFR mRNA by Real-Time Polymerase Chain Reaction and protein levels as assessed by western blot analysis. Reduced cell proliferation and migration were also observed by proliferation assays and scratch assays respectively. Combining EGFR knockdown with irradiation caused an additive effect on the ability of the cell line to form colonies. These results support the role of EGFR as a potential therapeutic target in FOSCCs.
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Hsieh, I.-chien, and 謝宜倩. "Association of Oct4, Sox2, and Nanog Expression with Development and Prognosis in Oral Tongue Squamous Cell Carcinoma and Buccal Mucosal Squamous Cell Carcinoma." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/8k5955.
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碩士國立中山大學
生物科學系研究所
102
In Taiwan, oral cancer is the 4th leading cause of cancer death for males and the top common cancer in young adult males. The most common subsites of oral cancer are the tongue and buccal mucosa in Taiwan. Cancer stem cells (CSCs) have been implicated in tumorigenesis and prognosis. Reprogramming factors employed to induce pluripotent stem cells are associated with CSCs formation. The purpose of this study was to investigate the relationship of the protein expression levels of three reprogramming factors, Octamer-binding Protein 4 (Oct4), Sex-determining Region Y (SRY)-related Box 2 (Sox2), and Nanog, with the tumorigenesis, clinicopathological outcomes and survival in oral tongue SCC and buccal mucosal SCC. Expression levels of Oct4, Sox2, and Nanog were evaluated by immunohistochemistry using tissue microarray slides. We compare the expression levels of the Oct4, Sox2, Nanog-N, and Nanog-C in normal, tumor adjacent normal, and tumor tissues by subsites of oral tongue and buccal mucosa. The expression levels of both Oct4 and Sox2 in oral tongue SCC and buccal mucosal SCC were significantly lower than those in the tumor adjacent normal tissue or normal tissue, except that for Oct4 in buccal mucosal SCC. However, the expression level of Nanog-C in oral tongue SCC and buccal mucosal SCC was significantly higher than those in the tumor adjacent normal tissue and normal tissue. Our IHC results showed that the median expression levels of Oct4, Sox2, Nanog-N, and Nanog-C were 40, 2.50, 0, and 90 in 248 oral tongue SCC specimens, respectively. In addition, the median expression levels of Oct4, Sox2, Nanog-N, and Nanog-C were 73.75, 4.75, 0, and 63.75 in 188 buccal mucosal SCC specimens, respectively. The expression levels of Oct4, Sox2, and Nanog-C gradually decreased when tumor progressed from early stage and advanced stage (AJCC pathological stage, T stage, or N stage). After adjustment of clinicopathologic outcomes, our results showed a significant association between the elevated Sox2 expression and prolonged disease-specific survival in oral tongue SCC. In conclusion, Oct4, Sox2, and Nanog-C could be biomarkers for tumorigenesis in both oral tongue SCC and buccal mucosal SCC, except for Oct4 in buccal mucosal SCC. Additionally, Sox2 might be a prognostic biomarker for oral tongue SCC.
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KUO, MEI-SHU, and 郭美秀. "Expression Level of REEP6 in Tumorigenesis and Prognosis of Oral Tongue Squamous Cell Carcinoma." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/px2374.
