Dissertations / Theses on the topic 'Squamous cell carcinoma'
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1
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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Hui, King-cheung, and 許景祥. "Biomarkers for esophageal squamous cell carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B41634020.
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Hui, King-cheung. "Biomarkers for esophageal squamous cell carcinoma." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B41634020.
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Law, Bic-fai Fian. "Molecular genetics of esophageal squamous cell carcinoma." Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B3660446X.
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Mallipeddi, Rajeev. "Understanding squamous cell carcinoma in epidermolysis bullosa." Thesis, King's College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.416097.
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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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Hu, Yingchuan, and 胡穎川. "Molecular pathogenesis of oesophageal squamous cell carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31241797.
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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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Law, Bic-fai Fian, and 羅璧輝. "Molecular genetics of esophageal squamous cell carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B3660446X.
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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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Lambert, Sally Ruth. "Molecular profiling of cutaneous squamous cell carcinoma." Thesis, Queen Mary, University of London, 2010. http://qmro.qmul.ac.uk/xmlui/handle/123456789/564.
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Cutaneous squamous cell carcinoma (cSCC) is the second most common form of non-melanoma skin cancer and accounts for the majority of deaths from this disease. Its incidence is increasing rapidly, contributing significant morbidity to patients and a burden on healthcare resources. The molecular events underlying cSCC development remain largely uncharacterised, despite the well established role of ultraviolet radiation as a principal carcinogen. Genomewide analyses of the genetic changes underlying cSCC development have shown they are subject to large chromosomal aberrations, which often involve whole chromosome arms. Many of these events occur in a high proportion of tumours, yet the genes they target are unknown. In this study, genomewide expression microarray data has been obtained from a series of cSCC and integrated with single nucleotide polymorphism (SNP) microarray data, to provide a comprehensive analysis of the events associated with tumour development. In total, 222 genes were identified as differentially expressed in cSCC, of which, 21% were concordant with copy number changes. Previous genomewide SNP data of cSCC had identified microdeletions within the PTPRD gene in a subset of tumours (Purdie et al., 2009). This was investigated in further detail and revealed microdeletions in this gene were significantly associated with metastatic cSCC. Sequencing analysis showed 37% of cSCC had a mutation at this locus, which suggests PTPRD is aberrant in a significant proportion of tumours. Decreased expression levels of PTPRD were correspondingly found in moderately and poorly differentiated tumours. The role of PTPRD in skin biology is not known and further functional work is required to elucidate its role in skin cancer. Taken together, these data provide a valuable insight into the genetic background against which cSCC develop. Furthermore, the association of PTPRD disruption with aggressive tumours may potentially be of future benefit as a prognostic biomarker and therapeutic target.
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Ota, Juri. "Local photodynamic therapy for equine squamous cell carcinoma in a murine model." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/4934.
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Thesis (M.S.)--University of Missouri-Columbia, 2007."May 2007" The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. Includes bibliographical references.
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Baldursson, Baldur. "Development of squamous cell carcinoma in venous ulcers /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4079-7/.
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Bennett, Kristi Lynn. "Methylation in head and neck squamous cell carcinoma." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1194544327.
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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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Carter, S. A. "Novel cytogenetic abnormalities in cervical squamous cell carcinoma." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.597332.
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SCC cell lines were karyotyped to identify recurrent aberrations and those providing a selective advantage in individual cases. Karyotypic heterogeneity provided evidence for ongoing chromosomal instability (CIN) in all cell lines but revealed discordance between the levels of numerical CIN (N-CIN) and structural CIN (S-CIN), supporting the notion that different mechanisms underlie these processes. This molecular cytogenetic analysis identified a novel reciprocal translocation t(8:12)(p21.3;p13.31) present in all cells of the SCC cell line MS751, indicative of a selective advantage. The rearrangement resulted in two novel fusion genes, PEX5-LPL on der(8) and LPL-PEX5 on der(12). LPL-PEX5 encodes a truncated transcript but PEX5-LPL encodes a full length chimeric protein, comprising the first exon of PEX5 followed by the majority of LPL coding region, and is the most likely candidate for having driven selection of the translocation. Reverse transcription PCR was used to show that LPL is generally expressed at negligible levels in the cervix whereas PEX5 is expressed constitutively. In concordance, PEX5-LPL was expressed at substantially higher levels than LPL-PEX5. The function of PEX5-LPL might be to drive aberrant expression of the 3’ partner or the chimeric protein might have a modified or novel function. Overexpression of LPL relative to normal cervix was found in over one third of cervical SCC cell lines and primary tumour samples, suggesting it is common in cervical SCC. Findings suggest that PEX5-LPL and LPL overexpression have similar roles in cervical carcinogenesis; functional studies of overexpression elucidated a role for both proteins in increased cellular invasion. The functionally important domain might be shared between these proteins and is most likely to be in the C terminal region of LPL. This C terminal domain may be considered as a novel candidate for targeted therapy of cervical SCC.
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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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Chung, Man-fai Yvonne, and 鍾文暉. "Investigation of biomarkers in esophageal squamous cell carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43704025.
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Yu, Zhuoyou, and 余卓由. "Role of DNAJB6 in esophageal squamous cell carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/196454.
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Esophageal cancer (EC), which is geographically diverse, has only a 10.7% five-year survival rate. One of the histologic forms, esophageal squamous cell carcinoma (ESCC), in Hong Kong accounts for 81.5% of the total EC cases and its five-year survival rate is only ~14%, due to its high frequency of metastasis.
In our previous studies, functional complementation study of chromosome 9 defects led to the discovery of a novel tumor suppressor gene, Deleted in Esophageal Cancer 1 (DEC1), mapping to 9q32. DEC1 was shown to reduce tumorigenicity in a mouse model and its expression was shown to be associated with lymph node metastasis, early onset of ESCC, and familial ESCC development in a tissue microarray (TMA) study. Moreover, DNAJ (Hsp40) homologue subfamily B member 6 (DNAJB6), a molecular co-chaperone protein and the focus of the current study, was identified as a DEC1-interacting protein through a yeast two-hybrid screening. The interaction was further confirmed by the GST pull-down assay and co-localization studies. Using a TMA constructed with ESCC tissues from Hong Kong, the clinical relevance of DNAJB6 expression was demonstrated.
In the present study, the role of DNAJB6 in ESCC was investigated using cell line-based in vivo and in vitro studies. DNAJB6 was shown to be down-regulated in ESCC cell lines. The two isoforms of DNAJB6 have distinct subcellular localizations, with DNAJB6a mainly localized to the nucleus and DNAJB6b diffused throughout the cell. Existence of a functional nuclear localization signal peptide and a functional nuclear export signal peptide was verified in DNAJB6a and DNAJB6b, respectively. In vitro evidence of possible DNAJB6a truncation was found.
In vivo subcutaneous nude mice tumorigenicity assays showed that over-expression of DNAJB6a, but not DNAJB6b, suppresses tumor growth at the primary site, while DNAJB6a silencing enhances tumor growth. The suppressive effect of DNAJB6a depends on nuclear localization of the protein and the HPD tripeptide motif in the N-terminal J domain. In vitro function studies show that DNAJB6a over-expression impairs cell proliferation by suppressing G1/S transition.
AKT1 phosphorylation is down-regulated in DNAJB6a over-expressed cells, leading to up-regulation of p27KIP1 protein expression and down-regulation of cyclin E1 protein expression, the G1/S transition promoter, in an AKT1-dependent manner. DNAJB6a silencing results in the opposite effect.
Over-expression of DNAJB6b, but not DNAJB6a, instead suppresses lung colonization in an experimental metastasis assay, and prolongs survival of the mice.
Silencing of DNAJB6a in immortalized normal esophageal epithelial cells initially induces a senescence-like phenotype with greatly reduced proliferation possibly due to oncogenic stress from up-regulation of AKT1 phosphorylation and cyclin E1 protein expression, but promotes EMT-like molecular alterations by up-regulating STAT3 phosphorylation and TWIST1 protein expression and resumes proliferation after prolonged culture.
In summary, these results suggest that DNAJB6 plays a critical role in ESCC initiation, development, and metastasis and provides valuable insight into the understanding of ESCC tumorigenesis and metastasis. This suggests its usefulness as a biomarker candidate for detecting early ESCC tumor initiation.published_or_final_version
Clinical Oncology
Doctoral
Doctor of Philosophy
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Clark, Richard R. "Lymph node metastasis in auricular squamous cell carcinoma." Thesis, University of Glasgow, 2009. http://theses.gla.ac.uk/547/.