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碩士嘉南藥理大學
生物科技系
105
Backgrounds: Oral Squamous Cell Carcinoma (OSCC) is one of the most prevalent cancers and ranks 6th most common malignancy worldwide. In Taiwan, oral cancer was the 4th most common cancer in males. Oral tongue squamous cell carcinoma (OTSCC) is the top 2 common form of oral cancer and represents 28.10% of oral cancer. OTSCC is known as an aggressive tumor with a propensity to metastasis, poorer locoregional control and a high recurrence rate. To date, there is no biomarker for diagnosis and treatment for OTSCC. Tumor surface protein is an ideal diagnostic biomarker and target for immunotherapy. The Receptor expression-enhancing protein 6 (REEP6) is a surfaced protein and highly expressed in many cancers. However, the expression level of REEP6 in OSCC has never been reported. We found that high REEP6 mRNA expression level is associated with poor prognosis in oral cancer through big data analysis with The Cancer Genome Atlas (TCGA) database analysis. Nevertheless, the association of REEP6 protein level with clinicopathological parameters and survival remains unknown. Therefore, the aim of this study was to investigate the effect of REEP6 protein expressjion on tumor progression and prognosis in patients with OTSCC. Materials and Methods: The expression of REEP6 protein in tissue microarray (TMA) was dstermined by immunohistochemistry staining (IHC) . In the tissue microarray, there were 250 surgically resected tongue squamous cell carcinoma core ( two cores in each patient) , 201 tumor adjacent normal tissue cores (one core per patient ) with another 35 ventilated patients with normal uvula tissue cores (1 core per patient) . Results: The results of immunohistochemical staining showed that the expression of REEP6 protein in tumor tissue and tumor adjacent tissues was significantly higher than that in uvula normal tissue (p = 0.05) . However, the expression of REEP6 was not significantly association with clinicopathological parameters and survival. Further, stratification analysis showed that high expression level of REEP6 in patients with small tumor (T1 / T2) had significantly poor disease-specific survival (DSS) (AHR = 1.90, p = 0.012). In patients with age ≦ 50 years (AHR = 1.87, p = 0.038) or tumors with small (T1 / T2) (AHR = 1.64, p = 0.043), high-expression level of REEP6 also had significantly worse disease-free survival (DFS). Conclusion: The expression of REEP6 in OTSCC may be associated with tumorigenesis, and the high protein level of REEP6 was not associated with shorter disease-specific survival (DSS) and disease-free recurrence (Disease-free survival, DFS) except in those patients with tumor size and age <50 years.
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Shen, Wei-Ren, and 沈威任. "Perineural invasion and expression of nerve growth factor in oral tongue squamous cell carcinoma." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/47850146832319060383.
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碩士國立臺灣大學
臨床牙醫學研究所
101
Background: Perineural invasion (PNI) is commonly seen in oral tongue squamous cell carcinoma (OTSCC). PNI can predict the prognosis in malignancies of low or high neurotropism. Nerve growth factor (NGF), a potential neurotropic factor promoting the PNI, is associated with tumor cell proliferation, angiogenesis, and stromal destruction. Methods: PNI was detected by reevaluation of H&E-stained and anti-S-100 immunostained tissue sections in 116 T1 to T4 OTSCC specimens. Immunohistochemical staining for nerve growth factor (NGF) was also performed in these 116 OTSCC cases. Results: The PNI rate increased from 22% of the original report, through 38% after reevaluation of H&E-stained tissue sections, to 51% with the help of anti-S-100 immunostaining. Univariate analyses showed a significant association of the presence of PNI with higher T status or N status, greater tumor thickness, close and positive tumor section margin, and higher grade of worst pattern of invasion (WPOI). Tumor thickness (p = 0.003) and WPOI (p = 0.001) were identified as independent predictors for the PNI by multivariate analyses. OTSCC patients with PNI had a poorer overall survival than those without PNI (log-rank test, p = 0.0352). OTSCCs with higher neurotrposim (intraneural spread, >3 PNI foci in each tissue section, and PNI focus diameter > 0.2 mm) demonstrated higher NGF labeling score than those with lower neurotropism (non-intraneural spread, 1-3 PNI foci in each tissue section, and PNI focus diameter ≤ 0.2 mm). Moreover, higher NGF expression level in OTSCCs had a significant and positive relation to higher T status or N status, greater tumor thickness, close and positive tumor section margin, and the presence of PNI by univariate analyses. However, only higher T status (p = 0.047) was identified as an independent factor for prediction of NGF expression level by multivariate analyses. In addition, OTSCC patients with high NGF expression level exhibited poorer overall survival than those with low NGF expression level (log-rank test, p = 0.0292). Conclusion: Cautious reevaluation of H&E-stained and anti-S-100 immunostained tissue sections is an effective method to detect occult PNI. Tumor thickness greater than 5 mm and markedly discrete invasion front pattern are two important factors to predict the presence of PNI. NGF expression level has a positive relation to neurotropism of OTSCCs. Horizontal tumor dimension is an independent predictor for NGF expression level in OTSCCs. Both PNI and NGF expression level can predict the prognosis of OTSCC patients.
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Saleem, Saira, A. Jamshed, S. Faisal, R. Hussain, M. Tahseen, A. Loya, and Chris W. Sutton. "Patterns of cancer cell sphere formation in primary cultures of human oral tongue squamous cell carcinoma and neck nodes." 2014. http://hdl.handle.net/10454/9890.