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Introduction Squamous cell carcinoma of the auricle has an unusually high rate of lymph node metastases when compared to similar tumours at other sites. The lymph nodes affected are close to the base of the skull and in the neck. Development of metastasis carries a poor prognosis and most patients will subsequently die of failure of loco-regional control. Despite the likelihood of a poor outcome nothing can be done for patients prior to development of metastasis, as the risk of spread is not sufficiently high to warrant intervention in all patients. They are therefore treated with a ‘wait and see policy’ and only offered treatment once clinical evidence of metastatic spread is detected. This thesis sets out to examine what can be done, at the time of initial presentation with an auricular squamous cell carcinoma to identify patients who would benefit from treatment to the regional lymph node basins. Materials and Methods The thesis is divided into four separate studies. A systematic review examines the evidence available to date, an anatomical study examines the lymphatic drainage of the auricle in cadavers, a sentinel lymph node biopsy study examines the use of this technique to identify early tumour spread and a retrospective analysis of cases of auricular squamous cell carcinoma in our unit examines histopathological prognostic indictors of metastatic spread. Results The systematic review found that these tumours have a metastatic rate of about 11%. Patients developing metastasis usually die from failure of loco-regional control. Depth of tumour invasion, tumour size and mode of invasion seem to be potential indicators of metastatic risk. There is a strong argument for prophylactic intervention to the regional lymph nodes but there is no consensus of opinion as to when this should be carried out The anatomical study comprised 5 cadaveric dissections. They showed that the first echelon nodes draining the auricle lie in the superficial parotid gland, post-auricular/ mastoid nodal group and level II of the neck. There are anastamotic pathways around the mastoid and post-auricular nodes that could permit embolic tumour cells to bypass them. Five lymphatic pathways draining the auricle are described and some of these lie on the lateral and anterior surfaces of the mastoid bone and traverse the insertion of sternocleidomastoid. 28 cases of auricular squamous cell carcinoma were enrolled for sentinel lymph node biopsy. None of them were found to have any metastatic spread. One case showed non-viable tumour cells in a lymph node. There was a high incidence of complications (14%) directly related to the sentinel node biopsy procedure. The retrospective analysis identified 229 cases of auricular squamous cell carcinoma treated in our unit from 1992 - 2004. 212 of these cases had the primary pathology available for analysis. 24 (of 212) patients developed metastasis. 17 patients died as a result of their disease usually due to failure of control at the regional lymph node basin. Primary tumours with a depth of invasion greater than 8mm have metastatic rate of 56%. Tumours with a depth of invasion between 2-8mm and evidence of cartilage destruction, lymphovascular invasion or a non-cohesive invasive front have 24% metastatic rate. Tumours outwith these high-risk groups did not metastasise. Conclusions Elective lymph node dissections of the superficial parotid gland, post-auricular/mastoid and level II nodes should be considered in patients with primary auricular squamous cell carcinomas with a depth of invasion >8mm or a depth of invasion between 2 - 8 mm and evidence of cartilage destruction, lymphatic invasion or a non-cohesive invasive front. This should ideally be done as part of an observational study to evaluate the cost / benefit ratio for these patients. The neck dissection must clear the mastoid bone to a sub-periosteal level on its anterior and lateral surfaces. This will require the removal of the upper portion of sternocleidomastoid. Sentinel lymph node biopsy requires further study to evaluate it as a method for early detection of metastatic spread in auricular squamous cell carcinoma. This could be done as part of an observational study of elective neck dissections.
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Chung, Man-fai Yvonne. "Investigation of biomarkers in esophageal squamous cell carcinoma." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B43704025.
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Sáenz, Sardà Xavier. "Progression pathways of squamous cell carcinoma associated with actinic damage: From cancer field to actinic keratosis and invasive squamous cell carcinoma." Doctoral thesis, Universitat Autònoma de Barcelona, 2019. http://hdl.handle.net/10803/667918.
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Se pensaba que la progresión de una queratosis actínica (AK) a carcinoma escamoso infiltrante (SCC) de piel ocurría siempre y cuando la neoplasia intra-epidérmica ocupara todo el espesor de la epidermis como ocurre en la vía clásica (CP) descrita en el cáncer de cérvix. Sin embargo, el carcinoma escamoso infiltrante cutáneo puede aparecer directamente desde una displasia que sólo ocupe el tercio inferior de la epidermis (AK I, vía diferenciada o DP). Esta segunda vía de progresión se ha descrito en el SCC de vulva y de cavidad oral , cuyo comportamiento biológico es además más agresivo.
Esta tesis empezó revisando todos los casos correspondientes a biopsias quirúrgicas, obtenidas mediante el BioBanco del Hospital Germans Trias y Pujol, de tres años consecutivos correspondientes al período 2004-2007. Seleccionamos 503 casos de SCC cutáneo, de los que finalmente estudiamos 196. La mayor parte mostraron AK I en superficie (63.8%) o en los bordes (77.9%), concluyendo así que la invasión directa desde AK I (DP) es la forma más frecuente de progresión a SCC cutáneo. Este estudio fue el primero que se propuso investigar la prevalencia de la CP y DP en la transformación de la AK en SCC infiltrante aportando evidencias de su existencia. Estos hallazgos se publicaron en J Eur Acad Dermatol Venereol. 2014 Oct; 29(5):991-7.).
La siguiente etapa del estudio consistió en la realización de una matriz de tejidos (TMA) de las biopsias ya estudiadas y se segregaron los casos con SCC entre los originados por DP y los originados por CP. En total se realizaron ocho TMA que supusieron 756 cores a evaluar. Mediante el uso de técnicas de inmunohistoquímica se evidenció que la transición epitelio-mesénquima participa en la transformación de AK I en SCC (DP) mientras que una capacidad proliferativa mayor facilita la extensión intra-epidérmica en la vía clásica y se hallaron diferencias significativas en cuanto a la expresión de CD31 (angiogénesis) y MMP (metaloproteinasas) hallándose estos marcadores elevados en los tumores que progresan por DP, lo que junto con la transición epitelio-mesenquima podría facilitar la progresión local. Una parte de estos resultados han sido publicados en la revista J Eur Acad Dermatol Venereol. 2018 Apr; 32(4):581-586). Tambien se procedio al uso de técnicas de CISH para el estudio de miRNA hallándose los tumores surgidos por DP expresan mayores niveles de miRNA31 tanto en su intensidad como en su extensión.
En la siguiente etapa se estudió la extensión de la atipia queratinocitaria por el epitelio de los anejos estando esta presente en el 25.9% de los casos y, de ellos, la infiltración del carcinoma escamoso directamente adyacente a la basal folicular estaba presente en el 58% de los casos. En consecuencia, seria altamente recomendable indicar la profundidad de la extensión folicular en el diagnóstico histológico de biopsias incisionales, dado el riesgo de recurrencia e infiltración que ello implica, así como las derivadas terapéuticas que conlleva. Los hallazgos han sido publicados en la revista J Eur Acad Dermatol Venereol. 2018 Oct; 32(10):1657-1661).
Consideramos que la serie de estudios que conforman esta tesis proporcionan conocimiento nuevo sobre las vías de progresión del SCC cutáneo y de sus lesiones precursoras. Se ha establecido que existen al menos dos vías de progresión de SCC a AK, se ha introducido el concepto de DP en la carcinogénesis cutánea, se han hallado bases moleculares que explican la progresión a través de ambas vías y se ha constatado el riesgo de la extensión folicular en la AK. Todos estos estudios han supuesto en algunos ámbitos un cambio de paradigma y tienen relevancia tanto en el diagnóstico como en el tratamiento de las AK.It was thought that the progression of an actinic keratosis (AK) to invasive squamous cell carcinoma (SCC) occurred as long as the intra-epidermal neoplasm occupied the entire thickness of the epidermis as in the classical pathway (PC) described in cervix cancer. However, cutaneous infiltrative squamous carcinoma can appear directly from a dysplasia that only occupies the lower third of the epidermis (AK I, differentiated pathweay or DP). This second pathway of progression has been described in SCC of the vulva and oral cavity, whose biological behavior is more aggressive. This thesis began by reviewing all cases corresponding to surgical biopsies, obtained through the BioBanco of the Germans Trias and Pujol Hospital, for three consecutive years corresponding to the period 2004-2007. We selected 503 cases of cutaneous SCC, of which we finally studied 196. Most showed AK I on the surface (63.8%) or on the edges (77.9%), thus concluding that the direct invasion from AK I (DP) is the most frequent form of progression to cutaneous SCC. This study was the first one that was proposed to investigate the prevalence of CP and DP in the transformation of AK into infiltrating SCC, providing evidence of its existence. These findings were published in J Eur Acad Dermatol Venereol. 2014 Oct; 29 (5): 991-7.). The next stage of the study consisted in the realization of a tissue microarrays (TMA) of the biopsies already studied and the cases with SCC were segregated between those originated by DP and those originated by CP. In total, eight TMAs were performed, which involved 756 cores to be evaluated. Through the use of immunohistochemical techniques it was demonstrated that the epithelial-mesenchymal transition participates in the transformation of AK I into SCC (DP) while a greater proliferative capacity facilitates the intra-epidermal extension in the classical pathway and significant differences were found in to the expression of CD31 (angiogenesis) and MMP (metalloproteinases), these markers being elevated in tumors that progress through DP, which together with the epithelium-mesenchymal transition could facilitate local progression. A part of these results have been published in the journal J Eur Acad Dermatol Venereol. 2018 Apr; 32 (4): 581-586). We also proceeded to the use of CISH techniques for the study of miRNA, finding that tumors arising from DP express higher levels of miRNA31 both in their intensity and in their extension. In the next stage the extension of the keratinocyte atypia among adnexal structures was studied, being present in 25.9% of the cases and, of them, the infiltration of the squamous carcinoma directly adjacent to the follicular basal was present in 58% of the cases. Consequently, it would be highly advisable to indicate the depth of follicular extension in the histological diagnosis of incisional biopsies, given the risk of recurrence and infiltration that this implies, as well as the therapeutic derivatives that it entails. The findings have been published in the journal J Eur Acad Dermatol Venereol. 2018 Oct; 32 (10): 1657-1661). We consider that the series of studies that make up this thesis provide new knowledge about the pathways of cutaneous SCC progression and its precursor lesions. It has been established that there are at least two pathways of progression from SCC to AK, the concept of PD has been introduced in cutaneous carcinogenesis, molecular bases have been found that explain the progression through both pathways and the risk of follicular extension in the AK. All these studies have led to a paradigm shift in some areas and are relevant both in the diagnosis and treatment of AKs.