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YesRecently a sub-population of cells with stem cell characteristics, reported to be associated with initiation, growth, spread and recurrence, has been identified in several solid tumors including oral tongue squamous cell carcinoma (OTSCC). The aim of our pilot study was to isolate CD44+ cancer stem cells from primary cultures of OTSCC and neck node Level I (node-I) biopsies, grow cell spheres and observe their characteristics in primary cultures. Parallel cultures of hyperplastic lesions of tongue (non-cancer) were set up as a control. Immunohistochemistry was used to detect CD44/CD24 expression and magnetic activated cell sorting to isolate CD44+ cell populations followed by primary cell culturing. Both OTSCC and node-I biopsies produced floating spheres in suspension, however those grown in hyperplastic and node-I primary cultures did not exhibit self-renewal properties. Lymph node metastatic OTSCC, express higher CD44/CD24 levels, produce cancer cell spheres in larger number and rapidly (24 hours) compared to node negative OTSCC (1 week) and non-cancer specimens (3 weeks). In addition, metastatic OTSCC have the capacity for proliferation for up to three generations in primary culture. This in vitro system will be used to study cancer stem cell behavior, therapeutic drug screening and optimization of radiation dose for elimination of resistant cancer cells.
SKMCH&RC, Yorkshire Cancer Research
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Berania, Ilyes. "La régulation des micro-ARNs dans les cancers de la langue mobile." Thèse, 2019. http://hdl.handle.net/1866/22306.
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Hung, Shiao-Chen, and 洪曉貞. "Role of L1 Cell Adhesion Molecule in Tongue Squamous Cell Carcinoma." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/46515746821572788673.
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碩士中國醫藥大學
癌症生物學研究所
97
Abstract: Oral cancer is one of the top 10 leading causes of death from cancer in Taiwan. This disease is characterized by poor prognosis and low survival rate. The molecular mechanisms of oral cancer progression are not well understood. Overexpression of L1 cell adhesion molecular (L1-CAM) has been found in many human carcinomas and is associated with tumor progression and poor prognosis. The aim of this study is to investigate the relationship between L1-CAM expression and tumor progression in tongue squamous cell carcinoma (TSCC) with a hope of understanding the molecular mechanisms of TSCC. The expression of L1-CAM in TSCC cell lines was determined by Western blotting, FACS, and ELISA analyses. Genetically manipulated TSCC stable cell lines with either over-expressed or down-regulated L1-CAM were generated by retroviral vector carrying L1-CAM cDNA transfection or lentiviral vector-mediated L1-CAM siRNA delivery, respectively. The resultant cell lines were determined and compared behavior changes including growth rate, migration and invasion in vitro using MTS and Transwell migration assay. We found that L1-CAM was detected in all testing TSCC cell lines (SAS, SCC4, SCC9, SCC25) with a variable expression level and negligible in human normal oral fibroblast cells. Over-expressed L1-CAM in L1-CAM low-expressing SCC25 cells enhanced cell growth, migration, invasion and attachment on fibronectin. Conversely, knockdown L1-CAM in L1-CAM highly-expressing SCC4 cells resulted in decreased cell ability in adhesion and motility. Moreover, L1-CAM mediated cell motility was in accordance with increased E-cadherin and decreased Vimentin and Fibronectin expression, suggesting that L1-CAM is involved in epithelial-mesenchymal transition (EMT) of TSCC. Our results demonstrated the first time that L1-CAM conferred TSCC tumor progression through the pathway of EMT. These findings also suggested that L1-CAM is a promising molecular target for the treatment of oral cancer.
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CHEN, JING-YI, and 陳靜宜. "Effect of BITC in human tongue squamous-cell carcinoma cells." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/rrnen3.
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碩士輔英科技大學
醫學檢驗生物技術系碩士班
106
Oral cancer is the fourth leading cause of cancer death for males in Taiwan. Epidemiological studies have indicated that co-administration of natural compounds with anticancer drugs can lead to increased therapeutic activity against various types of cancers. Benzyl isothiocyanate (BITC), one of the best studied members of the isothiocyanate family, has been found to exhibit prevention of cancers in laboratory animals and might also be chemoprotective in humans. However, the effects of BITC on tongue cancer remain unknown. In this study, we aimed to examine the early signaling effects of BITC on human tongue cancer cells SAS. Firstly, we evaluated the effect of BITC on cell viability of SAS cells using MTT assays. The results showed that BITC significantly decreased the viability of SAS cells in a concentration-dependent manner. Next, we assessed the effect of BITC (5, 10 μM) on reactive oxidative species (ROS) using DCF-DA reagent. ROS induced by BITC in OSCC cells was also in a dose-dependent manner. The experiment explored the mechanism of death of BITC against SAS cells. It was found that atypical DNA fragments after BITC treatment. Wound healing assay demonstrated that BITC exhibited an inhibitory effect on the abilities of migration in SAS cancer cells. Above results showed that BITC can inhibit the growth and proliferation of human tongue squamous cell carcinoma cells. It is expected that BITC can be a novel drug for the malignant progression of tongue cancer.