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Bruin, Alain de. "Loss of invasiveness in squamous cell carcinoma cells : overpressing desmosomal coadherins /." Bern : [s.n.], 1997. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Meier, Erica. "Untersuchung des posttherapeutischen Verlaufs von Patienten mit intraoralen Plattenepithelkarzinomen /." [S.l.] : [s.n.], 2009. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000297947.
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Frede, Julia. "Cellular dynamics in Oesophageal Squamous Carcinogenesis." Thesis, University of Cambridge, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708817.
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Wassberg, Cecilia. "Ultraviolet Radiation and Squamous Cell Carcinoma in Human Skin." Doctoral thesis, Uppsala University, Department of Medical Sciences, 2001. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1479.
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Ultraviolet radiation (UVR) is a major risk factor for development of skin cancer. UVR-induced DNA damage and a dysfunctional p53 protein are important steps in the development of squamous cell carcinoman in human skin (SCC). The aim of the present investigation was to analyze incidence trends of SCC in Sweden, quantify the risk of second primary cancer after SCC and further analyze the effects of UVR and p53 protein in human skin in vivo and in vitro. The effect of photoprotection by sunscreens was also evaluated.
We found that the age-standardized incidence rate of SCC in Sweden increased substantially in both men and women during the period 1961-1995, especially in men and at chronically sun-exposed skin sites. Patients with SCC are also at increased risk of developing new primary cancers, especially in the skin, squamous cell epithelium, hematopoietic tissues and respiratory organs. In experimental studies in vivo and in vitro in human skin we observed that repair of UV-induced DNA damage appears to be more efficient in chronically sun-exposed skin despite a less uniform p53 response. Non-sun- exposed skin is more homogeneous with respect to the epidermal p53 response. Keratinocytes in skin exposed frequently to the sun may be prone to react more easily to cytotoxic stress. Two different modalities of photoprotection significantly reduced the amount of DNA damage and the number of p53-positive cells. In addition, we demonstrated that a well-defined system for in vitro culture of explanted skin provides an excellent alternative to in vivo experiments.
In conclusion, this study has increased our knowledge of SCC epidemiology in Sweden and of the effects of artificial and solar UVR and sunscreens on chronically sun-exposed and non-sun-exposed sites, respectively, of human skin.
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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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LE, HOANG BA PATRICK. "Interet diagnostic du squamous cell carcinoma en pathologie pleuropulmonaire." Nice, 1988. http://www.theses.fr/1988NICE6550.
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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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Tang, Cheuk-on. "Cytogenetic and molecular study of oesophageal squamous cell carcinoma /." Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk:8888/cgi-bin/hkuto%5Ftoc%5Fpdf?B23339834.
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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.
Full textAbstract:
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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Akdeniz, Gözde. "Quantitative characterisation of cell fate in human keratinocytes and squamous cell carcinoma." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609952.
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Trotter, Martin James. "Intermittent blood flow in the murine SCCVII squamous cell carcinoma." Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/31344.
Full textAbstract:
Intermittent blood flow in tumour microvasculature is believed to contribute to heterogeneity in tumour oxygen delivery; transient vessel nonperfusion is thought to result in acutely hypoxic cells resistant to conventional radiotherapy. This thesis describes three main areas of work: (1) the development of a histologic method capable of detecting intermittent blood flow in experimental tumours at the single vessel level; (2) the quantification and characterization of tumour blood flow fluctuations in the murine SCCVII carcinoma; and (3) the modification of tumour blood flow and the reduction of flow heterogeneity using vasoactive drugs.
A double staining technique involving the sequential intravenous injection of two fluorescent vascular markers was used to detect transient episodes of tumour vessel nonperfusion. The stains employed were Hoechst 33342 and the carbocyanine dye, DiOC₇(3), both of which have short (< 3 minutes) circulation half-lives and preferentially stain cells adjacent to perfused blood vessels. When injections of the vascular markers are separated by some interval, each stain defines only those tumour vessels which were perfused during the few minutes immediately post-injection; thus, two "pictures" of tumour microvascular flow are obtained and tumour vessels subject to periods of nonperfusion can be easily visualized in frozen sections since they are outlined by one stain but not the other.