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Chiu, I.-Wen, and 邱意彣. "Genome wide analysis of oral squamous cell carcinoma." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/23630161363930884402.
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碩士亞洲大學
生物科技學系碩士班
97
Oncogenes serve as specific and unique targets for drug intervention to treat cancer, as their activation (amplification and activating mutation) is essential for tumor development. Targeting of oncogenes has proven clinically useful in treating patients with HER2/neu gene amplification and BCR/Abl oncogene activation. Likewise, amplification of specific oncogenes could be linked with disease stage and response of chemotherapy, suggesting oncogene amplification as potential biomarker for outcome prediction. Given significant clinical impact, identification and characterization of new oncogenes promise to advance clinical management of cancer patients. Unfortunately, only a few such crucial oncogenes have been identified in oral cancer. We propose to identify new oncogenes by screening amplified chromosomal regions in oral squamous cell carcinoma, most common type of oral cancer, using a rational and comprehensive approach. Recent completion of human genome project together with advances in genome-wide DNA and transcriptome-wide RNA analyses provides unprecedented opportunity for comprehensive analysis of human cancer genome in fine detail. With these innovations as robust tools, we can now measure gene copy number changes in cancer quantitatively, plus map those changes directly onto a human genome. Candidate genes with both amplification and over-expression were then analyzed for potential somatic activating mutation, using a high throughput sequencing platform. We expect analysis of oral cancer genome and identification of new oncogenes not only to shed light on pathogenesis of oral cancer but also lay groundwork for new diagnostic tests and novel therapeutic intervention for this devastating disease.
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Liu, Yi-Ching, and 柳依青. "Expression of Gα12 in oral squamous cell carcinoma." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/52690522087536223361.
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Lin, Chiao-Ying, and 林佼穎. "Annexin A1 expression in oral squamous cell carcinoma." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/37879704074756447770.
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博士國立臺灣大學
臨床牙醫學研究所
96
To investigate whether annexin A1 (ANXA1) expression is a marker in predicting the prognosis of oral cancer patients. We immunohistochemically examined the expression of ANXA1 in 66 cases of oral epithelial dysplasia (OED) and 115 cases of oral squamous cell carcinoma (OSCC). The results were correlated with the clinicopathological parameters of tumors and overall patient survival. In normal oral mucosa, ANXA1 staining was predominantly located on the cell membrane. In OED and OSCC specimens, membranous staining decreased, whereas nuclear staining increased. Positive nuclear staining was observed in 9 of 66 (13.64%) OED cases and 63 of 115 (54.8%) OSCCs. Kaplan–Meier curves showed that OSCC patients with ANXA1 nuclear staining had significantly shorter overall lengths of survival (P¼0.00036 by the log-rank test). Multivariate analysis showed that ANXA1 nuclear staining is a significant predictor of poor overall survival. And oral cancer SAS cells treated with hepatocyte growth factor (HGF) can induce ANXA1 protein translocation from cytoplasm to nucleus. Cells pretreated with LY294002 (PI3K inhibitor) almost completely inhibited (88.3% inhibition) HGF-mediated ANXA1 nuclear translocation. The nuclear localization of ANXA1 protein is a frequent event and could be used as a prognostic factor in OSCC.
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Chong-YiHong and 洪崇翊. "DNA methylation deregulation in oral squamous cell carcinoma." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/2brd9b.
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碩士國立成功大學
口腔醫學研究所
104
Oral squamous cell carcinoma (oral cancer) was ranked the fifth of cancer incidence and increasing annually in Taiwan. The carcinogenesis of oral cancer is deeply investigated, revealed the cumulative carcinogenesis at the genetic and epigenetic levels, and also the feasible biomarker in oral cancer. Oncogene could be expressed or tumor suppression gene repressed as result of DNA methylation deregulated of gene promoter region. Pyrosequencing assay was used to evaluate the methylation level in oral cancer cell lines and patient tissue samples, and AQP5 was hypermethylation in oral cancer cell lines and precancer tissue samples. The expression of AQP5 was low by using qPCR. We concluded that the hypermethylation of AQP5 in precancer could induce low expression of AQP5, and hypomethylation of AQP5 in oral cancer might be the oncogene in oral cancer carcinogenesis.
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LAI, PEI-YU, and 賴佩妤. "Roles Of CD164 In Oral Squamous Cell Carcinoma." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/csue42.
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碩士國防醫學院
牙醫科學研究所
106
Cancer has ranked the number one cause of death in Taiwan. Oral cancer rank fourth of male’s cancer, which has the highest rate of increase. Cancer metastasis to distant site is the most common cause of death of patient. This malignant progression is enhanced by tumor cell activation of an epithelial to mesenchymal transition (EMT). Therefore, understanding the main regulatory mechanism of this malignancy is the key to develop novel and effective therapeutic strategies for oral squamous cell carcinoma (OSCC). CD164, a sialomucin, also known as endolyn or MGC-24, was a cell adhesion molecule which regulates proliferation, adhesion, and differentiation of hematopoietic stem cells. Emerging evidences indicated that the expression of CD164 was involved in the tumorigenesis and cancer progression in colon, prostate and ovarian cancers. However, few data were available regarding the clinical significance of CD164 signaling axis in oral cancer. The objective of this study was to investigate the role of CD164 in the tumorigenesis of the oral cancer. In this study, we test the hypothesis that CD164 is a critical factor for oral cancer metastasis and regulator of epithelial to mesenchymal transition. First we screen CD164 expression in a panel of oral cancer lines and the effect of CD164 on cell functions. Our preliminary results showed that CD164 expression is required to maintain the mesenchymal-like invasiveness of oral cancer cell. Knockdown of CD164 can attenuate oral cancer cell migration, proliferation and decrease CXCR4 expression. We also demonstrate that EMT markers were induced by CD164 modulation in oral tumor. These findings suggest that CD164 participated in the process of EMT that is required for oral cancer malignancy. In conclusion, our data show that CD164 contributes to EMT and regulates cell functions in oral cancer. Moreover, identification of CD164 as a cancer cell marker would possibly provide valuable approaches to develop effective therapy for oral cancer.
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WU, I.-CHEN, and 吳怡貞. "Roles of PIAS2 in Oral Squamous Cell Carcinoma." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/77726549103735439874.
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碩士國防醫學院
生物化學研究所
105
Oral cancer is the ranked fifth most frequently diagnosed cancer worldwide, as well as the ranked fifth frequent cause of cancer death in Taiwan. In spite of its convenience for diagnosis, prognosis is still poor. The crux of the matter in treatment lies in the biological heterogeneity of the tumor. There are no effective therapies to cure most of oral cancer patients. Gene variation contains various types including post-translational modification (PTM) which involves phosphorylation, methylation, ubiquitylation and SUMOylatoin. Based on our previous results, PIAS2, a SUMO E3-ligase, revealed abnormal expression in oral cancer patients. Roles of PIAS2 in cancers has not clearly defined yet. Therefore, we try to elucidate the relationship between PIAS2 and oral cancer. In this study, we first examined the expression of PIAS2 in oral cancer and normal cell lines. Furthermore, we knocked down PIAS2 by siRNA in oral cancer cell lines. Then the cell functions including of epithelial-mesenchymal transition (EMT), migration, invasion, proliferation and cell cycle were examined. First, we showed the upregulation of PIAS2 expression is noted in oral cancer compared to normal cells. Our results also revealed that knocked down PIAS2 in oral cancer cell increased epithelial markers expression along with reduced cell migration, invasion and proliferation ability. Moreover, it also influenced cell cycle progression. Thus our observations suggest that PIAS2 may act as oncogene in oral cancer. We further investigated potential mechanism of PIAS2 in oral cancer cell. Using immunoprecipitation assay, we demonstrated PIAS2 interact with P53 and P53 SUMOylatoin is depend on PIAS2. Additionally, our data indicated that PIAS2 also affects protein expression level of androgen receptor (AR). In conclusion, our data suggest that PIAS2 is closely related with oral cancer, which might affect P53 SUMOylation and AR expression. These results provide the role of PIAS2 in oral cancer and a new direction of its future application.