Using the double staining technique, in which Hoechst 33342 and then DiOC₇(3) are administered intravenously 20 minutes apart to unrestrained C3H/He mice, staining mismatch (indicative of transient vessel nonperfusion) is regularly observed in subcutaneous SCCVII carcinoma. Vessels stained with DiOC₇(3) only (reperfusion of previously nonperfused vessels) or with H33342 only (nonperfusion of previously perfused vessels) are observed in approximately equal numbers. The percentage of tumour vessels subject to intermittent flow is a function of SCCVII tumour size: tumours ≤100 mg do not exhibit statistically significant amounts of mismatch. At sizes > 100 mg, overall staining mismatch is significantly increased over background levels and maximum mismatch is observed at tumour sizes >400 mg (8.6 ±2.9%). In most tumours, transient vessel nonperfusion is more pronounced in central tumour regions. In addition to mismatch observed in individual vessels, large "patches" of unequal staining are also seen. Anaesthesia or restraint do not significantly influence intermittent blood flow.
The above information suggests that transient episodes of tumour vessel nonperfusion occur as a consequence of flow reduction in a feeding vessel; vessels in central regions of large tumours may be susceptible to collapse as a result of elevated tumour interstitial pressure. In the SCCVII tumour, a small number of peripheral vessels possess vascular smooth muscle and thus may be capable of vasomotor activity.
The importance of perfusion pressure in the control of tumour microcirculatory flow was examined using vasoactive drugs. Hydralazine, a vasodilator which lowers blood pressure, causes a profound reduction in tumour RBC flow to 8.7 + 6.4% of pretreatment values in unanaesthetized mice. The drug causes collapse of central tumour vessels: following a dose of 10mg/kg intravenously, 36±16% of vessels are completely nonperfused, as detected using the double staining technique. Conversely, elevation of blood pressure using the vasoconstrictor angiotensin II results in a 2-3x increase in tumour blood flow. In addition, angiotensin II infusion significantly reduces the number of tumour vessels subject to transient nonperfusion from 8.1 % to 2.0%. However, intermittent blood flow in the SCCVII carcinoma can also be influenced by nonvasoactive drugs: nicotinamide, the amide form of vitamin B3, reduces episodes of transient nonperfusion.
In summary, intermittent blood flow has been characterized in a transplanted murine squamous cell carcinoma using a novel fluorescent double staining method which allows the detection of flow fluctuations in solid tumours at the microvascular level. If transient episodes of nonperfusion occur in human tumours and result in impaired oxygen or drug delivery, then such flow fluctuations may be an important factor limiting tumour cure or local control by radiotherapy or chemotherapy.Medicine, Faculty of
Pathology and Laboratory Medicine, Department of
Graduate
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Goldie, Stephen John. "Studies of FRMD4A in two models of squamous cell carcinoma." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648321.
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Torchia, Mark G. "Minimally invasive evaluation of head and neck squamous cell carcinoma." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/NQ57639.pdf.
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Bradburn, Jennifer Elizabeth. "Reactive species promotion of head and neck squamous cell carcinoma." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1166555968.
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Homer, Jarrod James. "Studies on angiogenesis in head and neck squamous cell carcinoma." Thesis, University of Hull, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342866.
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Ruban, Emily L. "PLC-β4 signalling & function in human squamous cell carcinoma." Thesis, Queen Mary, University of London, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612569.
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Zhu, Cailei, and 祝彩磊. "Identification and characterization of CHL1 in esophageal squamous cell carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B46329559.
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Leung, Cheuk-man, and 梁卓文. "A study of BARX2 expression in esophageal squamous cell carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B47560460.
Full textAbstract:
Background
Esophageal carcinoma mainly affects middle aged to elderly males. It ranks the
ninth most common cancer world-wide. The main histological types are squamous
cell carcinoma and adenocarcinoma. In Hong Kong, esophagus squamous cell
carcinoma (ESCC) is by far the more common. BARX2 is a human homeobox gene
located at 11q24-q25, encoding a protein of 254 amino acids. Recent researches show
that its expression in breast cancer promotes cellular invasion.
Objectives
The study aimed to test the hypothesis that BARX2 is a prognostic marker in
ESCC. BARX2 expression in ESCC was correlated with patient survival and other
clinicopathologic parameters in a cohort of patients.
Material and Methods
Records of ESCC patients were obtained retrospectively from the computerized
database of Queen Mary Hospital. ESCC patients, who underwent esophagectomy in
the hospital from 1998 to 2005 but without receiving prior chemotherapy or
radiotherapy directed to the tumor, were selected. Tumor staging was done according
to the 6th edition of AJCC Cancer Staging Manual. Immunohistochemical staining
for BARX2 expression was performed on paraffin sections of the primary ESCC
tissues sampled in a tissue microarray constructed for research purposes. The pattern
of BARX2 expression in nucleus and cell cytoplasm of tumor cells was recorded and
the staining intensity scored on a 4-point scale. The scores were statistically analyzed
together with the various clinicopathologic parameters. BARX2 expression and
patient survival time were analyzed by the log-rank test.
Results
A total of 78 ESCC patients were recruited. At the time of data analysis, 52
(66.7%) patients were dead. The overall median survival of patients was 14.3 months.
BARX2 was found to be mainly expressed in the cytoplasm of tumor cells while
non-tumor epithelium showed strong nuclear expression. Patients with high level
BARX2 expression had short survival time, though the difference did not reach
statistical significance (p=0.075). Within the subgroup of lower T-stage ESCC (T1-3),
high level BARX2 expression was significantly associated with shorter survival time
(p=0.042). However, differential BARX2 expression did not affect survival time
within the group of patients who had advanced stage (T4) disease (p=0.525). In
patients who had no regional lymph node metastasis (N0), high level BARX2
expression was associated with shorter survival time (p=0.023). However, when
patients had regional lymph node metastases (N1), BARX2 expression did not affect
patient survival time (p=0.533). Patients whose ESCC showed moderate
differentiation in a three-tier tumor grading system, when accompanied with low level
BARX2 expression, had longer survival time (p=0.029). However, BARX2
expression did not affect survival time when ESCC showed either well differentiation
(p=0.462) or poor differentiation (p=0.637). Multivariate analysis showed patient age
and T-stage to be the only two independent parameters of prognostic significance
(p=0.025 and p=0.036 respectively).
Conclusions
BARX2 expression in ESCC was aberrant and mainly cytoplasmic. It was
inversely correlated with patient survival time in early ESCC disease (T1-T3 or N0).
BARX2 expression evaluated by immunohistochemistry could be a useful and
practical prognostic marker of ESCC in its early stages, when the proper decision on
treatment would be critical for the patients.published_or_final_version
Pathology
Master
Master of Medical Sciences
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Robinson, Kim. "Identification of novel molecular targets for cutaneous squamous cell carcinoma." Thesis, University of Dundee, 2014. https://discovery.dundee.ac.uk/en/studentTheses/78349252-d233-40ad-9724-7b186baf531b.
Full textAbstract:
Cutaneous Squamous Cell Carcinoma (cSCC) is the most common human tumour with malignant potential which is responsible for over 1 in 4 skin cancer deaths in the UK. High risk groups exist such as, immunosuppressed patients and those with the genetic condition recessive dystrophic epidermolysis bullosa whom are burdened with increased cSCC incidence, metastasis and mortality. Current clinically available molecular targets for cSCC are limited. Moreover, the key molecular events in cSCC remain poorly defined, presumably including both loss/gain of DNA or through gene silencing by DNA modifications. Understanding the molecular events which lead to cSCC is paramount for developing successful, novel molecular targets for therapeutic purpose. Preceding this thesis, our group used two independent methods to identify potential molecular targets: microarray technology (Watt 2011) and Sanger sequencing (Wang 2011), of which some of the targets identified from these studies, formulate the basis of this thesis. Using microarray technology, a comparison between gene expression profiles of cultured cSCC and normal keratinocytes, identified a gene signature specific for cSCC. From this signature, five genes were identified as being over-expressed in cSCC compared to normal and whose gene expression was important for cell survival. Subsequently, three of these genes were further explored within this thesis: germ cell associated 2 (GSG2), bradykinin receptor B1 (BDKRB1) and protease serine 21 (PRSS21). To begin, genes were confirmed to be over-expressed at both mRNA and protein level. Following this conformation, several endpoints were monitored using standard assays of cell viability, proliferation and apoptosis, in cSCC keratinocytes using gene specific siRNA. Using this validation method, PRSS21 showed the most promise as a molecular target. Depletion of PRSS21 resulted in decreased cell viability through an increase in cytotoxicity and apoptosis. Therefore PRSS21 was further validated as a molecular target through stable overexpression in an immortalised normal human cell line with no endogenous PRSS21 expression. Subsequently, using 3D organotypic cultures, it was shown that the expression of PRSS21 clearly transformed these cells into an invasive phenotype, compared to the control. Finally, PRSS21 was shown to interact with the tumour suppressor maspin, potentially negatively regulating maspin dependant apoptosis. This data strongly suggests that both PRSS21 and maspin are potential targets in cSCC. The second method of identifying molecular targets was direct sequencing of tumour DNA, which identified loss of function notch mutations in ~75% of cSCC. It has been postulated that loss of notch function contributes to cSCC through a reduction in differentiation. Using three cSCC cell lines of known notch status (wild type/loss of function/notch null), cells were grown in organotypic culture, and the expression of markers associated with differentiation studied. With the aid of a gamma secretase inhibitor to inhibit notch signalling the contribution of notch to the expression of differentiation markers was studied in cSCC cells compared to normal human keratinocytes (NHK). There was a significant reduction in differentiation within the cSCC cell lines compared to NHK, regardless of notch status, and differentiation could be further reduced by the presence of GSI in the cSCC with wild type/loss of function notch expression. Furthermore, overexpression of a gamma secretase regulatable intracellular notch1 (ICN1) construct, showed an induction of involucrin in these cells, compared to cells overexpressing an empty vector control, confirming that notch1 contributes to differentiation. Overall this work highlights the importance of validating targets before embarking on expensive, time consuming experiments. In doing so, it reveals two potential molecular targets which could be important for the progression of cSCC, PRSS21 and maspin. Additionally it confirms the potential mechanism of notch loss of function in suppressing differentiation, suggesting that its re-activation would be is a valid approach to cSCC therapy.
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Garcia, Mayea Yoelsis. "Novel therapeutic approaches against Head and Neck Squamous Cell Carcinoma." Doctoral thesis, Universitat de Barcelona, 2020. http://hdl.handle.net/10803/672185.
Full textAbstract:
Head and neck squamous cell carcinoma (HNSCC) is usually diagnosed in advanced stages. The treatment has not changed much on the last decades, being limited to surgery followed by radiotherapy and/or chemotherapy [mainly cisplatin (CDDP) and 5-fluorouracil (5-FU)]. However, the acquisition of chemotherapy resistance is very common, which usually leads to recurrences and metastases. On the other hand, the role of autophagy in HNSCC is not clearly defined. This is the reason why in this thesis we have proposed: 1) to determine the role of autophagy in HNSCC models and its relationship with chemotherapy resistance and other clinical parameters; 2) to identify target proteins involved in the acquisition of chemotherapy resistance in HNSCC models whose modulation of its expression and/or activity could be of clinical and therapeutic interest.
From a retrospective immunohistochemistry (IHC) study, we found that the
expression of the autophagy markers sequestosome-1 (p62/SQSTM1) and microtubule-associated proteins 1A/1B light chain 3B (LC3), as well as prostate tumor-overexpressed gene 1 protein (PTOV1), could be considered markers of poor clinical prognosis in laryngeal cancer patients. We found overexpression of PTOV1 and the autophagy-related protein 5 (ATG5) in HNSCC biopsy-derived cell lines with innate resistance to CDDP. Likewise, in general, autophagy activation and/or PTOV1 overexpression occurred in three non-metastatic HNSCC cell lines in which resistance to CDDP and 5-FU had previously been generated, as well as in cancer stem cells (CSCs). Furthermore, PTOV1 overexpression induced autophagy in JHU029 laryngeal cell line. Finally, we found that autophagy inhibition with hydroxychloroquine (HCQ), alone or in combination with CDDP or 5-FU, could be an attractive therapeutic alternative for HNSCC patients with chemotherapy resistance.
In addition, a comparative proteomic study revealed tetraspanin 1 (TSPAN1) as a
target involved in chemotherapy resistance in HNSCC models. In this sense, TSPAN1 depletion decreased cell proliferation, induced apoptosis, and sensitized HNSCC cell lines and biopsy-derived cell lines to chemotherapeutic agents like CDDP and dasatinib. Moreover, TSPAN1 depletion reduced autophagy and blocked the activation of proto-oncogene tyrosine-protein kinase SRC (SRC), protein kinase B (AKT) and mitogen-activated protein kinase (ERK). In addition, TSPAN1 expression was associated to epithelial–mesenchymal transition (EMT) activation in mice tumors and HNSCC patient biopsies. Overall, TSPAN1 inhibition could be a promising therapeutic strategy to improve the current treatment against HNSCC patients.
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Ito, Tetsuo. "Involvement of TSLC1 in progression of esophageal squamous cell carcinoma." Kyoto University, 2005. http://hdl.handle.net/2433/144773.
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Quan, Jingjing, Nigel Morrison, Newell Johnson, and Jin Gao. "Molecular Mechanisms of Bone Invasion by Oral Squamous Cell Carcinoma." Thesis, Griffith University, 2014. http://hdl.handle.net/10072/366929.
Full textAbstract:
Invasion of bone is a common characteristic of oral squamous cell carcinoma (OSCC), which adversely affects on functionality and survival of patients. Recent studies suggst that osteoclasts, rather than OSCC cells, facilitate the entry of the tumour into bone and result in the progression of cancer within bone. Generation of osteoclasts is due to either an indirect effect involving stimulation of osteoblasts, or a direct effect initiated by OSCC cells. This study, consisting of three parts, aims to investigate the signalling pathways involved in the crosstalk between OSCC cells, osteoblasts and osteoclasts. Using research models both in vitro and in vivo, this study explores molecules with the potential to inhibit such bone invasion for the design of future biotherapies.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Griffith Health
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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/.
Full textAbstract:
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.